bluuebunny/crossref_metadata_2025 huggingface dataset:
Allele frequency misspecification: effect on power and Type I error of model-dependent linkage analysis of quantitative traits under random ascertainment
Authors: Mandal Diptasri M , Sorant Alexa JM , Atwood Larry D , Wilson Alexander F , Bailey-Wilson Joan E
Published: April 2006

Background

Studies of model-based linkage analysis show that trait or marker model misspecification leads to decreasing power or increasing Type I error rate. An increase in Type I error rate is seen when marker related parameters (e.g., allele frequencies) are misspecified and ascertainment is through the trait, but lod-score methods are expected to be robust when ascertainment is random (as is often the case in linkage studies of quantitative traits). In previous studies, the power of lod-score linkage analysis using the "correct" generating model for the trait was found to increase when the marker allele frequencies were misspecified and parental data were missing. An investigation of Type I error rates, conducted in the absence of parental genotype data and with misspecification of marker allele frequencies, showed that an inflation in Type I error rate was the cause of at least part of this apparent increased power. To investigate whether the observed inflation in Type I error rate in model-based LOD score linkage was due to sampling variation, the trait model was estimated from each sample using REGCHUNT, an automated segregation analysis program used to fit models by maximum likelihood using many different sets of initial parameter estimates.

Results

The Type I error rates observed using the trait models generated by REGCHUNT were usually closer to the nominal levels than those obtained when assuming the generating trait model.

Conclusion

This suggests that the observed inflation of Type I error upon misspecification of marker allele frequencies is at least partially due to sampling variation. Thus, with missing parental genotype data, lod-score linkage is not as robust to misspecification of marker allele frequencies as has been commonly thought.
Cotranscription and intergenic splicing of the PPARG and TSEN2 genes in cattle
Authors: Roux Matthieu , Levéziel Hubert , Amarger Valérie
Published: April 2006

Background

Intergenic splicing resulting in the combination of mRNAs sequences from distinct genes is a newly identified mechanism likely to contribute to protein diversity. Few cases have been described, most of them involving neighboring genes and thus suggesting a cotranscription event presumably due to transcriptional termination bypass.

Results

We identified bovine chimeric transcripts resulting from cotranscription and intergenic splicing of two neighboring genes, PPARG and TSEN2. These two genes encode the Peroxisome Proliferator Activated Receptors γ1 and γ2 and the tRNA Splicing Endonuclease 2 homolog and are situated in the same orientation about 50 kb apart on bovine chromosome 22q24. Their relative position is conserved in human and mouse. We identified two types of chimeric transcripts containing all but the last exon of the PPARG gene followed by all but the first exon of the TSEN2 gene. The two chimers differ by the presence/absence of an intermediate exon resulting from transcription of a LINE L2 sequence situated between the two genes. Both transcripts use canonical splice sites for all exons coming from both genes, as well as for the LINE L2 sequence. One of these transcripts harbors a premature STOP codon and the other encodes a putative chimeric protein combining most of the PPARγ protein and the entire TSEN2 protein, but we could not establish the existence of this protein.

Conclusion

By showing that both individual and chimeric transcripts are transcribed from PPARG and TSEN2, we demonstrated regulation of transcription termination. Further, the existence and functionality of a chimeric protein harboring active motifs that are a priori unrelated is hypothesized.
Microsatellite polymorphism across the M. tuberculosis and M. bovis genomes: Implications on genome evolution and plasticity
Authors: Sreenu Vattipally B , Kumar Pankaj , Nagaraju Javaregowda , Nagarajaram Hampapathalu A
Published: April 2006

Background

Microsatellites are the tandem repeats of nucleotide motifs of size 1–6 bp observed in all known genomes. These repeats show length polymorphism characterized by either insertion or deletion (indels) of the repeat units, which in and around the coding regions affect transcription and translation of genes.

Results

Systematic comparison of all the equivalent microsatellites in the coding regions of the three mycobacterial genomes, viz.Mycobacterium tuberculosisH37Rv,Mycobacterium tuberculosisCDC1551 andMycobacterium bovis, revealed for the first time the presence of several polymorphic microsatellites. The coding regions affected by frame-shifts owing to microsatellite indels have undergone changes indicative of gene fission/fusion, premature termination and length variation. Interestingly, the genes affected by frame-shift mutations code for membrane proteins, transporters, PPE, PE_PGRS, cell-wall synthesis proteins and hypothetical proteins.

