bluuebunny/crossref_metadata_2025 huggingface dataset:
Callosal connections of dorsal versus ventral premotor areas in the macaque monkey: a multiple retrograde tracing study
Authors: Boussaoud Driss , Tanné-Gariépy Judith , Wannier Thierry , Rouiller Eric M
Published: November 2005

Background

The lateral premotor cortex plays a crucial role in visually guided limb movements. It is divided into two main regions, the dorsal (PMd) and ventral (PMv) areas, which are in turn subdivided into functionally and anatomically distinct rostral (PMd-r and PMv-r) and caudal (PMd-c and PMv-c) sub-regions. We analyzed the callosal inputs to these premotor subdivisions following 23 injections of retrograde tracers in eight macaque monkeys. In each monkey, 2–4 distinct tracers were injected in different areas allowing direct comparisons of callosal connectivity in the same brain.

Results

Based on large injections covering the entire extent of the corresponding PM area, we found that each area is strongly connected with its counterpart in the opposite hemisphere. Callosal connectivity with the other premotor areas, the primary motor cortex, prefrontal cortex and somatosensory cortex varied from one area to another. The most extensive callosal inputs terminate in PMd-r and PMd-c, with PMd-r strongly connected with prefrontal cortex. Callosal inputs to PMv-c are more extensive than those to PMv-r, whose connections are restricted to its counterpart area. Quantitative analysis of labelled cells confirms these general findings, and allows an assessment of the relative strength of callosal inputs.

Conclusion

PMd-r and PMv-r receive their strongest callosal inputs from their respective counterpart areas, whereas PMd-c and PMv-c receive strong inputs from heterotopic areas as well (namely from PMd-r and PMv-r, respectively). Finally, PMd-r stands out as the lateral premotor area with the strongest inputs from the prefrontal cortex, and only the PMd-c and PMv-c receive weak callosal inputs from M1.
Role of rapid urease test and histopathology in the diagnosis of Helicobacter pylori infection in a developing country
Authors: Yakoob Javed , Jafri Wasim , Abid Shahab , Jafri Nadim , Abbas Zaigham , Hamid Saeed , Islam Muhammad , Anis Kashif , Shah Hasnain Ali , Shaikh Hizbullah
Published: November 2005

Background

The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.

Methods

One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard test for the diagnosis of H. pylori infection was histopathology.

Results

Sixty-one percent (66/109) patients were males with mean age of 43 ± 14.1 years and age range 17–80 years. Fifty-two percent (57/109) were not on any medications while 48% (52/109) used PPI before presentation to the outpatients. Pronto Dry was positive in 40% (44/109) and negative in 60% (65/109). Histopathology was positive for H. pylori in 57% (62/109) and negative in 43% (47/109). The sensitivity, specificity, PPV, NPV and like-hood ratio of a positive and negative Pronto Dry test with and without PPI were 43.3%, 86.4%, 81.3%, 3.18, 0.656 and 52.8% vs 71.9%, 80%, 82.1%, 69%, 3.59 and 0.35.

Conclusion

This study shows that the sensitivity, specificity, NPV and PPV of rapid urease test was reduced in patients who are on PPI. The exclusive use of the rapid urease test for the diagnosis of Helicobacter pylori cannot be recommended in patients with prior PPI use.
Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia
Authors: Endimiani Andrea , Brigante Gioconda , Bettaccini Alessia A , Luzzaro Francesco , Grossi Paolo , Toniolo Antonio Q
Published: November 2005

Background

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.

Case presentation

A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam.

Conclusion

This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.
Catheter-associated bacteremia by Mycobacterium senegalense in Korea
Authors: Oh Won Sup , Ko Kwan Soo , Song Jae-Hoon , Lee Mi Young , Ryu Seong Yeol , Heo Sangtaek , Kwon Ki Tae , Lee Jang-Ho , Peck Kyong Ran , Lee Nam Yong
Published: November 2005

Background

Rapidly growing mycobacteria is recognized as one of the causative agents of catheter-related infections, especially in immunocompromised hosts. To date, however, Mycobacterium senegalense, which was known as the principal pathogen of bovine farcy, has not been reported in human infection.

