bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Phosphatidylinositol 3,4,5-Trisphosphate Accumulation Recruits Vav2 and Vav3 to Activate Rac1/Cdc42 and Initiate Neurite Outgrowth in Nerve Growth Factor-stimulated PC12 Cells
Authors: Aoki Kazuhiro , Nakamura Takeshi , Fujikawa Keiko , Matsuda Michiyuki
Published: February 2005

Neurite outgrowth is an important process in the formation of neuronal networks. Rac1 and Cdc42, members of the Rho-family GTPases, positively regulate neurite extension through reorganization of the actin cytoskeleton. Here, we examine the dynamic linkage between Rac1/Cdc42 and phosphatidylinositol 3-kinase (PI3-kinase) during nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Activity imaging using fluorescence resonance energy transfer probes showed that PI3-kinase as well as Rac1/Cdc42 was transiently activated in broad areas of the cell periphery immediately after NGF addition. Subsequently, local and repetitive activation of PI3-kinase and Rac1/Cdc42 was observed at the protruding sites. Depletion of Vav2 and Vav3 by RNA interference significantly inhibited both Rac1/Cdc42 activation and the formation of short processes leading to neurite outgrowth. At the NGF-induced protrusions, local phosphatidylinositol 3,4,5-trisphosphate accumulation recruited Vav2 and Vav3 to activate Rac1 and Cdc42, and conversely, Vav2 and Vav3 were required for the local activation of PI3-kinase. These observations demonstrated for the first time that Vav2 and Vav3 are essential constituents of the positive feedback loop that is comprised of PI3-kinase and Rac1/Cdc42 and cycles locally with morphological changes.
The Prevalence of Encopresis in a Multicultural Population
Authors: van der Wal M F , Benninga M A , Hirasing R A
Published: February 2005

Background:

Population‐based studies on the prevalence of encopresis in children are scarce and generally outdated. Prevalence estimates based on clinical studies are unreliable because parents tend to be reticent to seek medical help for this problem. Professional help is necessary, however, because encopresis can lead to serious psychosocial health problems. The authors examined the prevalence of encopresis in children, the frequency of visits made to general practitioners for encopresis and the psychosocial health problems of encopretic children.

Methods:

This population‐based study involved 13,111 parents and their 5‐ to 6‐year‐old children and 9,780 parents and their 11‐ to 12‐year‐old children, all residents of Amsterdam, the Netherlands.

Results:

The prevalence of encopresis was 4.1% in the 5‐to‐6 age group and 1.6% in the 11‐to‐12 age group. Encopresis was more frequent among boys and children from the very depressed areas of the city. Encopresis was less frequent among Moroccan and Turkish children. A defecation frequency of less than three per week was found in 3.8% of the 5‐ to 6‐year‐olds and 10.1% of the 11‐ to 12‐year‐olds with encopresis. Only 37.7% of the 5‐ to 6‐year‐olds and 27.4% of the 11‐ to 12‐year‐olds who had encopresis had ever been taken to see a doctor for this problem. Psychosocial problems were far more common among children with encopresis than among normal children.

Conclusions:

Encopresis is a common condition that is often associated with psychosocial health disorders but only a small proportion of the children with encopresis are taken to a general practitioner to discuss their problem.
Shigella Antibiotic Resistance in Central Turkey: Comparison of the Years 1987‐1994 and 1995‐2002
Authors: Özmert Elif N , Göktürk Bahar , Yurdakök Kadriye , Yalçin S Songül , Gür Deniz
Published: February 2005

Background:

The epidemiology and antibiotic susceptibility of Shigella species changes over time. Updated susceptibility knowledge is necessary for appropriate empirical antibiotic treatment.

Methods:

In this study the clinical characteristics and the antibiotic susceptibility test results of Shigella species isolated from patients admitted to Hacettepe University Ihsan Doğramac Children's Hospital Diarrheal Diseases Training and Treatment Unit between 1995‐2002 (n = 218) were evaluated. The results were compared with the results of 1987‐1994 from the same center (n = 618).

Results:

The predominant species was S. sonnei in both periods with increasing prevalence in the later period (64% and 71.5% respectively, P < 0.05). Although the prevalence of bloody diarrhea among Shigella cases did not change between periods, the prevalence of mild to moderate dehydration (11% and 20.6%) increased. Approximately 40% of cases were prescribed antibiotics on the suspicion of shigellosis. When the two periods were compared, Shigella resistance to trimethoprim/sulfamethoxazole increased from 39% to 70% (P < 0.0001), whereas resistance to ampicillin decreased from 41% to 23% (P < 0.0001). However, the resistance of S. flexneri to ampicillin was found to be quite high (72.9%) between 1995‐2002. No Shigella species resistant to ciprofloxacin was detected. Multi‐drug resistance was present in 52 (24%) of the cases, of which 10 were S. sonnei (6.3%) and 42 S. flexneri (26.4%) (P < 0.0001).