Conclusion

This study has revealed the role of microsatellite indel mutations in imparting novel functions and a certain degree of plasticity to the mycobacterial genomes. There seems to be some correlation between microsatellite polymorphism and the variations in virulence, host-pathogen interactions mediated by surface antigen variations, and adaptation of the pathogens. Several of the polymorphic microsatellites reported in this study can be tested for their polymorphic nature by screening clinical isolates and various mycobacterial strains, for establishing correlations between microsatellite polymorphism and the phenotypic variations among these pathogens.
The Bacillus anthracis chromosome contains four conserved, excision-proficient, putative prophages
Authors: Sozhamannan Shanmuga , Chute Michael D , McAfee Farrell D , Fouts Derrick E , Akmal Arya , Galloway Darrell R , Mateczun Alfred , Baillie Leslie W , Read Timothy D
Published: April 2006

Background

Bacillus anthracis is considered to be a recently emerged clone within the Bacillus cereus sensu lato group. The B. anthracis genome sequence contains four putative lambdoid prophages. We undertook this study in order to understand whether the four prophages are unique to B. anthracis and whether they produce active phages.

Results

More than 300 geographically and temporally divergent isolates of B. anthracis and its near neighbors were screened by PCR for the presence of specific DNA sequences from each prophage region. Every isolate of B. anthracis screened by PCR was found to produce all four phage-specific amplicons whereas none of the non-B. anthracis isolates, produced more than one phage-specific amplicon. Excision of prophages could be detected by a PCR based assay for attP sites on extra-chromosomal phage circles and for attB sites on phage-excised chromosomes. SYBR-green real-time PCR assays indicated that prophage excision occurs at very low frequencies (2 × 10-5 - 8 × 10-8/cell). Induction with mitomycin C increased the frequency of excision of one of the prophages by approximately 250 fold. All four prophages appear to be defective since, mitomycin C induced culture did not release any viable phage particle or lyse the cells or reveal any phage particle under electron microscopic examination.

Conclusion

The retention of all four putative prophage regions across all tested strains of B. anthracis is further evidence of the very recent emergence of this lineage and the prophage regions may be useful for differentiating the B. anthracis chromosome from that of its neighbors. All four prophages can excise at low frequencies, but are apparently defective in phage production.
Mutacin H-29B is identical to mutacin II (J-T8)
Authors: Nicolas Guillaume , Morency Hélène , LaPointe Gisèle , Lavoie Marc C
Published: April 2006

Background

Streptococcus mutans produces bacteriocins named mutacins. Studies of mutacins have always been hampered by the difficulties in obtaining active liquid preparations of these substances. Some of them were found to be lantibiotics, defined as bacterial ribosomally synthesised lanthionine-containing peptides with antimicrobial activity. The goal of this study was to produce and characterize a new mutacin from S. mutans strain 29B, as it shows a promising activity spectrum against current human pathogens.

Results

Mutacin H-29B, produced by S. mutans strain 29B, was purified by successive hydrophobic chromatography from a liquid preparation consisting of cheese whey permeate (6% w/v) supplemented with yeast extract (2%) and CaCO3 (1%). Edman degradation revealed 24 amino acids identical to those of mutacin II (also known as J-T8). The molecular mass of the purified peptide was evaluated at 3246.08 ± 0.1 Da by MALDI-TOF MS.

Conclusion

A simple procedure for production and purification of mutacins along with its characterization is presented. Our results show that the amino acid sequence of mutacin H-29B is identical to the already known mutacin II (J-T8) over the first 24 residues. S. mutans strains of widely different origins may thus produce very similar bacteriocins.
The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond laser ablation
Authors: Chung Samuel H , Clark Damon A , Gabel Christopher V , Mazur Eric , Samuel Aravinthan DT
Published: April 2006

Background

Caenorhabditis elegans actively crawls down thermal gradients until it reaches the temperature of its prior cultivation, exhibiting what is called cryophilic movement. Implicit in the worm's performance of cryophilic movement is the ability to detect thermal gradients, and implicit in regulating the performance of cryophilic movement is the ability to compare the current temperature of its surroundings with a stored memory of its cultivation temperature. Several lines of evidence link the AFD sensory neuron to thermotactic behavior, but its precise role is unclear. A current model contends that AFD is part of a thermophilic mechanism for biasing the worm's movement up gradients that counterbalances the cryophilic mechanism for biasing its movement down gradients.

