bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea?
Authors: Lefebvre B. , Pépin J-L. , Baguet J-P. , Tamisier R. , Roustit M. , Riedweg K. , Bessard G. , Lévy P. , Stanke-Labesque F.
Published: March 2008

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B4is a lipid mediator involved in atherogenesis.

In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB4production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB4production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB4production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB4production, which was measured by liquid chromatography–tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls.

LTB4production was increased in OSA patients compared with controls. LTB4levels correlated with the mean and minimal arterial oxygen saturation (Sa,O2). LTB4production correlated with luminal diameter data in patients with a meanSa,O2of ≤94% but not with IMT. Lastly, CPAP significantly reduced LTB4production by 50%.

Leukotriene B4production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B4could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
Clock gene dysfunction in patients with obstructive sleep apnoea syndrome
Authors: Burioka N. , Koyanagi S. , Endo M. , Takata M. , Fukuoka Y. , Miyata M. , Takeda K. , Chikumi H. , Ohdo S. , Shimizu E.
Published: March 2008

Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnoea syndrome (OSAS) influences clock gene function, the present authors examinedPeriod1(Per1) mRNA expressionin vitroandin vivo.

In eight healthy subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) andPer1mRNA expression in peripheral whole blood were measured. Expression ofPer1mRNA in cultured cells was examined under IL-6 or noradrenaline stimulationin vitro. After noradrenaline was administered to micein vivo,Per1mRNA expression in the brain was examined.

The concentrations of serum IL-6, hsCRP and plasma noradrenaline were elevated in OSAS patients, but improved by continuous positive airway pressure (CPAP) therapy.Per1mRNA expression in the peripheral blood significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL-6 did not directly inducePer1mRNAin vitro. Administration of noradrenaline inducedPer1mRNA in the cerebral cortex of micein vivo.

The current study revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction, and continuous positive airway pressure helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in obstructive sleep apnoea syndrome may be one of the factors involved in disorders ofPeriod1mRNA expression.
The association between serum osmolality and lung function among adults
Authors: Pogson Z. E. K. , McKeever T. M. , Fogarty A.
Published: March 2008

The extensive pulmonary vasculature results in the lungs being intimately exposed to circulating blood. As increased serum osmolality may be associated with an increase in pro-inflammatory activity, this has the potential to result in damage to the lungs and reduced lung function. The objective of the present study was to test the hypothesis that increased serum osmolality is associated with a lower forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).

The present study was a cross-sectional study of 10,602 participants in the Third National Health and Nutrition Examination Survey aged ≥17 yrs for whom there were adequate data on all outcomes and exposures.

After adjustment for age, smoking and other confounding factors, increased serum osmolality was inversely associated with both FEV1and FVC. An increase of 1 sdin serum osmolality was associated with a decrease in both FEV1of 19.8 mL and FVC of 35.3 mL. The constituent assays demonstrated a complex relationship with both FEV1and FVC.

Increased serum osmolality was associated with decreased forced expiratory volume in one second and forced vital capacity. If causal, this may have implications for the understanding of the processes that are involved in the pathophysiology of decline in lung function.
Sex differences in physiological progression of idiopathic pulmonary fibrosis
Authors: Han M. K. , Murray S. , Fell C. D. , Flaherty K. R. , Toews G. B. , Myers J. , Colby T. V. , Travis W. D. , Kazerooni E. A. , Gross B. H. , Martinez F. J.
Published: March 2008

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for malesversusfemales.

Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences.

Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity.

These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.
TGF-β receptor II in epitheliaversusmesenchyme plays distinct roles in the developing lung
Authors: Chen H. , Zhuang F. , Liu Y-H. , Xu B. , del Moral P. , Deng W. , Chai Y. , Kolb M. , Gauldie J. , Warburton D. , Moses H. L. , Shi W.
Published: March 2008

Transforming growth factor (TGF)-β signalling plays important roles in regulating lung development. However, the specific regulatory functions of TGF-β signalling in developing lung epithelialversusmesenchymal cells are still unknown.

By immunostaining, the expression pattern of the TGF-β type II receptor (TβRII) was first determined in the developing mouse lung. The functions of TβRII in developing lung were then determined by conditionally knocking out TβRII in the lung epithelium of floxed-TβRII/surfactant protein C-reverse tetracycline transactivator/TetO-Cre miceversusmesenchyme of floxed-TβRII/Dermo1-Cre mice.