Conclusion:

The need to treat all Shigella cases in areas where S. sonnei is predominant should be reevaluated, as should the appropriate empirical antibiotic.
Altered Bone Mass in Children at Diagnosis of Crohn Disease: A Pilot Study
Authors: Harpavat Manisha , Greenspan Susan L , O'Brien Carey , Joyce Chang Chung‐Chou , Bowen A'Delbert , Keljo David J
Published: February 2005

Objectives:

Recent studies have indicated that bone mineral density is reduced in children with inflammatory bowel disease. The exact cause of this reduction is unclear, but it is often attributed to corticosteroid use. This study examined the prevalence of reduced bone mass in otherwise healthy children newly diagnosed with Crohn disease without previous corticosteroid exposure.

Methods:

Eighteen steroid‐naïve children newly diagnosed with Crohn disease underwent dual energy x‐ray absorptiometry. Disease activity, growth and pubertal development, nutritional assessment and bone mass measurements were recorded. z scores were adjusted for bone age.

Results:

Five of the 18 patients (28%) had a total bone mineral density z score less than −1 (one had a z score less than −2). Ten (56%) subjects had lumbar spine bone mineral density z scores less than −1 (two had z score less than −2). The subjects had significantly reduced mean lumbar spine bone mineral density z scores (P = 0.002). Delayed pubertal development correlated with whole body bone mineral density z scores (r = 0.64; P = 0.004). Most subjects were not meeting United States recommended dietary allowances for daily intake of calcium, vitamin D and total calories. The majority of subjects were not participating in weight‐bearing physical activity.

Conclusion:

Decreased bone mass is common in steroid naïve children newly diagnosed with Crohn disease. Crohn disease appears to contribute to impaired bone mass independent of corticosteroid therapy.
Can We Alter The Natural History Of Crohn Disease In Children?
Authors: Hyams Jeffrey S , Markowitz James F
Published: February 2005

The natural history of Crohn disease is characterized by recurrent bouts of active disease, the consequences of which can severely impair sufferers' physical and social functioning. Not only does the illness cause day‐to‐day morbidity for children but the consequence of the chronic inflammatory process also commonly results in the need for major intestinal surgery. The present challenge facing physicians treating children with Crohn disease is to alleviate symptoms and prolong periods of remission via the use of specifically targeted therapies while minimizing toxicity and promoting normal growth and development. Although systemic corticosteroids are effective in inducing clinical remission, they are of little or no benefit in maintaining remission and can contribute to linear growth retardation. Immunomodulating drugs such as azathioprine, 6‐mercaptopurine and methotrexate have proved effective for inducing and maintaining remission of active Crohn disease. These agents are now commonly prescribed in children at diagnosis, after a severe attack or after surgery or in those who become corticosteroid‐dependent or corticosteroid‐resistant. Their use is not without potential adverse effects and not all patients respond well to these agents. With the introduction of biologic agents, notably the tumor necrosis factor‐α monoclonal antibody infliximab, progress has been made in targeting specific pathogenetic mechanisms of Crohn disease and potentially altering the underlying disease process. Published experience in children is currently limited, but infliximab has been shown to improve symptoms and achieve corticosteroid independence in this age group. Unresolved issues with infliximab and other emerging biologic agents, including long‐term safety, necessitate a degree of caution in selecting appropriate patients for treatment and with careful monitoring of their effects. The collection of contemporary natural history data is crucial to facilitate the better integration of current and emerging therapies in an attempt to alter the natural history of Crohn disease in children.
Efficacy and Safety of Lansoprazole in Adolescents with Symptomatic Erosive and Non‐erosive Gastroesophageal Reflux Disease
Authors: Fiedorek Stephen , Tolia Vasundhara , Gold Benjamin D , Huang Bidan , Stolle Julie , Lee Chang , Gremse David
Published: February 2005

Objectives:

To assess the efficacy and safety of lansoprazole in the treatment of adolescents with symptomatic, endoscopically proven, non‐erosive gastroesophageal reflux disease and erosive esophagitis.

Methods:

Adolescents between 12 and 17 years of age with esophagitis were enrolled in this open‐label trial and treated with lansoprazole 15 mg (non‐erosive) or 30 mg (erosive) once daily for 8 weeks. If unhealed at week 8, those with erosive esophagitis were treated with an additional 4 weeks of lansoprazole 30 mg once daily.

Results:

Lansoprazole produced a significant reduction from baseline in the median percentage of days with reflux symptoms (91 to 43% in the 64 adolescents with non‐erosive disease and 85 to 16% in the 23 adolescents with erosive esophagitis, P ≤ 0.001 for each comparison). At week 8, mucosal healing had occurred in 95% (21 of 22) of those with erosive esophagitis. Treatment‐related adverse events were reported by 19% of patients with non‐erosive and 4% of patients with erosive esophagitis. Headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%) were the most frequently reported adverse events. One patient discontinued treatment early because of dizziness and vomiting. An elevation in mean serum gastrin from baseline (59 pg/mL at pretreatment to 80 pg/mL at final visit) was observed.

