bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of linkage disequilibrium and its effect on non-parametric multipoint linkage analysis using two high density single-nucleotide polymorphism mapping panels
Authors: Murray Sarah Shaw
Published: January 2006

Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of linkage disequilibrium (LD) between SNPs in a linkage analysis in the Collaborative Study on the Genetics of Alcoholism pedigree collection (143 pedigrees; 1,614 individuals). The average r
2 between adjacent markers across the genetic map was 0.099 ± 0.003 in the Illumina III panel and 0.17 ± 0.003 in the Affymetrix 10 k array. In order to determine the effect of LD between marker loci in a nonparametric multipoint linkage analysis, markers in strong LD with another marker (r
2 > 0.40) were removed (n = 471 loci in the Illumina panel; n = 1,804 loci in the Affymetrix panel) and the linkage analysis results were compared to the results using the entire marker sets. In all analyses using the ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were detected (peak markers p < 0.01), and the Illumina panel detected an additional region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3 chromosomes (peak markers p < 0.01). These results suggest that in this pedigree set, LD between loci with spacing similar to the SNP panels tested may not significantly affect the overall detection of linkage regions in a genome scan. Moreover, since the data quality and information content are greatly improved in the SNP panels over STR genotyping methods, new linkage regions may be identified due to higher information content and data quality in a dense SNP linkage panel.
Linkage disequilibrium across two different single-nucleotide polymorphism genome scans
Authors: Peralta Juan Manuel , Dyer Thomas D , Warren Diane M , Blangero John , Almasy Laura
Published: January 2006

Linkage disequilibrium (LD) content was calculated for the Genetic Analysis Workshop 14 Affymetrix and Illumina single-nucleotide polymorphism (SNP) genome scans of the Collaborative Study on the Genetics of Alcoholism samples. Pair-wise LD was measured as both D' and r
2 on 505 pedigree founder individuals. The r
2 estimates were then used to correct the multipoint identity by descent matrix (MIBD) calculation to account for LD and LOD scores on chromosomes 3 and 18 were calculated for COGA's ttdt3 electrophysiological trait using those MIBDs. Extensive LD was observed throughout both marker sets, and it was higher in Affymetrix's more dense SNP map. However, SNP density did not solely account for Affymetrix's higher LD. MIBD estimation procedures assume linkage equilibrium to construct genotypes of non-genotyped pedigree founder individuals, and dense SNP genotyping maps are likely to contain moderate to high LD between markers. LOD score plots calculated after correction for LD followed the same general pattern as uncorrected ones. Since in our study almost half of the pedigree founders were genotyped, it is possible that LD had a minor impact on the LOD scores. Caution should probably be taken when using high density SNP maps when many non-genotyped founders are present in the study pedigrees.
A comparison in association and linkage genome-wide scans for alcoholism susceptibility genes using single-nucleotide polymorphisms
Authors: Chiu Yen-Feng , Liu Su-Yun , Tsai Ya-Yu
Published: January 2006

We conducted genome-wide linkage scans using both microsatellite and single-nucleotide polymorphism (SNP) markers. Regions showing the strongest evidence of linkage to alcoholism susceptibility genes were identified. Haplotype analyses using a sliding-window approach for SNPs in these regions were performed. In addition, we performed a genome-wide association scan using SNP data. SNPs in these regions with evidence of association (P ≦ 0.0001) were identified. We found that the general patterns for nonparametric linkage (NPL) scores from SNP and microsatellite genome scans are fairly consistent; however, the peaks of the NPL scores are mostly higher in the SNP-based scan than those using microsatellite markers, which might be located at different regions. Furthermore, SNPs identified from linkage screens were not so strongly associated with alcoholism (the most significant SNP had a p-value of 0.030) as those identified from association genomic screening (the most significant SNP had a p-value of 2.0 × 10-8).
Impact of non-ignorable missingness on genetic tests of linkage and/or association using case-parent trios
Authors: Guo Chao-Yu , Cui Jing , Cupples L Adrienne
Published: January 2006