TβRII was expressed only in distal airway epithelium at early gestation (embryonic day (E)11.5), but in both airway epithelium and mesenchyme from mid-gestation (E14.5) to post-natal day 14. Abrogation of TβRII in mouse lung epithelium resulted in retardation of post-natal lung alveolarisation, with markedly decreased type I alveolar epithelial cells, while no abnormality in prenatal lung development was observed. In contrast, blockade of TβRII in mesoderm-derived tissues, including lung mesenchyme, resulted in mildly abnormal lung branching and reduced cell proliferation after mid-gestation, accompanied by multiple defects in other organs, including diaphragmatic hernia. The primary lung branching defect was verified in embryonic lung explant culture.

The novel findings of the present study suggest that transforming growth factor-β type II receptor-mediated transforming growth factor-β signalling plays distinct roles in lung epitheliumversusmesenchyme to differentially control specific stages of lung development.
Identification of transcripts overexpressed during airway epithelium differentiation
Authors: Chhin B. , Pham J. T. , El Zein L. , Kaiser K. , Merrot O. , Bouvagnet P.
Published: March 2008

Human airway epithelium, the defence at the forefront of protecting the respiratory tract, evacuates inhaled particles by a permanent beating of epithelial cell cilia. When deficient, this organelle causes primary ciliary dyskinesia, and, despite numerous studies, data regarding ciliated cell gene expression remain incomplete. The aim of the present study was to identify genes specifically expressed in human ciliated respiratory cellsviatranscriptional analysis.

The transcriptome of dedifferentiated epithelial cells was subtracted from that of fully redifferentiated cells using complementary DNA representational difference analysis. In order to validate the results, gene overexpression in ciliated cells was confirmed by real-time PCR, and by comparing the present list of genes overexpressed in ciliated cells to lists obtained in previous studies.

A total of 53 known and 12 unknown genes overexpressed in ciliated cells were identified. The majority (66%) of known genes had never previously been reported as being involved in ciliogenesis, and the unknown genes represent hypothetical novel transcript isoforms or new genes not yet reported in databases. Finally, several genes identified here were located in genomic regions involved in primary ciliary dyskinesia by linkage analysis.

In conclusion, the present study revealed sequences of new cilia-related genes, new transcript isoforms and novel genes which should be further characterised to aid understanding of their function(s) and their probable disorder-related involvement.
Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein
Authors: Soehnlein O. , Oehmcke S. , X  , Rothfuchs A. G. , Frithiof R. , van Rooijen N. , Mörgelin M. , Herwald H. , Lindbom L.
Published: March 2008

Streptococcus pyogenesof the M1 serotype can cause streptococcal toxic shock syndrome commonly associated with acute lung injury. The aim of the present study was to investigate the role of neutrophils and their secretion products in M1 protein-induced lung damage.

The degranulation of neutrophils by M1 protein was studied in whole blood using marker analysis for individual granule subsets. In mice, M1 protein was injected intravenously and the lung damage was assessed by histology, electron microscopy, cell count in bronchoalveolar lavage fluid and analysis of lung vascular permeability. Comparisons were made in mice with intact white blood count, neutropenic mice and neutropenic mice injected with the secretion of activated neutrophils.

In whole blood, M1 protein forms complexes with fibrinogen that bind to β2-integrins on the neutrophil surface, resulting in degranulation of all four subsets of neutrophil granules. Intravenous injection of M1 protein into mice induced neutrophil accumulation in the lung, increase in vascular permeability and acute lung damage. Depletion of neutrophils from the circulation completely abrogated lung injury and vascular leakage. Interestingly, the lung damage was restored by injecting neutrophil secretion.

The present data suggest that neutrophil granule proteins are directly responsible for lung damage induced by the streptococcal M1 protein.
Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes and its regulation by the COP9 signalosome
Authors: Menon Suchithra , Tsuge Tomohiko , Dohmae Naoshi , Takio Koji , Wei Ning
Published: March 2008

Background

Cullin-RING ubiquitin E3 ligases (CRLs) are regulated by modification of an ubiquitin-like protein, Nedd8 (also known as Rub1) on the cullin subunit. Neddylation is shown to facilitate E3 complex assembly; while un-neddylated cullins are bound by CAND1 that prevents recruitment of the substrates. The level of Nedd8 modification is critically dependent on the COP9 signalosome (CSN), an eight-subunit protein complex containing Nedd8 isopeptidase activity.

