bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Effect of Cholinesterase Inhibitor Medications on Recognition Memory Performance in Mild to Moderate Alzheimer’s Disease: Preliminary Findings
Authors: Crowell Timothy A. , Paramadevan Juno , Abdullah Laila , Mullan Michael
Published: January 2006

Cholinesterase inhibitor (ChEI) medications (ie, donepezil, rivastigmine, and galantamine) have been useful in slowing the progression of the mild to moderate stages of Alzheimer’s disease (AD). Findings supporting this have largely relied on a global error score from the Alzheimer’s Disease Assessment Scale and have not described the nature of the memory problems. We examined this issue by comparing learning, recall, and recognition scores among 2 groups of mild to moderately demented AD patients. Participants were patients from a memory clinic who either were on ChEI treatment (AD+ChEI, n = 14) or had never taken a ChEI (AD-ChEI, n = 14). Participants underwent a comprehensive neuropsychological evaluation, including administration of the CERAD Word List Memory test. Results indicated no significant group difference for learning and delayed free recall, but the AD+ChEI group had significantly fewer errors than the AD-ChEI group on the CERAD Recognition test. Our findings provide preliminary evidence that the aspect of memory that is most affected by ChEIs appears to be facilitation of retention of new information in memory. The implications of this on clinical care and functional abilities as well as future directions are discussed.
Frontal Assessment Battery and Brain Perfusion Image in Parkinson’s Disease
Authors: Matsui Hideaki , Udaka Fukashi , Miyoshi Takafumi , Hara Narihiro , Tamura Akiko , Oda Masaya , Kubori Tamotsu , Nishinaka Kazuto , Kameyama Masakuni
Published: January 2006

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson’s disease patients with a high frontal assessment battery score and those with a low frontal assessment battery score. Thirty nondemented patients with Parkinson’s disease were studied. Patients were divided into 2 groups: a high-scoring group whose frontal assessment battery score was 12 or more and a low-scoring group whose frontal assessment battery score was 11 or less. The high-scoring group included 21 patients, and the low-scoring group included 9 patients. They underwent N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography, and we analyzed the data by the 3-dimensional stereotactic surface projection method. Results showed that left inferior parietal lobule and left supramarginal gyrus perfusion of the low-scoring group were significantly decreased compared with the high-scoring group. It is concluded that_patients with Parkinson’s disease may have frontal lobe dysfunction, but the decreased frontal assessment battery score may be caused not by progressed frontal lobe dysfunction but by parietal lobe dysfunction added to their preexisting frontal lobe impairment.
Performance Monitoring and Error Processing During a Lexical Decision Task in Patients With Parkinson’s Disease
Authors: Ito Junko , Kitagawa Junko
Published: January 2006

To evaluate performance monitoring and error processing during lexical decision tasks, event-related potentials (ERPs) obtained by time-locked to correct and error responses were studied in 17 Parkinson’s disease (PD) patients without dementia and 15 healthy elderly participants. The amplitude of error negativity (Ne) obtained by averages time-locked to error response was significantly reduced in the PD patients, whereas there were no significant differences in the negative component for the correct response (Nc) between the two participant groups. The amplitude of the error positivity (Pe) and correct positivity (Pc) after the Ne and Nc components was also significantly reduced in the PD patients. The PD patients showed significantly slower reaction times and higher error rates. The reduced amplitude of the Ne, Pe, and Pc components in the PD patients suggested impaired performance and conflict monitoring as well as abnormal response strategy adjustments and deviant in later error monitoring processes associated with emotional, conscious evaluation of the error.
Factors Contributing to Women’s Ability to Maintain a Walking Program
Authors: Nies Mary A. , Motyka Carrie L.
Published: January 2006

Purpose:The purpose of this descriptive study is to determine what strategies were most helpful for women to begin and maintain awalking program. Method:Data from the field notes of a randomized clinical trial to promotewalking in 97women were used for the qualitative analysis discussed in this article. Findings:Overall, the majority of participants met the study goal of walking 90 minutes per week. Conclusions:In addition, the participants reported other benefits, including becoming more physically fit, mental and emotional satisfaction, and stress reduction. Some of the barriers mentioned by participants were personal and/or professional obligations, weather, injuries and/or illnesses, and psychosocial factors. When benefits outweighed barriers, the participants had greater success meeting their walking goals. Implications:Furthermore, the participants stated that making time, problem solving, internal motivation, and the support of family and/or friends were the most helpful factors in achieving their walking goals.
Effects of Therapeutic Touch on Blood Hemoglobin and Hematocrit Level
Authors: Movaffaghi Zahra , Hasanpoor Morteza , Farsi Mohammad , Hooshmand Poory , Abrishami Fatemeh
Published: January 2006