The transmission/disequilibrium test was introduced to test for linkage disequilibrium between a marker and a putative disease locus using case-parent trios. However, parental genotypes may be incomplete in such a study. When parental information is non-randomly missing, due, for example, to death from the disease under study, the impact on type I error and power under dominant and recessive disease models has been reported. In this paper, we examine non-ignorable missingness by assigning missing values to the genotypes of affected parents. We used unrelated case-parent trios in the Genetic Analysis Workshop 14 simulated data for the Danacaa population. Our computer simulations revealed that the type I error of these tests using incomplete trios was not inflated over the nominal level under either recessive or dominant disease models. However, the power of these tests appears to be inflated over the complete information case due to an excess of heterozygous parents in dyads.
The quantitative trait linkage disequilibrium test: a more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification
Authors: Havill Lorena M , Dyer Thomas D , Richardson Dawn K , Mahaney Michael C , Blangero John
Published: January 2006

Linkage analysis based on identity-by-descent allele-sharing can be used to identify a chromosomal region harboring a quantitative trait locus (QTL), but lacks the resolution required for gene identification. Consequently, linkage disequilibrium (association) analysis is often employed for fine-mapping. Variance-components based combined linkage and association analysis for quantitative traits in sib pairs, in which association is modeled as a mean effect and linkage is modeled in the covariance structure has been extended to general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT approach accommodates data not only from parents and siblings, but also from all available relatives. QTDT is also robust to population stratification. However, when population stratification is absent, it is possible to utilize even more information, namely the additional information contained in the founder genotypes. In this paper, we introduce a simple modification of the allelic transmission scoring method used in the QTDT that results in a more powerful test of linkage disequilibrium, but is only applicable in the absence of population stratification. This test, the quantitative trait linkage disequilibrium (QTLD) test, has been incorporated into a new procedure in the statistical genetics computer package SOLAR. We apply this procedure in a linkage/association analysis of an electrophysiological measurement previously shown to be related to alcoholism. We also demonstrate by simulation the increase in power obtained with the QTLD test, relative to the QTDT, when a true association exists between a marker and a QTL.
Analysis of binary traits: testing association in the presence of linkage
Authors: Jonasdottir Gudrun , Palmgren Juni , Humphreys Keith
Published: January 2006

Most methods for testing association in the presence of linkage, using family-based studies, have been developed for continuous traits. FBAT (family-based association tests) is one of few methods appropriate for discrete outcomes. In this article we describe a new test of association in the presence of linkage for binary traits. We use a gamma random effects model in which association and linkage are modelled as fixed effects and random effects, respectively. We have compared the gamma random effects model to an FBAT and a generalized estimating equation-based alternative, using two regions in the Genetic Analysis Workshop 14 simulated data. One of these regions contained haplotypes associated with disease, and the other did not.
A regression based transmission/disequilibrium test for binary traits: the power of joint tests for linkage and association
Authors: Larkin Emma K , Cartier Kevin C , Gray-McGuire Courtney
Published: January 2006

Background

In this analysis we applied a regression based transmission disequilibrium test to the binary trait presence or absence of Kofendred Personality Disorder in the Genetic Analysis Workshop 14 (GAW14) simulated dataset and determined the power and type I error rate of the method at varying map densities and sample sizes. To conduct this transmission disequilibrium test, the logit transformation was applied to a binary outcome and regressed on an indicator variable for the transmitted allele from informative matings. All 100 replicates from chromosomes 1, 3, 5, and 9 for the Aipotu and the combined Aipotu, Karangar, and Danacaa populations were used at densities of 3, 1, and 0.3 cM. Power and type I error were determined by the number of replicates significant at the 0.05 level.

Results

The maximum power to detect linkage and association with the Aipotu population was 93% for chromosome 3 using a 0.3-cM map. For chromosomes 1, 5, and 9 the power was less than 10% at the 3-cM scan and less than 22% for the 0.3-cM map. With the larger sample size, power increased to 38% for chromosome 1, 100% for chromosome 3, 31% for chromosome 5, and 23% for chromosome 9. Type I error was approximately 7%.