Results

We report isolation of SAP130 (SF3b-3) as a CSN1 interacting protein. SAP130 is homologous to DDB1, and is a component of SF3b RNA splicing complex and STAGA/TFTC transcription complexes, but its specific function within these complexes is unknown. We show that SAP130 can interact with a variety of cullin proteins. It forms tertiary complexes with fully assembled CRL E3 complexes such as SCFSkp2, Elongin B/C -Cul2- VHL and Cul4-DDB complex by binding to both N-terminal and C-terminal domain of cullins. SAP130 preferentially associates with neddylated cullins in vivo. However knock-down of CAND1 abolished this preference and increased association of SAP130 with Cul2. Furthermore, we provide evidence that CSN regulates SAP130-Cul2 interaction and SAP130-associated polyubiquitinating activity.

Conclusion

SAP130 is a cullin binding protein that is likely involved in the Nedd8 pathway. The association of SAP130 with various cullin member proteins such as Cul1, Cul2 and Cul4A is modulated by CAND1 and CSN. As an established component of transcription and RNA processing complexes, we hypothesis that SAP130 may link CRL mediated ubiquitination to gene expression.
Analysis of four achaete-scute homologs in Bombyx mori reveals new viewpoints of the evolution and functions of this gene family
Authors: Zhou Qingxiang , Zhang Tianyi , Xu Weihua , Yu Linlin , Yi Yongzhu , Zhang Zhifang
Published: March 2008

Background

achaete-scutecomplexe (AS-C) has been widely studied at genetic, developmental and evolutional levels. Genes of this family encode proteins containing a highly conserved bHLH domain, which take part in the regulation of the development of central nervous system and peripheral nervous system. ManyAS-Chomologs have been isolated from various vertebrates and invertebrates. Also,AS-Cgenes are duplicated during the evolution of Diptera. Functions besides neural development controlling have also been found inDrosophila AS-Cgenes.

Results

We cloned fourachaete-scutehomologs (ASH) from the lepidopteran model organismBombyx mori, including three proneural genes and one neural precursor gene. Proteins encoded by them contained the characteristic bHLH domain and the three proneural ones were also found to have the C-terminal conserved motif. These genes regulated promoter activity through the Class A E-boxesin vitro. Though bothBm-ASHandDrosophila AS-Chave four members, they are not in one by one corresponding relationships. Results of RT-PCR and real-time PCR showed thatBm-ASHgenes were expressed in different larval tissues, and had well-regulated expressional profiles during the development of embryo and wing/wing disc.

Conclusion

There are fourachaete-scutehomologs inBombyx mori, the second insect having fourAS-Cgenes so far, and these genes have multiple functions in silkworm life cycle.AS-Cgene duplication in insects occurs after or parallel to, but not before the taxonomic order formation during evolution.
Transcriptome analysis of grain development in hexaploid wheat
Authors: Wan Yongfang , Poole Rebecca L , Huttly Alison K , Toscano-Underwood Claudia , Feeney Kevin , Welham Sue , Gooding Mike J , Mills Clare , Edwards Keith J , Shewry Peter R , Mitchell Rowan AC
Published: March 2008

Background

Hexaploid wheat is one of the most important cereal crops for human nutrition. Molecular understanding of the biology of the developing grain will assist the improvement of yield and quality traits for different environments. High quality transcriptomics is a powerful method to increase this understanding.

Results

The transcriptome of developing caryopses from hexaploid wheat (Triticum aestivum, cv. Hereward) was determined using Affymetrix wheat GeneChip® oligonucleotide arrays which have probes for 55,052 transcripts. Of these, 14,550 showed significant differential regulation in the period between 6 and 42 days after anthesis (daa). Large changes in transcript abundance were observed which were categorised into distinct phases of differentiation (6–10 daa), grain fill (12–21 daa) and desiccation/maturation (28–42 daa) and were associated with specific tissues and processes. A similar experiment on developing caryopses grown with dry and/or hot environmental treatments was also analysed, using the profiles established in the first experiment to show that most environmental treatment effects on transcription were due to acceleration of development, but that a few transcripts were specifically affected. Transcript abundance profiles in both experiments for nine selected known and putative wheat transcription factors were independently confirmed by real time RT-PCR. These expression profiles confirm or extend our knowledge of the roles of the known transcription factors and suggest roles for the unknown ones.

