bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis
Authors: Bramlage Carsten P , Häupl Thomas , Kaps Christian , Ungethüm Ute , Krenn Veit , Pruss Axel , Müller Gerhard A , Strutz Frank , Burmester Gerd-R
Published: April 2006

Bone morphogenetic proteins (BMPs) have been identified as important morphogens with pleiotropic functions in regulating the development, homeostasis and repair of various tissues. The aim of this study was to characterize the expression of BMPs in synovial tissues under normal and arthritic conditions. Synovial tissue from normal donors (ND) and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analyzed for BMP expression by using microarray hybridization. Differential expression of BMP-4 and BMP-5 was validated by semiquantitative RT-PCR, in situ hybridization and immunohistochemistry. Activity of arthritis was determined by routine parameters for systemic inflammation, by histological scoring of synovitis and by semiquantitative RT-PCR of IL-1β, TNF-α, stromelysin and collagenase I in synovial tissue. Expression of BMP-4 and BMP-5 mRNA was found to be significantly decreased in synovial tissue of patients with RA in comparison with ND by microarray analysis (p < 0.0083 and p < 0.0091). Validation by PCR confirmed these data in RA (p < 0.002) and also revealed a significant decrease in BMP-4 and BMP-5 expression in OA compared with ND (p < 0.015). Furthermore, histomorphological distribution of both morphogens as determined by in situ hybridization and immunohistochemistry showed a dominance in the lining layer of normal tissues, whereas chronically inflamed tissue from patients with RA revealed BMP expression mainly scattered across deeper layers. In OA, these changes were less pronounced with variable distribution of BMPs in the lining and sublining layer. BMP-4 and BMP-5 are expressed in normal synovial tissue and were found decreased in OA and RA. This may suggest a role of distinct BMPs in joint homeostasis that is disturbed in inflammatory and degenerative joint diseases. In comparison with previous reports, these data underline the complex impact of these factors on homeostasis and remodeling in joint physiology and pathology.
Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells
Authors: Mathsson Linda , Lampa Jon , Mullazehi Mohammed , Rönnelid Johan
Published: April 2006

Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells. We also examined the relationship between RF and IC induced cytokine production. Parallel sera and SF from 47 RA patients and sera from 15 healthy control individuals were PEG precipitated. The precipitates were added to serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor (TNF)-α levels were measured after 20 hours. In separate cell culture experiments FcγRIIa and FcγRIII were blocked and monocytes were depleted or enriched. RF in serum was determined by nephelometry, and IgG levels in precipitates and anti-cyclic citrullinated peptide antibodies in serum were measured using ELISA. Clinical data were collected from the patients' charts. In two separate investigations, we demonstrated a correlation between RF, PEG-precipitated IgG levels and induction of the proinflammatory cytokine TNF-α by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF-α levels induced by SF precipitates, but not serum precipitates, correlated with the number of swollen and tender joints. Monocytes/macrophages were shown to be the main responder cells, and blockade of FcγRIIa, but not blockade of FcγRIII, inhibited TNF-α production in cultures stimulated with precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but exhibited no association with IgG content in PEG precipitates or with precipitate-induced TNF-α levels. These findings support the hypothesis that SF ICs and correlated RF production are directly linked to cytokine-dependent inflammation in RA. Suppression of monocytes/macrophages in RA joints or blockade of the primate-specific activating FcγRIIa receptor might be ways to reduce IC-induced TNF-α production in the joints of seropositive RA patients.
IFNGR1single nucleotide polymorphisms in rheumatoid arthritis
Authors: Mattyasovszky Stefan , Skapenko Alla , Kalden Joachim R , Lipsky Peter E , Schulze-Koops Hendrik
Published: April 2006

On the basis of their biological function, potential genetic candidates for susceptibility to rheumatoid arthritis can be postulated. IFNGR1, encoding the ligand-binding chain of the receptor for interferon gamma, IFNγR1, is one such gene because interferon gamma is involved in the pathogenesis of the disease. In the coding sequence of IFNGR1, two nucleotide positions have been described to be polymorphic in the Japanese population. We therefore investigated the association of those two IFNGR1 single nucleotide polymorphisms with rheumatoid arthritis in a case-control study in a central European population. Surprisingly, however, neither position was polymorphic in the 364 individuals examined, indicating that IFNGR1 does not contribute to susceptibility to rheumatoid arthritis, at least in Caucasians.
Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-γ and anti-double-stranded DNA antibody production
Authors: Kawamoto Manabu , Harigai Masayoshi , Hara Masako , Kawaguchi Yasushi , Tezuka Katsunari , Tanaka Michi , Sugiura Tomoko , Katsumata Yasuhiro , Fukasawa Chikako , Ichida Hisae , Higami Satomi , Kamatani Naoyuki
Published: April 2006

Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T-lymphocyte associated antigen-4 family and is involved in the proliferation and activation of T cells. A detailed functional analysis of ICOS on peripheral blood T cells from patients with systemic lupus erythematosus (SLE) has not yet been reported. In the present study we developed a fully human anti-human ICOS mAb (JTA009) with high avidity and investigated the immunopathological roles of ICOS in SLE. JTA009 exhibited higher avidity for ICOS than a previously reported mAb, namely SA12. Using JTA009, ICOS was detected in a substantial proportion of unstimulated peripheral blood T cells from both normal control individuals and patients with SLE. In CD4+CD45RO+ T cells from peripheral blood, the percentage of ICOS+ cells and mean fluorescence intensity with JTA009 were significantly higher in active SLE than in inactive SLE or in normal control individuals. JTA009 co-stimulated peripheral blood T cells in the presence of suboptimal concentrations of anti-CD3 mAb. Median values of [3H]thymidine incorporation were higher in SLE T cells with ICOS co-stimulation than in normal T cells, and the difference between inactive SLE patients and normal control individuals achieved statistical significance. ICOS co-stimulation significantly increased the production of IFN-γ, IL-4 and IL-10 in both SLE and normal T cells. IFN-γ in the culture supernatants of both active and inactive SLE T cells with ICOS co-stimulation was significantly higher than in normal control T cells. Finally, SLE T cells with ICOS co-stimulation selectively and significantly enhanced the production of IgG anti-double-stranded DNA antibodies by autologous B cells. These findings suggest that ICOS is involved in abnormal T cell activation in SLE, and that blockade of the interaction between ICOS and its receptor may have therapeutic value in the treatment of this intractable disease.
The matrix-forming phenotype of cultured human meniscus cells is enhanced after culture with fibroblast growth factor 2 and is further stimulated by hypoxia
Authors: Adesida Adetola B , Grady Lisa M , Khan Wasim S , Hardingham Timothy E
Published: April 2006

Human meniscus cells have a predominantly fibrogenic pattern of gene expression, but like chondrocytes they proliferate in monolayer culture and lose the expression of type II collagen. We have investigated the potential of human meniscus cells, which were expanded with or without fibroblast growth factor 2 (FGF2), to produce matrix in three-dimensional cell aggregate cultures with a chondrogenic medium at low (5%) and normal (20%) oxygen tension. The presence of FGF2 during the expansion of meniscus cells enhanced the re-expression of type II collagen 200-fold in subsequent three-dimensional cell aggregate cultures. This was increased further (400-fold) by culture in 5% oxygen. Cell aggregates of FGF2-expanded meniscus cells accumulated more proteoglycan (total glycosaminoglycan) over 14 days and deposited a collagen II-rich matrix. The gene expression of matrix-associated proteoglycans (biglycan and fibromodulin) was also increased by FGF2 and hypoxia. Meniscus cells after expansion in monolayer can therefore respond to chondrogenic signals, and this is enhanced by FGF2 during expansion and low oxygen tension during aggregate cultures.
A promoter haplotype of the interleukin-18gene is associated with juvenile idiopathic arthritis in the Japanese population
Authors: Sugiura Tomoko , Maeno Nobuaki , Kawaguchi Yasushi , Takei Syuji , Imanaka Hiroyuki , Kawano Yoshifumi , Terajima-Ichida Hisae , Hara Masako , Kamatani Naoyuki
Published: April 2006

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population.
Spontaneous and therapeutic abortions and the risk of breast cancer among BRCAmutation carriers
Authors: Friedman Eitan , Kotsopoulos Joanne , Lubinski Jan , Lynch Henry T , Ghadirian Parviz , Neuhausen Susan L , Isaacs Claudine , Weber Barbara , Foulkes William D , Moller Pal , Rosen Barry , Kim-Sing Charmaine , Gershoni-Baruch Ruth , Ainsworth Peter , Daly Mary , Tung Nadine , Eisen Andrea , Olopade Olufunmilayo I , Karlan Beth , Saal Howard M , Garber Judy E , Rennert Gad , Gilchrist Dawna , Eng Charis , Offit Kenneth , Osborne Michael , Sun Ping , Narod Steven A ,   the Hereditary Breast Cancer Clinical Study Group
Published: April 2006

Introduction

BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk of breast cancer in mutation carriers, but the effects of spontaneous and therapeutic abortions on the risk of hereditary breast cancer risk have not been well studied to date.