Conclusion

The power of this method is highly dependent on the amount of information in a region. This study suggests that single-point methods are not particularly effective in narrowing a fine-mapping region, particularly when using single-nucleotide polymorphism data and when linkage disequilibrium in the region is variable.
A global definition of expression context is conserved between orthologs, but does not correlate with sequence conservation
Authors: Dutilh Bas E , Huynen Martijn A , Snel Berend
Published: January 2006

Background

The massive scale of microarray derived gene expression data allows for a global view of cellular function. Thus far, comparative studies of gene expression between species have been based on the level of expression of the gene across corresponding tissues, or on the co-expression of the gene with another gene.

Results

To compare gene expression between distant species on a global scale, we introduce the "expression context". The expression context of a gene is based on the co-expression with all other genes that have unambiguous counterparts in both genomes. Employing this new measure, we show 1) that the expression context is largely conserved between orthologs, and 2) that sequence identity shows little correlation with expression context conservation after gene duplication and speciation.

Conclusion

This means that the degree of sequence identity has a limited predictive quality for differential expression context conservation between orthologs, and thus presumably also for other facets of gene function.
Comprehensive analysis of the renal transcriptional response to acute uranyl nitrate exposure
Authors: Taulan Magali , Paquet Francois , Argiles Angel , Demaille Jacques , Romey Marie-Catherine
Published: January 2006

Background

Chemical and radiological toxicities related to uranium acute exposure have been widely studied in nuclear fuel workers and military personnel. It is well known that uranyl nitrate induces acute renal failure (ARF). However, the mechanisms of this metal-induced injury are not well defined at the molecular level.

Results

Renal function and histology were assessed in mice receiving uranyl nitrate (UN(+)) and controls (UN(-)). To identify the genomic response to uranium exposure, serial analysis gene expression (SAGE) of the kidney was performed in both groups. Over 43,000 mRNA SAGE tags were sequenced. A selection of the differentially expressed transcripts was confirmed by real-time quantitative PCR and Western blotting. UN(+) animals developed renal failure and displayed the characteristic histological lesions of UN nephropathy. Of the >14,500 unique tags identified in both libraries, 224 had a modified expression level; they are known to participate in inflammation, ion transport, signal transduction, oxidative stress, apoptosis, metabolism, and catabolism. Several genes that were identified had not previously been evaluated within the context of toxic ARF such as translationally controlled tumor protein, insulin like growth factor binding protein 7 and ribosomal protein S29, all apoptosis related genes.

Conclusion

We report a comprehensive description of the UN induced modifications in gene expression levels, including the identification of genes previously unrelated to ARF. The study of these genes and the metabolisms they control should improve our understanding of toxic ARF and enlighten on the molecular targets for potential therapeutic interventions.
Structural and functional properties of genes involved in human cancer
Authors: Furney Simon J , Higgins Desmond G , Ouzounis Christos A , López-Bigas Núria
Published: January 2006

Background

One of the main goals of cancer genetics is to identify the causative elements at the molecular level leading to cancer.

Results

We have conducted an analysis of a set of genes known to be involved in cancer in order to unveil their unique features that can assist towards the identification of new candidate cancer genes.

Conclusion

We have detected key patterns in this group of genes in terms of the molecular function or the biological process in which they are involved as well as sequence properties. Based on these features we have developed an accurate Bayesian classification model with which human genes have been scored for their likelihood of involvement in cancer.
Genomic analysis of a 1 Mb region near the telomere of Hessian fly chromosome X2 and avirulence gene vH13
Authors: Lobo Neil F , Behura Susanta K , Aggarwal Rajat , Chen Ming-Shun , Collins Frank H , Stuart Jeff J
Published: January 2006

Background

To have an insight into theMayetiola destructor(Hessian fly) genome, we performed anin silicocomparative genomic analysis utilizing genetic mapping, genomic sequence and EST sequence data along with data available from public databases.

Results

Chromosome walking and FISH were utilized to identify a contig of 50 BAC clones near the telomere of the short arm of Hessian fly chromosome X2 and near the avirulence genevH13. These clones enabled us to correlate physical and genetic distance in this region of the Hessian fly genome. Sequence data from these BAC ends encompassing a 760 kb region, and a fully sequenced and assembled 42.6 kb BAC clone, was utilized to perform a comparative genomic study.In silicogene prediction combined with BLAST analyses was used to determine putative orthology to the sequenced dipteran genomes of the fruit fly,Drosophila melanogaster, and the malaria mosquito,Anopheles gambiae, and to infer evolutionary relationships.