Background: Therapeutic Touch (TT) is a widely used complementary therapy. This study investigated the effects of TT on hemoglobin and hematocrit level in students who were basically healthy. Method: The volunteers with a hemoglobin level less than 12 grams per deciliter (g/dl) were randomly assigned to three groups of TT, mimic therapeutic touch (MT), and control. Blood samples were collected before the first treatment and again a week after the last one and measurements were taken. Results: TT increased the level of hemoglobin (.99 .13 g/dl) and hematocrit (2.82 .43%) significantly. MT also increased the level of hemoglobin (.55 .11 g/dl) and hematocrit (2.75 .44%) significantly. No significant changes were found in the control group. TT increased hemoglobin more effectively than MT ( p< .05). Conclusions: Significant changes of both variables in TT and MTgroups suggest that more careful precision might be needed while selecting individuals as sham therapists in further experiments.
Implementation of a Statewide Outcome Monitoring System: Lessons Learned From Substance Abuse Treatment Provider Staff
Authors: Teruya Cheryl , Hardy Mary , Hser Yih-Ing , Evans Elizabeth
Published: January 2006

The authors analyze the pilot implementation of a statewide automated outcome monitoring system (OMS) in California, using the perspectives of substance abuse treatment providers responsible for its day-to-day operation. To gain a better understanding of changes experienced by staff and their perceptions of barriers and facilitators of implementation, they conducted 28 focus groups designed to inform midstream adjustments to the system prior to its possible roll-out. Qualitative analysis of the focus group data revealed five important factors influencing implementation: the treatment provider's ethos, the time-consuming nature of the OMS, staff buy-in, resources, and counselor and program discretion. Lessons learned underscored the importance of taking into consideration aspects of organizational change and institutional resources and infrastructure when implementing a major change such as an automated OMS. Findings might be useful to those designing and implementing similar systems or other large organizational change initiatives.
The Four Cornerstones of Qualitative Research
Authors: Gilgun Jane F.
Published: January 2006

Evidence-based practice (EBP) is more than the application of best research evidence to practice. Advocates for evidence-based medicine (EBM), the parent discipline of EBP, state that EBP has three, and possibly four, components: best research evidence, clinical expertise, and patient preferences and wants. Person-centered physicians also advocate for the person of the practitioner as a fourth component. In this article, the author shows the centrality of qualitative research to this fuller version of EBP. She also shows how qualitative research has four cornerstones that parallel the four components of EBP.
The Politics of Evidence
Authors: Morse Janice M.
Published: January 2006

The evidenced-based movement has influenced medical research to the point that the agendas and methods of qualitative inquiry are often excluded from resources of medical granting agencies. Yet, its narrow definition of what constitutes evidence and its myopic vision about health must be challenged. In this article, the author argues that qualitative research does contribute to a reduction in morbidity and mortality without the cost in dollars and lives that are necessarily incurred in evidence-based inquiry. She asserts that we must reframe our definition of evidence to meet this new ethic of inquiry—which she calls the ultimate ethic—as a way of conducting research.
Reconceptualizing Qualitative Evidence
Authors: Morse Janice M.
Published: January 2006

As qualitative researchers, we have not explored our own work from the qualitative evidence perspective. The author suggests that qualitative researchers need to explore the conflicting agendas of evidence-based medicine and qualitative inquiry, compare the anatomy of qualitative data and evidenced-based data, and explore the autonomy of qualitative inquiry within the context of evidenced-based medicine. By attending to and communicating the differences in qualitative and quantitative evidence, and by accepting the differences in our research agendas, qualitative researchers will achieve the legitimacy that they deserve and which they require.
Developing and Implementing a Triangulation Protocol for Qualitative Health Research
Authors: Farmer Tracy , Robinson Kerry , Elliott Susan J. , Eyles John
Published: January 2006

In this article, the authors present an empirical example of triangulation in qualitative health research. The Canadian Heart Health Dissemination Project (CHHDP) involves a national examination of capacity building and dissemination undertaken within a series of provincial dissemination projects. The Project's focus is on the context, processes, and impacts of health promotion capacity building and dissemination. The authors collected qualitative data within a parallel–case study design using key informant interviews as well as document analysis. Given the range of qualitative data sets used, it is essential to triangulate the data to address completeness, convergence, and dissonance of key themes. Although one finds no shortage of admonitions in the literature that it must be done, there is little guidance with respect to operationalizing a triangulation process. Consequently, the authors are feeling their way through the process, using this opportunity to develop, implement, and reflect on a triangulation protocol.
Structural Determinants of Police Effectiveness in Market Democracies
Authors: Sung Hung-En
Published: January 2006

This study examined structural correlates of police effectiveness in 28 market democracies. It found that perceptions of police effectiveness rose in countries with low homicide rates, independent judiciaries, and high income. Greater political freedoms and a lower robbery rate were associated with low police effectiveness. The size of police forces and population and unemployment rates were largely irrelevant. Findings demonstrated the basic dependence of quality policing on good judicial governance and a healthy economy. Making the police more effective requires reform of more than the police. In postmodern democracies, effective policing will require improved media portrayal of crime and increased democratization of police tactics and strategies.
Understanding and Preventing Gang Violence: Problem Analysis and Response Development in Lowell, Massachusetts
Authors: Braga Anthony A. , McDevitt Jack , Pierce Glenn L.
Published: January 2006