Methods

In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer.

Results

There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio = 0.36; 95% confidence interval 0.16–0.83; p = 0.02).

Conclusion

Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers.
Breast asymmetry and predisposition to breast cancer
Authors: Scutt Diane , Lancaster Gillian A , Manning John T
Published: April 2006

Introduction

It has been shown in our previous work that breast asymmetry is related to several of the known risk factors for breast cancer, and that patients with diagnosed breast cancer have more breast volume asymmetry, as measured from mammograms, than age-matched healthy women.

Methods

In the present study, we compared the breast asymmetry of women who were free of breast disease at time of mammography, but who had subsequently developed breast cancer, with that of age-matched healthy controls who had remained disease-free to time of the present study. The study group consisted of 252 asymptomatic women who had normal mammography, but went on to develop breast cancer. The control group were 252 age-matched healthy controls whose mammograms were also normal and who remained free of cancer during the study period. Breast volume was calculated from the cranio-caudal mammograms for each group, and the relationships between asymmetry, established risk factors and the presence or absence of breast cancer were explored.

Results

The group who went on to develop breast cancer had higher breast asymmetry than controls (absolute asymmetry odds ratio 1.50 per 100 ml, confidence interval (CI) 1.10, 2.04; relative asymmetry 1.09, CI 1.01, 1.18), increased incidence of family history of breast cancer, lower age at menarche, later menopause, later first pregnancies and a higher frequency of high risk breast parenchyma types. Conditional logistic regression analysis showed that breast asymmetry, height, family history of breast cancer, age at menarche, parenchyma type and menopausal status were significant independent predictors of breast cancer. When age at menopause was included in the model for the subgroup of post-menopausal women, absolute breast fluctuating asymmetry (FA) and relative breast FA remained significant effects.

Conclusion

Breast asymmetry was greater in healthy women who later developed breast cancer than in women who did not.
Germline polymorphisms in SIPA1are associated with metastasis and other indicators of poor prognosis in breast cancer
Authors: Crawford Nigel PS , Ziogas Argyrios , Peel David J , Hess James , Anton-Culver Hoda , Hunter Kent W
Published: April 2006

Introduction

There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer.

Method

The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR.

Results

The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively).

Conclusion

Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols.
Antithrombin supplementation for anticoagulation during continuous hemofiltration in critically ill patients with septic shock: a case-control study
Authors: du Cheyron Damien , Bouchet Bruno , Bruel Cédric , Daubin Cédric , Ramakers Michel , Charbonneau Pierre
Published: April 2006

Introduction

Acquired antithrombin III (AT) deficiency may induce heparin resistance and premature membrane clotting during continuous renal replacement therapy (CRRT). The purpose of this study was to evaluate the effect of AT supplementation on filter lifespan in critically ill patients with septic shock requiring CRRT.

Methods

We conducted a retrospective case-control analysis based on a 4-year observational study with prospectively collected data in two medical intensive care units in a university hospital. In all, 106 patients with septic shock underwent CRRT during the study period (55 during 2001 to 2002 and 51 during 2003 to 2004). Of these, 78 had acquired AT deficiency (plasma level below 70%) at onset of renal supportive therapy, 40 in the first 2-year period and 38 in the last 2-year period. In the latter intervention period, patients received AT supplementation (50 IU/kg) during CRRT each time that plasma AT activity, measured once daily, fell below 70%.

Results

In a case-control analysis of the 78 patients with acquired AT deficiency, groups were similar for baseline characteristics, except in severity of illness as assessed by a higher Simplified Acute Physiology Score (SAPS) II after 2002. In comparison with controls, cases had a significantly greater AT level after AT supplementation, but not at baseline, and a smaller number of episodes of clots, without excess bleeding risk. The median hemofilter survival time was longer in the AT group than in the heparin group (44.5 versus 33.4 hours; p = 0.0045). The hemofiltration dose, assessed by the ratio of delivered to prescribed ultrafiltration, increased during intervention. AT supplementation was independently associated with a decrease in clotting rate, whereas femoral angioaccess and higher SAPS II were independent predictors of filter failure. However, mortality did not differ between periods, in the control period the observed mortality was significantly higher than predicted by the SAPS II score, unlike in the treatment period.

