bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic characteristics of Chinese hereditary non‐polyposis colorectal cancer
Authors: CUI Long , JIN Hei Ying , CHENG Hui Yu , YAN Yu Di , MENG Rong Gui , YU De Hong 
Published: November 2003

OBJECTIVE:  The aim of the present study was to examine the clinicopathologic characteristics of Chinese patients with hereditary non‐polyposis colorectal cancer (HNPCC) and those with suspected (atypical) HNPCC.METHODS:  Personal and family cancer histories were obtained by reviewing the charts and interviewing the proband and participating relatives. Families were identified and classified into three groups by either the Amsterdam or Japanese criteria for HNPCC. Clinical characteristics including onset, localization, stage of colorectal cancer (CRC), tumor multiplicity, survival and mucinous histology were evaluated.RESULTS:  Ninety‐eight subjects comprising 92 CRC patients and six extracolonic cancer patients from 13 typical and 19 non‐typical HNPCC kindreds were enrolled. There were 53 patients with CRC, one with both CRC and extracolonic cancer and five with extracolonic cancer in the typical HNPCC group, and in the atypical group there were 38 patients with CRC and one with extracolonic cancer. The average onset age of typical HNPCC and atypical HNPCC was 48 and 50 years, respectively, without statistical difference. There were no statistical differences in sex, pathological type, stage, site distribution of the tumor or survival between typical HNPCC and atypical HNPCC groups. There were 11.1% (6/54) metachronous CRC in the typical HNPCC group, and 7.9% (3/38) metachronous and 2.6% (1/38) synchronous CRC in the atypical HNPCC group.CONCLUSION:  The Amsterdam criteria are important, but inappropriate for the establishing the clinical diagnosis of HNPCC in Chinese patients, with some atypical families that did not fulfil all the Amsterdam criteria probably possessing similar clinicopathogical features and genetic alterations. It seems that HNPCC should be considered in some suspected cases.
Efficacy of a 1‐week rabeprazole triple therapy for eradicating Helicobacter pylori and ulcer healing: an ‘in‐clinical‐practice’ study
Authors: GOH KL , ROSAIDA MS , SALEM O , CHEAH PL , RANJEEV P , TAN YM , ROSMAWATI M , CHIN SC 
Published: November 2003

OBJECTIVE:  To determine the efficacy and tolerability of a 1‐week treatment regimen consisting of rabeprazole and two antibiotics, clarithromycin and amoxicillin, in the eradication of Helicobacter pylori in an ‘in‐clinical‐practice’ setting.METHODS:  Patients selected had unequivocal evidence of H. pylori infection based on urease test and histology of antral and corpus biopsies obtained at endoscopy. Patients with complicated ulcers were not included. Patients received rabeprazole 10 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by histology and urease test. Ulcer patients did not receive continued acid suppression therapy following the 1‐week course of treatment.RESULTS:  The study recruited 205 patients of whom 25 were not compliant with the medications or defaulted on follow‐up and were therefore not included in the per‐protocol analysis. Eradication of H. pylori was successful in 166/180 of patients on per‐protocol analysis (92.2% [95% CI: 87.3, 95.7]) and in 169/205 patients on intention‐to‐treat analysis (82.4% [95% CI: 80.5, 90.2]; P = 1.000). There were 47 patients with active ulcers: DU 27, GU 18, DU/GU 2. Overall, ulcer healing was achieved in 42 of 44 (95.5%) patients who had successful eradication of H. pylori infection, but ulcers did not heal in any of the three patients (DU 2, GU 1) who did not eradicate the infection. Of the total group, 199 were assessed for compliance and side‐effects of treatment. Side‐effects were in general mild and tolerable. Of 14 patients who were not compliant with medication, 4 (2.0%) attributed it to side‐effects of treatment (increased abdominal pain, dizziness and taste disturbances) and the remaining 10 did not give specific reasons. The most common side‐effect was bitter taste, reported by 39.2% of patients. Other side‐effects, such as giddiness, increased abdominal pain, lethargy, loose bowel motions and skin rash, were mild and found in only a small percentage of patients.CONCLUSIONS:  The rabeprazole 1‐week triple therapy with amoxicillin and clarithromycin is effective in eradicating H. pylori in an ‘in‐clinical‐practice’ setting. The treatment was well tolerated by patients. Good ulcer healing was achieved with short‐course H. pylori eradication therapy without the need for continued acid suppression.
Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation
Authors: Bolis Annalisa , Corbetta Sara , Cioce Antonella , De Curtis Ivan 
Published: November 2003