Gang violence presents a major challenge to police departments in the United States. Problem-oriented policing has been suggested as a promising way to understand and prevent complex gang violence problems. Unfortunately, problem analysis, as currently practiced, is generally weak and the resulting responses usually consist of mostly traditional enforcement tactics. Academic-police partnerships can be very productive in understanding and responding to serious crime problems. Unfortunately, such collaborations are rare. The U.S. Department of Justice-sponsored Project Safe Neighborhoods initiative provides an important opportunity to facilitate academicpolice partnerships. In Lowell, Massachusetts, academics and practitioners collaborated on a problem analysis that shed important light on the nature of gang violence and led to the implementation of problem-oriented responses that have been promising in preventing gang violence.
Complementary medicines in psychiatry
Authors: Werneke Ursula , Turner Trevor , Priebe Stefan
Published: January 2006

Background

The use of complementary medicines in those with mental health problems
is well documented. However, their effectiveness is often not established
and they may be less harmless than commonly assumed.

Aims

To review the complementary medicines routinely encountered in
psychiatric practice, their effectiveness, potential adverse effects and
interactions.

Method

Electronic and manual literature search on the effectiveness and safety
of psychotropic complementary medicines.

Results

Potentially useful substances include ginkgo and hydergine as cognitive
enhancers, passion flower and valerian as sedatives, St John's wort and
sadenosylmethionine as antidepressants, and selenium and folate to
complement antidepressants. The evidence is less conclusive for the use
of omega-3 fatty acids as augmentation treatment in schizophrenia,
melatonin for tardive dyskinesia and 18-methoxycoronaridine, an ibogaine
derivative, for the treatment of cocaine and heroin addiction.

Conclusions

Systematic clinical trials are needed to test promising substances.
Meanwhile, those wishing to take psychotropic complementary medicines
require appropriate advice.
Suicide within 12 months of mental health service contact in
different age and diagnostic groups
Authors: Hunt Isabelle M. , Kapur Navneet , Robinson Jo , Shaw Jenny , Flynn Sandra , Bailey Hayley , Meehan Janet , Bickley Harriet , Parsons Rebecca , Burns James , Amos Tim , Appleby Louis
Published: January 2006

Background

Suicide prevention is a health service priority but the most effective
approaches to prevention may differ between different patient groups.

Aims

To describe social and clinical characteristics in cases of suicide from
different age and diagnostic groups.

Method

A national clinical survey of a 4-year (1996–2000) sample of cases of
suicide in England and Wales where there had been recent (< 1 year)
contact with mental health services (n=4859).

Results

Deaths of young patients were characterised by jumping from a height or
in front of a vehicle, schizophrenia, personality disorder, unemployment
and substance misuse. In older patients, drowning, depression, living
alone, physical illness, recent bereavement and suicide pacts were more
common. People with schizophrenia were often in-patients and died by
violent means. About athird of people with depressive disorder died
within a year of illness onset. Those with substance dependence or
personality disorder had high rates of disengagement from services.

Conclusions

Prevention measures likely to benefit young people include targeting
schizophrenia, dual diagnosis and loss of service contact; those aimed at
depression, isolation and physical ill-health should have more effect on
elderly people.
Psychiatric morbidity among sentenced prisoners: prevalence
study in Iran
Authors: Assadi Seyed Mohammad , Noroozian Maryam , Pakravannejad Mahdi , Yahyazadeh Omid , Aghayan Shahrokh , Shariat Seyed Vahid , Fazel Seena
Published: January 2006

Background

Information on psychiatric morbidity of prisoners has almost entirely
been based on research in Western countries and it is uncertain whether
these research findings are applicable to other settings.

Aims

The primary objective was to investigate the prevalence of psychiatric
disorders in Iranian prisoners.

Method

Through stratified random sampling, 351 prisoners were interviewed using
the clinical version of the Structured Clinical Interview for DSM-IVAxis
I Disorders and the Psychopathy Checklist: Screening Version.

Results

The majority (88%) of prisoners met DSM – IV criteria for lifetime
diagnosis of at least one Axis I disorder and 57% were diagnosed with
current Axis I disorders. Opioid dependence (73%) had the highest
prevalence among lifetime diagnoses, whereas major depressive disorder
(29%) was the most common current diagnosis. Psychopathy was recorded in
23%. Prevalence rates of psychiatric disorders were significantly
different among offence categories.