Conclusion

This initial effort enables us to advance our understanding of the structure, composition and evolution of the genome of this important agricultural pest and is an invaluable tool for a whole genome sequencing effort.
A molecular signature of epithelial host defense: comparative gene expression analysis of cultured bronchial epithelial cells and keratinocytes
Authors: Vos Joost B , Datson Nicole A , van Kampen Antoine H , Luyf Angela C , Verhoosel Renate M , Zeeuwen Patrick L , Olthuis Diana , Rabe Klaus F , Schalkwijk Joost , Hiemstra Pieter S
Published: January 2006

Background

Epithelia are barrier-forming tissues that protect the organism against external noxious stimuli. Despite the similarity in function of epithelia, only few common protective mechanisms that are employed by these tissues have been systematically studied. Comparative analysis of genome-wide expression profiles generated by means of Serial Analysis of Gene Expression (SAGE) is a powerful approach to yield further insight into epithelial host defense mechanisms. We performed an extensive comparative analysis of previously published SAGE data sets of two types of epithelial cells, namely bronchial epithelial cells and keratinocytes, in which the response to pro-inflammatory cytokines was assessed. These data sets were used to elucidate a common denominator in epithelial host defense.

Results

Bronchial epithelial cells and keratinocytes were found to have a high degree of overlap in gene expression. Using an in silico approach, an epithelial-specific molecular signature of gene expression was identified in bronchial epithelial cells and keratinocytes comprising of family members of keratins, small proline-rich proteins and proteinase inhibitors. Whereas some of the identified genes were known to be involved in inflammation, the majority of the signature represented genes that were previously not associated with host defense. Using polymerase chain reaction, presence of expression of selected tissue-specific genes was validated.

Conclusion

Our comparative analysis of gene transcription reveals that bronchial epithelial cells and keratinocytes both express a subset of genes that is likely to be essential in epithelial barrier formation in these cell types. The expression of these genes is specific for bronchial epithelial cells and keratinocytes and is not seen in non-epithelial cells. We show that bronchial epithelial cells, similar to keratinocytes, express components that are able to form a cross-linked protein envelope that may contribute to an effective barrier against noxious stimuli and pathogens.
Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT) in the chicken
Authors: Mosenson Jeffrey A , McNulty John A
Published: January 2006

Background

Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle.

Results

PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+(80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+), which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+(75–80%), CD8+(20–25%), TCRαβ/Vβ1+(60%), and TCRγδ+(15%). All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+and TCRγδ+/TCRαβ/Vβ1+within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+and TCRγδ+/TCRαβ/Vβ1+each approximated 1:4. Bu-1+cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRαβ/Vβ1+cells, and a decline in the area density of Bu-1+microglia at the light:dark interphase (1900 h) compared to the dark:light interphase (0700 h).

Conclusion

The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light:dark cycle and that CD8+and TCRγδ+T-cells are preferentially recruited to the pineal follicles. Pineal microglia/macrophages were common and represent an important candidate for mediating these lymphocyte-pineal interactions via secretion of cytokines and chemokines.
Non-rapid eye movement sleep with low muscle tone as a marker of rapid eye movement sleep regulation
Authors: Tinguely Gilberte , Huber Reto , Borbély Alexander A , Achermann Peter
Published: January 2006

Background

It was recently reported that epochs of non-REM sleep (NREMS) with low muscle tone represent a partial correlate of REM sleep (REMS). To further investigate this phenomenon, episodes of restricted night-time sleep (23:00 – 03.00h) and subsequent morning sleep (10:00 – 13:00h) were analysed.

Results

Epochs of NREMS with low muscle tone (NLMT) were identified. Their frequency was higher in morning sleep than in night sleep. At night, the latency to the first occurrence of NLMT showed a bimodal distribution with modes at sleep onset and close to REMS onset. In morning sleep, the distribution was unimodal with the mode at sleep onset. An episode of NLMT at sleep onset occurred in 35.5% of the night sleep episodes and in 60.9% of the morning sleep episodes without sleep onset REMS (SOREMS). Also SOREMS occurred predominantly in morning sleep. REMS episodes were longer and NREMS episodes shorter in morning sleep than in night sleep, whereas cycle duration did not differ. Simulating the time course of slow-wave activity revealed a close correspondence between empirical and computed values for night sleep, and some discrepancies for morning sleep.