Case presentation

We describe the first case of human infection by M. senegalense, which has caused catheter-related bloodstream infection in a cancer patient in Korea. The microorganism was identified by the 16S rRNA gene, rpoB, and 16S-23S rRNA gene internal transcribed spacer (ITS) sequence analyses.

Conclusion

Our first report of catheter-associated bacteremia caused by M. senegalense suggests the zoonotic nature of this species and indicates the expansion of mycobacterial species relating to human infection. M. senegalense should be considered as one of the causes of human infections in the clinical practice.
Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study
Authors: Bakker Mirjam I , May Linda , Hatta Mochammad , Kwenang Agnes , Klatser Paul R , Oskam Linda , Houwing-Duistermaat Jeanine J
Published: November 2005

Background

It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity.

Methods

The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA.

Results

For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity.

Conclusion

Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance.
Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635]
Authors: Agurto-Rivera Ricardo , Diaz-Rubio Jose , Torres-Bernal Luis , Macky Tamer A , Colina-Luquez Juner , Papa-Oliva Gabriela , Jager Rama D , Martinez-Jardon Susana , Fromow-Guerra Jans , Quiroz-Mercado Hugo
Published: November 2005

Background

To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD).

Methods

This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT).

Results

All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively.

Conclusion

The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached.
Patient and health service delay in pulmonary tuberculosis patients attending a referral hospital: a cross-sectional study
Authors: Kiwuwa Mpungu S , Charles Karamagi , Harriet Mayanja Kizza
Published: November 2005

Background

Delays in diagnosis and initiation of effective treatment increase morbidity and mortality from tuberculosis as well as the risk of transmission in the community. The aim of this study was to determine the time taken for patients later confirmed as having TB to present with symptoms to the first health provider (patient delay) and the time taken between the first health care visit and initiation of tuberculosis treatment (health service delay). Factors relating to these 'delays' were analyzed.

Methods

A cross-sectional survey, of 231 newly diagnosed smear-positive tuberculosis patients was conducted in Mulago National referral Hospital Kampala, from January to May 2002. Socio-demographic, lifestyle and health seeking factors were evaluated for their association with patient delay (>2 weeks) and health service delay (>4 weeks), using odds ratios with 95% confidence intervals (CI) including multivariate logistic regression.

Results

The median total delay to treatment initiation was 12 weeks. Patients often presented to drug shops or pharmacies (39.4%) and private clinics (36.8%) more commonly than government health units (14%) as initial contacts. Several independent predictors of 'patient delay' were identified: being hospitalized (odds ratio [0R] = 0.32; 95% CI: 0.12–0.80), daily alcohol consumption (OR = 3.7; CI: 1.57–9.76), subsistence farming (OR = 4.70; CI: 1.67–13.22), and perception of smoking as a cause of TB (OR = 5.54; CI: 2.26–13.58). Independent predictors of 'health service delay' were: >2 health seeking encounters per month (OR = 2.74; CI: 1.10–6.83), and medical expenditure on TB related symptoms >29 US dollars (OR = 3.88; CI: 1.19–12.62). Perceived TB stigma and education status was not associated with either form of delay.

Conclusion

Delay in diagnosis of TB is prolonged at the referral centre with a significant proportion of Health service delay. More specific and effective health education of the general public on tuberculosis and seeking of appropriate medical consultation is likely to improve case detection. Certain specific groups require further attention. Alcoholics and subsistence farmers should be targeted to improve accessibility to TB treatment. Continuing medical education about TB management procedures for health providers and improvement in the capacity of TB control services should be undertaken.
An economic way of reducing health, environmental, and other pressures of urban traffic: a decision analysis on trip aggregation
Authors: Tuomisto Jouni T , Tainio Marko
Published: November 2005

Background

Traffic congestion is rapidly becoming the most important obstacle to urban development. In addition, traffic creates major health, environmental, and economical problems. Nonetheless, automobiles are crucial for the functions of the modern society. Most proposals for sustainable traffic solutions face major political opposition, economical consequences, or technical problems.