Conclusion

This transcriptome data will provide a valuable resource for molecular studies on wheat grain. It has been demonstrated how it can be used to distinguish general developmental shifts from specific effects of treatments on gene expression and to diagnose the probable tissue specificity and role of transcription factors.
The Innate Immune Database (IIDB)
Authors: Korb Martin , Rust Alistair G , Thorsson Vesteinn , Battail Christophe , Li Bin , Hwang Daehee , Kennedy Kathleen A , Roach Jared C , Rosenberger Carrie M , Gilchrist Mark , Zak Daniel , Johnson Carrie , Marzolf Bruz , Aderem Alan , Shmulevich Ilya , Bolouri Hamid
Published: March 2008

Background

As part of a National Institute of Allergy and Infectious Diseases funded collaborative project, we have performed over 150 microarray experiments measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like receptor stimuli. These microarray expression profiles are available freely from our project web site http://www.innateImmunity-systemsbiology.org. Here, we report the development of a database of computationally predicted transcription factor binding sites and related genomic features for a set of over 2000 murine immune genes of interest. Our database, which includes microarray co-expression clusters and a host of web-based query, analysis and visualization facilities, is available freely via the internet. It provides a broad resource to the research community, and a stepping stone towards the delineation of the network of transcriptional regulatory interactions underlying the integrated response of macrophages to pathogens.

Description

We constructed a database indexed on genes and annotations of the immediate surrounding genomic regions. To facilitate both gene-specific and systems biology oriented research, our database provides the means to analyze individual genes or an entire genomic locus. Although our focus to-date has been on mammalian toll-like receptor signaling pathways, our database structure is not limited to this subject, and is intended to be broadly applicable to immunology. By focusing on selected immune-active genes, we were able to perform computationally intensive expression and sequence analyses that would currently be prohibitive if applied to the entire genome. Using six complementary computational algorithms and methodologies, we identified transcription factor binding sites based on the Position Weight Matrices available in TRANSFAC. For one example transcription factor (ATF3) for which experimental data is available, over 50% of our predicted binding sites coincide with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database can be interrogated via a web interface. Genomic annotations and binding site predictions can be automatically viewed with a customized version of the Argo genome browser.

Conclusion

We present the Innate Immune Database (IIDB) as a community resource for immunologists interested in gene regulatory systems underlying innate responses to pathogens. The database website can be freely accessed at http://db.systemsbiology.net/IIDB.
C4B null alleles are not associated with genetic polymorphisms in the adjacent gene CYP21A2in autism
Authors: Sweeten Thayne L , Odell Daniel W , Odell J Dennis , Torres Anthony R
Published: March 2008

Background

Research indicates that the etiology of autism has a strong genetic component, yet so far the search for genes that contribute to the disorder, including several whole genome scans, has led to few consistent findings. However, three studies indicate that the complement C4B gene null allele (i.e. the missing or nonfunctional C4B gene) is significantly more frequent in individuals with autism. Due to the close proximity of the CYP21A2 gene to the C4B locus (3 kb) it was decided to examine samples from autistic subjects, including many with known C4B null alleles for common CYP21A2 mutations.

Methods

Samples from subjects diagnosed with autism and non-autistic controls (controls) previously typed for C4B null alleles were studied. Allele specific polymerase chain reaction (PCR) methods were used to determine 8 of the most common CYP21A2 genetic mutations, known to completely or partially inhibit 21-hydroxylase, the enzyme encoded by the CYP21A2 gene.

Results

Although the combined autism and control study subjects had 50 C4B null alleles only 15 CYP21A2 mutations were detected in over 2250 genotypes. Eight mutations were detected in the autistic samples and 7 in the controls. The frequency of CYP21A2 mutations was similar between the autism and control samples. Only one individual (autistic) carried a chromosome containing both C4B null allele and CYP21A2 mutations.
Comparison of different real-time PCR chemistries and their suitability for detection and quantification of genetically modified organisms
Authors: Buh Gašparič Meti , Cankar Katarina , Žel Jana , Gruden Kristina
Published: March 2008

Background

The real-time polymerase chain reaction is currently the method of choice for quantifying nucleic acids in different DNA based quantification applications. It is widely used also for detecting and quantifying genetically modified components in food and feed, predominantly employing TaqMan® and SYBR® Green real-time PCR chemistries. In our study four alternative chemistries: Lux™, Plexor™, Cycling Probe Technology and LNA® were extensively evaluated and compared using TaqMan® chemistry as a reference system.

Results

Amplicons were designed on the maize invertase gene and the 5'-junction of inserted transgene and plant genomic DNA in MON 810 event. Real-time assays were subsequently compared for their efficiency in PCR amplification, limits of detection and quantification, repeatability and accuracy to test the performance of the assays. Additionally, the specificity of established assays was checked on various transgenic and non-transgenic plant species. The overall applicability of the designed assays was evaluated, adding practicability and costs issues to the performance characteristics.