Conclusions

The results suggest that a substantial burden of psychiatric morbidity
exists in the prison population of Iran, with treatment challenges that
appear to be different from those observed in inmates in Western
countries.
Long-term outcome of two forms of randomised benzodiazepine
discontinuation
Authors: Voshaar R. C. Oude , Gorgels W. J. M. J. , Mol A. J. J. , Van Balkom A. J. L. M. , Mulder J. , Van De Lisdonk E. H. , Breteler M. H. M. , Zitman F. G.
Published: January 2006

Abouttwo-thirds of long-term users of benzodiazepines in the population are
able to discontinue this drug with the aid of supervised programmes for
tapering off. Little is known about the long-term outcome of such
programmes, and they have never been compared with usual care. After a
15-month follow-up of a randomised controlled trial comparing such a
programme with and without psychotherapy with usual care, we found
significantly higher longitudinal abstinence rates in long-term
benzodiazepine users who received a benzodiazepine tapering-off programme
without psychotherapy (25 out of 69, 36%) compared with those who received
usual care (5 out of 33, 15%; P=0.03).
The future of cognitive-behavioural therapy for psychosis: not a
quasi-neuroleptic
Authors: Birchwood Max , Trower Peter
Published: January 2006

Some 20 trials of cognitive-behavioural therapy (CBT) for psychosis have
re-established psychotherapy as a credible treatment for psychosis. However,
it is not without its detractors and problems, including uncertainty about
the nature of its active ingredients. We believe that the way forward is to
abandon the neuroleptic metaphor of CBT for psychosis and to develop
targeted interventions that are informed by the growing understanding of the
interface between emotion and psychosis.
Achieving evidence-based prescribing practice in an adult community mental health service
Authors: Moran Maria , Raju Bangaru , Saunders Jean , Meagher David
Published: January 2006

Aims and Method

Prescribing in everyday practice frequently deviates from evidence-based guidelines. Previous work compared practice in a community mental health service with evidence-based guidelines and identified factors related to suboptimal prescribing. This study reports the impact of a multifaceted intervention on prescribing practice. A Prescribing Practice Quality (PPQ) score was generated from six key aspects of prescribing at initial assessment and again 1 year later after an intervention to reduce suboptimal prescribing practices.

Results

A total of 264 patients were attending the service at both the initial and follow-up phase and were thus exposed to the prescribing intervention. In this population, PPQ scores were significantly lower at follow-up (0.96v.0.67,P<0.001). Improved prescribing practice was predicted by receipt of adjunctive supportive inputs, such as anxiety management (P=0.003).

Similarly, mean PPQ scores substantially decreased when the total patient population was considered at each time point (0.75 in 2001 and 0.52 in 2002). These results suggest a reduction in both the initiation and continuation of suboptimal practices.

Clinical Implications

Prescribing in real-world settings can be improved by interventions that target multiple aspects of service activity. The provision of supportive inputs is a key factor in improving practice.
Off-label prescribing by psychiatrists
Authors: Hodgson Richard , Belgamwar Ravindra
Published: January 2006

Aims and Method

To report on the use of atypical antipsychotics in one health district by examining secondary care prescribing patterns for these medicines in North Staffordshire between 1994 and 2001. With one exception, these drugs were licensed solely for use in schizophrenia during the study period.

Results

A total of 502 patients were initiated on atypical antipsychotics in the study period. Of these, 297 (59.2%) had a diagnosis of schizophrenia (ICD–10 codes F20–29). Off-label prescribing was common, but psychiatrists were least likely to prescribe clozapine off-label (2.2%). Affective (18.4%) and organic disorders (12.4%) were the main disorders treated off-label. Olanzapine had the highest off-label use (44.5%).

Clinical Implications

The high off-label use of atypical antipsychotics has clinical and economic implications. Although off-label prescribing may be in the patient's best interests, they should be informed and give their consent. Commissioning bodies, such as primary care organisations, are basing their budgets on guidance from the National Institute for Clinical Excellence, which can have implications for funding this off-label use.
Prognostic Value of International Neuroblastoma Pathology Classification in Localized Resectable Peripheral Neuroblastic Tumors: A Histopathologic Study of Localized Neuroblastoma European Study Group 94.01 Trial and Protocol
Authors: Navarro Samuel , Amann Gabriele , Beiske Klaus , Cullinane Catherine J. , d'Amore Emanuele S.G. , Gambini Claudio , Mosseri Véronique , De Bernardi Bruno , Michon Jean , Peuchmaur Michel
Published: January 2006

Purpose

To assess the prognostic value of clinical, biologic, and morphologic data in peripheral neuroblastic tumors, International Neuroblastoma Staging System (INSS) stages 2A and 2B MYCN nonamplified, a multinational protocol entitled Localized Neuroblastoma European Study Group trial 94.01, with a trial of surgery as the only treatment, was initiated in 1995. We present the prognostic value of the revised International Neuroblastoma Pathology Classification (INPC) applied to the patients included in this protocol until its closure in 1999.

Materials and Methods

A total of 120 neuroblastic tumors from trial patients were reviewed by the European International Society of Pediatric Oncology neuroblastoma pathology panel and assigned to a favorable or unfavorable prognostic category according to the INPC guidelines. Overall survival and relapse-free survival (RFS) were estimated by the Kaplan-Meier method and compared by the log-rank test.