Methods

We performed a decision analysis in a poorly studied area, trip aggregation, and studied decisions from the perspective of two different stakeholders, the passenger and society. We modelled the impact and potential of composite traffic, a hypothetical large-scale demand-responsive public transport system for the Helsinki metropolitan area, where a centralised system would collect the information on all trip demands online, would merge the trips with the same origin and destination into public vehicles with eight or four seats, and then would transmit the trip instructions to the passengers' mobile phones.

Results

We show here that in an urban area with one million inhabitants, trip aggregation could reduce the health, environmental, and other detrimental impacts of car traffic typically by 50–70%, and if implemented could attract about half of the car passengers, and within a broad operational range would require no public subsidies.

Conclusion

Composite traffic provides new degrees of freedom in urban decision-making in identifying novel solutions to the problems of urban traffic.
Cardiovascular health knowledge and behavior in patient attendants at four tertiary care hospitals in Pakistan – a cause for concern
Authors: Jafary Fahim H , Aslam Fawad , Mahmud Hussain , Waheed Abdul , Shakir Murtaza , Afzal Atif , Qayyum Mohammad A , Akram Javed , Khan Iqbal S , Haque Irshad U
Published: November 2005

Background

Knowledge about coronary heart disease (CHD) and its risk factors is an important pre-requisite for an individual to implement behavioral changes leading towards CHD prevention. There is scant data on the status of knowledge about CHD in the general population of Pakistan. The objective of this study was to assess knowledge of CHD in a broad Pakistani population and identify the factors associated with knowledge.

Methods

Cross sectional study was carried out at four tertiary care hospitals in Pakistan using convenience sampling. Standard questionnaire was used to interview 792 patient attendants (persons accompanying patients). Knowledge was computed as a continuous variable based on correct answers to fifteen questions. Multivariable linear regression was conducted to determine the factors independently associated with knowledge.

Results

The mean age was 38.1 (±13) years. 27.1% had received no formal education. The median knowledge score was 3.0 out of a possible maximum of 15. Only 14% were able to correctly describe CHD as a condition involving limitation in blood flow to the heart. Majority of respondents could identify only up to two risk factors for CHD. Most commonly identified risk factors were stress (43.4%), dietary fat (39.1%), smoking (31.9%) and lack of exercise (17.4%). About 20% were not able to identify even a single risk factor for CHD. Factors significantly associated with knowledge included age (p = 0.023), income (p < 0.001), education level (p < 0.001), residence (p < 0.001), a family history of CHD (p < 0.001) and a past history of diabetes (p = 0.004). Preventive practices were significantly lacking; 35%, 65.3% and 84.6% had never undergone assessment of blood pressure, glucose or cholesterol respectively. Only a minority felt that they would modify their diet, stop smoking or start exercising if a family member was to develop CHD.

Conclusion

This is the first study assessing the state of CHD knowledge in a relatively diverse non-patient population in Pakistan. There are striking gaps in knowledge about CHD, its risk factors and symptoms. These translate to inadequate preventive behavior patterns. Educational programs are urgently required to improve the level of understanding of CHD in the Pakistani population.
Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina
Authors: Leiros Gustavo J , Galliano Silvia R , Sember Mario E , Kahn Tomas , Schwarz Elisabeth , Eiguchi Kumiko
Published: November 2005

Background

Infections with high-risk human papillomaviruses (HPVs), causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline) of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype.

Methods

HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I). Fischer's test with Woolf's approximation was used for statistical analysis.

Results

HPV DNA was detected in 17 out of 41 (41.5 %) carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas.

Conclusion

These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas.
What factors explain the number of physical therapy treatment sessions in patients referred with low back pain; a multilevel analysis
Authors: Swinkels Ilse CS , Wimmers Raymond H , Groenewegen Peter P , van den Bosch Wil JH , Dekker Joost , van den Ende Cornelia HM
Published: November 2005

Background

It is well-known that the number of physical therapy treatment sessions varies over treatment episodes. Information is lacking, however, on the source and explanation of the variation. The purposes of the current study are: 1) to determine how the variance in the number of physical therapy treatment sessions in patients with non-specific low back pain (LBP) in the Netherlands is distributed over patient level, therapist level and practice level; and 2) to determine the factors that explain the variance.