Conclusion

The results provide further evidence that NREMS with low muscle tone is a marker of REMS regulation. NLMT at sleep onset may represent an early manifestation of REMS.
The relationship between obesity, hyperglycemia symptoms, and health-related quality of life among Hispanic and non-Hispanic white children and adolescents
Authors: Arif Ahmed A , Rohrer James E
Published: January 2006

Background

The current study was conducted to evaluate the effects of overweight, hyperglycemia symptoms, Hispanic ethnicity, and language barriers on health-related quality of life (HRQoL) among children and adolescents.

Methods

Parents'/guardians of a population based sample of 5530 children between ages 3 and 18 were administered the parents' version of the KINDL® survey instrument to assess HRQoL in children and adolescents. Multiple linear regression analysis was used to assess relationships between HRQoL, body mass index, and hyperglycemia symptoms categories.

Results

The mean age of children was 10.6 (SD = 4.3). The mean KINDL® total score was 79.7 (SD = 11.6) and the mean physical functioning score was 81.9 (SD = 20.3). Male children exhibited better physical health as compared to the female children (p < 0.001). Overweight children had lower overall HRQoL (p = 0.008). However, the association was not significant for the four of the six subscales including the physical health domain. Children with hyperglycemia symptoms and a family history of diabetes also had significantly lower overall and physical health HRQoL (p < 0.05). Children diagnosed with diabetes and in lower income strata also had significantly lower overall HRQoL (p < 0.05). No significant association between the Hispanic ethnicity and HRQoL was observed. However, those who reported mostly speaking Spanish exhibited significantly lower overall HRQoL (p = 0.001).

Conclusion

Results suggest that overweight may reduce overall quality of life among children, though it does not directly influence physical functioning. However, hyperglycemia symptoms may affect both overall health and physical functioning. Findings also suggest the need for developing programs directed at overcoming language barriers that may face Spanish-speaking children or their parents. Furthermore, targeting children who have hyperglycemia symptoms with public information campaigns may be more appropriate than targeting overweight children.
A comparison of oral omeprazole and intravenous cimetidine in reducing complications of duodenal peptic ulcer
Authors: Khoshbaten Manouchehr , Fattahi Ebrahim , Naderi Nosratollah , Khaleghian Farzaneh , Rezailashkajani Mohammadreza
Published: January 2006

Background

Gastrointestinal bleeding is a common problem and its most common etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous complication for patients. To reduce the rate of rebleeding and to fasten the improvement of patients' general conditions, most emergency departments in Iran use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not available in Iran). The aim of this study was to compare therapeutic effects of oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration of hospitalization, and the need for blood transfusion in duodenal ulcer patients.

Methods

In this clinical trial, 80 patients with upper gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of rebleeding referring to emergency departments of Imam and Sina hospitals in Tabriz, Iran were randomly assigned to two equal groups; one was treated with intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole per day.

Results

No statistically significant difference was found between cimetidine and omeprazole groups in regards to sex, age, alcohol consumption, cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean hemoglobin and mean BUN levels on admission, duration of hospitalization and the mean time of rebleeding. However, the need for blood transfusion was much lower in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units, respectively; p < 0.003). Moreover, rebleeding rate was significantly lower in omeprazole group (15%) than in cimetidine group (50%) (p < 0.001).

Conclusion

This study demonstrated that oral omeprazole significantly excels intravenous cimetidine in reducing the need for blood transfusion and lowering rebleeding rates in patients with upper gastrointestinal bleeding. Though not statistically significant (p = 0.074), shorter periods of hospitalization were found for omeprazole group which merits consideration for cost minimization.
Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals
Authors: Larsen Inger K , Grotmol Tom , Almendingen Kari , Hoff Geir
Published: January 2006

Background

Lifestyle is a well-established risk factor for colorectal cancer (CRC) and is also found to be associated with occurrence of adenomas. In the present study we evaluated risk factors for both low-risk adenomas and advanced neoplasia in asymptomatic individuals using a single-paged questionnaire. Aiming to see if the questionnaire was a useful tool in picking up high-risk individuals.

