bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of health services in relation to mental health problems in adolescents: A population based survey
Authors: Zachrisson Henrik D , Rödje Kjetil , Mykletun Arnstein
Published: February 2006

Background

Only a minority of adolescents reporting symptoms above case-levels on screenings for mental health seeks and receives help from specialist health services. The objective of this study was to a) examine help-seeking for symptoms of anxiety and depression in relation to symptom load dimensionally, b) identify the level of specialization in mental health among service-providers, and c) identify associations between mental health problems and contact with different types of health services.

Methods

This cross-sectional school-based study (response-rate 88%, n = 11154) is based on Norwegian health surveys among 15 and 16 year olds.

Results

We found a dose-response association between symptom-load and help seeking. Only 34% of individuals with mental symptom-load above 99th percentile reported help-seeking in the last 12 months. Forty percent of help seekers were in contact with specialists (psychiatrists or psychologists), the remaining were mainly in contact with GPs. Mental health problems increased help seeking to all twelve service providers examined.

Conclusion

It might not be reasonable to argue that all adolescents with case-level mental health problems are in need of treatment. However, concerning the 99th percentile, claiming treatment need is less controversial. Even in the Norwegian context where mental health services are relatively available and free of charge, help-seeking in individuals with the highest symptom-loads is still low. Most help seekers achieved contact with health care providers, half of them at a non specialized level. Our results suggest that adolescents' recognition of mental health problems or intention to seek help for these are the major "filters" restricting treatment.
The importance of comorbidity in analysing patient costs in Swedish primary care
Authors: Engström Sven G , Carlsson Lennart , Östgren Carl-Johan , Nilsson Gunnar H , Borgquist Lars A
Published: February 2006

Background

The objective was to explore the usefulness of the morbidity risk adjustment system Adjusted Clinical Groups® (ACG), in comparison with age and gender, in explaining and estimating patient costs on an individual level in Swedish primary health care. Data were retrieved from two primary health care centres in southeastern Sweden.

Methods

A cross-sectional observational study. Data from electronic patient registers from the two centres were retrieved for 2001 and 2002, and patients were grouped into ACGs, expressing the individual combination of diagnoses and thus the comorbidity. Costs per patient were calculated for both years in both centres. Cost data from one centre were used to create ACG weights. These weights were then applied to patients at the other centre. Correlations between individual patient costs, age, gender and ACG weights were studied. Multiple linear regression analyses were performed in order to explain and estimate patient costs.

Results

The variation in individual patient costs was substantial within age groups as well as within ACG weight groups. About 37.7% of the individual patient costs could be explained by ACG weights, and age and gender added about 0.8%. The individual patient costs in 2001 estimated 22.0% of patient costs in 2002, whereas ACG weights estimated 14.3%.

Conclusion

ACGs was an important factor in explaining and estimating individual patient costs in primary health care. Costs were explained to only a minor extent by age and gender. However, the usefulness of the ACG system appears to be sensitive to the accuracy of classification and coding of diagnoses by physicians.
Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: Study protocol of a randomized clinical trial [NCT00257998]
Authors: Cleland Joshua A , Fritz Julie M , Childs John D , Kulig Kornelia
Published: February 2006

Background

Recently a clinical prediction rule (CPR) has been developed and validated that accurately identifies patients with low back pain (LBP) that are likely to benefit from a lumbo-pelvic thrust manipulation. The studies that developed and validated the rule used the identical manipulation procedure. However, recent evidence suggests that different manual therapy techniques may result similar outcomes. The purpose of this study is to investigate the effectiveness of three different manual therapy techniques in a subgroup of patient with low back pain that satisfy the CPR.

Methods/Design

Consecutive patients with LBP referred to physical therapy clinics in one of four geographical locations who satisfy the CPR will be invited to participate in this randomized clinical trial. Subjects who agree to participate will undergo a standard evaluation and complete a number of patient self-report questionnaires including the Oswestry Disability Index (OSW), which will serve as the primary outcome measure. Following the baseline examination patients will be randomly assigned to receive the lumbopelvic manipulation used in the development of the CPR, an alternative lumbar manipulation technique, or non-thrust lumbar mobilization technique for the first 2 visits. Beginning on visit 3, all 3 groups will receive an identical standard exercise program for 3 visits (visits 3,4,5). Outcomes of interest will be captured by a therapist blind to group assignment at 1 week (3rd visit), 4 weeks (6th visit) and at a 6-month follow-up. The primary aim of the study will be tested with analysis of variance (ANOVA) using the change in OSW score from baseline to 4-weeks (OSWBaseline – OSW4-weeks) as the dependent variable. The independent variable will be treatment with three levels (lumbo-pelvic manipulation, alternative lumbar manipulation, lumbar mobilization).