Results

A total of 115 of 120 patients were assessable and were assigned to the favorable (90 patients; 78.3%) or unfavorable (25 patients; 21.7%) category. The 60-month survival rate was 97.7% in favorable patients compared with 73.8% in unfavorable patients (P = .0002). RFS analysis showed a 60-month relapse rate of 13.4% and 32% in favorable and unfavorable patients (P < .025), respectively. Statistical analysis demonstrated a significant association of unfavorable INPC category and high lactate dehydrogenase level (P < .045).

Conclusion

This European study shows for the first time that the INPC prognostic categorization has a significant impact on outcome prediction in INSS stage 2 localized peripheral neuroblastic tumors.
Sharing BRCA1/2 Test Results With First-Degree Relatives: Factors Predicting Who Women Tell
Authors: Patenaude Andrea Farkas , Dorval Michel , DiGianni Lisa S. , Schneider Katherine A. , Chittenden Anu , Garber Judy E.
Published: January 2006

Purpose

Patient communication with relatives about cancer genetic test results is the primary means for alerting those who may benefit from identification of hereditary risk. This study identifies factors predicting patterns of disclosure of BRCA1/2 test results to first-degree relatives (FDRs) among women tested in a clinical protocol.

Patients and Methods

A total of 273 women completed a family communication measure 4 months after BRCA1/2 result disclosure. χ2 analyses and logistic regression models identified factors predicting sharing of the test result.

Results

Most FDRs were informed of the participant's test result by 4 months; female relatives were more likely to be informed than males. Tested women conveyed inconclusive results (variant or negative without known familial mutation) less frequently to their sisters than conclusive (positive/true negative) results (P = .03). Twenty-three percent of participants did not inform their father. Informing brothers was more likely when BRCA1/2 was inherited through paternal lineage (P = .04), but 29% of brothers were not informed. Women older than age 40 were less likely to share their result with their parents (P = .03) than were women ≤ 40. Children's ages influenced communication to offspring; most children were told.

Conclusion

Demographic, health-, and test-related factors predicted genetic test result communication to FDRs. Additional research investigating the full spectrum of discussion within families and motives for incomplete sharing of genetic test results with relatives may suggest strategies for providers and targeted educational interventions for patients to enhance family communication.
Optimal Selection of Individuals for BRCA Mutation Testing: A Comparison of Available Methods
Authors: James Paul A. , Doherty Rebecca , Harris Marion , Mukesh Bickol N. , Milner Alvin , Young Mary-Anne , Scott Clare
Published: January 2006

Purpose

Several methods have been described that estimate the likelihood that a family history of cancer is a result of a mutation in the BRCA1 or BRCA2 genes. We examined the performance of six different methods with the aim of identifying an optimal strategy for selecting individuals for mutation testing in clinical practice.

Patients and Methods

Two hundred fifty-seven families who had completed BRCA1 and BRCA2 mutation screening were assessed by six models representing the major methodologies used to assess the likelihood of a pathogenic mutation. The performance of each method as a selection criterion was compared with the result of mutation testing to produce sensitivity, specificity, and receiver operating curve data. The impact of incorporating breast cancer pathology data in the assessment was also analyzed.

Results

The highest accuracy was achieved by the Bayesian probabilistic model (BRCAPRO). The formal probabilistic methods were significantly more accurate than clinical scoring methods. The methods were further improved by the incorporation of information on breast cancer pathology (tumor grade and estrogen receptor/progesterone receptor status). The resulting combined probability figure was highly accurate when selecting individuals for BRCA1 testing. Some BRCA2 mutation carriers were missed by all of the models examined.

Conclusion

Formal probabilistic models provide significantly greater accuracy in the selection of families for gene testing than the use of clinical criteria or scoring methods. The accuracy is further enhanced by incorporating information on the pathology of breast cancers occurring in the families.
Tamoxifen Treatment After Adjuvant Chemotherapy Has Opposite Effects on Bone Mineral Density in Premenopausal Patients Depending on Menstrual Status
Authors: Vehmanen Leena , Elomaa Inkeri , Blomqvist Carl , Saarto Tiina
Published: January 2006

Purpose

Adjuvant chemotherapy followed by tamoxifen is a standard treatment option for women with intermediate or high-risk hormone receptor–positive breast cancer. Premenopausal women treated with chemotherapy often develop early menopause and thus, enter a period of accelerated bone loss. We conducted a prospective study of the effect of sequential adjuvant therapy with chemotherapy followed by tamoxifen on bone mineral density (BMD) in premenopausal patients.

Patients and Methods

One hundred eleven premenopausal women with early breast cancer were treated with adjuvant chemotherapy. Patients with hormone receptor–positive tumors went on to tamoxifen 6 months after the beginning of the chemotherapy (tamoxifen group), while those with hormone receptor–negative tumors received no further therapy (control group). The effect of tamoxifen and menstrual status on BMD was studied.