Methods

A cross-sectional study was carried out within a randomised controlled colorectal cancer screening trial (n = 6961). The population comprised men and women born between 1946 and 1950. Before screening in year 2001 they were asked to fill in a questionnaire about their present lifestyle. Cases were categorised according to the most severe findings at screening. Analyses were then conducted to find risk factors associated with the presence of either low-risk adenomas or advanced neoplasia.

Results

The response rate among attendees was 97% (3998/4111). Among these, 3447 (86%) had no neoplasia, 443 (11%) had low-risk adenomas, and 108 (3%) had advanced neoplasia. Low-risk adenomas were significantly associated with current smoking, and obesity. Participants with advanced neoplasia had a two-fold increased risk of not adhering to any of the selected lifestyle recommendations compared to controls. However, current smoking was the only variable that reached statistical significance in the multivariate analysis for these lesions. A dose-response relationship to the consumption of cigarettes per day was shown, where OR was 2.04 (CI 1.07–3.89) for the lowest consumption category.

Conclusion

The present findings indicate that a short questionnaire may be adequate in picking up the most consistent associations between lifestyle risk factors and colorectal neoplasia. Smoking and BMI were found to be the most significant risk factors for neoplasia, but adhering to recommendations on diet, and physical activity seems also to be of importance.
Bloodstream and endovascular infections due to Abiotrophia defectiva and Granulicatellaspecies
Authors: Senn Laurence , Entenza José M , Greub Gilbert , Jaton Katia , Wenger Aline , Bille Jacques , Calandra Thierry , Prod'hom Guy
Published: January 2006

Background

Abiotrophia and Granulicatella species, previously referred to as nutritionally variant streptococci (NVS), are significant causative agents of endocarditis and bacteraemia. In this study, we reviewed the clinical manifestations of infections due to A. defectiva and Granulicatella species that occurred at our institution between 1998 and 2004.

Methods

The analysis included all strains of NVS that were isolated from blood cultures or vascular graft specimens. All strains were identified by 16S rRNA sequence analysis. Patients' medical charts were reviewed for each case of infection.

Results

Eleven strains of NVS were isolated during the 6-year period. Identification of the strains by 16S rRNA showed 2 genogroups: Abiotrophia defectiva (3) and Granulicatella adiacens (6) or "para-adiacens" (2). The three A. defectiva strains were isolated from immunocompetent patients with endovascular infections, whereas 7 of 8 Granulicatella spp. strains were isolated from immunosuppressed patients, mainly febrile neutropenic patients. We report the first case of "G. para-adiacens" bacteraemia in the setting of febrile neutropenia.

Conclusion

We propose that Granulicatella spp. be considered as a possible agent of bacteraemia in neutropenic patients.
Spontaneous regression of bone metastasis from renal cell carcinoma; A case report
Authors: Nakajima Takahiro , Suzuki Makoto , Ando Soichiro , Iida Tomohiko , Araki Akinobu , Fujisawa Takehiko , Kimura Hideki
Published: January 2006

Background

Spontaneous regression of metastatic renal cell carcinoma is rarely observed.

Case presentation

Metastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells.

Conclusion

We report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously.
Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment
Authors: Brubaker Kristen D , Brown Lisha G , Vessella Robert L , Corey Eva
Published: January 2006

Background

After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment.

Methods

Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis.

Results

ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone.

Conclusion

In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.
Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study
Authors: Pignata Sandro , De Placido Sabino , Biamonte Rosalbino , Scambia Giovanni , Di Vagno Giovanni , Colucci Giuseppe , Febbraro Antonio , Marinaccio Marco , Vernaglia Lombardi Alessandra , Manzione Luigi , Cartenì Giacomo , Nardi Mario , Danese Saverio , Valerio Maria Rosaria , de Matteis Andrea , Massidda Bruno , Gasparini Giampietro , Di Maio Massimo , Pisano Carmela , Perrone Francesco
Published: January 2006

Background

Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer.

Methods

120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria.

Results

55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy.