Conclusion:

Lansoprazole 15 mg or 30 mg once daily reduced symptoms of gastroesophageal reflux in adolescents with non‐erosive gastroesophageal reflux disease and erosive esophagitis, respectively. Lansoprazole 30 mg once daily for 8 weeks was effective in healing erosive esophagitis. Both treatment regimens were considered safe.
Dipole Modeling of Epileptic Spikes Can Be Accurate or Misleading
Authors: Kobayashi Katsuhiro , Yoshinaga Harumi , Ohtsuka Yoko , Gotman Jean
Published: February 2005

Summary:  Purpose: We investigated the accuracy and potential for serious error when representing cortical generators of epileptic spikes with the common single‐dipole model. Spike generators were realistically simulated with cortical areas of different extents.

Methods: The source was simulated by using a patch that comprised small triangles on the cortical surface, each triangle having an elementary dipole generator with a moment corresponding to real intracerebral fields of spikes. The source‐patch covered various clinically important parts of the temporal and frontal lobes, with an area ranging from 6 to 120 cm2. The scalp field was computed for each source‐patch by using a realistic head model and was fitted by the single‐dipole model to determine the best‐fit dipole and the intracerebral distribution of residual variance (RV). Dipole modeling also was performed for the simulated scalp field with additional real EEG background.

Results: The RV after fitting a dipole to the scalp field without noise was at most 1.34%. Scalp spikes arising from sources of 6 cm2 were of small amplitude, and the dipoles estimated for these spikes were inconsistent. Extension of the source area was associated with increase of scalp potential amplitude, only very small increase of RV, and increased consistency of the estimated dipoles. When the source was very large, the dipoles clustered at very misleading locations.

Conclusions: Pitfalls in dipole source localization are caused by the procedure of fitting the simplistic dipole model to real cortical sources with spatial extent and complex configuration.
Increased Seizure Susceptibility of the Hippocampus Compared with the Neocortex of the Immature Mouse Brain in vitro
Authors: Abdelmalik Peter A. , Burnham W. McIntyre , Carlen Peter L.
Published: February 2005

Summary:  Purpose: The temporal lobe seems particularly susceptible to seizure activity. Mesial temporal lobe structures, including the hippocampus, have the lowest seizure thresholds in the brain. Conversely, thresholds in the frontal neocortex are significantly higher. The development of intact, isolated preparations of hippocampus and neocortex in vitro allows for study into mechanisms governing seizure threshold.

Methods: Epileptiform discharges in isolated mouse neocortical blocks were compared with the contralateral intact hippocampus, isolated from the same brain, by using the low‐Mg2+, 4 aminopyridine (4‐AP), and low‐Ca2+ in vitro seizure models. The pharmacology of low Mg2+–induced ictal‐like events (ILEs) generated in the hippocampus and neocortex was then compared by using glutamatergic antagonists dl‐2‐amino‐5‐phosphonovaleric acid (APV) and 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX), and the Ca2+ channel antagonist, nifedipine.

Results: Neocortical blocks generated both recurrent, spontaneous ILEs and interictal‐like events under low‐Mg2+ artificial CSF (aCSF) perfusion, distinct from those generated in the hippocampus. ILEs from the hippocampus displayed lower thresholds and longer durations as compared with isolated neocortical blocks. Similar results were obtained during 4‐AP perfusion. Perfusion with low‐Ca2+ ACSF did not produce stereotypical ILEs in the neocortical block, producing instead recurrent, slow depolarizations. Both ILEs and recurrent, slow depolarizations were produced in the hippocampus. Application of APV and nifedipine exacerbated low Mg2+–induced ILEs in the hippocampus but not the neocortex, indicating a distinct pharmacology for partial seizures of different brain regions.

Conclusions: The developing mouse hippocampus demonstrates increased ictogenesis compared with the developing neocortex in vitro, consistent with clinical observations and in vivo experimental models.
Irwin Abrams—Historian and Champion of the Nobel Peace Prize
Authors: Van Den Dungen Peter
Published: February 2005

Although the subject of much interest and admiration around the world, scholarly interest in the Nobel Peace Prize, as well as exploration of its potential as an instrument of peace education, has been limited. Irwin Abrams's many publications in the field, especially during the past quarter century, has made him both the prime scholar‐historian of the prize, and its leading publicist and popularizer. His writings on the subject comprise three related but distinct aspects: documentation, education and outreach, and interpretation and evaluation.
Politics of Peace‐Building: Critical Evaluation of Interethnic Contact and Peace Education in Georgian–Abkhaz Peace Camp, 1998–2002
Authors: Ohanyan Anna , Lewis John E.
Published: February 2005