Methods

Data were used from a national registration network on physical therapy. Our database contained information on 1,733 patients referred with LBP, treated by 97 therapists working in 41 practices. The variation in the number of treatment sessions was investigated by means of multilevel regression analyses.

Results

Eighty-eight per cent of the variation in the number of treatment sessions for patients with LBP is located at patient level and seven per cent is located at practice level. It was possible to explain thirteen per cent of all variance. The duration of the complaint, prior therapy, and the patients' age and gender in particular are related to the number of physical therapy treatment sessions.

Conclusion

Our results suggest that the number of physical therapy treatment sessions in patients with LBP mainly depends on patient characteristics. More variation needs to be explained, however, to improve the transparency of care. Future research should examine the contribution of psychosocial factors, baseline disability, and the ability to learn motor behavior as possible factors in the variation in treatment sessions.
Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc
Authors: Iskandar Monica , Swist Eleonora , Trick Keith D , Wang Bingtuan , L'Abbé Mary R , Bertinato Jesse
Published: November 2005

Background

Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status.

Methods

Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status.

Results

Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4).

Conclusion

Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn.
Nurr1 dependent regulation of pro-inflammatory mediators in immortalised synovial fibroblasts
Authors: Davies Mark R , Harding Christine J , Raines Stephanie , Tolley Kurt , Parker Andrew E , Downey-Jones Mark , Needham Maurice RC
Published: November 2005

Background

Nurr1 is an orphan member of the nuclear receptor superfamily; these orphan receptors are a group for which a ligand has yet to be identified. Nurr1 has been shown to regulate the expression of a small number of genes as a monomeric, constitutively active receptor. These Nurr1 regulated genes are primarily associated with dopamine cell maturation and survival. However, previous reports have shown an increased expression of Nurr1 in the synovium of patients with rheumatoid arthritis (RA) suggesting a pro-inflammatory role for Nurr1 in RA. In this study we investigate the potential pro-inflammatory role of Nurr1 by monitoring Nurr1 dependent gene expression in an immortalised synoviocyte cell line, K4IM.

Methods

We overexpressed the wild type and a dominant negative form of the orphan nuclear receptor Nurr1, in a model synoviocyte cell line. Using the Affymetrix HG-U133 Genechips we demonstrate the effects on the transcriptome by the receptor. Further evidence of gene expression change was demonstrated using quantitative RT-PCR and ELISA analysis.

Results

We show that Nurr1 regulates transcription of a small number of genes for pro-inflammatory modulators of which the most significant is interleukin-8 (IL-8). We also demonstrate increased synthesis and secretion of IL-8 further supporting a role for Nurr1 in inflammatory signalling pathways.

Conclusion

Using microarray analysis we show that elevated levels of Nurr1 leads to increased gene expression of pro-inflammatory genes: IL-8, Amphiregulin and Kit ligand in a model cell line. This data provides further evidence for an additional role for Nurr1 in inflammation and may play a role in the pathogenesis of rheumatoid arthritis.
Immunosenescence and Vaccination
Authors: Pawelec Graham
Published: November 2005

The problems associated with the ageing immune system and vaccination were discussed recently at an international workshop at the Jenner Institute for Vaccine Research, Compton, UK, 6–7 October, 2005. This is a commentary on that session. The meeting included discussions on T and B cell differentiation and ageing, as well as dendritic cell and neutrophil data, with the emphasis on T cell immunosenescence, perceived as the most important hindrance to satisfactory responses to vaccines in the elderly. The main questions to be addressed in this context are the reasons for dysfunctionality of T cells in the elderly and what to do to improve T cell function. Several of the major reasons for poor T cell responses in the elderly were discussed; however, many important questions remain: The next meeting at the Jenner Institute may already be able to provide some of the answers to these questions, which have serious implications for public health issues in increasingly elderly populations.
Phosphodiesterase 3 inhibition and cough in elderly asthmatics
Authors: Ishiura Yoshihisa , Fujimura Masaki , Nobata Kouichi , Abo Miki , Oribe Takayoshi , Myou Shigeharu , Nakamura Hiroyuki
Published: November 2005