Conclusion

A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.
The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma
Authors: Trefzer Uwe , Chen Yingwen , Herberth Gunda , Hofmann Maja Ann , Kiecker Felix , Guo Yajun , Sterry Wolfram
Published: January 2006

Background

Previously we have generated the monoclonal antibody SM5-1 by using a subtractive immunization protocol of human melanoma. This antibody exhibits a high sensitivity for primary melanomas of 99% (248/250 tested) and for metastatic melanoma of 96% (146/151 tested) in paraffin embedded sections. This reactivity is superior to the one obtained by HMB-45, anti-MelanA or anti-Tyrosinase and is comparable to anti-S100. However, as compared to anti-S100, the antibody SM5-1 is highly specific for melanocytic lesions since 40 different neoplasms were found to be negative for SM5-1 by immunohistochemistry. The antigen recognized by SM5-1 is unknown.

Methods

In order to characterize the antigen recognized by mAb SM5-1, a cDNA library was constructed from the metastatic human melanoma cell line SMMUpos in the Uni-ZAP lambda phage and screened by mAb SM5-1. The cDNA clones identified by this approach were then sequenced and subsequently analyzed.

Results

Sequence analysis of nine independent overlapping clones (length 3100–5600 bp) represent fibronectin cDNA including the ED-A, but not the ED-B region which are produced by alternative splicing. The 89aa splicing variant of the IIICS region was found in 8/9 clones and the 120aa splicing variant in 1/9 clones, both of which are included in the CS1 region of fibronectin being involved in melanoma cell adhesion and spreading.

Conclusion

The molecule recognized by SM5-1 is a melanoma associated FN variant expressed by virtually all primary and metastatic melanomas and may play an important role in melanoma formation and progression. This antibody is therefore not only of value in immunohistochemistry, but potentially also for diagnostic imaging and immunotherapy.
Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a Prospective follow-up study
Authors: Delorme Richard , Bille Arnaud , Betancur Catalina , Mathieu Flavie , Chabane Nadia , Mouren-Simeoni Marie Christine , Leboyer Marion
Published: January 2006

Background

Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed.

Methods

This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years).

Results

We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another.

Conclusion

These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach.
Urbanization and traffic related exposures as risk factors for Schizophrenia
Authors: Pedersen Carsten Bøcker , Mortensen Preben Bo
Published: January 2006

Background

Urban birth or upbringing increase schizophrenia risk. Though unknown, the causes of these urban-rural differences have been hypothesized to include, e.g., infections, diet, toxic exposures, social class, or an artefact due to selective migration.

Methods

We investigated the hypothesis that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register.

Results

The geographical distance from place of residence to nearest major road had a significant effect. The highest risk was found in children living 500–1000 metres from nearest major road (RR = 1.30 (95% Confidence Interval: 1.17–1.44). However, when we accounted for the degree of urbanization, the geographical distance to nearest major road had no significant effect.

Conclusion

The cause(s) or exposure(s) responsible for the urban-rural differences in schizophrenia risk were closer related to the degree of urbanization than to the geographical distance to nearest major road. Traffic related exposures might thus be less likely explanations for the urban-rural differences in schizophrenia risk.
Concurrent crack and powder cocaine users from Sao Paulo: Do they represent a different group?
Authors: Guindalini Camila , Vallada Homero , Breen Gerome , Laranjeira Ronaldo
Published: January 2006

Background

Cocaine abuse is a serious and socially damaging illegal drug problem. Different routes of administration are associated with a specific progression of use, different degrees of abuse liability, propensity for dependence and treatment response. There have been relatively few studies comparing different cocaine users groups and no studies into the characterization of the group of individuals reporting concurrent use of powder cocaine and crack cocaine.

Methods

Six hundred and ninety-nine cocaine users were assessed during the period August 1997 to October 1998 in one outpatient and six inpatient clinics located in the São Paulo, Brazil. Patients were interviewed using a structured questionnaire schedule in Portuguese, designed specifically for the Brazilian population. The statistical analyses were performed using either ANOVA or a chi-squared test and focusing on their preferred form of use/route of administration and other variables.

Results

For 83% of the variables tested in this study, the Dual Users subgroup (using both powder and crack cocaine) demonstrated statistical differences from the single drug user subgroups. Those differences include the initiation of cocaine, the abuse of other illicit drugs, and rates of criminal history.