Discussion

This trial will be the first to investigate the effectiveness of various manual therapy techniques for patients with LBP who satisfy a CPR.
Gastrointestinal obstruction due to plaster ingestion: a case-report
Authors: Yegane Rooh- Allah , Bashashati Mohammad , Bashtar Reza , Ahmadi Mina
Published: February 2006

Background

Plaster ingestion forming gastric bezoar is a strange way to attempt suicide and this method has not yet been reported. It may lead to a mechanical obstruction of the gut, especially the pyloric region, and could manifest with abdominal pain, epigastric distress, nausea, vomiting, and fullness.

Case presentation

Herein we report a case of a 37 year-old woman presenting with plaster ingestion and gastric outlet obstruction, who underwent surgery. At six months follow-up the patient was fully recovered.

Conclusion

Plaster has no toxic or erosive effects. Endoscopic or surgical removing of such material is recommended. Moreover, psychiatric intervention and management is imperative to prevent recurrence in such cases.
Death from colonic disease in epidermolysis bullosa dystrophica
Authors: Hsieh Chih-Hsin , Huang Che-Jen , Lin Gau-Tyan
Published: February 2006

Background

Squamous cell carcinomas and renal failure were reported the causes of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Death from colonic disease in epidermolysis bullosa (EB) is never reported.

Case presentation

We demonstrate a male patient with RDEB. He suffered megacolon due to fecal impaction and died from sigmoid colon perforation with peritonitis at age 35 years.

Conclusion

Constipation is a common clinical feature of RDEB, but fetal complications of chronic constipation are rarely reported. To the author's best knowledge, it has not been reported or recognized in the English literature previously. The aggressive assessment of constipation with fecal impaction is recommended in patients with RDEB.
A novel expression system of domain I of human beta2 glycoprotein I in Escherichia coli
Authors: Ioannou Yiannis , Giles Ian , Lambrianides Anastasia , Richardson Chris , Pearl Laurence H , Latchman David S , Isenberg David A , Rahman Anisur
Published: February 2006

Background

The antiphospholipid syndrome (APS), characterised by recurrent miscarriage and thrombosis, is a significant cause of morbidity and mortality. Domain I (DI) of human beta 2 glycoprotein I (β2GPI) is thought to contain crucial antibody binding epitopes for antiphospholipid antibodies (aPL), which are critical to the pathogenesis of APS. Expressing this protein in bacteria could facilitate studies investigating how this molecule interacts with aPL.

Methods

Using a computer programme called Juniper, sequentially overlapping primers were designed to be used in a recursive polymerase chain reaction (PCR) to produce a synthetic DI gene. Specifically Juniper incorporates 'major' codons preferred by bacteria altering 41 codons out of 61. This was cloned into the expression plasmid pET(26b) and expressed in BL21(DE3)Escherichia coli(E. coli). By virtue of apelB leader sequence, periplasmic localisation of DI aided disulphide bond formation and toxicity was addressed by tightly regulating expression through the high stringency T7lacpromoter.

Results

Purified, soluble his-tagged DI in yields of 750 μg/L bacterial culture was obtained and confirmed on Western blot. Expression using the native human cDNA sequence of DI in the same construct under identical conditions yielded significantly less DI compared to the recombinant optimised sequence. This constitutes the first description of prokaryotic expression of soluble DI of β2GPI. Binding to murine monoclonal antibodies that recognise conformationally restricted epitopes on the surface of DI and pathogenic human monoclonal IgG aPL was confirmed by direct and indirect immunoassay. Recombinant DI also bound a series of 21 polyclonal IgG samples derived from patients with APS.