Conclusion

Although none of the chemistries significantly outperformed the others, there are certain characteristics that suggest that LNA® technology is an alternative to TaqMan® when designing assays for quantitative analysis. Because LNA® probes are much shorter they might be especially appropriate when high specificity is required and where the design of a common TaqMan® probe is difficult or even impossible due to sequence characteristics. Plexor™ on the other hand might be a method of choice for qualitative analysis when sensitivity, low cost and simplicity of use prevail.
Lymphangiogenesis and lymph node metastasis in breast cancer
Authors: Cunnick Giles H , Jiang Wen G , Douglas-Jones Tony , Watkins Gareth , Gomez Kelvin F , Morgan Mike J , Subramanian Ashok , Mokbel Kefah , Mansel Robert E
Published: March 2008

Introduction

There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival.

The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival.

Results

There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression.

Conclusion

In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.
Hospital Anxiety and Depression Scale (HADS): validation in a Greek general hospital sample
Authors: Michopoulos Ioannis , Douzenis Athanasios , Kalkavoura Christina , Christodoulou Christos , Michalopoulou Panayiota , Kalemi Georgia , Fineti Katerina , Patapis Paulos , Protopapas Konstantinos , Lykouras Lefteris
Published: March 2008

Background

The Hospital Anxiety and Depression Scale (HADS) has been used in several languages to assess anxiety and depression in general hospital patients with good results.

Methods

The HADS was administered to 521 participants (275 controls and 246 inpatients and outpatients of the Internal Medicine and Surgical Departments in 'Attikon' General Hospital in Athens). The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used as 'gold standards' for depression and anxiety respectively.

Results

The HADS presented high internal consistency; Cronbach's α cofficient was 0.884 (0.829 for anxiety and 0.840 for depression) and stability (test-retest intraclass correlation coefficient 0.944). Factor analysis showed a two-factor structure. The HADS showed high concurrent validity; the correlations of the scale and its subscales with the BDI and the STAI were high (0.722 – 0.749).

Conclusion

The Greek version of HADS showed good psychometric properties and could serve as a useful tool for clinicians to assess anxiety and depression in general hospital patients.
Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case report
Authors: Otrock Zaher K , Hatoum Hassan A , Uthman Imad W , Taher Ali T , Saab Shahrazad , Shamseddine Ali I
Published: March 2008

Introduction

Adult onset Still's disease is a chronic multisystemic inflammatory disorder characterized by high spiking fever, polyarthralgia and rash. Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen in about 65% of patients. Searching the medical literature using the MEDLINE database from January 1966 through November 2007 we could only find two reported cases of adult onset Still's disease that had progressed to lymphoma.

Case presentation

We describe a woman who was diagnosed with adult onset Still's disease and developed lymphoma 10 months after the onset of her symptoms. She initially presented with fever and arthritis of the knees, ankles and shoulders, along with a nonpruritic skin rash, myalgia and weight loss. On physical examination she was found to have several enlarged anterior cervical lymph nodes and left posterior auricular lymph nodes all of which were non-tender, immobile and rubbery. Excisional biopsy of the cervical lymph nodes was negative for malignancy. Bone marrow biopsy was also negative for malignancy. She was treated with prednisone. She remained in good health until she presented 10 months later with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma. She was treated with chemotherapy and was doing well until she presented with abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our knowledge, this is the third reported case of such an occurrence.

Conclusion

Although the association between adult onset Still's disease and lymphoma has been rarely reported, careful screening for this malignancy in patients suspected to have adult onset Still's disease is warranted.
Predictors of Depressed Mood in Spouses of Women With Breast Cancer
Authors: Lewis Frances Marcus , Fletcher Kristin A. , Cochrane Barbara B. , Fann Jesse R.
Published: March 2008

Purpose

Depressed mood in spouses of women with breast cancer deleteriously affects their own and their wife's functioning and their marital communication. However, no study has examined why some spouses get depressed whereas others do not, particularly during the first months of diagnosis and treatment, a known difficult time for couples. The current study has two purposes: to test a predictive model of spouses’ depressed mood and to evaluate the model's accuracy in distinguishing between normal and clinically depressed spouses.

Methods

Data were obtained from standardized questionnaires completed by 206 spouses and 206 wives recently diagnosed with nonmetastatic breast cancer. Spouses’ depressed mood was measured by the Center for Epidemiological Studies–Depression Scale. A total of 19 variables were extracted from the literature for testing in the model, including psychological, social, demographic, and disease- and treatment-related variables.

Results

Spouses were more likely to be depressed if they were older, less well educated, more recently married, reported heightened fears over their wife's well-being, worried about their job performance, were more uncertain about their future, or were in less well-adjusted marriages. The model correctly classified 89.2% of spouses’ mood (χ2 = 79.1; P < .001).