Results

Tamoxifen treatment and menopausal status correlated significantly with the changes in lumbar spine BMD (P < .0001). A significant bone loss was noted in those tamoxifen-treated patients who continued to menstruate after chemotherapy. At 3 years of follow-up, menstruating patients on tamoxifen had lost −4.6% of their baseline BMD values, while a modest gain of +0.6% was noted in the control group. In contrast, bone loss was reduced among tamoxifen-treated women as compared with controls in patients who developed chemotherapy-induced early menopause. In amenorrheic patients, the lumbar spine BMD values decreased −6.8% in tamoxifen users and −9.5% in the controls, respectively.

Conclusion

We conclude that tamoxifen usage was associated with bone loss in patients who continued to menstruate after adjuvant chemotherapy. On the contrary, tamoxifen decreased bone loss in those women who developed chemotherapy-induced amenorrhea.
Neoadjuvant Capecitabine and Oxaliplatin Followed by Synchronous Chemoradiation and Total Mesorectal Excision in Magnetic Resonance Imaging–Defined Poor-Risk Rectal Cancer
Authors: Chau Ian , Brown Gina , Cunningham David , Tait Diana , Wotherspoon Andrew , Norman Andrew R. , Tebbutt Niall , Hill Mark , Ross Paul J. , Massey Alison , Oates Jacqueline
Published: January 2006

Purpose

To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed patients with magnetic resonance imaging (MRI) –defined poor-risk rectal cancer.

Patients and Methods

MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3 tumors at or below levators, tumors extending ≥ 5 mm into perirectal fat, T4 tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy. TME was planned 6 weeks after CRT. Postoperatively, patients received another 12 weeks of capecitabine.

Results

Between November 2001 and August 2004, 77 eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the radiologic response rate was 88%. In addition, 86% of patients had symptomatic responses in a median of 32 days (ie, just over one cycle of capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to 97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME, and all but one patient had R0 resection. Pathologic complete response was observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32 patients (48%), only microscopic tumor foci were found on surgical specimens. Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism, ischemic heart disease, sudden death with history of chest pain, and neutropenic colitis.

Conclusion

Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.
Pregnancy Among Patients With Chronic Myeloid Leukemia Treated With Imatinib
Authors: Ault Patricia , Kantarjian Hagop , O'Brien Susan , Faderl Stefan , Beran Miloslav , Rios Mary Beth , Koller Charles , Giles Francis , Keating Michael , Talpaz Moshe , Cortes Jorge
Published: January 2006

Purpose

Imatinib has potential teratogenicity in animals, but the effect of exposure to imatinib during conception and pregnancy in humans is not known.

Patients and Methods

The records of all patients with chronic myeloid leukemia (CML) treated with imatinib were reviewed. We report the experience on 19 pregnancies involving 18 patients (10 females and eight males) who conceived while receiving imatinib for the treatment of CML.

Results

All female patients discontinued therapy immediately on recognition of pregnancy. Three pregnancies (involving two female patients and one male patient) ended in spontaneous abortion, and one patient had an elective abortion. All other pregnancies were uneventful. Two of the 16 babies had minor abnormalities at or shortly after birth (hypospadias in one baby and rotation of small intestine in one baby) that were surgically repaired. All babies have continued normal growth and development. Among female patients who interrupted therapy, five of nine in complete hematologic remission (CHR) at the time of treatment interruption eventually lost CHR, and six experienced an increase in Philadelphia chromosome–positive metaphases. At a median of 18 months after resuming therapy with imatinib, eight patients had a cytogenetic response (complete in three patients).

Conclusion

Although there is no evidence that a brief exposure to imatinib during conception and pregnancy adversely affects the developing fetus, most patients lose their response after treatment interruption. Patients receiving imatinib should be advised to practice adequate contraception.
Impacting Quality of Life for Patients With Advanced Cancer With a Structured Multidisciplinary Intervention: A Randomized Controlled Trial
Authors: Rummans Teresa A. , Clark Matthew M. , Sloan Jeff A. , Frost Marlene H. , Bostwick John Michael , Atherton Pamela J. , Johnson Mary E. , Gamble Gail , Richardson Jarrett , Brown Paul , Martensen James , Miller Janis , Piderman Katherine , Huschka Mashele , Girardi Jean , Hanson Jean
Published: January 2006

Purpose

The primary goal of this study was to evaluate the feasibility and effectiveness of a structured, multidisciplinary intervention targeted to maintain the overall quality of life (QOL), which is more comprehensive than psychosocial distress, of patients undergoing radiation therapy for advanced-stage cancer.

Patients and Methods

Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0% to 50% were randomly assigned to either an eight-session structured multidisciplinary intervention arm or a standard care arm. The eight 90-minute sessions addressed the five domains of QOL including cognitive, physical, emotional, spiritual, and social functioning. The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale (Linear Analog Scale of Assessment or modified Spitzer Uniscale). QOL was assessed at baseline, week 4 (end of multidisciplinary intervention), week 8, and week 27.