Results

We used tightly-focused femtosecond laser pulses to dissect the AFD neuronal cell bodies and the AFD sensory dendrites in C. elegans to investigate their contribution to cryophilic movement. We establish that femtosecond laser ablation can exhibit submicrometer precision, severing individual sensory dendrites without causing collateral damage. We show that severing the dendrites of sensory neurons in young adult worms permanently abolishes their sensory contribution without functional regeneration. We show that the AFD neuron regulates a mechanism for generating cryophilic bias, but we find no evidence that AFD laser surgery reduces a putative ability to generate thermophilic bias. In addition, although disruption of the AIY interneuron causes worms to exhibit cryophilic bias at all temperatures, we find no evidence that laser killing the AIZ interneuron causes thermophilic bias at any temperature.

Conclusion

We conclude that laser surgical analysis of the neural circuit for thermotaxis does not support a model in which AFD opposes cryophilic bias by generating thermophilic bias. Our data supports a model in which the AFD neuron gates a mechanism for generating cryophilic bias.
Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio
Authors: Voisard Rainer , Alan Mustafa , Müller Lutz von , Baur Regine , Hombach Vinzenz
Published: April 2006

Background

The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation.

Methods

ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days.

Results

ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002 – 2 μg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 μg/ml (p < 0.05), 0.002 μg/ml (p < 0.001), and 0.2 μg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 μg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1.

Conclusion

Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation.
The relationship between self-reported alcohol intake and the morbidities managed by GPs in Australia
Authors: Proude Elizabeth M , Britt Helena , Valenti Lisa , Conigrave Katherine M
Published: April 2006

Background

One in five Australians consume alcohol at risky or harmful levels. Most (85%) attend a general practitioner at least once a year, giving opportunity for detecting and providing brief interventions for reducing alcohol-related harm. Historically, detection rates of problem drinking have been low in general practice, producing lower prevalence estimates of heavy drinking than expected from population surveys.

Method

The BEACH program collects data from 100 consecutive patient consultations with 1000 GPs annually. For 40 consecutive encounters, GPs ask adult patients three questions on alcohol consumption (AUDIT-C). This paper reports the problems managed and treatments provided at encounters with heavy and non-heavy drinkers, grouped by their response to the 3rd question, and compares the two groups before and after standardisation for age and sex. Heavy drinking was defined as having 6 or more standard drinks at least once a week or more often.

Results

Heavy drinking was reported by 7.3% patients overall; more prevalent among men (13.8%) than women (3.9%); and among Indigenous patients (18.5%). Prevalence was highest in young adults (18–24 years)(12.7%) and decreased with age. Patients from a non-English speaking background were less likely to be heavy drinkers. Heavy drinkers had more problems managed at encounters, more chronic problems, physical injuries and psychological problems (particularly depression) managed than non-heavy drinkers. They were less likely to have respiratory complaints, ischaemic heart disease or diabetes managed.

Conclusion

Heavy drinkers are more likely than non- or light drinkers to see their GP for management of chronic problems, psychological problems and physical injuries. However, the wide range of morbidity managed in heavy drinkers means that relying on clinical impression alone to detect this group will not suffice and should be augmented with routine screening. Given the pressures of general practice, finding efficient methods of screening for alcohol problems remains a priority.
Primary care patients reporting concerns about their gambling frequently have other co-occurring lifestyle and mental health issues
Authors: Goodyear-Smith Felicity , Arroll Bruce , Kerse Ngaire , Sullivan Sean , Coupe Nicole , Tse Samson , Shepherd Robin , Rossen Fiona , Perese Lana
Published: April 2006

Background

Problem gambling often goes undetected by family physicians but may be associated with stress-related medical problems as well as mental disorders and substance abuse. Family physicians are often first in line to identify these problems and to provide a proper referral. The aim of this study was to compare a group of primary care patients who identified concerns with their gambling behavior with the total population of screened patients in relation to co-morbidity of other lifestyle risk factors or mental health issues.

Methods

This is a cross sectional study comparing patients identified as worrying about their gambling behavior with the total screened patient population for co morbidity. The setting was 51 urban and rural New Zealand practices. Participants were consecutive adult patients per practice (N = 2,536) who completed a brief multi-item tool screening primary care patients for lifestyle risk factors and mental health problems (smoking, alcohol and drug misuse, problem gambling, depression, anxiety, abuse, anger). Data analysis used descriptive statistics and non-parametric binomial tests with adjusting for clustering by practitioner using STATA survey analysis.