Conclusion

By producing a synthetic gene globally optimised for expression inE. coli, tightly regulating expression and utilising periplasmic product translocation, efficient, solubleE. coliexpression of the eukaryotic protein DI of β2GPI is possible. This novel platform of expression utilising pan-gene prokaryote codon optimisation for DI production will aid future antigenic studies. Furthermore if DI or peptide derivatives of DI are eventually used in the therapeutic setting either as toleragen or as a competitive inhibitor of pathogenic aPL, then anE. coliproduction system may aid cost-effective production.
High-throughput isolation of ultra-pure plasmid DNA by a robotic system
Authors: Kachel Volker , Sindelar Georg , Grimm Stefan
Published: February 2006

Background

With the availability of complete genomes, a systematic inventory of cellular processes becomes achievable. This requires assessing the function of all individual genes. Transfection of plasmid DNA into cell culture cells is an essential technique for this aim as it allows functional overexpression or downregulation of genes. While many robotic systems isolate plasmids for sequencing purposes, for more demanding applications such as transfections there is a shortage of robots for the high-throughput isolation of plasmid DNA.

Results

Here we describe a custom-made, automated device, which uses a special protocol to isolate plasmid DNAs with a purity sufficient for efficient transfections into mammalian cells. Approximately 1,600 ultra pure plasmids can be isolated in a 96-well plate format within 12 hours. As a unique feature the robot comprises the integration of a centrifuge instead of expensive columns, the use of a custom-made pipetting head with a movable gripper, especially designed shaking platforms and an acetone wash facility.

Conclusion

Using this robot we demonstrate how centrifugation steps with multiple precipitations, most notably through a precipitation step of SDS in isopropanol, lead to high purity plasmid DNA and make possible high-throughput transfections into mammalian cells for functional gene annotations.
Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists
Authors: Crockett Elahé T , Galligan James J , Uhal Bruce D , Harkema Jack , Roth Robert , Pandya Kinnari
Published: February 2006

Background

Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury.

Methods

Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine) or saline-vehicle were administeredi.p.before ischemia. Plasma cytokine tumor necrosis factor (TNF)-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and liver histopathology.

Results

A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR.

Conclusion

Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury.
All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions – an observational study
Authors: Wetzels Gwenn EC , Nelemans Patricia J , Schouten Jan SAG , van Wijk Boris LG , Prins Martin H
Published: February 2006

Background

Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses.

The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance.

Methods

161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient.

Results

There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005.

Conclusion

While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance.
Personal protection of long lasting insecticide-treated nets in areas of Anopheles gambiae s.s. resistance to pyrethroids
Authors: Dabiré Roch K , Diabaté Abdoulaye , Baldet Thierry , Paré-Toé Léa , Guiguemdé Robert T , Ouédraogo Jean-Bosco , Skovmand Ole
Published: February 2006

Background

The development of mosquito nets pre-treated with insecticide, Long Lasting Impregnated Nets (LLINs) that last the life span of the net, is a solution to the difficulty of the re-impregnation of conventional nets. Even if they showed a good efficacy in control conditions, their efficacy in the field, particularly in areas with resistance of Anopheles gambiae to pyrethroids, is not well documented. This study compares wide (Olyset®) and small (Permanet®) mesh LLINs in field conditions, using entomological parameters.

Methods

The two LLINs were tested in a rice-growing area of south-western Burkina Faso (West Africa) with year around high density of the main malaria vector An. gambiae s.s. In the study village (VK6), there is a mixed population of two molecular forms of An. gambiae, the S-form which dominates during the rainy season and the M-form which dominates the rest of the year. The two LLINs Olyset® and Permanet® were distributed in the village and 20 matched houses were selected for comparison with four houses without treated nets.

Results

Mosquito entrance rate was ten fold higher in control houses than in houses with LLINs and there was no difference between the two net types. Among mosquitoes found in the houses, 36 % were dead in LLIN houses compared to 0% in control houses. Blood feeding rate was 80 % in control houses compared to 43 % in LLIN houses. The type of net did not significantly impact any of these parameters. No mosquitoes were found inside Permanet®, whereas dead or dying mosquitoes were collected inside the Olyset®. More than 60% of mosquitoes found on top or inside the nets had had blood meals from cattle, as shown by ELISA analysis.