Conclusion

Spouses of women with local or regional breast cancer need to be screened for depressed mood and triaged into supportive services to better assist them manage the threat of their wife's breast cancer.
How To Build and Interpret a Nomogram for Cancer Prognosis
Authors: Iasonos Alexia , Schrag Deborah , Raj Ganesh V. , Panageas Katherine S.
Published: March 2008

Nomograms are widely used for cancer prognosis, primarily because of their ability to reduce statistical predictive models into a single numerical estimate of the probability of an event, such as death or recurrence, that is tailored to the profile of an individual patient. User-friendly graphical interfaces for generating these estimates facilitate the use of nomograms during clinical encounters to inform clinical decision making. However, the statistical underpinnings of these models require careful scrutiny, and the degree of uncertainty surrounding the point estimates requires attention. This guide provides a nonstatistical audience with a methodological approach for building, interpreting, and using nomograms to estimate cancer prognosis or other health outcomes.
Treatment of Advanced Hormone-Sensitive Breast Cancer in Postmenopausal Women With Exemestane Alone or in Combination With Celecoxib
Authors: Dirix Luc Yves , Ignacio Jorge , Nag Shona , Bapsy Poonamally , Gomez Henry , Raghunadharao Digumarti , Paridaens Robert , Jones Stephen , Falcon Silvia , Carpentieri Marina , Abbattista Antonello , Lobelle Jean-Pierre
Published: March 2008

Purpose

Preclinical data showed that the combination of exemestane and celecoxib has synergistic effects. Therefore, a study was undertaken to explore the efficacy and tolerability of this combination in postmenopausal patients with advanced, hormone-sensitive breast cancer.

Patients and Methods

A randomized phase II study was conducted in postmenopausal patients with hormone-sensitive breast cancer and measurable disease who had progressive disease after treatment with tamoxifen. Patients were randomly assigned to either exemestane 25 mg daily or the combination of exemestane 25 mg daily with celecoxib 400 mg twice daily. Response Evaluation Criteria in Solid Tumors Group criteria were used to determine antitumor efficacy. Primary end point was the rate of clinical benefit. Secondary end points were tolerability, objective response rate, time to progression (TTP), and duration of clinical benefit. A pharmacodynamic and a pharmacokinetic study were conducted in parallel.

Results

One hundred eleven patients (exemestane, n = 55; combination, n = 56) were enrolled in 2002. The demographic characteristics and prognostic factors were similar in both arms. In the assessable population, 24 of 51 patients in the combination arm and 24 of 49 patients in the exemestane arm achieved clinical benefit. TTP was similar in both groups. Duration of clinical benefit was longer in the combination group (median, 96.6 v 49.1 weeks). The addition of celecoxib did not change the tolerability profile of exemestane alone.

Conclusion

Similar rates of clinical benefit were achieved in both groups.
Understanding of Prognosis and Goals of Care Among Couples Whose Child Died of Cancer
Authors: Edwards Kelly E. , Neville Bridget A. , Cook Earl F. , Aldridge Sarah H. , Dussel Veronica , Wolfe Joanne
Published: March 2008

Purpose

Little is known about how couples care for the terminally ill child with cancer. We assessed both parents’ understanding of prognosis and treatment goals for children with cancer and explored whether sex mediates these views. We also investigated whether discordance within couples regarding treatment goals was related to parental perception of the child's end-of-life (EOL) experience.

Methods

We surveyed mothers and fathers of children who died of cancer and were cared for at Children's Hospital (Boston, MA) and the Dana-Farber Cancer Institute (Boston, MA) between 2000 and 2004. Our sample included 38 couples (response rate, 56%).

Results

Willingness to participate did not differ by sex. At diagnosis, fathers and mothers held a similar understanding of the child's prognosis, and 58% of couples agreed on the goal of cure. During the EOL period, a majority of fathers and mothers reported lessening suffering as the primary goal. However, within couples there was poor agreement about the primary goal of care (κ = 0.07). When parents did not agree on the primary goal of lessening suffering, both parents were more likely to report that the child suffered significantly from cancer-directed treatment (P = .03).

Conclusion

Though parent goals are often concurrent at diagnosis, they frequently differ during the EOL period. Parent disagreement about the goal of lessening suffering at the EOL appears to impact how parents describe their child's experience of suffering. Creating opportunities for parents to work through their goals together may lead to improvements in the child's EOL experience.
Role of Extent of Resection in the Long-Term Outcome of Low-Grade Hemispheric Gliomas
Authors: Smith Justin S. , Chang Edward F. , Lamborn Kathleen R. , Chang Susan M. , Prados Michael D. , Cha Soonmee , Tihan Tarik , VandenBerg Scott , McDermott Michael W. , Berger Mitchel S.
Published: March 2008

Purpose

The prognostic role of extent of resection (EOR) of low-grade gliomas (LGGs) is a major controversy. We designed a retrospective study to assess the influence of EOR on long-term outcomes of LGGs.