Conclusion

These data suggest cocaine-dependent individuals who report use of both powder and crack cocaine are an at least partially, distinct subgroup. However, further studies will be necessary to confirm this and to determine if they also show a different treatment response.
Study Protocol – Diabetes and related conditions in urban Indigenous people in the Darwin, Australia region: aims, methods and participation in the DRUID Study
Authors: Cunningham Joan , O'Dea Kerin , Dunbar Terry , Weeramanthri Tarun , Zimmet Paul , Shaw Jonathan
Published: January 2006

Background

Diabetes mellitus is a serious and increasing health problem in Australia and is a designated national health priority. Diabetes and related conditions represent an even greater health burden among Indigenous Australians (Aborigines and Torres Strait Islanders), but there are critical gaps in knowledge relating to the incidence and prevalence, aetiology, and prevention of diabetes in this group, including a lack of information on the burden of disease among Indigenous people in urban areas. The DRUID Study (Diabetes and Related conditions in Urban Indigenous people in the Darwin region) was designed to address this knowledge gap.

Methods/design

The study was conducted in a specified geographic area in and around Darwin, Australia. Eligible participants underwent a health examination, including collection of blood and urine samples, clinical and anthropometric measurements, and administration of questionnaires, with an additional assessment for people with diabetes. The study was designed to incorporate local Indigenous leadership, facilitate community engagement, and provide employment and training opportunities for local Indigenous people. A variety of recruitment methods were used. A total of 1,004 eligible people gave consent and provided at least one measurement. When compared with census data for the Indigenous population living in the study area, there was a marked under-representation of males, but no substantial differences in age, place of residence, Indigenous group, or household income. Early participants were more likely than later participants to have previously diagnosed diabetes.

Discussion

Despite lower than anticipated recruitment, this is, to our knowledge, the largest study ever conducted on the health of Indigenous Australians living in urban areas, a group which comprises the majority of Australia's Indigenous population but about whose health and wellbeing relatively little is known. The study is well-placed to provide new information that can be used by policy makers and service providers to improve the delivery of services and programs that affect the health of Indigenous people. It also represents a valuable opportunity to establish an urban Indigenous cohort study, provided participants can be followed successfully over time.
Prevalence of cardiovascular risk factors in a middle-income country and estimated cost of a treatment strategy
Authors: Bovet Pascal , Shamlaye Conrad , Gabriel Anne , Riesen Walter , Paccaud Fred
Published: January 2006

Background

We assessed the prevalence of risk factors for cardiovascular disease (CVD) in a middle-income country in rapid epidemiological transition and estimated direct costs for treating all individuals at increased cardiovascular risk, i.e. following the so-called "high risk strategy".

Methods

Survey of risk factors using an age- and sex-stratified random sample of the population of Seychelles aged 25–64 in 2004. Assessment of CVD risk and treatment modalities were in line with international guidelines. Costs are expressed as US$ per capita per year.

Results

1255 persons took part in the survey (participation rate of 80.2%). Prevalence of main risk factors was: 39.6% for high blood pressure (≥140/90 mmHg or treatment) of which 59% were under treatment; 24.2% for high cholesterol (≥6.2 mmol/l); 20.8% for low HDL-cholesterol (<1.0 mmol/l); 9.3% for diabetes (fasting glucose ≥7.0 mmol/l); 17.5% for smoking; 25.1% for obesity (body mass index ≥30 kg/m2) and 22.1% for the metabolic syndrome. Overall, 43% had HBP, high cholesterol or diabetes and substantially increased CVD risk. The cost for medications needed to treat all high-risk individuals amounted to US $45.6, i.e. $11.2 for high blood pressure, $3.8 for diabetes, and $30.6 for dyslipidemia (using generic drugs except for hypercholesterolemia). Cost for minimal follow-up medical care and laboratory tests amounted to $22.6.

Conclusion

High prevalence of major risk factors was found in a rapidly developing country and costs for treatment needed to reduce risk factors in all high-risk individuals exceeded resources generally available in low or middle income countries. Our findings emphasize the need for affordable cost-effective treatment strategies and the critical importance of population strategies aimed at reducing risk factors in the entire population.