Results

Approximately 3/100 (3%) answered yes to the gambling question. Those worried about gambling more likely to be male OR 1.85 (95% CI 1.1 to 3.1). Increasing age reduced likelihood of gambling concerns – logistic regression for complex survey data OR = 0.99 (CI 95% 0.97 to 0.99) p = 0.04 for each year older. Patients concerned about gambling were significantly more likely (all p < 0.0001) to have concerns about their smoking, use of recreational drugs, and alcohol. Similarly there were more likely to indicate problems with depression, anxiety and anger control. No significant relationship with gambling worries was found for abuse, physical inactivity or weight concerns. Patients expressing concerns about gambling were significantly more likely to want help with smoking, other drug use, depression and anxiety.

Conclusion

Our questionnaire identifies patients who express a need for help with gambling and other lifestyle and mental health issues. Screening for gambling in primary care has the potential to identify individuals with multiple co-occurring disorders.
Candidaemia and cancer: patients are not all the same
Authors: Pasqualotto Alessandro Comarú , Rosa Daniela Dornelles , Medeiros Lidia Rosi , Severo Luiz Carlos
Published: April 2006

Background

Most of the studies about invasive Candida infections in cancer patients have focused on haematological patients. The aim of this study was to provide information about risk factors for candidaemia in patients with solid tumours.

Methods

Retrospective cohort study. During a 9-year period (1995–2003) we reviewed all cases of candidaemia that affected cancer patients in Santa Casa Complexo Hospitalar, Brazil.

Results

During the period of study, 210 patients had the diagnosis of candidaemia in our medical centre, and 83 of these patients had cancer (39.5%). The majority of patients with cancer had solid tumours (77.1%), mostly in the alimentary tract. Most of solid cancers were non-metastatic (71.9%). Major diagnoses in patients with haematological neoplasia were acute leukaemia (n = 13), high grade non-Hodgkin lymphoma (n = 5) and Hodgkin's disease (n = 1). Non-Candida albicans species caused 57.8% of the episodes of candidaemia in patients with cancer, mainly in patients with haematological malignancies (p = 0.034). Neutropenia and treatment with corticosteroids were more frequent in the haematological group, in comparison with patients with solid tumours. Only 22.2% of patients with solid tumours were neutropenic before candidaemia. Nonetheless, the presence of ileus and the use of anaerobicides were independent risk factors for candidaemia in patients with solid cancers. The overall mortality in cancer patients with candidaemia was 49.4%. We then compared 2 groups of adult patients with candidaemia. The first was composed of non-neutropenic patients with solid tumours, and the second group included patients without cancer. We found that central venous catheters and gastrointestinal surgery were independently associated with candidaemia in patients with solid tumour.

Conclusion

Cancer patients with candidaemia seem to have very different predisposing factors to acquire the infection when stratified according to baseline diseases. This study provides some useful clinical information regarding risk for candidaemia in patients with solid tumours.
La cuerda dulce – a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis
Authors: Chow Felicia , Espiritu Nora , Gilman Robert H , Gutierrez Rosmery , Lopez Sonia , Escombe A Roderick , Evans Carlton AW , Moore David AJ
Published: April 2006

Background

Recent data demonstrate the utility of the string test for the diagnosis of sputum-scarce HIV-associated TB in adults. We hypothesized that, if well-tolerated by children, this simple tool might offer a breakthrough in paediatric TB diagnosis. Thus the objective of this study, undertaken in the paediatric service of the Hospital Nacional Dos de Mayo, Lima, Perú, was to determine the tolerability and acceptability of the string test to paediatric TB suspects, their parents and nursing staff.

Methods

22 paediatric subjects aged 3–14 years (median 8) under investigation for TB were invited to undergo 2 string tests (four-hour downtime each). Subjective and objective pain and discomfort rating scales were used to assess the perception of the subject, parent and attending nurse.

Results

Patients as young as 4 years tolerated the procedure extremely well with 84% willing to undergo a second procedure. Peak discomfort at the time of swallowing and of string retrieval was mild (30% of maximum possible score) and brief as judged by visual analogue ratings and objective indicators. Good concordance of parent/child and objective/subjective ratings strengthened the validity of these findings.