AbstractRac3 is one of the three known Rac GTPases in vertebrates. Rac3 shows high sequence homology to Rac1, and its transcript is specifically expressed in the developing nervous system, where its localization and function are unknown. By using Rac3‐specific antibodies, we show that the endogenous Rac3 protein is differentially expressed during mouse brain development, with a peak of expression at times of neuronal maturation and synaptogenesis. Comparison with Rac1 shows clear‐cut differences in the overall distribution of the two GTPases in the developing brain, and in their subcellular distribution in regions of the brain where both proteins are expressed. At P7, Rac3 staining is particularly marked in the deep cerebellar nuclei and in the pons, where it shows a discontinuous distribution around the neuronal cell bodies, in contrast with the diffuse staining of Rac1. Rac3 does not evidently co‐localize with pre‐ and post‐synaptic markers, nor with GFAP‐positive astrocytes, but it clearly co‐localizes with actin filaments, and with the terminal portions of calbindin‐positive Purkinje cell axons in the deep cerebellar nuclei. Our data implicate Rac3 in neuronal differentiation, and support a specific role of this GTPase in actin‐mediated remodelling of Purkinje cell neuritic terminals at time of synaptogenesis.
A quantitative and morphological study of projection neurons in lamina I of the rat lumbar spinal cord
Authors: Spike R. C. , Puskár Z. , Andrew D. , Todd A. J. 
Published: November 2003

AbstractIn the rat lumbar spinal cord the major supraspinal targets for lamina I projection neurons are the caudal ventrolateral medulla (CVLM), lateral parabrachial area (LPb) and periaqueductal grey matter (PAG). In this study we have estimated the number of lamina I neurons retrogradely labelled from each of these sites in the L4 segment, as well as the proportion that can be labelled by injecting different tracers into two separate sites. Our results suggest that this segment contains approximately 400 lamina I projection neurons on each side, and that approximately 85% of these can be labelled from either the CVLM or the LPb on the contralateral side. Around 120 lamina I cells in L4 project to the PAG, and over 90% of these cells can also be labelled from the CVLM or LPb. Most lamina I neurons projecting to CVLM or LPb are located in the contralateral dorsal horn, but in each case some cells were found to have bilateral projections. We also examined horizontal sections to investigate morphology and the expression of the neurokinin 1 (NK1) receptor in cells labelled from CVLM, LPb or PAG. There were no consistent morphological differences between these groups, however, while cells with strong or moderate NK1 receptor‐immunostaining were labelled from LPb or CVLM, they seldom projected to the PAG. These results suggest that many lamina I cells project to more than one site in the brain and that those projecting to PAG may represent a distinct subclass of lamina I projection neuron.
α2‐γ‐Aminobutyric acid (GABA)A receptors are the molecular substrates mediating precipitation of narcosis but not of sedation by the combined use of diazepam and alcohol in vivo
Authors: Täuber Marcus , Calame‐Droz Elisabeth , Prut Laetitia , Rudolph Uwe , Crestani Florence 
Published: November 2003