Patients and Methods

The study population (N = 216) included adults undergoing initial resection of hemispheric LGG. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging.

Results

Median preoperative and postoperative tumor volumes and EOR were 36.6 cm3 (range, 0.7 to 246.1 cm3), 3.7 cm3 (range, 0 to 197.8 cm3) and 88.0% (range, 5% to 100%), respectively. There was no operative mortality. New postoperative deficits were noted in 36 patients (17%); however, all but four had complete recovery. There were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant progression were identified in 95 (44%) and 44 (20%) cases, respectively. Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of 97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8-year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor burden for age, Karnofsky performance score (KPS), tumor location, and tumor subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to 0.983; P < .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to 12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to 1.019; P = .03), progression-free survival was predicted by log preoperative tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P ≤ .001) and postoperative tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to 0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to 8.969; P = .002).

Conclusion

Improved outcome among adult patients with hemispheric LGG is predicted by greater EOR.
Effect of Race on the Outcome of Pediatric Patients With Hodgkin's Lymphoma
Authors: Metzger Monika L. , Castellino Sharon M. , Hudson Melissa M. , Rai Shesh N. , Kaste Sue C. , Krasin Matthew J. , Kun Larry E. , Pui Ching-Hon , Howard Scott C.
Published: March 2008

Purpose

Some cooperative groups have found a survival disadvantage in black children with various childhood cancers. We examine the effects of race on clinical outcomes among children with Hodgkin's lymphoma (HL) treated with contemporary therapy at a tertiary care children's hospital.

Patients and Methods

Retrospective analysis of 327 children and adolescents diagnosed with HL between 1990 and 2005. Patients were treated with risk-directed multimodal therapy regardless of race, ethnicity, or ability to pay. Event-free and overall survival rates were compared for black and white children. Clinical characteristics, socioeconomic factors, and biologic features were analyzed for prognosis of treatment failure.

Results

The 262 white and 65 black patients did not differ significantly in presenting features, clinical characteristics, or enrollment in a clinical trial. More black patients (71% v 45%) resided in poor counties (P < .001). While black and white children were equally likely to have progressive disease or early relapse, black children were 3.7 times (95% CI, 1.7 to 8.0) more likely to relapse 12 months or more after diagnosis. The 5-year event-free survival was 71% ± 6.1% (SE) for black and 84% ± 2.4% for white children (P = .01). However, the 5-year survival rate did not differ between white and black children (94.4% v 94.7%). While black race and low hemoglobin concentration were independent predictors of treatment failure, only low hemoglobin concentration independently predicted poor survival.

Conclusion

Black children with Hodgkin's lymphoma have lower event-free survival than white children, but both populations have the same 5-year overall survival.
The Body Image and Relationships Scale: Development and Validation of a Measure of Body Image in Female Breast Cancer Survivors
Authors: Hormes Julia M. , Lytle Leslie A. , Gross Cynthia R. , Ahmed Rehana L. , Troxel Andrea B. , Schmitz Kathryn H.
Published: March 2008

Purpose

A self-report measure of body image in female breast cancer survivors, the Body Image and Relationships Scale (BIRS), was developed to address attitudes about appearance, health, physical strength, sexuality, relationships, and social functioning following treatment.

Methods

The 32-item measure, generated by expert consensus and revised based on focus group feedback, was administered to 95 female breast cancer participants twice within 1 to 2 weeks. Test-retest reliability, internal consistency, and validity of the measure were assessed using standard-scale construction techniques. The structure of the proposed measure was evaluated using exploratory factor analysis. Associations of the resulting factors and other variables were assessed using extreme groups analyses.

Results

The BIRS had satisfactory test-retest reliability and internal consistency. Principal axis factoring revealed three factors: (1) health and strength, (2) social barriers, and (3) appearance and sexuality. Correlations of the subscales with standardized measures of related constructs were significant and in the anticipated directions. Extreme groups analyses suggested associations between less physical activity and more impairment on factors 1 and 3, premenopausal status at first diagnosis and more impairment on factor 2, and younger age at the time of survey administration and more impairment on factor 3.