Conclusion

The string test is well tolerated and achievable for most paediatric TB suspects as young as 4 years. A formal prospective paediatric efficacy study is now needed.
Mycobacterium haemophilum osteomyelitis: case report and review of the literature
Authors: Elsayed Sameer , Read Ron
Published: April 2006

Background

Mycobacterium haemophilum is a slow-growing, fastidious, iron-requiring microorganism that, relative to other non-tuberculous mycobacterial species, has rarely been documented as a cause of human infection. This microorganism appears to be acquired via environmental exposure although its natural habitat and mode of acquisition are unknown. It has primarily been implicated as a cause of ulcerating cutaneous or subcutaneous nodular skin lesions, particularly in immunocompromised patients, although infections at extracutaneous sites have also been described. Osteomyelitis, while rarely documented, appears to be an important complication of infection with M. haemophilum in these patients.

Case presentation

We describe a unique case of culture-confirmed M. haemophilum osteomyelitis in an adult woman with polycythemia vera and review the world literature on bone infections due to this organism.

Conclusion

Mycobacterium haemophilum is an important but infrequently encountered cause of osteomyelitis in immunocompromised patients, often requiring months to years of medical therapy, with or without surgery, to effect a clinical cure.
Effect of Native American ancestry on iron-related phenotypes of Alabama hemochromatosis probands with HFEC282Y homozygosity
Authors: Barton James C , Barton Ellen H , Acton Ronald T
Published: April 2006

Background

In age-matched cohorts of screening study participants recruited from primary care clinics, mean serum transferrin saturation values were significantly lower and mean serum ferritin concentrations were significantly higher in Native Americans than in whites. Twenty-eight percent of 80 Alabama white hemochromatosis probands with HFE C282Y homozygosity previously reported having Native American ancestry, but the possible effect of this ancestry on hemochromatosis phenotypes was unknown.

Methods

We compiled observations in these 80 probands and used univariate and multivariate methods to analyze associations of age, sex, Native American ancestry (as a dichotomous variable), report of ethanol consumption (as a dichotomous variable), percentage transferrin saturation and loge serum ferritin concentration at diagnosis, quantities of iron removed by phlebotomy to achieve iron depletion, and quantities of excess iron removed by phlebotomy.

Results

In a univariate analysis in which probands were grouped by sex, there were no significant differences in reports of ethanol consumption, transferrin saturation, loge serum ferritin concentration, quantities of iron removed to achieve iron depletion, and quantities of excess iron removed by phlebotomy in probands who reported Native American ancestry than in those who did not. In multivariate analyses, transferrin saturation (as a dependent variable) was not significantly associated with any of the available variables, including reports of Native American ancestry and ethanol consumption. The independent variable quantities of excess iron removed by phlebotomy was significantly associated with loge serum ferritin used as a dependent variable (p < 0.0001), but not with reports of Native American ancestry or reports of ethanol consumption. Loge serum ferritin was the only independent variable significantly associated with quantities of excess iron removed by phlebotomy used as a dependent variable (p < 0.0001) (p < 0.0001; ANOVA of regression).

Conclusion

We conclude that the iron-related phenotypes of hemochromatosis probands with HFE C282Y homozygosity are similar in those with and without Native American ancestry reports.
A functional PTPN22polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population
Authors: Núñez Concepción , López-Mejías Raquel , Martínez Alfonso , García-Rodríguez M Cruz , Fernández-Arquero Miguel , de la Concha Emilio G , Urcelay Elena
Published: April 2006

Background

The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study.

Methods

A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary.

Results

No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72–1.79), p= 0.56; TDT p = 0.08).

Conclusion

The result obtained seems to reinforce the consideration of IgA deficiency as a primary immunodeficiency rather than an autoimmune disease.
Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population
Authors: Gamundi María José , Hernan Imma , Martínez-Gimeno María , Maseras Miquel , García-Sandoval Blanca , Ayuso Carmen , Antiñolo Guillermo , Baiget Montserrat , Carballo Miguel
Published: April 2006

Background

Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP). Most of these mutations are clustered in a 500 bp region of exon 4 of RP1.

Methods

Denaturing gradient gel electrophoresis (DGGE) analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out.

Results

Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population.

Conclusion

Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations.
Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449]
Authors: Hemmelgarn Brenda R , Moist Louise , Pilkey Rachel M , Lok Charmaine , Dorval Marc , Tam Paul YW , Berall Murray J , LeBlanc Martine , Toffelmire Edwin B , Manns Braden J , Scott-Douglas Nairne ,   the Canadian Hemodialysis Catheter Working Group
Published: April 2006

Background

Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction.