Conclusion

In sepsis patients requiring CRRT and with acquired AT deficiency, anticoagulation with unfractionated heparin plus AT supplementation prevent premature filter clotting and may contribute to improving outcome, but the cost-effectiveness of AT remains to be determined.
Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: a prospective observational study
Authors: de Mendonça-Filho Hugo Tannus Furtado , Pereira Kelly Cristina , Fontes Mariane , Vieira Daniel Augusto de Souza Aranha , de Mendonça Maria Lucia A Furtado , Campos Luiz Antonio de Almeida , Castro-Faria-Neto Hugo Caire
Published: April 2006

Introduction

Cardiovascular surgery with cardiopulmonary bypass (CPB) has improved in past decades, but inflammatory activation in this setting is still unpredictable and is associated with several postoperative complications. Perioperative levels of macrophage migration inhibitory factor (MIF) and other inflammatory mediators could be implicated in adverse outcomes in cardiac surgery.

Methods

Serum levels of MIF, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, IL-6 and IL-10 from 93 patients subjected to CPB were measured by enzyme-linked immunosorbent assay and compared with specific and global postoperative organ dysfunctions through multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA).

Results

Most of the cytokines measured had a peak of production between 3 and 6 hours after CPB, but maximum levels of MIF occurred earlier, at the cessation of CPB. Among specific organ dysfunctions, the most frequent was hematological, occurring in 82% of the patients. Circulatory impairment was observed in 73.1% of the patients, and 51% of these needed inotropics or vasopressors within the first 24 hours after surgery. The third most frequent dysfunction was pulmonary, occurring in 48.4% of the patients. Preoperative levels of MIF showed a relevant direct correlation with the intensity of global organ dysfunction measured by SOFA (ρ = 0.46, p < 0.001) and MODS (ρ = 0.50, p < 0.001) on the third day after surgery. MCP-1 production was associated with postoperative thrombocytopenia, and MIF was related to the use of a high dose of vasopressors in patients with cardiovascular impairment and also to lower values of the ratio of partial arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) registered in the first 24 hours after CPB.

Conclusion

Despite the multifactorial nature of specific or multiple organ dysfunctions, MIF should be explored as a predicting factor of organ dysfunction, or even as a potential therapeutic target in decreasing postoperative complications.
Activated protein C increases sensitivity to vasoconstriction in rabbit Escherichia coli endotoxin-induced shock
Authors: Wiel Eric , Costecalde Marion Elizabeth , Lebuffe Gilles , Corseaux Delphine , Jude Brigitte , Bordet Régis , Tavernier Benoît , Vallet Benoît
Published: April 2006

Introduction

The aim of this study was to investigate the effects of activated protein C (aPC) on vascular function, endothelial injury, and haemostasis in a rabbit endotoxin-induced shock model.

Method

This study included 22 male New Zealand rabbits weighing 2.5 to 3 kg each. In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors and monocyte tissue factor (TF) expression were performed 5 days (D5) after onset of endotoxic shock (initiated by 0.5 mg/kg intravenous bolus of Escherichia coli lipopolysaccharide (LPS)) with or without treatment with aPC injected as an intravenous 2 mg/kg bolus 1 hour after LPS (LPS+aPC group and LPS group, respectively).

Results

LPS decreased the sensitivity to phenylephrine (PE) in aortic rings without endothelium (E-) when compared to E- rings from the control group (p < 0.05). This was abolished by NG-nitro-L-arginine methyl ester and not observed in E- rings from aPC-treated rabbits. Although aPC failed to decrease monocyte TF expression in endotoxinic animals at D5, aPC treatment restored the endothelium-dependent sensitivity in response to PE (2.0 ± 0.2 μM in rings with endothelium (E+) versus 1.0 ± 0.2 μM in E- rings (p < 0.05) in the LPS+aPC group versus 2.4 ± 0.3 μM in E+ rings versus 2.2 ± 0.2 μM in E- rings (p value not significant), in the LPS group). Endotoxin-induced de-endothelialisation was reduced by aPC at D5 (28.5 ± 2.3% in the LPS+aPC group versus 40.4 ± 2.4% in the LPS group, p < 0.05).