This article presents an evaluation of a second‐track diplomacy project sponsored by the U.S. Agency for International Development and organized between Georgian and Abkhaz youth and teachers. It examines the effects of interethnic contact and peace education components of the program on the participants and evaluates the potential of the entire program for the peace processes between the Georgian and Abkhaz sides. The findings indicate that the program succeeded in cultivating a willingness to engage in joint programs, despite more marginal attitudinal changes among the participants. Equally intriguing and significant was the observed impact of ethnicity.Georgians and Abkhaz experienced the program differently, an outcome that exposed the impact of the larger sociopolitical context of the conflicts on the program outputs. The resulting theoretical and policy implications of the study raise issues of program design and training development, in order to maximize the “transfer effects” of such programs for larger social and political environments of peace processes.
The Human Rights Dimensions of War in Iraq: Framework for Peace Studies
Authors: Mertus Julie , Carter Hallward Maia
Published: February 2005

This article considers the advantage of the adoption of a human rights framework in analysis of issues of pressing concern to peace studies, such as the use of force, the imposition of sanctions, and general neglect of nonviolent alternative responses to state violence. Although the invocation of a human rights framework may not provide definitive answers on the appropriate responses, the framework can provide a vocabulary and space within which possible solutions may be considered. Using a case study of Iraq, this article demonstrates how the human rights framework may be applied to identify abuses and to inform policy options. Had a human rights framework been employed prior to the U.S. bombing of Iraq in 2000, the authors urge, alternatives to violence would have been exposed and the legality and legitimacy of the attacks called into question. Furthermore, the authors conclude, a human rights framework exposes the illegality of the treatment of Iraqi prisoners by U.S. military and intelligence officers.
A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence
Authors: Berger S. Paul , Winhusen Theresa M. , Somoza Eugene C. , Harrer Judy M. , Mezinskis Juris P. , Leiderman Deborah B. , Montgomery Margaret A. , Goldsmith R. Jeffrey , Bloch Daniel A. , Singal Bonita M. , Elkashef Ahmed
Published: February 2005

Aims  To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence.

Design  A 10‐week out‐patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.

Setting  The study was conducted at the Cincinnati Medication Development Research Unit (MDRU).

Participants  Participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures.

Intervention  The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.

Measurements  Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale—observer and self‐report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests.

Findings  Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non‐significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well.

Conclusions  The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.
The value of an acute octreotide suppression test in predicting long‐term responses to depot somatostatin analogues in patients with active acromegaly
Authors: Karavitaki Niki , Botusan Ileana , Radian Serban , Coculescu Mihail , Turner Helen E. , Wass John A. H.
Published: February 2005

Background  The long‐acting depot somatostatin analogues [octreotide LAR (LAR) and lanreotide (LAN)] are among the most effective available medical therapies for acromegaly. However, published data on a biochemical test suitable for predicting the responsiveness to these depot agents are lacking.

Aim  To investigate the value of an acute octreotide suppression test (OST) in predicting the responses to treatment with long‐acting somatostatin analogues in patients with active acromegaly.

Patients and Methods  Thirty patients with active acromegaly [mean GH in GH day curve (GHDC) > 5 mU/l] were subjected to an OST [hourly GH measurements for 6 h following 100 µg subcutaneous (s.c.) octreotide]. Subsequently, 14 patients were treated with LAR, 10 with LAN and 6 received both drugs at different times. The final response to treatment was evaluated when the subjects had achieved ‘safe’ GH levels (mean GH < 5 mU/l) or after receiving the maximal dose of each drug (maximum duration of treatment 6 months).

Results  The nadir GH values during the OST were 2·6 ± 2·5 mU/l (mean ± SD, range 0·2–8·7) with a percentage fall of 84·8 ± 15·7% (mean ± SD, range 26–99%) from the baseline levels (26·2 ± 31·5 mU/l, mean ± SD). All the patients except one showed a decrease of greater than 50%. The mean time to achieve the nadir GH value was 3·8 ± 1·6 h (mean ± SD, range 1–6). The nadir GH levels showed a positive correlation with both pre‐treatment (i.e. before commencing LAN or LAR) GH values during the GHDC (r = 0·63, P < 0·01) and IGF‐I levels (r = 0·56, P < 0·05). The nadir GH values during the OST showed a positive correlation with the achieved mean GH levels in patients treated with LAR (r = 0·66, P < 0·01) but not in the ones treated with LAN. The criterion of GH < 5·25 mU/l during the OST had sensitivity 100%, specificity 80%, positive predictive value (PPV) 94% and negative predictive value (NPV) 100% in predicting achievement of ‘safe’ GH levels in patients treated with LAR. A less optimal prognostic profile was obtained for subjects treated with LAN with the criterion of GH < 6·05 mU/l during the OST providing sensitivity 92%, specificity 67%, PPV 92% and NPV 67%. The above cut‐off GH levels had a PPV of only 77% and 60% in predicting normalization of IGF‐I on treatment with LAR or LAN, respectively.