Results

Of the 103 participants, overall QOL at week 4 was maintained by the patients in the intervention (n = 49), whereas QOL at week 4 significantly decreased for patients in the control group (n = 54). This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group (P = .009). Intervention participants maintained their QOL, and controls gradually returned to baseline by the end of the 6-month follow-up period.

Conclusion

Although intervention participants maintained and actually improved their QOL during radiation therapy, control participants experienced a significant decrease in their QOL. Thus, a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment.
Constrained optimization in human running
Authors: Gutmann Anne K. , Jacobi Brian , Butcher Michael T. , Bertram John E. A.
Published: January 2006

Walking humans spontaneously select different speed, frequency and step length combinations, depending on which of these three parameters is specified. This behavior can be explained by constrained optimization of cost of transport (metabolic cost/distance) where cost of transport is seen as the main component of an underlying objective function that is minimized within the limitations of specified constraints. It is then of interest to ask whether or not such results are specific to walking only, or indicate a more general feature of locomotion control. The current study examines running gait selection within the framework of constrained optimization by comparing self-selected running gaits to the gaits predicted by constrained optimization of a cost surface constructed from cost data available in the literature. Normalizing speed and frequency values in the behavioral data by preferred speed and frequency reduced inter-subject variability and made group behavioral trends more visible. Although actual behavior did not coincide exactly with running cost optimization, self-selected gait and predictions from the general human cost surface did agree to within the 95% confidence interval and the region of minimal cost+0.005 ml O2 kg-1m-1. This was similar to the level of agreement between actual and predicted behavior observed in walking. Thus, there seems to be substantial evidence to suggest that (i) selection of gait parameters in running can largely be predicted using constrained optimization, and (ii) general cost surfaces can be constructed using metabolic data from one group that will largely predict the behavior of other groups.
A potassium channel (Kv4) cloned from the heart of the tunicateCiona intestinalisand its modulation by a KChIP subunit
Authors: Salvador-Recatalà Vicenta , Gallin Warren J. , Abbruzzese Jennifer , Ruben Peter C. , Spencer Andrew N.
Published: January 2006

Voltage-gated ion channels of the Kv4 subfamily produce A-type currents whose properties are tuned by accessory subunits termed KChIPs, which are a family of Ca2+ sensor proteins. By modifying expression levels and the intrinsic biophysical properties of Kv4 channels, KChIPs modulate the excitability properties of neurons and myocytes. We studied how a Kv4 channel from a tunicate, the first branching clade of the chordates, is modulated by endogenous KChIP subunits. BLAST searches in the genome of Ciona intestinalis identified a single Kv4 gene and a single KChIP gene, implying that the diversification of both genes occurred during early vertebrate evolution, since the corresponding mammalian gene families are formed by several paralogues. In this study we describe the cloning and characterization of a tunicate Kv4 channel, CionaKv4, and a tunicate KChIP subunit, CionaKChIP. We demonstrate that CionaKChIP strongly modulates CionaKv4 by producing larger currents that inactivate more slowly than in the absence of the KChIP subunit. Furthermore, CionaKChIP shifted the midpoints of activation and inactivation and slowed deactivation and recovery from inactivation of CionaKv4. Modulation by CionaKChIP requires the presence of the intact N terminus of CionaKv4 because, except for a minor effect on inactivation, CionaKChIP did not modulate CionaKv4 channels that lacked amino acids 2-32. In summary, our results suggest that modulation of Kv4 channels by KChIP subunits is an ancient mechanism for modulating electrical excitability.
Effect of pH on the rate of myosin head detachment in molluscan catch muscle: are myosin heads involved in the catch state?
Authors: Höpflinger Marion Christine , Andruchova Olena , Andruchov Oleg , Grassberger Herbert , Galler Stefan
Published: January 2006

Moderate alkalisation is known to terminate the catch state of bivalve mollusc smooth muscles such as the anterior byssus retractor muscle (ABRM) of Mytilus edulis L. In the present study, we investigated the effect of moderate alkalisation (pH 7.2-7.7 vs control pH 6.7) on the myosin head detachment rate in saponin-skinned fibre bundles of ABRM in order to investigate the possible role of myosin heads in the force maintenance during catch. The detachment rate of myosin heads was deduced from two types of experiments. (1) In stretch experiments on maximally Ca2+-activated fibre bundles (pCa 4.5), the rate of force decay after stepwise stretch was assessed. (2) In ATP step experiments, the rate of force decay from high force rigor (pCa>8) was evaluated. The ATP step was induced by photolysis of caged ATP. We found that moderate alkalisation induces relaxation of skinned fibres in catch, thereby reducing both force and stiffness, whereas it does not accelerate the rate of myosin head detachment. This acceleration, however,would be expected if catch would be simply due to myosin heads remaining sustainably attached to actin filaments. Thus, the myosin heads may be less involved in catch than generally assumed. Catch may possibly depend on a different kind of myofilament interconnections, which are abolished by moderate alkalisation.
Classical conditioning of activities of salivary neurones in the cockroach
Authors: Watanabe Hidehiro , Mizunami Makoto
Published: January 2006