Methods/Design

The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin.

Discussion

Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions.
Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer
Authors: Han Wonshik , Han Mi-Ryung , Kang Jason Jongho , Bae Ji-Yeon , Lee Ji Hyun , Bae Young Ju , Lee Jeong Eon , Shin Hyuk-Jae , Hwang Ki-Tae , Hwang Sung-Eun , Kim Sung-Won , Noh Dong-Young
Published: April 2006

Background

A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer.

Methods

We performed array comparative genomic hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones to assess copy number changes in 28 fresh-frozen ER-positive breast cancer tissues. All of the patients included had received at least 1 year of tamoxifen treatment. Nine patients had distant recurrence within 5 years (Recurrence group) of diagnosis and 19 patients were alive without disease at least 5 years after diagnosis (Non-recurrence group).

Results

Potential prognostic variables were comparable between the two groups. In an unsupervised clustering analysis, samples from each group were well separated. The most common regions of gain in all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as called by CGH-Explorer software. The average frequency of copy number changes was similar between the two groups. The most significant chromosomal alterations found more often in the Recurrence group using two different statistical methods were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjustedpvalues <0.001). In subgroup analysis according to lymph node status, loss of 11p15 and 1p36 were found more often in Recurrence group with borderline significance within the lymph node positive patients (adjustedp= 0.052).

Conclusion

Our array CGH analysis with BAC clones could detect various genomic alterations in ER-positive breast cancers, and Recurrence group samples showed a significantly different pattern of DNA copy number changes than did Non-recurrence group samples.
Lactate: creatinine ratio in babies with thin meconium staining of amniotic fluid
Authors: Ojha Rishi Kant , Singh Saroj K , Batra Sanjay , Sreenivas V , Puliyel Jacob M
Published: April 2006

Background

ACOG states meconium stained amniotic fluid (MSAF) as one of the historical indicators of perinatal asphyxia. Thick meconium along with other indicators is used to identify babies with severe intrapartum asphyxia. Lactate creatinine ratio (L: C ratio) of 0.64 or higher in first passed urine of babies suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic Encephalopathy (HIE). Literature review shows that meconium is passed in distress and thin meconium results from mixing and dilution over time, which may be hours to days. Thin meconium may thus be used as an indicator of antepartum asphyxia. We tested L: C ratios in a group of babies born through thin and thick meconium, and for comparison, in a group of babies without meconium at birth.

Methods

86 consecutive newborns, 36 to 42 weeks of gestation, with meconium staining of liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of these 27 had thick meconium and 25 had thin meconium at birth. 42 others, who did not have meconium or any other signs of asphyxia at birth provided controls. Lactate and creatinine levels in urine were tested by standard enzymatic methods in the three groups.

Results

Lactate values are highest in the thin MSAF group followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF, followed by thick MSAF and controls. Normal babies had an average L: C ratio of 0.13 (± 0.09). L: C ratio was more among thin MSAF babies (4.3 ± 11.94) than thick MSAF babies (0.35 ± 0.35). Median L: C ratio was also higher in the thin MSAF group. Variation in the values of these parameters is observed to be high in the thin MSAF group as compared to other groups. L: C ratio was above the cutoff of 0.64 of Huang et al in 40% of those with thin meconium. 2 of these developed signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital stay. One had L: C Ratio of 93 and the other of 58.6. A smaller proportion (20%) of those with thick meconium had levels above the cutoff and 2 developed HIE and convulsions with L: C ratio of 1.25 and 1.1 respectively.

Conclusion

In evolving a cutoff of L: C ratios that would be highly sensitive and specific (0.64), Huang et al studied it in a series of babies with severe intrapartum asphyxia. Our study shows that the specificity may not be as good if babies born through thin meconium are also included. L: C ratios are much higher in babies with thin meconium. It may be that meconium alone is not a good indicator of asphyxia and the risk of HIE. However, if the presence of meconium implies asphyxia then perhaps a higher cut-off than 0.64 is needed. L: C ratios should be tested in a larger sample that includes babies with thin meconium, before L: C ratios can be applied universally.
An exploratory mixed methods study of the acceptability and effectiveness of mindfulness -based cognitive therapy for patients with active depression and anxiety in primary care
Authors: Finucane Andy , Mercer Stewart W
Published: April 2006