Aims

Cough is a common symptom of bronchial asthma, a chronic inflammatory airway disease. Recently, the therapeutic effects of selective phosphodiesterase (PDE) inhibitors have been focused on bronchial asthma. This study was designed to investigate the clinical effect of PDE 3 inhibition on cough reflex sensitivity in elderly patients with bronchial asthma.

Methods

Effects of cilostazol, a PDE 3 inhibitor, on cough response to inhaled capsaicin were examined in 11 patients over 70 years with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity.

Results

The cough threshold was significantly (p < 0.05) increased after two-week treatment with cilostazol (100 mg twice a day orally) compared with placebo [48.8 (GSEM 1.4) vs. 29.2 (GSEM 1.3) μM].

Conclusion

These findings indicate that PDE 3 inhibition may be a novel therapeutic option for elderly patients with asthma, especially for their cough symptoms.
A Chiropracticness Test
Authors: Charlton Keith H
Published: November 2005

Background

There is little homogeneity of opinion in the chiropractic profession about its essence and identity. Matters compromising the establishment of a coherent identity include the issue of vertebral subluxation, philosophy, mercantilism, poverty of qualifications in some chiropractic college faculty, and lack of intellectual productivity in some chiropractic college faculty.

Discussion

The Chiropractic profession has mislabeled rhetoric, supposition and cant as philosophy, whilst showing sparse evidence for the existence of more than a few chiropractors writing in philosophy as a discipline. There is no evidence for "Chiropractic Philosophy".

I propose, however, that a better use of the discipline of philosophy can be of great use to the Chiropractic profession. Various thinkers throughout the ages have written about deduction, induction and falsificationism as methods to discover more reliably the nature of things in the world about us. Each method has strengths and frailties, but some of the latter are insurmountable for our purposes.

Using a contrivance of that method which seems most suited, sui generis, for the purpose, I propose a Chiropracticness Test as a tool to assist the search for essence and identity in Chiropractic.
High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization
Authors: Naylor Tara L , Greshock Joel , Wang Yan , Colligon Theresa , Yu QC , Clemmer Virginia , Zaks Tal Z , Weber Barbara L
Published: November 2005

Introduction

Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.

Methods

We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.

Results

Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.

Conclusion

High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.
Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas
Authors: Schindlbeck Christian , Kampik Theresa , Janni Wolfgang , Rack Brigitte , Jeschke Udo , Krajewski Stan , Sommer Harald , Friese Klaus
Published: November 2005

Introduction

The prognostic significance of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has been demonstrated in many studies. Yet, it is not clear which of the primary tumors' biological factors predict hematogenous dissemination. We therefore examined 'tissue micro arrays' (TMAs) of 265 primary breast carcinomas from patients with known bone marrow (BM) status for HER2, Topoisomerase IIα (Top IIa), Ki 67, and p53.

Methods

BM analysis was performed by cytospin preparation and immunocytochemical staining for cytokeratin (CK). TMAs were examined by immunohistochemistry (IHC) for HER2, Top IIa, Ki 67 and p53, and fluorescence in situ hybridization (FISH) for HER2.

Results

HER2 (2+/3+) was positive in 35/167 (21%) cases (FISH 24.3%), Top IIa (>10%) in 87/187 (46%), Ki 67 in 52/184 (28%) and p53 (>5%) in 61/174 cases (34%). Of 265 patients, 68 (25.7%) showed DTC-BM with a median of 2/2 × 106 cells (1 to 1,500). None of the examined factors significantly predicted BM positivity. Significant correlation was seen between HER2 IHC and Top IIa (p = 0.06), Ki 67 (p = 0.031), and p53 (p < .001). Top IIa correlated with Ki 67 and p53, and Ki 67 also with p53 (p = 0.004). After a median follow-up of 60.5 months (7 to 255), the presence of DTC-BM showed prognostic relevance for overall survival (p = 0.03), whereas HER2 (IHC, p = 0.04; FISH, p = 0.03) and Ki 67 (p = 0.04) correlated with disease free survival, and HER2 with distant disease free survival (IHC, p = 0.06; FISH, p = 0.05).