Conclusion

The percentage of blood-fed mosquitoes in a bed net study does not necessarily determine net success. The efficacy of the two types of LLINs was comparable, during a period when the S-form of An. gambiae was carrying the kdr gene. Significantly higher numbers of mosquitoes were collected in control houses compared to intervention houses, indicating that the LLINs provided an additional deterrent effect, which enhanced their expected prevention capacity.
Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor
Authors: Chen Jiezhong , Raymond Kenneth
Published: February 2006

Rifampicin, an important drug in the treatment of tuberculosis, is used extensively despite its broad effects on drug-drug interactions, creating serious problems. The clinical importance of such interactions includes autoinduction leading to suboptimal or failed treatment. The concomitantly administered effects of rifampicin on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by p-glycoprotein in the gastrointestinal tract and liver. This review paper summarises recent findings with emphases on the molecular mechanisms used to explain these broad drug-drug interactions. In general, rifampicin can act on a pattern: rifampicin activates the nuclear pregnane X receptor that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. This pattern of action may explain many of the rifampicin inducing drug-drug interactions. However, effects through other mechanisms have also been reported and these make any explanation of such drug-drug interactions more complex.
Effects of study area size on geographic characterizations of health events: Prostate cancer incidence in Southern New England, USA, 1994–1998
Authors: Gregorio David I , Samociuk Holly , DeChello Laurie , Swede Helen
Published: February 2006

Background

We consider how representations of geographic variation in prostate cancer incidence across Southern New England, USA may be affected by selection of study area and/or properties of the statistical analysis.

Method

A spatial scan statistic was used to monitor geographic variation among 35,167 incident prostate cancer cases diagnosed in Massachusetts, Connecticut and Rhode Island from 1994 to 1998, in relation to the 1990 populations of men 20+ years of age living in that region. Results from the combined-states analysis were compared to those from single-states. Impact of scanning procedures set to examine up to 50% or no more than10% of at-risk populations also was evaluated.

Results

With scanning set to 50%, 5 locations in the combined-states analysis were identified with markedly distinct incidence rates. Fewer than expected cases were estimated for nearly all Connecticut, Rhode Island and West Central Massachusetts, whereas census tracts on and around Cape Cod, and areas of Southwestern Connecticut and adjacent to greater Boston were estimated to have yielded more than expected incidence. Results of single-state analyses exhibited several discrepancies from the combined-states analysis. More conservative scanning found many more locations with varying incidence, but discrepancies between the combined- and single-state analysis were fewer.

Conclusion

It is important to acknowledge the conditional nature of spatial analyses and carefully consider whether a true cluster of events is identified or artifact stemming from selection of study area size and/or scanning properties.
Socioeconomic inequality of cancer mortality in the United States: a spatial data mining approach
Authors: Vinnakota Srinivas , Lam Nina SN
Published: February 2006

Background

The objective of this study was to demonstrate the use of an association rule mining approach to discover associations between selected socioeconomic variables and the four most leading causes of cancer mortality in the United States. An association rule mining algorithm was applied to extract associations between the 1988–1992 cancer mortality rates for colorectal, lung, breast, and prostate cancers defined at the Health Service Area level and selected socioeconomic variables from the 1990 United States census. Geographic information system technology was used to integrate these data which were defined at different spatial resolutions, and to visualize and analyze the results from the association rule mining process.

Results

Health Service Areas with high rates of low education, high unemployment, and low paying jobs were found to associate with higher rates of cancer mortality.

Conclusion

Association rule mining with geographic information technology helps reveal the spatial patterns of socioeconomic inequality in cancer mortality in the United States and identify regions that need further attention.
Complete probabilistic analysis of RNA shapes
Authors: Voß Björn , Giegerich Robert , Rehmsmeier Marc
Published: February 2006

Background

Soon after the first algorithms for RNA folding became available, it was recognised that the prediction of only one energetically optimal structure is insufficient to achieve reliable results. An in-depth analysis of the folding space as a whole appeared necessary to deduce the structural properties of a given RNA molecule reliably. Folding space analysis comprises various methods such as suboptimal folding, computation of base pair probabilities, sampling procedures and abstract shape analysis. Common to many approaches is the idea of partitioning the folding space into classes of structures, for which certain properties can be derived.

Results

In this paper we extend the approach of abstract shape analysis. We show how to compute the accumulated probabilities of all structures that share the same shape. While this implies a complete (non-heuristic) analysis of the folding space, the computational effort depends only on the size of the shape space, which is much smaller. This approach has been integrated into the tool RNAshapes, and we apply it to various RNAs.