AbstractClassical benzodiazepines such as diazepam are widely used tranquillisers and hypnotics in various neuropsychiatric diseases including alcohol‐related disorders. One of the major drawbacks of benzodiazepine therapy, however, is an exacerbation of the sedative and hypnotic effects associated with alcohol intake, even at low doses. Even though the γ‐aminobutyric acid (GABA)A receptor complex is a common target for the actions of both classes of drugs, the molecular mechanisms underlying the enhanced pharmacological properties of the combined use of benzodiazepines and alcohol remain to be identified. The present experiments aimed at clarifying which of the GABAA receptor subtypes mediate the augmented hypnotic‐like and sedative effects of combined diazepam and alcohol using the righting reflex and motor activity assays, respectively, in histidine‐to‐arginine point mutated mice that possess diazepam‐insensitive α1‐, α2‐, α3‐ or α5‐GABAA receptors. The combination of diazepam (2 or 3 mg/kg) and ethanol (3 g/kg) induced loss of righting reflex with a significantly dose‐dependent increase of the latency to its full recovery in wild‐type, α1(H101R), α3(H126R) and α5(H105R) but not in α2(H101R) mice. A combined treatment with diazepam (1 mg/kg) and ethanol (2.5 g/kg) precipitated motor inhibition similarly in wild‐type and α2(H101R) mice. Responsiveness of the α2(H101R) mice to ethanol alone was similar to that of wild‐type mice. These results demonstrate that induction of loss of righting reflex by combined diazepam and alcohol is closely dependent on the activation of the α2‐GABAA receptors by the benzodiazepine whereas precipitation of sedation involves GABAA receptors other than the α2‐GABAA receptors.
Light‐induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6‐38 or PACAP immunoneutralization
Authors: Bergström A. L. , Hannibal J. , Hindersson P. , Fahrenkrug J. 
Published: November 2003

AbstractCircadian rhythms generated by the suprachiasmatic nucleus (SCN) are daily adjusted (entrained) by light via the retinohypothalamic tract (RHT). The RHT contains two neurotransmitters, glutamate and pituitary adenylate cyclase‐activating polypeptide (PACAP), which are believed to mediate the phase‐shifting effects of light on the clock. In the present study we have elucidated the role of PACAP in light‐induced phase shifting at early night in hamsters and shown that (i) light‐induced phase delay of running‐wheel activity was significantly attenuated by a specific PAC1 receptor antagonist (PACAP6‐38) or by immunoblockade with a specific anti‐PACAP antibody injected intracerebroventricularly before light stimulation; (ii) PACAP administered close to the SCN was able to phase‐delay the circadian rhythm of running‐wheel activity in a similar way to light; (iii) PACAP was present in the hamster RHT, colocalized with melanopsin, a recently identified opsin which has been suggested to be a circadian photopigment. The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP‐expressing cells of the RHT.
Complexity and temporal dynamics of frequency coding in the awake rat auditory cortex
Authors: Gaese Bernhard H. , Ostwald Joachim 
Published: November 2003

AbstractAuditory cortical neurons are elements of a neuronal network that decomposes sounds into spectral and temporal information. In particular, their frequency selectivity has been investigated in great detail. Most studies used anaesthetized preparations and found mainly simple V‐shaped tuning. The few data available from awake animals indicate that more complex forms of spectral receptive fields, i.e. frequency response areas, can be found there. We investigated frequency response areas in the awake rat primary auditory cortex using statistical evaluation and found complex forms of frequency response areas with several separate subregions in many neurons, besides classical V‐shaped tuning. Response areas, as determined with narrow band noise, were very similar to those measured with pure tones. Their width was well correlated to the response strength to white noise stimulation. These results suggest that the excitatory subregions of frequency response areas were the neurons' predominant characteristic, relevant also for the processing of more complex types of stimuli. Investigating the spectrotemporal dynamics of frequency response areas revealed that approximately one‐third of the neurons showed long‐lasting excitatory or inhibitory components in addition to the typical ON‐response. Inhibition was usually of longer duration and occurred mainly in frequency ranges outside the range of initial excitatory responses. These results indicate that auditory cortical neurons in awake animals can represent spectrotemporal information of rather different complexity.
The “Employment‐first” Welfare State: Lessons from the New Deal for Young People
Authors: Finn Dan 
Published: November 2003

Abstract New Labour is constructing an “employment‐first” welfare state. It plans through Jobcentre Plus to transform the passive culture of the benefit system by creating more explicit links between individual behaviour and engagement with labour market programmes. The New Deal for Young People (NDYP) has been at the forefront of these changes. This paper reports on the findings from four case studies that explored how the NDYP has changed young people's experience of the welfare state. It establishes that NDYP offers a mixture of employment assistance and “pressure” and has made progress in developing front‐line services and helping young long‐term unemployed people into work. NDYP does not, however, work for all. In areas of high unemployment and for some disadvantaged groups intermediate labour markets could enhance the New Deal and make real the offer of “employment opportunities for all”.
New Firms in Former Farms: A Process with Two Faces
Authors: Daalhuizen Femke , Van Dam Frank , Goetgeluk Roland 
Published: November 2003