Discussion

The congruence of the examined factors' expression rates indicates a causal line of suppressor, proliferation, and mitosis markers, and growth factor receptors. Hematogenous tumor cell spread seems to be an independent process. The examination of these factors on DTC-BM is the aim of ongoing research.
Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients
Authors: Meisner Michael , Adina Heide , Schmidt Joachim
Published: November 2005

Background

A comparison of the amount of and the kinetics of induction of procalcitonin (PCT) with that of C-reactive protein (CRP) during various types of and severities of multiple trauma, and their relation to trauma-related complications, was performed.

Methods

Ninety adult trauma patients admitted to the intensive care unit of our tertiary care hospital were evaluated in a prospective case study. During the initial 24 hours after trauma the Injury Severity Score, the Sepsis-related Organ Failure Assessment score, and the Acute Physiology and Chronic Health Evaluation II score were evaluated. PCT, CRP, the sepsis criteria (American College of Chest Physicians/Society of Critical Care Medicine definitions), and the Sepsis-related Organ Failure Assessment score were measured at days 1–7, as well as at days 14 and 21, concluding the observation period with the 28-day survival.

Results

The induction of PCT and CRP varied in patients suffering from trauma. PCT increased only moderately in most patients and peaked at day 1–2 after trauma, the concentrations rapidly declining thereafter. CRP ubiquitously increased and its kinetics were much slower. Complications such as sepsis, infection, blood transfusion, prolonged intensive care unit treatment, and poor outcome were more frequent in patients with initially high PCT (>1 ng/ml), whereas increases of CRP showed no positive correlation.

Conclusion

In patients with multiple trauma due to an accident, the PCT level provides more information than the CRP level since only moderate amounts of PCT are induced, and higher concentrations correlate with more severe trauma and a higher frequency of various complications, including sepsis and infection. Most importantly, the moderate trauma-related increase of PCT and the rapidly declining concentrations provide a baseline value near to the normal range at an earlier time frame than for CRP, thus allowing a faster and more valid prediction of sepsis during the early period after trauma.
Bronchoalveolar lavage cytological alveolar damage in patients with severe pneumonia
Authors: Grigoriu Bogdan , Jacobs Frédéric , Beuzen Fabienne , El Khoury Rony , Axler Olivier , Brivet Francois G , Capron Frédérique
Published: November 2005

Introduction

Histological examination of lung specimens from patients with pneumonia shows the presence of desquamated pneumocytes and erythrophages. We hypothesized that these modifications should also be present in bronchoalveolar lavage fluid (BAL) from patients with hospital-acquired pneumonia.

Methods

We conducted a prospective study in mechanically ventilated patients with clinical suspicion of pneumonia. Patients were classified as having hospital-acquired pneumonia or not, in accordance with the quantitative microbiological cultures of respiratory tract specimens. A group of severe community-acquired pneumonias requiring mechanical ventilation during the same period was used for comparison. A specimen of BAL (20 ml) was taken for cytological analysis. A semiquantitative analysis of the dominant leukocyte population, the presence of erythrophages/siderophages and desquamated type II pneumocytes was performed.

Results

In patients with confirmed hospital-acquired pneumonia, we found that 13 out of 39 patients (33.3%) had erythrophages/siderophages in BAL, 18 (46.2%) had desquamated pneumocytes and 8 (20.5%) fulfilled both criteria. Among the patients with community-acquired pneumonia, 7 out of 15 (46.7%) had erythrophages/siderophages and 6 (40%) had desquamated pneumocytes on BAL cytology. Only four (26.7%) fulfilled both criteria. No patient without hospital-acquired pneumonia had erythrophages/siderophages and only 3 out of 18 (16.7%) had desquamated pneumocytes on BAL cytology.