Conclusion

Analyses of conformational switches show the existence of two shapes with probabilities approximately

2
3

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1
3

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, whereas the analysis of a microRNA precursor reveals one shape with a probability near to 1.0. Furthermore, it is shown that a shape can outperform an energetically more favourable one by achieving a higher probability. From these results, and the fact that we use a complete and exact analysis of the folding space, we conclude that this approach opens up new and promising routes for investigating and understanding RNA secondary structure.
A multiscale mathematical model of cancer, and its use in analyzing irradiation therapies
Authors: Ribba Benjamin , Colin Thierry , Schnell Santiago
Published: February 2006

Background

Radiotherapy outcomes are usually predicted using the Linear Quadratic model. However, this model does not integrate complex features of tumor growth, in particular cell cycle regulation.

Methods

In this paper, we propose a multiscale model of cancer growth based on the genetic and molecular features of the evolution of colorectal cancer. The model includes key genes, cellular kinetics, tissue dynamics, macroscopic tumor evolution and radiosensitivity dependence on the cell cycle phase. We investigate the role of gene-dependent cell cycle regulation in the response of tumors to therapeutic irradiation protocols.

Results

Simulation results emphasize the importance of tumor tissue features and the need to consider regulating factors such as hypoxia, as well as tumor geometry and tissue dynamics, in predicting and improving radiotherapeutic efficacy.

Conclusion

This model provides insight into the coupling of complex biological processes, which leads to a better understanding of oncogenesis. This will hopefully lead to improved irradiation therapy.
Determinants of bone mass and bone size in a large cohort of physically active young adult men
Authors: Ruffing JA , Cosman F , Zion M , Tendy Susan , Garrett P , Lindsay R , Nieves JW
Published: February 2006

The determinants of bone mineral density (BMD) at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years) entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA). Peripheral-quantitative computed tomography (pQCT) was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159). Mean BMD at all sites was approximately one standard deviation above young normal (p < 0.05). African Americans had significantly higher hip, spine and heel BMD and greater tibial mineral content and cortical thickness than Caucasians and Asians. In Caucasians (n = 653), weight was a significant determinant of BMD at every skeletal site. Prior exercise levels and milk intake positively related to bone density and size, while caffeine had a negative impact. There was an apparent interaction between milk and exercise in BMD at the heel, spine, hip and tibial mineral content and cortical thickness. Our data confirm the importance of race, body size, milk intake and duration of weekly exercise as determinants of BMD and bone size.
Effect of food deprivation and hormones of glucose homeostasis on the acetyl CoA carboxylase activity in mouse brain: a potential role of acc in the regulation of energy balance
Authors: Karami Kristophe J , Coppola John , Krishnamurthy Karthik , Llanos Domingo J , Mukherjee Amrita , Venkatachalam KV
Published: February 2006

We studied the regulation of brain acetyl CoA carboxylase (ACC) activity during food deprivation and under the influence of hormones of glucose homeostasis: glucagon and insulin. Mice were deprived of food and water for time periods of 1, 3, 6, 9, 12 and 24 hours and were then allowed to re-feed for 5, 30 and 60 minutes. Mice that were deprived for up to 6 h, and then re-fed for 60 min, consumed the same amount of food compared to the ad libitum (control) animals. However, after 9 h of deprivation, mice consumed only 50% of food present even after 1 h of re-feeding, compared to the controls. The ACC activity was measured in the whole mouse brain of controls and after 1, 3, 6, 9, 12, and 24 h of food deprivation. Brain extracts assayed from control mice expressed an ACC activity of 0.988 ± 0.158 fmol/min/mg tissue without citrate and 0.941 ± 0.175 fmol/min/mg tissue with citrate. After 1 h of food deprivation, the total ACC activity without citrate decreased to 0.575 ± 0.087 fmol/min/mg and in the presence of citrate, 0.703 ± 0.036 fmol/min/mg activity was measured. The citrate-dependent ACC activity decreased over time, with only 0.478 ± 0.117 fmol/min/mg of activity remaining after 24 h. Intraperitoneal (i.p.) injections of insulin, glucagon and phosphate buffered saline (PBS) were performed and whole brain ACC activity measured. After hormone administration, there were no significant differences in ACC activity in the presence of citrate. However, in the absence of citrate, there was a significant 20% decrease in ACC activity with glucagon (1.36 ± 0.09 fmol/min/mg) and a 33% increase with insulin (2.49 ± 0.11 fmol/min/mg) injections compared to PBS controls (1.67 ± 0.08 fmol/min/mg). Neuropeptide Y (NPY) levels of corresponding brain extracts were measured by ELISA (OD) using anti-NPY antibody and showed an 18% decrease upon insulin injection (0.093 ± 0.019) and a 50% increase upon glucagon injection (0.226 ± 0.084) as compared to controls injected with PBS (0.114 ± 0.040). Thus, we postulate that the changes in ACC levels under metabolic conditions would result in a fluctuation of malonyl CoA levels, and subsequent modulation of NPY levels and downstream signaling.
Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology
Authors: Lindberg Johan , af Klint Erik , Ulfgren Ann-Kristin , Stark André , Andersson Tove , Nilsson Peter , Klareskog Lars , Lundeberg Joakim
Published: February 2006