Conclusion

These data indicate that aPC increased the sensitivity to a vasoconstrictor agent (PE) associated with restoration of endothelial modulation, and protected against endothelial histological injury in endotoxin-induced shock. It failed to inhibit TF expression at D5 after LPS injection.
Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study
Authors: Gaïni Shahin , Koldkjær Ole Græsbøll , Pedersen Court , Pedersen Svend Stenvang
Published: April 2006

Introduction

Clinicians are in need of better diagnostic markers in diagnosing infections and sepsis. We studied the ability of procalcitonin, lipopolysaccharide-binding protein, IL-6 and C-reactive protein to identify patients with infection and sepsis.

Methods

Plasma and serum samples were obtained on admission from patients with suspected community-acquired infections and sepsis. Procalcitonin was measured with a time-resolved amplified cryptate emission technology assay. Lipopolysaccharide-binding protein and IL-6 were measured with a chemiluminescent immunometric assay.

Results

Of 194 included patients, 106 had either infection without systemic inflammatory response syndrome or sepsis. Infected patients had significantly elevated levels of procalcitonin, lipopolysaccharide-binding protein, C-reactive protein and IL-6 compared with noninfected patients (P < 0.001). In a receiver-operating characteristic curve analysis, C-reactive protein and IL-6 performed best in distinguishing between noninfected and infected patients, with an area under the curve larger than 0.82 (P < 0.05). IL-6, lipopolysaccharide-binding protein and C-reactive protein performed best in distinguishing between systemic inflammatory response syndrome and sepsis, with an area under the curve larger than 0.84 (P < 0.01). Procalcitonin performed best in distinguishing between sepsis and severe sepsis, with an area under the curve of 0.74 (P < 0.01).

Conclusion

C-reactive protein, IL-6 and lipopolysaccharide-binding protein appear to be superior to procalcitonin as diagnostic markers for infection and sepsis in patients admitted to a Department of Internal Medicine. Procalcitonin appears to be superior as a severity marker.
Chest wall mechanics during pressure support ventilation
Authors: Aliverti Andrea , Carlesso Eleonora , Dellacà Raffaele , Pelosi Paolo , Chiumello Davide , Pedotti Antonio , Gattinoni Luciano
Published: April 2006

Introduction

During pressure support ventilation (PSV) a part of the breathing pattern is controlled by the patient, and synchronization of respiratory muscle action and the resulting chest wall kinematics is a valid indicator of the patient's adaptation to the ventilator. The aim of the present study was to analyze the effects of different PSV settings on ventilatory pattern, total and compartmental chest wall kinematics and dynamics, muscle pressures and work of breathing in patients with acute lung injury.

Method

In nine patients four different levels of PSV (5, 10, 15 and 25 cmH2O) were randomly applied with the same level of positive end-expiratory pressure (10 cmH2O). Flow, airway opening, and oesophageal and gastric pressures were measured, and volume variations for the entire chest wall, the ribcage and abdominal compartments were recorded by opto-electronic plethysmography. The pressure and the work generated by the diaphragm, rib cage and abdominal muscles were determined using dynamic pressure-volume loops in the various phases of each respiratory cycle: pre-triggering, post-triggering with the patient's effort combining with the action of the ventilator, pressurization and expiration. The complete breathing pattern was measured and correlated with chest wall kinematics and dynamics.

Results

At the various levels of pressure support applied, minute ventilation was constant, with large variations in breathing frequency/ tidal volume ratio. At pressure support levels below 15 cmH2O the following increased: the pressure developed by the inspiratory muscles, the contribution of the rib cage compartment to the total tidal volume, the phase shift between rib cage and abdominal compartments, the post-inspiratory action of the inspiratory rib cage muscles, and the expiratory muscle activity.

Conclusion

During PSV, the ventilatory pattern is very different at different levels of pressure support; in patients with acute lung injury pressure support greater than 10 cmH2O permits homogeneous recruitment of respiratory muscles, with resulting synchronous thoraco-abdominal expansion.
Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case-control studies
Authors: Falagas Matthew E , Bliziotis Ioannis A , Siempos Ilias I
Published: April 2006

Introduction

There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors.

Methods

We performed a systematic review of matched case-control and cohort studies examining the mortality attributable to infection with or acquisition of A. baumannii (infection or colonization). We included in our review studies that compared mortality and/or morbidity of patients with acquisition of or infection with A. baumannii (cases) with the outcomes of matched patients without A. baumannii isolation from clinical specimens (controls). The relevant studies were identified from searches of the PubMed and the Cochrane Library databases. Two independent reviewers performed the literature search, study selection, and data extraction from nine identified relevant studies.