Conclusion

Cytological analysis of BAL from patients with pneumonia (either community-acquired or hospital-acquired) shows elements of cytological alveolar damage as hemorrhage and desquamated type II pneumocytes much more frequently than in BAL from patients without pneumonia. These elements had a high specificity for an infectious cause of pulmonary infiltrates but low specificity. These lesions could serve as an adjunct to diagnosis in patients suspected of having ventilator-associated pneumonia.
A comparison of admission and worst 24-hour Acute Physiology and Chronic Health Evaluation II scores in predicting hospital mortality: a retrospective cohort study
Authors: Ho Kwok M , Dobb Geoffrey J , Knuiman Matthew , Finn Judith , Lee Kok Y , Webb Steven AR
Published: November 2005

Introduction

The Acute Physiology and Chronic Health Evaluation (APACHE) II score is widely used in the intensive care unit (ICU) as a scoring system for research and clinical audit purposes. Physiological data for calculation of the APACHE II score are derived from the worst values in the first 24 hours after admission to the ICU. The collection of physiological data on admission only is probably logistically easier, and this approach is used by some ICUs. This study compares the performance of APACHE II scores calculated using admission data with those obtained from the worst values in the first 24 hours.

Materials and Methods

This was a retrospective cohort study using prospectively collected data from a tertiary ICU. There were no missing physiological data and follow-up for mortality was available for all patients in the database. The admission and the worst 24-hour physiological variables were used to generate the admission APACHE II score and the worst 24-hour APACHE II score, and the corresponding predicted mortality, respectively.

Results

There were 11,107 noncardiac surgery ICU admissions during 11 years from 1 January 1993 to 31 December 2003. The mean admission and the worst 24-hour APACHE II score were 12.7 and 15.4, and the derived predicted mortality estimates were 15.5% and 19.3%, respectively. The actual hospital mortality was 16.3%. The overall discrimination ability, as measured by the area under the receiver operating characteristic curve, of the admission APACHE II model (83.8%, 95% confidence interval = 82.9–84.7) and the worst 24-hour APACHE II model (84.6%, 95% confidence interval = 83.7–85.5) was not significantly different (P = 1.00).

Conclusion

Substitution of the worst 24-hour physiological variables with the admission physiological variables to calculate the admission APACHE II score maintains the overall discrimination ability of the traditional APACHE II model. The admission APACHE II model represents a potential alternative model to the worst 24-hour APACHE II model in critically ill nontrauma patients.
Using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome
Authors: Abrahamson Simon D , Canzian Sonya , Brunet Fabrice
Published: November 2005

Introduction

During the 2003 severe acute respiratory syndrome (SARS) crisis, we proposed and tested a new protocol for cardiac arrest in a patient with SARS. The protocol was rapidly and effectively instituted by teamwork training using high-fidelity simulation.

Methods

Phase 1 was a curriculum design of a SARS-specific cardiac arrest protocol in three steps: planning the new protocol, repeated simulations of this protocol in a classroom, and a subsequent simulation of a cardiac arrest on a hospital ward. Phase 2 was the training of 275 healthcare workers (HCWs) using the new protocol. Training involved a seminar, practice in wearing the mandatory personal protection system (PPS), and cardiac arrest simulations with subsequent debriefing.

Results

Simulation provided insights that had not been considered in earlier phases of development. For example, a single person can don a PPS worn for the SARS patient in 1 1/2 minutes. However, when multiple members of a cardiac arrest team were dressing simultaneously, the time to don the PPS increased to between 3 1/2 and 5 1/2 minutes. Errors in infection control as well as in medical management of advanced cardiac life support (ACLS) were corrected.