Conclusions  The OST is a reliable tool for the selection of patients with active acromegaly who will achieve ‘safe’ GH levels on therapy with LAR. Its prognostic profile is less optimal for patients treated with LAN. If GH values during the test fall < 5·25 mU/l (in case of LAR treatment) or < 6·05 mU/l (in case of LAN treatment), there is a 92–94% chance of subsequently achieving ‘safe’ GH levels after up to 6 months treatment with either of these agents.
Polycystic ovarian syndrome: marked differences between endocrinologists and gynaecologists in diagnosis and management
Authors: Cussons Andrea J. , Stuckey Bronwyn G. A. , Walsh John P. , Burke Valerie , Norman Robert J.
Published: February 2005

Background  Women with polycystic ovarian syndrome (PCOS) commonly consult endocrinologists or gynaecologists and it is not known whether these specialty groups differ in their approach to management.

Objective  To compare the investigation, diagnosis and treatment practices of endocrinologists and gynaecologists who treat PCOS.

Design and Setting  A mailed questionnaire containing a hypothetical patient's case history with varying presentations − oligomenorrhoea, hirsutism, infertility and obesity − was sent to Australian clinical endocrinologists and gynaecologists in teaching hospitals and private practice.

Results  Evaluable responses were obtained from 138 endocrinologists and 172 gynaecologists. The two specialty groups differed in their choice of essential diagnostic criteria and investigations. Endocrinologists regarded androgenization (81%) and menstrual irregularity (70%) as essential diagnostic criteria, whereas gynaecologists required polycystic ovaries (61%), androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio (47%) (all P‐values < 0·001). In investigation, gynaecologists were more likely to request ovarian ultrasound (91%vs. 44%, P < 0·001) and endocrinologists more likely to measure adrenal androgens (80%vs. 58%, P < 0·001) and lipids (67%vs. 34%, P < 0·001). Gynaecologists were less likely to assess glucose homeostasis but more likely to use a glucose tolerance test to do so. Diet and exercise were chosen by most respondents as first‐line treatment for all presentations. However, endocrinologists were more likely to use insulin sensitizers, particularly metformin, for these indications. In particular, for infertility, endocrinologists favoured metformin treatment whereas gynaecologists recommended clomiphene.

Conclusions  There is a lack of consensus between endocrinologists and gynaecologists in the definition, diagnosis and treatment of PCOS. As a consequence, women may receive a different diagnosis or treatment depending on the type of specialist consulted.
Bovine spinal muscular atrophy: AFG3L2 is not a positional candidate gene
Authors: Joerg H. , Muntwyler J. , Glowatzki‐Mullis M.‐L. , Ahrens E. , Asai‐Coakwell M. , Stranzinger G.
Published: February 2005

Bovine spinal muscular atrophy (BSMA) is a neurodegenerative disorder, which is widespread in Brown Swiss cattle. Main symptoms of the disease are muscular atrophy and recumbency. Affected calves die within few days or weeks. BSMA seems to be inherited as a recessive trait and the disease allele appears to have a common origin. In this study, a pedigree with 30 affected BSMA calves was used to genetically localize the BSMA locus. Linkage analysis was performed between microsatellite markers of seven chromosomes, where the homologous genes of human neurodegenerative disorders are located according to comparative mapping data, and the disease genotype. BSMA was mapped to chromosome 24 confirming the recently published localization (Medugorac et al. 2003). The candidate gene AFG3L2 was physically mapped to chromosome 24q24 using fluorescence in situ hybridization. Due to their different localizations AFG3L2 is not a positional candidate for BSMA. An informative marker localized on the telomeric side of the BSMA locus would be beneficial for marker‐assisted selection as well as searching for the causative gene. However, finding a marker distal to BSMA locus is difficult because of its position at the end of the chromosome.
Identification and characterization of novel peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) transcriptional variants in pig and human
Authors: Omi T. , Brenig B. , Špilar Kramer Š. , Iwamoto S. , Stranzinger G. , Neuenschwander S.
Published: February 2005

The peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) is a member of the steroid/thyroid/retinoid receptor superfamily, and is primarily expressed in fat tissue. To date, two major PPAR‐γ isoforms have been identified in pig, PPAR‐γ1 and PPAR‐γ2. Porcine PPAR‐γ1a consists of two leader exons, designated A1 and A2, followed by six exons containing the open reading frame. Here, we report the isolation and characterization of three novel PPAR‐γ1 transcripts. PPAR‐γ1b is derived from exon A1, with exon A2 spliced out. PPAR‐γ1c and PPAR‐γ1d are derived from the new exon, A′, containing exon A2 (γ1c) or without exon A2 (γ1d). Based on PCR analysis of PAC clones that included sequences from the 5′‐untranslated region of the PPAR‐γ gene, the new A′ exon is located between the known exons A1 and A2. We also isolated the human homologue to exon A′, as well as the two new PPAR‐γ1c and ‐γ1d splice variants, from human adipose tissue. Studies of the expression of porcine PPAR‐γ by real time reverse transcription‐polymerase chain reaction analysis show that transcripts derived from exon A1 were not expressed at significantly different levels in visceral fat (lamina subserosa) or subcutaneous fat (back fat, inner and outer layer). In contrast, exon A′‐derived transcripts were expressed at progressively higher levels in the inner and outer layers of subcutaneous fat than in visceral fat. The same expression pattern was also observed for PPAR‐γ2. We hypothesize that there are three promoters, which differentially regulate PPAR‐γ1 and PPAR‐γ2 gene expression, depending on the specific localization of the fat tissue.
An investigation of aged care mental health knowledge of Queensland aged care nurses
Authors: Hsu Mei Chi , Moyle Wendy , Creedy Debra , Venturato Lorraine
Published: February 2005