In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.
Medical Emergency Team syndromes and an approach to their management
Authors: Jones Daryl , Duke Graeme , Green John , Briedis Juris , Bellomo Rinaldo , Casamento Andrew , Kattula Andrea , Way Margaret
Published: February 2006

Introduction

Most literature on the medical emergency team (MET) relates to its effects on patient outcome. Less information exists on the most common causes of MET calls or on possible approaches to their management.

Methods

We reviewed the calling criteria and clinical causes of 400 MET calls in a teaching hospital. We propose a set of minimum standards for managing a MET review and developed an approach for managing common problems encountered during MET calls.

Results

The underlying reasons for initiating MET calls were hypoxia (41%), hypotension (28%), altered conscious state (23%), tachycardia (19%), increased respiratory rate (14%) and oliguria (8%). Infection, pulmonary oedema, and arrhythmias featured as prominent causes of all triggers for MET calls. The proposed minimum requirements for managing a MET review included determining the cause of the deterioration, documenting the events surrounding the MET, establishing a medical plan and ongoing medical follow-up, and discussing the case with the intensivist if certain criteria were fulfilled. A systematic approach to managing episodes of MET review was developed based on the acronym 'A to G': a sk and a ssess; b egin b asic investigations and resuscitation, c all for help if needed, d iscuss, d ecide, and d ocument, e xplain aetiology and management, f ollow-up, and g raciously thank staff. This approach was then adapted to provide a management plan for episodes of tachycardia, hypotension, hypoxia and dyspnoea, reduced urinary output, and altered conscious state.

Conclusion

A suggested approach permits audit and standardization of the management of MET calls and provides an educational framework for the management of acutely unwell ward patients. Further evaluation and validation of the approach are required.
Predicting genes for orphan metabolic activities using phylogenetic profiles
Authors: Chen Lifeng , Vitkup Dennis
Published: February 2006

Homology-based methods fail to assign genes to many metabolic activities present in sequenced organisms. To suggest genes for these orphan activities we developed a novel method that efficiently combines local structure of a metabolic network with phylogenetic profiles. We validated our method using known metabolic genes in Saccharomyces cerevisiae and Escherichia coli. We show that our method should be easily transferable to other organisms, and that it is robust to errors in incomplete metabolic networks.
Global analysis of X-chromosome dosage compensation
Authors: Gupta Vaijayanti , Parisi Michael , Sturgill David , Nuttall Rachel , Doctolero Michael , Dudko Olga K , Malley James D , Eastman P Scott , Oliver Brian
Published: February 2006

Background

Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation.

Results

To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice.

Conclusion

Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.
Allelic Variation on Chromosome 5 Controls β-Cell Mass Expansion during Hyperglycemia in Leptin Receptor-Deficient Diabetes Mice
Authors: Luo Na , Liu Shun Mei , Liu Hong , Li Qiong , Xu Qun , Sun Xi , Davis Brandi , Li Jing , Chua Streamson
Published: February 2006