Results

The attributable mortalities, in the hospital and in the intensive care unit, of patients with A. baumannii infection in six matched case-control studies included in our review ranged from 7.8% to 23% and from 10% to 43%, respectively. In addition, a statistically significantly higher mortality was reported for patients with A. baumannii acquisition; that is, colonization or infection (cases) compared with controls without such an acquisition in all four reviewed studies that reported data on this comparison.

Conclusion

Although definitive statements about the mortality attributable to the acquisition of A. baumannii cannot be made from the available studies because of their methodological heterogeneity, the reviewed data suggest that infection with or acquisition of A. baumannii seems to be associated with increased mortality.
Decompressive laparotomy for abdominal compartment syndrome – a critical analysis
Authors: De Waele Jan J , Hoste Eric AJ , Malbrain Manu LNG
Published: April 2006

Introduction

Abdominal compartment syndrome (ACS) is increasingly recognized in critically ill patients, and the deleterious effects of increased intraabdominal pressure (IAP) are well documented. Surgical decompression through a midline laparotomy or decompressive laparotomy remains the sole definite therapy for ACS, but the effect of decompressive laparotomy has not been studied in large patient series.

Methods

We reviewed English literature from 1972 to 2004 for studies reporting the effects of decompressive laparotomy in patients with ACS. The effect of decompressive laparotomy on IAP, patient outcome and physiology were analysed.

Results

Eighteen studies including 250 patients who underwent decompressive laparotomy could be included in the analysis. IAP was significantly lower after decompression (15.5 mmHg versus 34.6 mmHg before, p < 0.001), but intraabdominal hypertension persisted in the majority of the patients. Mortality in the whole group was 49.2% (123/250). The effect of decompressive laparotomy on organ function was not uniform, and in some studies no effect on organ function was found. Increased PaO2/FIO2 ratio (PaO2 = partial pressure of oxygen in arterial blood, FiO2 = fraction of inspired oxygen) and urinary output were the most pronounced effects of decompressive laparotomy.

Conclusion

The effects of decompressive laparotomy have been poorly investigated, and only a small number of studies report its effect on parameters of organ function. Although IAP is consistently lower after decompression, mortality remains considerable. Recuperation of organ dysfunction after decompressive laparotomy for ACS is variable.
Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779]
Authors: Damas Pierre , Garweg Christophe , Monchi Mehran , Nys Monique , Canivet Jean-Luc , Ledoux Didier , Preiser Jean-Charles
Published: April 2006

Introduction

Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy.

Methods

Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter.

Results

Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed.

Conclusion

Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.
Comparative profiling of the sense and antisense transcriptome of maize lines
Authors: Ma Jiong , Morrow Darren J , Fernandes John , Walbot Virginia
Published: April 2006

Background

There are thousands of maize lines with distinctive normal as well as mutant phenotypes. To determine the validity of comparisons among mutants in different lines, we first address the question of how similar the transcriptomes are in three standard lines at four developmental stages.

Results

Four tissues (leaves, 1 mm anthers, 1.5 mm anthers, pollen) from one hybrid and one inbred maize line were hybridized with the W23 inbred on Agilent oligonucleotide microarrays with 21,000 elements. Tissue-specific gene expression patterns were documented, with leaves having the most tissue-specific transcripts. Haploid pollen expresses about half as many genes as the other samples. High overlap of gene expression was found between leaves and anthers. Anther and pollen transcript expression showed high conservation among the three lines while leaves had more divergence. Antisense transcripts represented about 6 to 14 percent of total transcriptome by tissue type but were similar across lines. Gene Ontology (GO) annotations were assigned and tabulated. Enrichment in GO terms related to cell-cycle functions was found for the identified antisense transcripts. Microarray results were validated via quantitative real-time PCR and by hybridization to a second oligonucleotide microarray platform.

Conclusion

Despite high polymorphisms and structural differences among maize inbred lines, the transcriptomes of the three lines displayed remarkable similarities, especially in both reproductive samples (anther and pollen). We also identified potential stage markers for maize anther development. A large number of antisense transcripts were detected and implicated in important biological functions given the enrichment of particular GO classes.
Anopheles gambiae genome reannotation through synthesis of ab initioand comparative gene prediction algorithms
Authors: Li Jun , Riehle Michelle M , Zhang Yan , Xu Jiannong , Oduol Frederick , Gomez Shawn M , Eiglmeier Karin , Ueberheide Beatrix M , Shabanowitz Jeffrey , Hunt Donald F , Ribeiro José MC , Vernick Kenneth D
Published: April 2006

Background

Complete genome annotation is a necessary tool as Anopheles gambiae researchers probe the biology of this potent malaria vector.