Conclusion

During the SARS crisis, real-time use of a high-fidelity simulator allowed the training of 275 HCWs in 2 weeks, with debriefing and error management. HCWs were required to manage the SARS cardiac arrest wearing unfamiliar equipment and following a modified ACLS protocol. The insight gained from this experience will be valuable for future infectious disease challenges in critical care.
TNF-α-induced chemokine production and apoptosis in human neural precursor cells
Authors: Sheng Wen S , Hu Shuxian , Ni Hsiao T , Rowen Tim N , Lokensgard James R , Peterson Phillip K
Published: November 2005

Recent studies have shown that proinflammatory cytokines damage rodent neural precursor cells (NPCs), a source of self-renewing, multipotent cells that play an important role in the developing as well as adult brain. In this study, the effects of tumor necrosis factor α (TNF-α) on cytokine and chemokine production by human NPCs (>98% nestin- and >90% A2B5-positive), obtained from 6- to 8-week-old fetal brain specimens, were evaluated. NPCs stimulated with this proinflammatory cytokine were found to produce abundant amounts of the chemokines monocyte chemoattractant protein 1 (MCP-1)/CC chemokine ligand 2 (CCL2) and interferon-inducible protein 10 (IP-10)/CXC chemokine ligand 10 (CXCL10) in a time- and concentration-dependent manner. TNF-α treatment also induced NPC apoptosis. Receptors for TNF [TNFRI (p55) and TNFRII (p75)] mRNA were constitutively expressed on NPCs. However, only TNFRI was involved in TNF-α-induced chemokine production and apoptosis by NPCs, as anti-TNFRI but not anti-TNFRII antibodies blocked the stimulatory effect. TNF-α treatment induced p38 mitogen-activated protein kinase (MAPK) phosphorylation in NPCs, and SB202190, an inhibitor of p38 MAPK, blocked TNF-α-induced chemokine production. Thus, this study demonstrated that NPCs constitutively express receptors for TNF-α, which when activated, trigger via a p38 MAPK signaling pathway production of two chemokines, MCP-1/CCL2 and IP-10/CXCL10, which are involved in infectious and inflammatory diseases of the brain.
Recent and future advances in roof drainage design and performance
Authors: Arthur S , Wright GB
Published: November 2005

The past 10 years have witnessed significant changes in the way roof drainage systems are understood and designed. In particular, there has been a stepchange in the confidence with which siphonic roof drainage systems may be specified and expected to perform. These changes have occurred whilst urban drainage design in general has been revolutionized by wider acceptance of Sustainable Urban Drainage Systems and greater public concern regarding pluvial flooding within the context of climate change. This text considers, in detail, both how roof drainage systems are designed and how they should be expected to perform. Particular attention is drawn to weaknesses in accepted design methods. Consideration is also given to ‘innovative’ roof drainage related approaches such as green roofs and rainwater harvesting.

Practical application: Over the past few years there have been many changes in how roof drainage systems are specified and designed. On large buildings, technologies such as ‘siphonic roof drainage’ are now commonplace and there is an ever increasing demand for ‘green roofs’ to be specified due to their potential to ‘green’ developments. Based on ongoing research, this paper details how these different types of roof drainage solutions can be efficiently designed and what levels of performance can be expected.
A simplified radiosity algorithm for general urban radiation exchange
Authors: Robinson D , Stone A
Published: November 2005

The radiant external environment may be described by two hemispheres, above and below the horizontal plane, which are discretized into a number of patches of known solid angle. Occlusions to these patches may be combined and represented as some patch fraction for which the radiant characteristics are defined by the dominant occlusion. By solving for radiant exchanges between each surface in a scene and its associated (un)occluded patches, we have a simplified radiosity algorithm (SRA). This paper describes the application of this SRA to solve for urban scale predictions of: (i) solar radiation; (ii) interior daylight; and (iii) longwave radiation. Comparisons of solar and daylight predictions with the ray-tracing program RADIANCE show that accurate results are achieved at a computational cost several orders of magnitude lower.

Practical application: This paper describes a new model for predicting external irradiance (shortwave and longwave) and internal illuminance in an accurate and very efficient way, in a single computational module. This module may be incorporated into existing software to improve the quality of predictions from single building thermal simulations as well as emerging software for urban scale predictions of integrated resource (energy, water, waste) flows, for which the model was developed.