Leptin signaling is a critical component of normal insulin sensitivity. Overt hyperglycemia and type 2 diabetes mellitus can be manifested in states of leptin signaling deficiencies by the additional effects of other genetic factors. We have previously described the contrasting insulin sensitivities and glycemic states of two congenic diabetes (db/db) mouse strains. C57BL/6J db/db mice have mild insulin resistance and achieve euglycemia with mild hyperinsulinemia. FVB db/db mice have severe insulin resistance and are hyperglycemic despite escalating hyperinsulinemia with expanded pancreatic β-cell mass. Analysis of obese progeny from the two reciprocal backcrosses suggests that genetic modifiers for insulin sensitivity are separable from loci that modulate β-cell mass. A genome scan of the backcross to FVB suggests that one or more modifier genes are present on chromosome 5. This evidence is supported by the phenotypes of multiple incipient congenic strains wherein the hyperglycemia observed in obese FVB mice is reproduced. With similar degrees of hyperglycemia in obese mice of these strains, the haplotype at chromosome 5 is associated with β-cell mass and circulating insulin concentrations. Finally, we offer arguments that production of multiple incipient congenic lines is an economical alternative to the production of speed congenic strains.
Gonadotropin-Induced Superovulation Drives Ovarian Surface Epithelia Proliferation in CD1 Mice
Authors: Burdette Joanna E. , Kurley Sarah J. , Kilen Signe M. , Mayo Kelly E. , Woodruff Teresa K.
Published: February 2006

The ovarian surface epithelium (OSE) is a monolayer of cells that surround the ovary and accommodate repeated tear and repair in response to ovulation. OSE cells are thought to be the progenitors of 90% of ovarian cancers. Currently, the total amount of proliferation of the OSE has not been reported in response to one ovulatory event. In this study, proliferation of the OSE was quantified in response to superovulation induced by ip injection of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) in immature 27-d-old CD1 mice using bromodeoxyuridine (BrdU). BrdU incorporation into the OSE cells was measured from the time of hCG injection for a total cumulative label of 12 h. BrdU incorporation was also measured from the time of PMSG injection for a total label of 60 h to correlate proliferation with specific gonadotropin stimulation. The OSE proliferation was significantly higher in superovulated animals compared with control mice at all time points. Proliferation was also analyzed in discrete anatomical sections and indicated that OSE covering antral follicles and corpora lutea proliferated more rapidly than OSE distal to follicular growth. Finally, apoptosis was assessed in response to ovulation, and virtually no cell death within the OSE was detected. These data demonstrate that the OSE, especially near antral follicles and corpora lutea, proliferates significantly in response to the gonadotropins PMSG and hCG. Therefore, ovarian surface cell division in response to ovulation could contribute to ovarian cancer by proliferation-induced DNA mutations and transformed cell progression.
Peroxisome Proliferator-Activated Receptor γ Recruits the Positive Transcription Elongation Factor b Complex to Activate Transcription and Promote Adipogenesis
Authors: Iankova Irena , Petersen Rasmus K. , Annicotte Jean-Sébastien , Chavey Carine , Hansen Jacob B. , Kratchmarova Irina , Sarruf David , Benkirane Monsef , Kristiansen Karsten , Fajas Lluis
Published: February 2006

Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis. Overexpression of cdk9 increases the adipogenic potential of 3T3-L1 cells, whereas inhibition of cdk9 by specific cdk inhibitors, and dominant-negative cdk9 mutant impairs adipogenesis. We show that the positive effects of cdk9 on the differentiation of 3T3-L1 cells are mediated by a direct interaction with and phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ), which is the master regulator of this process, on the promoter of PPARγ target genes. PPARγ-cdk9 interaction results in increased transcriptional activity of PPARγ and therefore increased adipogenesis.
Estrogen-Related Receptors-Stimulated Monoamine Oxidase B Promoter Activity Is Down-Regulated by Estrogen Receptors
Authors: Zhang Zhiping , Chen Kevin , Shih Jean C. , Teng Christina T.
Published: February 2006