Results

We reannotate the A. gambiae genome by synthesizing comparative and ab initio sets of predicted coding sequences (CDSs) into a single set using an exon-gene-union algorithm followed by an open-reading-frame-selection algorithm. The reannotation predicts 20,970 CDSs supported by at least two lines of evidence, and it lowers the proportion of CDSs lacking start and/or stop codons to only approximately 4%. The reannotated CDS set includes a set of 4,681 novel CDSs not represented in the Ensembl annotation but with EST support, and another set of 4,031 Ensembl-supported genes that undergo major structural and, therefore, probably functional changes in the reannotated set. The quality and accuracy of the reannotation was assessed by comparison with end sequences from 20,249 full-length cDNA clones, and evaluation of mass spectrometry peptide hit rates from an A. gambiae shotgun proteomic dataset confirms that the reannotated CDSs offer a high quality protein database for proteomics. We provide a functional proteomics annotation, ReAnoXcel, obtained by analysis of the new CDSs through the AnoXcel pipeline, which allows functional comparisons of the CDS sets within the same bioinformatic platform. CDS data are available for download.

Conclusion

Comprehensive A. gambiae genome reannotation is achieved through a combination of comparative and ab initio gene prediction algorithms.
Ranked prediction of p53 targets using hidden variable dynamic modeling
Authors: Barenco Martino , Tomescu Daniela , Brewer Daniel , Callard Robin , Stark Jaroslav , Hubank Michael
Published: April 2006

Full exploitation of microarray data requires hidden information that cannot be extracted using current analysis methodologies. We present a new approach, hidden variable dynamic modeling (HVDM), which derives the hidden profile of a transcription factor from time series microarray data, and generates a ranked list of predicted targets. We applied HVDM to the p53 network, validating predictions experimentally using small interfering RNA. HVDM can be applied in many systems biology contexts to predict regulation of gene activity quantitatively.
The contributions of normal variation and genetic background to mammalian gene expression
Authors: Pritchard Colin , Coil David , Hawley Sarah , Hsu Li , Nelson Peter S
Published: April 2006

Background

Qualitative and quantitative variability in gene expression represents the substrate for external conditions to exert selective pressures for natural selection. Current technologies allow for some forms of genetic variation, such as DNA mutations and polymorphisms, to be determined accurately on a comprehensive scale. Other components of variability, such as stochastic events in cellular transcriptional and translational processes, are less well characterized. Although potentially important, the relative contributions of genomic versus epigenetic and stochastic factors to variation in gene expression have not been quantified in mammalian species.

Results

In this study we compared microarray-based measures of hepatic transcript abundance levels within and between five different strains of Mus musculus. Within each strain 23% to 44% of all genes exhibited statistically significant differences in expression between genetically identical individuals (positive false discovery rate of 10%). Genes functionally associated with cell growth, cytokine activity, amine metabolism, and ubiquitination were enriched in this group. Genetic divergence between individuals of different strains also contributed to transcript abundance level differences, but to a lesser extent than intra-strain variation, with approximately 3% of all genes exhibiting inter-strain expression differences.

Conclusion

These results indicate that although DNA sequence fixes boundaries for gene expression variability, there remain considerable latitudes of expression within these genome-defined limits that have the potential to influence phenotypes. The extent of normal or expected natural variability in gene expression may provide an additional level of phenotypic opportunity for natural selection.
San Francisco 1906 and 2006: An Emergency Management Perspective
Authors: Canton Lucien G.
Published: April 2006

Despite a distance of 100 years the Great San Francisco Earthquake and Fire still has much to teach the emergency managers of 2006. The response to the 1906 disaster foreshadows many modern emergency management techniques and sounds a cautionary note about areas where work still needs to be done. By comparing the city's response in 1906 with modern emergency plans, this paper examines how San Francisco might deal with a similar event in 2006. While many issues that marred the 1906 response have been resolved and much has been done to build resiliency, San Francisco in 2006 is in many ways still very similar in attitude to the San Francisco of 1906. Further, the recent example of Hurricane Katrina suggests that some of the more critical issues that arose in 1906 have still not been fully resolved.
Observations of Surface Fault Rupture from the 1906 Earthquake in the Context of Current Practice
Authors: Bray Jonathan D. , Kelson Keith I.
Published: April 2006