Background

Mindfulness Based Cognitive Therapy (MBCT) is an 8-week course developed for patients with relapsing depression that integrates mindfulness meditation practices and cognitive theory. Previous studies have demonstrated that non-depressed participants with a history of relapsing depression are protected from relapse by participating in the course. This exploratory study examined the acceptability and effectiveness of MBCT for patients in primary care with active symptoms of depression and anxiety

Methods

13 patients with recurrent depression or recurrent depression and anxiety were recruited to take part in the study. Semi-structured qualitative interviews were conducted three months after completing the MBCT programme. A framework approach was used to analyse the data. Beck depression inventories (BDI-II) and Beck anxiety inventories (BAI) provided quantitative data and were administered before and three months after the intervention.

Results

The qualitative data indicated that mindfulness training was both acceptable and beneficial to the majority of patients. For many of the participants, being in a group was an important normalising and validating experience. However most of the group believed the course was too short and thought that some form of follow up was essential. More than half the patients continued to apply mindfulness techniques three months after the course had ended. A minority of patients continued to experience significant levels of psychological distress, particularly anxiety.

Statistically significant reductions in mean depression and anxiety scores were observed; the mean pre-course depression score was 35.7 and post-course score was 17.8 (p = 0.001). A similar reduction was noted for anxiety with a mean pre-course anxiety score of 32.0 and mean post course score of 20.5 (p = 0.039). Overall 8/11 (72%) patients showed improvements in BDI and 7/11 (63%) patients showed improvements in BAI. In general the results of the qualitative analysis agreed well with the quantitative changes in depression and anxiety reported.

Conclusion

The results of this exploratory mixed methods study suggest that mindfulness based cognitive therapy may have a role to play in treating active depression and anxiety in primary care.
The impact of smoking on adherence to treatment for latent tuberculosis infection
Authors: Lavigne Mélanie , Rocher Isabelle , Steensma Colin , Brassard Paul
Published: April 2006

Background

Studies have shown an association between smoking and tuberculosis (TB) infection, disease and TB-related mortality. We hypothesized that smokers with latent tuberculosis infection (LTBI) are less likely to comply with their LTBI treatment regimen, thus increasing their risk of developing active disease. We thus documented the impact of smoking on adherence to LTBI treatment.

Method

Between 1998 and 2000, a convenience sample of patients undergoing treatment for LTBI completed a questionnaire on smoking status. Level of adherence to LTBI treatment was tested for associations with socio-demographic profile, and smoking status

Results

320 patients were recruited, and 302 (94%) completed the questionnaire. Smoking prevalence was 21%. 72% of patients were adherent to LTBI treatment. Women (OR = 2.0; 95% CI: 1.2–3.3) and non-smokers (OR = 1.8; 95% CI: 1.0–3.3) were associated with adherence to LTBI treatment. Only gender was found as an independent predictor of adherence after adjusting for age and smoking status (OR = 1.9; 95% CI: 1.06–3.3).

Conclusion

Males and smokers need to have extra supervision to ensure compliance with LTBI treatment.
An epidemiological study on anemia among institutionalized people with intellectual and/or motor disability with special reference to its frequency, severity and predictors
Authors: Ohwada Hiroko , Nakayama Takeo , Nara Nobuo , Tomono Yuji , Yamanaka Keiko
Published: April 2006

Background

To examine the type, frequency, severity, and predictors of anemia and its relationship with co-morbid conditions among institutionalized people with intellectual and/or motor disability.

Methods

We conducted a cross-sectional study at a public facility for people with intellectual and/or motor disability in Ibaraki prefecture, Japan. Health checkup data obtained in 2001 from 477 people with intellectual disability (male: 286, average age 40.6 ± 12.3; female: 191, average age 45.1 ± 11.6) were retrospectively reviewed.

Results

The prevalence of anemia among male participants was higher than in female participants for each disability category (intellectual disability, 41.1%, 4.2%; cerebral palsy, 37.5%, 4.8%; Down's syndrome, 15.0%, 0%; severe motor and intellectual disabilities, 61.9%, 16.7%). Most participants with anemia (93.8 – 100%) showed a normocytic normochromic anemia pattern. Multivariate analysis revealed that factors related to an increase in frequency included sex (male), low body mass index (BMI), use of anticonvulsants or major tranquilizers, and a high zinc sulfate turbidity test (ZTT) value. No clinically diagnosed co-morbid condition was found to be related to the presence of anemia.