Although there are studies published about the neuroprotective effect of estrogen, little is known about the mechanisms and cellular targets of the hormone. Recent reports demonstrate that estrogen down-regulates the expression of monoamine oxidase A and B (MAO-A and MAO-B) in the hypothalamus of the Macaques monkey, both of which are key isoenzymes in the neurotransmitter degradation pathway. Additionally, estrogen-related receptor α (ERRα) up-regulates MAO-B gene expression in breast cancer cells. ERRα recognizes a variety of estrogen response elements and shares many target genes and coactivators with estrogen receptor α (ERα). In this study, we investigate the interplay of ERs and ERRs in the regulation of MAO-B promoter activity. We demonstrate that ERRα and ERRγ up-regulate MAO-B gene activity, whereas ERα and ERβ decrease stimulation in both a ligand-dependent and -independent manner. Ectopically expressed ERRα and ERRγ stimulate the expression of MAO-B mRNA and protein as well as increase the MAO-B enzymatic activity in ER-negative HeLa cells. The ability of ERRs to stimulate MAO-B promoter activity was reduced in ER-positive MCF-7 and T47D cells. Several AGGTCA motifs of the MAO-B promoter are responsible for up-regulation by ERRs. Interestingly, ERα or ERβ alone have no effect on MAO-B promoter activity but can down-regulate the activation function of ERRs, whereas glucocorticoid receptor does not. By using chromatin immunoprecipitation assay, we demonstrate that ERs compete with ERRs for binding to the MAO-B promoter at selective AGGTCA motifs, thereby changing the chromatin status and cofactor recruitment to a repressed state. These studies provide new insight into the relationship between ERα, ERβ, ERRα, and ERRγ in modulation of MAO-B gene activity.
Bowel Perforation Caused by Peritoneal Shunt Catheters:Diagnosis and Treatment
Authors: Vinchon Matthieu , Baroncini Marc , Laurent Thines , Patrick Dhellemmes
Published: February 2006

OBJECTIVE:

The peritoneum is the preferred site for insertion of shunts used for the treatment of hydrocephalus. Bowel perforation by peritoneal catheters (BPPC) is a rare but devastating complication. Its pathophysiology, diagnosis, and treatment are debated.

METHODS:

Retrospective review of cases of BPPC in a series of 1956 patients having a peritoneal catheter followed up for a mean duration of 10.0 years.

RESULTS:

Nineteen observations of BPPC, representing 1.0% of the total series. Nine of 19 patients were nonambulatory, and nine of 19 had a previous history of meningeal infection. At the time of diagnosis, only three of the 19 patients had anal extrusion of the catheter, 14 had fever, nine had abdominal signs and symptoms, and six had cutaneous signs of infection. Radiological investigations were often negative or inconclusive. In seven of the patients, the initial diagnosis was shunt failure, and BPPC was diagnosed only during shunt revision. Once the correct diagnosis was made, the treatment was total shunt removal, external drainage, and antibiotic therapy for 2 weeks. Three patients, all severely impaired before BPPC, died, one of meningeal sepsis, the others of multiorgan failure related to spastic tetraparesis. Three were considered shunt-independent, two had a ventriculoatrial shunt, and the others had a new shunt with a peritoneal catheter without complication.

CONCLUSION:

BPPC is a neurosurgical emergency. Anal extrusion is present in only a minority of patients; the diagnosis of BPPC is often difficult, delayed, and its incidence is likely underestimated. The majority of patients can be treated with a new peritoneal shunt after cure of the infection.
Experience with Microelectrode Guided Subthalamic Nucleus Deep Brain Stimulation
Authors: Amirnovin Ramin , Williams Ziv M. , Cosgrove G. Rees , Eskandar Emad N.
Published: February 2006

OBJECTIVE:

Subthalamic deep brain stimulation (DBS) has rapidly become the standard surgical therapy for medically refractory Parkinson disease. However, in spite of its wide acceptance, there is considerable variability in the technical approach. This study details our technique and experience in performing microelectrode recording (MER) guided subthalamic nucleus (STN) DBS in the treatment of Parkinson disease.

METHODS:

Forty patients underwent surgery for the implantation of 70 STN DBS electrodes. Stereotactic localization was performed using a combination of magnetic resonance and computed tomographic imaging. We used an array of three microelectrodes, separated by 2 mm, for physiological localization of the STN. The final location was selected based on MER and macrostimulation through the DBS electrode.

RESULTS:

The trajectory selected for the DBS electrode had an average pass through the STN of 5.6 ± 0.4 mm on the left and 5.7 ± 0.4 mm on the right. The predicted location was used in 42% of the cases but was modified by MER in the remaining 58%. Patients were typically discharged on the second postoperative day. Eighty-five percent of patients were sent home, 13% required short-term rehabilitation, and one patient required long-term nursing services. Seven complications occurred over 4 years. Four patients suffered small hemorrhages, one patient experienced a lead migration, one developed an infection of the pulse generator, and one patient suffered from a superficial cranial infection.

CONCLUSION:

Simultaneous bilateral MER-guided subthalamic DBS is a relatively safe and well-tolerated procedure. MER plays an important role in optimal localization of the DBS electrodes.