Many important insights are embedded in the detailed observations of surface rupture of the 1906 San Francisco earthquake, during which surface faulting interacted with pipelines, earth embankments, and buildings. Lessons gleaned from the 1906 rupture, combined with parallel and new insights from recent earthquakes, illustrate how various geologic conditions alter the surface expression of faulting and how surface fault rupture interacts with engineered systems. Geologic and engineering procedures can be employed to evaluate the hazards associated with surface faulting and to develop sound designs. Illustrative examples are used to demonstrate how the hazards associated with surface fault rupture can be addressed. Effective design measures include constructing earth fills to partially absorb underlying ground movements; isolating foundations from the underlying ground movements; and designing strong, ductile foundations that can accommodate some deformation without compromising the functionality of the structure.
A Retrospective on the 1906 Earthquake's Impact on Bay Area and California Public Policy
Authors: Perkins Jeanne B. , Chakos Arrietta , Olson Robert A. , Tobin L.Thomas , Turner Fred
Published: April 2006

The 1906 earthquake's influence has been both a blessing and curse on the Bay Area's and California's progress to effectively manage earthquake risk. This earthquake, and its impacts noted in the historical record, have both motivated and discouraged policymakers to act through mitigation and improved emergency response. This paper scrutinizes the 1906 earthquake using a public policy perspective. Building from that experience improves the region's future earthquake risk management efforts.
The Performance of Steel-Frame Buildings with Infill Masonry Walls in the 1906 San Francisco Earthquake
Authors: Hamburger Ronald O. , Meyer John D.
Published: April 2006

Following the great 1906 San Francisco earthquake and fire, engineers recognized the superior performance of buildings with complete vertical load–carrying steel frames and infill masonry walls. These buildings were noteworthy in their ability to survive both the ground shaking and fire, many remaining in service today. Observation of this superior performance led many California structural engineers to believe that steel frames were the best structural system for resisting earthquake damage, in turn, leading to a proliferation of steel-frame construction in California cities. Not until the 1994 Northridge earthquake did many California engineers recognize that steel-frame structures can and do experience severe earthquake damage. The performance capability of early steel-frame buildings with infill masonry walls, however, remains unclear, despite improved understanding of their structural response characteristics.
Liquefaction and Ground Failures in San Francisco
Authors: O'Rourke T. D. , Bonneau A. L. , Pease J. W. , Shi P. , Wang Y.
Published: April 2006

This paper examines the liquefaction and ground failures observed in San Francisco after the 1906 earthquake. It summarizes soil conditions, land development, and local seismic intensities within the city. Earthquake damage of the San Francisco water distribution system is discussed, and an account is provided of how city planners used the water supply damage to map locations of “infirm ground,” which are used today in the design and operation of the city fire protection system. Maps are presented that show subsurface conditions, current street system, permanent ground deformation, and infrastructure damage in 1906. With the use of approximately 500 soil borings and soundings compiled in a geographical information system (GIS), liquefaction hazard maps are generated for the Mission Creek and South of Market areas of the city.
Using Modified Mercalli Intensities to Estimate Acceleration Response Spectra for the 1906 San Francisco Earthquake
Authors: Boatwright John , Bundock Howard , Seekins Linda C.
Published: April 2006

We derive and test relations between the Modified Mercalli Intensity (MMI) and the pseudo-acceleration response spectra at 1.0 and 0.3 s— SA(1.0 s) and SA(0.3 s)—in order to map response spectral ordinates for the 1906 San Francisco earthquake. Recent analyses of intensity have shown that MMI ≥ 6 correlates both with peak ground velocity and with response spectra for periods from 0.5 to 3.0 s. We use these recent results to derive a linear relation between MMI and log SA(1.0 s), and we refine this relation by comparing the SA(1.0 s) estimated from Boatwright and Bundock's (2005) MMI map for the 1906 earthquake to the SA(1.0 s) calculated from recordings of the 1989 Loma Prieta earthquake. South of San Jose, the intensity distributions for the 1906 and 1989 earthquakes are remarkably similar, despite the difference in magnitude and rupture extent between the two events. We use recent strong motion regressions to derive a relation between SA(1.0 s) and SA(0.3 s) for a M7.8 strike-slip earthquake that depends on soil type, acceleration level, and source distance. We test this relation by comparing SA(0.3 s) estimated for the 1906 earthquake to SA(0.3 s) calculated from recordings of both the 1989 Loma Prieta and 1994 Northridge earthquakes, as functions of distance from the fault.