ABSTRACTThe number of farms in the Netherlands is decreasing. As a result, many agricultural buildings are losing their original function and designation. This article describes the re‐use of former agricultural buildings by non‐agricultural entrepreneurs. These new activities imply changes to the rural landscape, rural economy and rural society, which can be valued both as positive and as negative outcomes.
Clinical effectiveness of different approaches to peritoneal dialysis catheter exit‐site care
Authors: Lockwood Craig , Hodgkinson Brent , Page Tamara 
Published: November 2003

Executive summaryObjective  The objective of this review was to appraise and synthesise the best available evidence on the clinical effectiveness of peritoneal dialysis catheter exit‐site care.Inclusion criteria  This review considered all randomised controlled trials that evaluated the effectiveness of peritoneal exit‐site care. In the absence of randomised controlled trials, other controlled research designs such as non‐randomised controlled trials were considered for inclusion in a narrative summary to enable the identification of current approaches and possible future strategies. Participants of interest were adults with chronic renal failure on maintenance peritoneal dialysis. Interventions of interest were those used to manage peritoneal catheter exit sites, and included types of dressings, frequency of dressings, types of skin care, and use of topical antiseptic or antimicrobial agents.Search strategy  The search sought to find both published and unpublished studies. An initial limited search of MEDLINE and CINAHL databases was undertaken to identify key words contained in the title or abstract, and index terms used to describe relevant articles. A second extensive search was undertaken using all identified key words and index terms. The third step was a search of the reference lists and bibliographies of all relevant articles.Methodological quality  All identified studies that met the inclusion criteria were assessed for methodological validity by two reviewers prior to inclusion in the review. Critical appraisal of studies focused on identifying bias in selection, performance, attrition and detection.Results This review found few studies of sufficient quality to meet the inclusion criteria. The included studies often utilised historical control groups, potentially confounding measurement of their outcomes. The outcome measures varied considerably, thus meta‐analysis was not possible.Conclusions This review suggests topical mupirocin may reduce the risk of exit‐site infection; however, the clinical effectiveness of any one antibiotic, antiseptic or dressing procedure was not established for the prevention or reduction of exit‐site infection rates or peritonitis. This review has underlined large gaps in the existing knowledge on the care of exit sites in patients on peritoneal dialysis.
Alcohol‐Induced Suppression of Lung Chemokine Production and the Host Defense Response to Streptococcus pneumoniae
Authors: Boé Darren M. , Nelson Steve , Zhang Ping , Quinton Lee , Bagby Gregory J. 
Published: November 2003

Background: Acute alcohol intoxication impairs neutrophil migration in response to intrapulmonary infection with Streptococcus pneumoniae, the most common bacterial cause of pneumonia. Many of the same host defense functions that are impaired in the alcohol‐intoxicated host are mechanistically associated with chemokines, a group of proinflammatory molecules that enhance neutrophil adhesion and direct neutrophil migration to sites of inflammation. The purpose of this study was to determine whether alcohol‐induced chemokine suppression is responsible for impaired neutrophil recruitment into the lung during infection of the alcohol‐intoxicated host.Methods: S. pneumoniae was administered (107 colony‐forming units) intratracheally 30 min after intraperitoneal injection of 20% alcohol (5.5 g/kg) or saline. Four hours after bacterial challenge, bronchoalveolar lavage fluid (BALF) was collected, and the ability of BALF to induce neutrophil chemotaxis and adhesion molecule expression was measured by using chemotactic and flow cytometric assays. In another experiment, intratracheal challenge was performed by using recombinant macrophage inflammatory protein‐2 (MIP‐2), and BALF neutrophils were measured.Results: BALF MIP‐2 and cytokine‐induced neutrophil chemoattractant were decreased by alcohol, and BALF from alcohol‐intoxicated animals had decreased chemotactic activity for neutrophils, as well as a decreased ability to up‐regulate neutrophil adhesion molecule expression, compared with controls. This decreased chemotactic activity was significantly increased in the alcohol group by repletion of chemokines to control levels. Alcohol also suppressed neutrophil recruitment after intrapulmonary challenge with MIP‐2, suggesting that mechanisms other than chemokine suppression contribute to the alcohol‐induced effect.Conclusions: At least two mechanisms, suppressed chemokine production and impaired neutrophil adhesion molecule expression, likely work in concert in the alcohol‐intoxicated host to impair neutrophil adhesion and migration into the lung during pneumococcal infection. These alterations in neutrophil function likely increase the susceptibility of alcohol‐consuming hosts to pneumonia.
Ondansetron Reduces Mood Disturbance Among Biologically Predisposed, Alcohol‐Dependent Individuals
Authors: Johnson Bankole A. , Ait‐Daoud Nassima , Ma Jennie Z. , Wang Yanmei 
Published: November 2003