ABSTRACT:  Older people are at risk for developing psychiatric disorders and require highly skilled and knowledgeable nurse practitioners to provide early recognition and intervention of psychiatric problems. This study sought to identify the aged care mental health knowledge of registered nurses (RNs) employed in long‐term aged care and test the validity and reliability of a North American tool for use in an Australian context. The Mary Starke Harper Ageing Knowledge Exam (MSHAKE) was sent to RNs (n = 350) in 70 long‐term care facilities (LTCF) in Queensland, Australia, and 107 surveys were returned (30.5% response). Participants were found to be unprepared for the reality of caring for the mental health needs of an older population and to have knowledge deficits related to suicide, prevalence of mental illness, mental health and ethnicity, and a number of issues regarding dementia.
Reorganization of the human motor cortex by sensory signals: A selective review
Authors: Miles Timothy S
Published: February 2005

1. The normal human motor cortex can be made to reorganize by repeated stimulation of proprioceptive inputs, with or without concurrent stimulation of the motor cortex by transcranial magnetic nerve stimulation. Appropriate stimulation induces a focal increase in the excitability of corticospinal projections to specific muscles and, possibly, an increase in the area of the cortex projecting to those muscles.

2. We have shown that repeated stimulation on several successive days causes this ‘plastic’ reorganization to persist for at least several days. We have also used this approach to determine whether increases in the excitability of the motor cortex can be induced in stroke patients (in whom cortical excitability is usually depressed) and whether this is accompanied by functional changes.

3. The results of these studies were mixed but, in patients in whom plastic changes were induced, there were improvements and sometimes marked improvements in both motor function and some electrophysiological parameters. The reasons for the inconsistent results are not clear, but do not appear to relate to the site, size or nature of the lesion.
Caffeine–herbal ephedra combination increases resting energy expenditure, heart rate and blood pressure
Authors: Vukovich Matthew D , Schoorman Rana , Heilman Chris , Jacob Peyton , Benowitz Neal L
Published: February 2005

1. The purpose of the present study was to determine whether the consumption of an acute dose of caffeine and Ma Huang increases resting energy expenditure (REE), heart rate (HR) and blood pressure (BP) over a 3 h period.

2. A randomized, double‐blind cross‐over study was performed evaluating the acute effects of caffeine (150 mg)/herbal ephedra (Ma Huang; 20 mg ephedra alkaloids) versus a placebo. A total of eight healthy subjects (four males and four females) with a mean (±SD) age of 23.4 ± 0.8 years (mean ages for males and females: 25.3 ± 0.7 and 22.0 ± 0.7 years, respectively) and 22.5 ± 3.1% body fat (15.7 ± 1.2 and 27.6 ± 3.5% body fat for males and females, respectively) were recruited to the study. Participants were moderate caffeine users (approximately 150–300 mg/day).

3. Subjects reported to the laboratory following a 12 h fast and 48 h of a caffeine‐free diet. Resting energy expenditure was measured prior to supplementation and for 15 min every 30 min for 3 h following supplementation. Heart rate and BP were obtained every 15 min. Blood samples were obtained every 30 min following the measurement of REE and analysed for caffeine, ephedrine, free fatty acids and glucose.

4. By 3 h, HR was 22.7 ± 5.5% higher (P < 0.05) than baseline for the caffeine/ephedra trial compared with 8.9 ± 2.2% higher for the placebo grou. At 3 h, systolic BP was 9.1 ± 2.2% higher (P < 0.05) than baseline for the caffeine/ephedra trial compared with only 1.9 ± 2.9% different from baseline for the placebo trial. There was no effect of the caffeine/ephedra combination on diastolic BP. Resting energy expenditure during the last 30 min was 4.5 ± 2.5% higher in the placebo trial and 10.7 ± 2.5% higher (P < 0.05) in the caffeine/ephedra trial; REE was 8.5 ± 2.0% higher (P < 0.05) in the caffeine/ephedra trial compared with the placebo trial. Free fatty acids increased over time in the placebo and caffeine/ephedra trials (from 0.5 ± 0.05 to 0.63 ± 0.05 mEq/L and from 0.48 ± 0.06L to 0.8 ± 0.05 mEq/L, respectively).