Secretion of saliva to aid swallowing and digestion is a basic physiological function found in many vertebrates and invertebrates. For mammals, classical conditioning of salivation in dogs was reported by Pavlov a century ago. However, conditioning of salivation or of related neural activities in non-mammalian species has not been reported. In many species of insects, salivation is regulated by salivary neurones. In this study, we found that salivary neurones of the cockroach Periplaneta americanaexhibited a strong response to sucrose solution applied to the mouth and a weak response to odours applied to an antenna, and we studied the effect of conditioning on the activities of salivary neurones. After three sets of differential conditioning trials in which an odour was presented just before the presentation of sucrose solution and the other odour was presented alone,the response of salivary neurones to sucrose-associated odour significantly increased but that to the odour presented alone was unchanged. Backward pairing trials in which an odour was presented after the presentation of sucrose solution were not effective in achieving conditioning. Our study of the change in the level of saliva secretion in response to electrical stimulation of salivary neurones suggested that the magnitude of increase in odour response of salivary neurones by conditioning is sufficient to lead to an increased level of salivation. This study suggests classical conditioning of salivation in an insect.
Suppression of Na+/K+-ATPase activity during estivation in the land snailOtala lactea
Authors: Ramnanan Christopher J. , Storey Kenneth B.
Published: January 2006

Entry into the hypometabolic state of estivation requires a coordinated suppression of the rate of cellular ATP turnover, including both ATP-generating and ATP-consuming reactions. As one of the largest consumers of cellular ATP, the plasma membrane Na+/K+-ATPase is a potentially key target for regulation during estivation. Na+/K+-ATPase was investigated in foot muscle and hepatopancreas of the land snail Otala lactea, comparing active and estivating states. In both tissues enzyme properties changed significantly during estivation: maximal activity was reduced by about one-third, affinity for Mg.ATP was reduced (Km was 40% higher), and activation energy (derived from Arrhenius plots) was increased by ∼45%. Foot muscle Na+/K+-ATPase from estivated snails also showed an 80%increase in Km Na+ and a 60% increase in Ka Mg2+ as compared with active snails, whereas hepatopancreas Na+/K+-ATPase showed a 70% increase in I50 K+ during estivation. Western blotting with antibodies recognizing the alpha subunit of Na+/K+-ATPase showed no change in the amount of enzyme protein during estivation. Instead, the estivation-responsive change in Na+/K+-ATPase activity was linked to posttranslational modification. In vitro incubations manipulating endogenous kinase and phosphatase activities indicated that Na+/K+-ATPase from estivating snails was a high phosphate, low activity form, whereas dephosphorylation returned the enzyme to a high activity state characteristic of active snails. Treatment with protein kinases A, C or G could all mediate changes in enzyme properties in vitro that mimicked the effect of estivation, whereas treatments with protein phosphatase 1 or 2A had the opposite effect. Reversible phosphorylation control of Na+/K+-ATPase can provide the means of coordinating ATP use by this ion pump with the rates of ATP generation by catabolic pathways in estivating snails.
Asymmetric craniofacial remodeling and lateralized behavior in larval flatfish
Authors: Schreiber Alexander M.
Published: January 2006

Flatfishes, such as flounder, are the world's most asymmetric vertebrates. It is unknown if the development of lateralized swimming behavior during metamorphosis is an adaptive response to bilaterally asymmetric eye positioning, or if this results from a vestibular response to thyroid hormone. This study describes larval development in left-sided, right-sided and bilaterally symmetric variants of southern flounder (Paralichthys lethostigma). Behavior and skull asymmetries precede metamorphosis, and the development of lateralized behaviors was independent of eye position in larvae treated with thyroid hormone and in symmetrical variants. Therefore,lateralized behavior is not an adaptive response to eye translocation, but rather must result from changing vestibular responses to thyroid hormone.
Human ATP-Binding Cassette Transporter TaqMan Low-Density Array: Analysis of Macrophage Differentiation and Foam Cell Formation
Authors: Langmann Thomas , Mauerer Richard , Schmitz Gerd
Published: January 2006

Background: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance.

Methods: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-μL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro–differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading.

Results: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run.

Conclusions: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.
Insights into Japan-U.S. Relations on the Eve of the Iraq War: Dilemmas over “Showing the Flag”
Authors: Yasuaki Chijiwa
Published: January 2006

When the Iraq War began in 2003, the Japanese government declared support for the United States without a new U.N. Security Council resolution. However, this was not followed by direct logistical support. By using the two-level games theory, this article suggests reasons behind Japan's decision.