Background: Early‐onset alcoholics (EOA) differ from late‐onset alcoholics (LOA) by developing problem drinking during youth, experiencing severe behavioral problems, having a familial disease history, and possessing a tendency toward subsyndromal mood disturbance, including symptoms of depression, anxiety, and hostility. Subsyndromal mood disturbance is, therefore, an important component of the early‐onset syndrome and may be mediated by serotonin dysfunction. Therefore, the serotonin‐3 antagonist ondansetron, which has been shown to be effective at improving drinking outcomes and promoting abstinence among EOA, presumably by ameliorating serotonin dysfunction, also may exert its beneficial effects by alleviating mood disturbance among EOA.Methods: After one lead‐in week of single‐blind placebo administration, subjects underwent 11 weeks of double‐blind outpatient treatment using a 2 × 4 factorial design that examined age of onset (EOA versus LOA) and medication dose (placebo, or ondansetron 1, 4, or 16 μg/kg twice daily) combined with weekly standardized group cognitive‐behavioral therapy. The placebo lead‐in week was used to adjust for study entrance effects but not for excluding subjects. Assessments of mood were performed by using the overall score and subscales of the Profile of Mood States both at screening and at weekly intervals during the study.Results: Subsyndromal mood disturbance was shown to be an important component of early‐onset alcoholism. Ondansetron (16 μg/kg twice daily) showed greater therapeutic efficacy at alleviating symptoms of overall mood disturbance, fatigue, vigor, confusion/bewilderment, and depression among EOA compared with LOA. EOA‐associated improvements in mood disturbance seemed to be independent of drinking behavior.Conclusions: Ondansetron has been shown to be an effective treatment for early‐onset alcoholism. Ondansetron's ability to improve symptoms of depression, anxiety, and hostility among EOA may make an additional contribution to its therapeutic effect. Mechanistic studies are needed to delineate more clearly the relationship between serotonin dysfunction and pathophysiology among various subtypes of alcohol‐dependent individuals.
Analyses of Quantitative Trait Loci Contributing to Alcohol Preference in HAD1/LAD1 and HAD2/LAD2 Rats
Authors: Carr Lucinda G. , Habegger Kirk , Spence John , Ritchotte Aimee , Liu Lixiang , Lumeng Lawrence , Li Ting‐Kai , Foroud Tatiana 
Published: November 2003

Background: The high‐alcohol‐drinking (HAD1/HAD2) and low‐alcohol‐drinking (LAD1/LAD2) rat lines, derived from the N/NIH rat, were developed by using a within‐family selection and rotational breeding design for alcohol preference and alcohol consumption. Previously, a 20‐cM genome screen identified quantitative trait loci (QTLs) on chromosomes 5, 10, 12, and 16 by using F2 progeny from HAD1 and LAD1 animals.Methods: A total of 459 F2 HAD1 × LAD1 animals had been previously genotyped, and 428 HAD2 × LAD2 F2 animals were genotyped for microsatellite markers within the identified QTL regions. Linkage analyses were performed with the program QTL Express, a recently developed Web‐based interface that implements a least‐squares method.Results: The linkage peaks previously identified in the HAD1 × LAD1 genome scan relied on one or two markers. Placement of additional markers in and around the QTL regions provided further support for each of the QTLs. Two of the QTLs on chromosomes 10 and 16 were confirmed in the replicate line; these QTLs exhibited linkage in both the HAD1/LAD1 and HAD2/LAD2 studies.Conclusions: This study demonstrated the importance of confirmation of QTLs in a replicate line, as well as the complexity of the genetic contribution to alcohol preference. Assessing these QTL regions in the inbred HAD/LAD animals will further facilitate characterization of these regions.