5. Caffeine and herbal ephedra, at doses of 150 mg and 20 mg (ephedrine), respectively, result in a significant elevation in REE, HR and BP. Although significant, the increase in energy expenditure is negligible in terms of weight loss.
Effects of post‐treatment with low‐dose propofol on inflammatory responses to lipopolysaccharide‐induced shock in conscious rats
Authors: Hsu Bang Gee , Yang Fwu Lin , Lee Ru Ping , Peng Tai Chu , Chen Hsing I
Published: February 2005

1. In the present study, we used a low dose of propofol (5 mg/kg per h) to investigate its effects on the pro‐inflammatory cytokines (tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐10) and changes in nitric oxide (NO) following lipopolysaccharide (LPS) for a period of 12 h in conscious rats.

2. Experiments were designed to induce endotoxin shock by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Arterial pressure (AP) and heart rate (HR) were monitored continuously for 12 h after LPS administration. Tumour necrosis factor‐α, IL‐1β, IL‐10 and plasma nitrates/nitrites were determined before and 0.5, 1, 3, 6, 9 and 12 h after LPS administration. A low dose of intravenous propofol (5 mg/kg per h) was administered to investigate the effects on cytokine responses and changes in NO in endotoxin shock.

3. Lipopolysaccharide significantly increased TNF‐α, IL‐1β, IL‐10, nitrites/nitrates and HR, whereas mean AP was decreased. Post‐treatment with propofol suppressed the release of TNF‐α, IL‐1β, IL‐10 and NO production after endotoxin shock.

4. Lipopolysaccharide also caused a decrease in the white blood cell count and haematocrit.

5. Post‐treatment with propofol slightly, but not significantly, affected the LPS‐induced systemic hypotension, tachycardia, leukocytopenia and anaemia.

6. These findings suggest that low‐dose propofol may be beneficial to the inflammatory change in sepsis.
A channel in a transporter
Authors: Ryan Renae M , Vandenberg Robert J
Published: February 2005

1. Glutamate transporters (or excitatory amino acid transporters (EAAT)) are responsible for removing synaptically released glutamate from the extracellular space. The failure of EAAT to carry out this role will lead to excessive stimulation of glutamatergic receptors, causing excitotoxicity and cell death.

2. Glutamate is cotransported into the cell with three Na+ and one H+, followed by the counter‐transport of one K+. In addition, glutamate and Na+ binding activates an uncoupled chloride conductance. Thus, glutamate transporters can function as both a transporter and an ion channel. At present, there is no clear understanding of the structural basis for the dual functions of glutamate transporters and, in the present review, we shall discuss some recent studies that have started to address this question.

3. It is possible to modulate one function of glutamate transporters without affecting the other, which suggests that the two functions have separate molecular determinants, and a number of models have been suggested to account for the dual functions of the EAAT that predict both single and dual pores for transporter function.

4. It appears that the two functions of glutamate transporters arise from separate transmembrane domains. The C‐terminal region of the transporters forms the glutamate translocation domain, whereas the second transmembrane domain in the N‐terminal half of the protein plays a crucial role in chloride channel function. Although the two functions arise from separate molecular determinants, the two functional domains are likely to be in close proximity. The significance of these observations will be discussed in terms of likely functional models for the transport and channel processes.
Antibacterial and antimycobacterial treatment for inflammatory bowel disease
Authors: OHKUSA TOSHIFUMI , SATO NOBUHIRO
Published: February 2005

Abstract  A variety of medicines have been used for the treatment of inflammatory bowel disease. Antibacterial therapy has demonstrated promise by both improving symptoms and causing disease remission. The mechanism is unknown, but may be related to either eliminating a key pathogen, decreasing the number of bacterial secretory products or defective particles, a direct immunomodulating effect, or reducing secondary bacterial invasion. Historically, a large number of bacterial species have been suspected as being major contributors to the etiology of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. Many trials of antibacterial agents have been carried out in inflammatory bowel disease. Recently, treatments have focused on Gram‐negative anaerobes and mycobacteria. The present paper briefly reviews antimicrobial and antimycobacterial treatments in inflammatory bowel disease.
Stress and the gastrointestinal tract
Authors: BHATIA VIKRAM , TANDON RAKESH K
Published: February 2005

Abstract  Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short‐ and long‐term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain–gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus–pituitary–adrenal axis and pain modulatory systems. Severe or long‐term stress can induce long‐term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4+ lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.
Helicobacter pylori reinfection rate 3 years after successful eradication
Authors: ZENDEHDEL NASRIN , NASSERI‐MOGHADDAM SIAVOSH , MALEKZADEH REZA , MASSARRAT SADEGH , SOTOUDEH MASOUD , SIAVOSHI FARIDEH
Published: February 2005

Background and Aim: Helicobacter pylori (HP) infection is one of the most prevalent human infections and has been implicated as a predisposing factor in gastric cancer, chronic active gastritis, duodenal ulcer, gastric ulcer and gastric lymphoma. Reinfection after successful eradication is quite uncommon in adults. In the only study carried out in Iran, a reinfection rate of 19.1% after 1 year has been reported. We studied the rate of reinfection 3 years after successful HP eradication.