Conclusion

The proposed scale demonstrated satisfactory reliability and internal consistency. Factor analysis revealed three subscales with coherent item content and differential associations with measures of activity level, menopause status, and age. Observed relationships with other measures support convergent and divergent validity. Results suggest that the proposed scale is useful for clinical and research applications.
Job Loss and Re-Employment of Cancer Patients in Korean Employees: A Nationwide Retrospective Cohort Study
Authors: Park Jae-Hyun , Park Eun-Cheol , Park Jong-Hyock , Kim Sung-Gyeong , Lee Sang-Yi
Published: March 2008

Purpose

The aim of this study was to investigate whether a diagnosis of cancer has an impact on the cancer patients’ job loss and re-employment and to identify the factors affecting job loss and re-employment during 6 years of follow-up of Korean employees with cancer.

Patients and Methods

All employees except for the self-employed in Korea who were diagnosed with cancer during the 2001 calendar year (n = 5,396) were identified as the first baseline patients and were followed every 3 months over 6 years to estimate the time taken to job loss. Patients who lost their job within the first year after a diagnosis of cancer (n = 1,398) were identified as the second baseline patients and were followed up over 5 years to estimate the time taken to re-employment using the National Health Insurance claims data. Patient demographic, socioeconomic, and clinical variables were investigated as factors that affected job loss and re-employment.

Results

Among the first baseline cancer patients, 47.0% lost their job, and among the second baseline patients, 30.5% were re-employed over 69 to 72 months of follow-up. Female sex, younger age and older age, company employee, lower income, blood cancer, and brain and CNS, lung, and liver cancer were significant predictors of early job loss or delayed re-employment.

Conclusion

The diagnosis of cancer affects cancer patients’ employment status differently according to different factors: sex, age, type of job, income, and cancer site. Efforts should be made to support re-employment and reduce unnecessary work cessation and disparity between different demographic and socioeconomic groups of cancer survivors.
A Road Map for Universal Coverage: Finding a Pass Through the Financial Mountains
Authors: Sessions Samuel Y. , Lee Philip R.
Published: March 2008

Government already pays for more than half of U.S. health care costs, and nearly all universal health insurance proposals assume continued government involvement through tax subsidies and other means. The question of what specific taxes could be used to finance universal coverage is, however, seldom carefully examined, in part due to efforts by health care reform proponents to downplay tax issues. In this article we undertake such an examination. We argue that the challenges of relying on taxes for universal coverage are even greater than is generally appreciated, but that they can nevertheless be met. A proposal to fund a universal health insurance voucher system with a value-added tax illustrates issues that would arise for tax-financed plans in general and provides a broad framework for a bipartisan approach to universal coverage. We discuss significant problems that such an approach would face and suggest solutions. We outline a long-term political and legislative strategy for enacting universal coverage that draws upon precedents set by comparable legislative initiatives, including tax reform and Medicare. The results are an improved understanding of the relationship between systemic health care finance reform and taxation and a politically realistic plan for universal coverage that employs undisguised taxes.
The Truth About Health Care: Why Reform Is Not Working in America; The Health Care Mess: How We Got into It and What It Will Take to Get Out; The Health Care Mess: How We Got into It and How We'll Get Out of It
Authors: Peterson Mark A.
Published: March 2008

Health care reform is once again rising toward the top of the nation's political and policy agendas. Informed by three recent works on the subject, this review essay examines the recent history and reform climate as the country runs full throttle into the renewed debate. The central question is: will something not only, finally, succeed politically, but will it also be sensible substantively?
Attrition in the RAND Health Insurance Experiment: A Response to Nyman
Authors: Newhouse Joseph P. , Brook Robert H. , Duan Naihua , Keeler Emmett B. , Leibowitz Arleen , Manning Willard G. , Marquis M. Susan , Morris Carl N. , Phelps Charles E. , Rolph John E.
Published: March 2008

In a prior article in this journal, John Nyman argues that the effect on health care use and spending found in the RAND Health Insurance Experiment is an artifact of greater voluntary attrition in the cost-sharing plans relative to the free care plan. Specifically, he speculates that those in the cost-sharing plans, when faced with a hospitalization, withdrew. His argument is implausible because (1) families facing a hospitalization would be worse off financially by withdrawing; (2) a large number of observational studies find a similar effect of cost sharing on use; (3) those who left did not differ in their utilization prior to leaving; (4) if there had been no attrition and cost sharing did not reduce hospitalization rates, each adult in each family that withdrew would have had to have been hospitalized once each year for the duration of time they would otherwise have been in the experiment, an implausibly high rate; (5) there are benign explanations for the higher attrition in the cost-sharing plans. Finally, we obtained follow-up health-status data on the great majority of those who left prematurely. We found the health-status findings were insensitive to the inclusion of the attrition cases.