Conclusion

A high frequency of mild normocytic normochromic anemia in institutionalized people with intellectual and/or motor disability was observed, particularly among males. Medications and chronic inflammation may increase the risk of anemia.
Health care utilization among Medicare-Medicaid dual eligibles: a count data analysis
Authors: Moon Sangho , Shin Jaeun
Published: April 2006

Background

Medicare-Medicaid dual eligibles are the beneficiaries of both Medicare and Medicaid. Dual eligibles satisfy the eligibility conditions for Medicare benefit. Dual eligibles also qualify for Medicaid because they are aged, blind, or disabled and meet the income and asset requirements for receiving Supplement Security Income (SSI) assistance. The objective of this study is to explore the relationship between dual eligibility and health care utilization among Medicare beneficiaries.

Methods

The household component of the nationally representative Medical Expenditure Panel Survey (MEPS) 1996–2000 is used for the analysis. Total 8,262 Medicare beneficiaries are selected from the MEPS data. The Medicare beneficiary sample includes individuals who are covered by Medicare and do not have private health insurance during a given year. Zero-inflated negative binomial (ZINB) regression model is used to analyse the count data regarding health care utilization: office-based physician visits, hospital inpatient nights, agency-sponsored home health provider days, and total dental visits.

Results

Dual eligibility is positively correlated with the likelihood of using hospital inpatient care and agency-sponsored home health services and the frequency of agency-sponsored home health days. Frequency of dental visits is inversely associated with dual eligibility. With respect to racial differences, dually eligible Afro-Americans use more office-based physician and dental services than white duals. Asian duals use more home health services than white duals at the 5% statistical significance level. The dual eligibility programs seem particularly beneficial to Afro-American duals.

Conclusion

Dual eligibility has varied impact on health care utilization across service types. More utilization of home healthcare among dual eligibles appears to be the result of delayed realization of their unmet healthcare needs under the traditional Medicare-only program rather than the result of overutilization in response to the expanded benefits of the dual eligibility program. The dual eligibility program is particularly beneficial to Asian and Afro-American duals in association with the provision of home healthcare and dental benefits.
Epidemiology of recreational exposure to freshwater cyanobacteria – an international prospective cohort study
Authors: Stewart Ian , Webb Penelope M , Schluter Philip J , Fleming Lora E , Burns John W , Gantar Miroslav , Backer Lorraine C , Shaw Glen R
Published: April 2006

Background

Case studies and anecdotal reports have documented a range of acute illnesses associated with exposure to cyanobacteria and their toxins in recreational waters. The epidemiological data to date are limited; we sought to improve on the design of some previously conducted studies in order to facilitate revision and refinement of guidelines for exposure to cyanobacteria in recreational waters.

Methods

A prospective cohort study was conducted to investigate the incidence of acute symptoms in individuals exposed, through recreational activities, to low (cell surface area <2.4 mm2/mL), medium (2.4–12.0 mm2/mL) and high (>12.0 mm2/mL) levels of cyanobacteria in lakes and rivers in southeast Queensland, the central coast area of New South Wales, and northeast and central Florida. Multivariable logistic regression analyses were employed; models adjusted for region, age, smoking, prior history of asthma, hay fever or skin disease (eczema or dermatitis) and clustering by household.

Results

Of individuals approached, 3,595 met the eligibility criteria, 3,193 (89%) agreed to participate and 1,331 (37%) completed both the questionnaire and follow-up interview. Respiratory symptoms were 2.1 (95%CI: 1.1–4.0) times more likely to be reported by subjects exposed to high levels of cyanobacteria than by those exposed to low levels. Similarly, when grouping all reported symptoms, individuals exposed to high levels of cyanobacteria were 1.7 (95%CI: 1.0–2.8) times more likely to report symptoms than their low-level cyanobacteria-exposed counterparts.

Conclusion

A significant increase in reporting of minor self-limiting symptoms, particularly respiratory symptoms, was associated with exposure to higher levels of cyanobacteria of mixed genera. We suggest that exposure to cyanobacteria based on total cell surface area above 12 mm2/mL could result in increased incidence of symptoms. The potential for severe, life-threatening cyanobacteria-related illness is likely to be greater in recreational waters that have significant levels of cyanobacterial toxins, so future epidemiological investigations should be directed towards recreational exposure to cyanotoxins.