Methods: All patients who had undergone HP eradication 3 years before the study and had successful eradication verified by a negative 14C urea breath test (UBT) 1 year after eradication were invited to complete a questionnaire and undergo another UBT. In addition, spouses and the offspring of those testing positive were offered an UBT.

Results: Ninety‐eight patients were enrolled (49% male). Mean age was 44 ± 13 years (range: 18–75 years). Twenty patients (20.4%) had a positive UBT. Epigastric burning (25%vs 69%) and pyrosis (50%vs 67%) were seen less commonly in those who were HP free at 3 years compared to those who tested positive for HP.

Conclusions: According to our data, in our region the HP reinfection rate is 20.4% 3 years after successful eradication.
Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis
Authors: MOAYYERI ALIREZA , DARYANI NASER EBRAHIMI , BAHRAMI HOSSEIN , HAGHPANAH BABAK , NAYYER‐HABIBI ATOOSA , SADATSAFAVI MOHSEN
Published: February 2005

Background and Aim: We noticed in our practice that patients with ulcerative colitis (UC) who have developed primary sclerosing cholangitis (PSC) experience a milder course of colonic disease. Our objective in this study was to define whether or not there is any difference between UC activity and its course in patients with and without PSC.

Methods: Nineteen patients with UC and PSC (eight male, mean age 25 years) were enrolled. To every patient with UC and PSC, three patients with UC alone (total of 57 patients, 28 male, mean age 24 years) matched for age at onset, duration of the disease and extension of colonic disease were selected as the control group. We used number of hospitalizations due to activity of UC and number of short corticosteroid administrations in various years of follow‐up as variables indicating course and severity of the colonic disease in this period. For comparing trends of UC activity between two groups, we used repeated measures two‐way analysis of variances.

Results: Mean duration of follow up in case and control groups was 12.2 ± 5.7 and 11.4 ± 4.9 years, respectively. Two groups had no significant difference in use of sulfasalzine or aminosalicylates. Number of hospitalizations and courses of steroid therapy because of UC activity decreased significantly over time (P < 0.000) in both groups, and it was significantly higher in controls than in cases (P = 0.045 and 0.032, respectively).

Conclusions: Development of PSC in patients with UC might have a positive effect on colonic disease. Further investigations to evaluate the basis of this improvement are warranted.
Classification of hydatid liver cysts
Authors: KJOSSEV KIRIEN T , LOSANOFF JULIAN E
Published: February 2005

Abstract  A number of investigations advocate various classification systems for liver hydatid cysts. However, none permits predicting the treatment outcome or making clinical decisions regarding medical treatment; open surgery; punction, aspiration, injection, reaspiration (PAIR); or laparoscopy. An international hydatid disease registry employing an uniform nomenclature and consistent reporting methods would allow more rational comparison of different management strategies. TN(R)C (topography, nature, recurrent, complication) classification is a comprehensive system based on four criteria: location (T), natural history (N), recurrence (R) and complications (C) of the cyst. This pictorial review illustrates the classification and puts accent of its clinical usefulness. The TN(R)C classification provides a standardized description formula of every liver hydatid cyst, permitting multiple comparisons and analyses.
Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry
Authors: TAKEHARA KOUSUKE , SAKAI HIDEKI , SHONO TAKEFUMI , IRIE JUNJI , KANETAKE HIROSHI
Published: February 2005

Background: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms.

Methods: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non‐functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin‐fixed, paraffin‐embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki‐67 and p53. For FISH analysis, we used an α‐centromeric enumeration probe for chromosome 17.

Results: The mean Ki‐67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein.

Conclusions: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor.
Sarcomatoid carcinoma of the renal pelvis with giant cell tumor‐like features: Case report with immunohistochemical findings
Authors: ACIKALIN MUSTAFA FUAT , KABUKCUOGLU SARE , CAN CAVIT
Published: February 2005

Abstract  Sarcomatoid transitional cell carcinoma is a rare entity, in which a malignant, overtly epithelial component coexists with areas having a sarcoma‐like appearance. Histological distinction of sarcomatoid carcinomas from carcinosarcomas is often difficult and immunohistochemistry is a helpful diagnostic adjunct in the correct diagnosis. In the present report, we describe an uncommon case of sarcomatoid transitional cell carcinoma of the renal pelvis, associated with giant cell tumor‐like features. Immunoperoxidase staining for cytokeratin was positive in spindle cell component, indicating an epithelial origin. The carcinomatous component showed a diffuse membranous reactivity for E‐cadherin, whereas the reactivity was sporadic and weaker in the sarcomatoid component, suggesting that the decrease of E‐cadherin expression might be associated with the acquisition of sarcomatous morphology. Osteoclast‐like multinucleated giant cells were positive for CD68 and negative for p53 oncoprotein, suggesting that they represent a non‐neoplastic component that is reactively induced in the tumor stroma.