bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical Delivery of Retinyl Ascorbate Co-Drug
Authors: Abdulmajed K. , McGuigan C. , Heard C.M.
Published: June 2006

Chemical and enzymatic hydrolysis of the co-drug of retinoic acid (vitamin A) and ascorbic acid (vitamin C) – retinyl ascorbate (RA-AsA) – have been studied. Firstly, the amount of protein and ester hydrolysis activity was determined in crude cellular extracts from freshly excised porcine ear skin (<3 h) and stored porcine ear skin (frozen >6 months) using ethyl butyrate as model substrate. The stability of RA-AsA was then determined in the crude cell extracts with and without additional antioxidants. Lastly, the enzymatic hydrolysis of RA-AsA and retinyl-2-carboxy-2-hydroxy-ethanoate were determined by incubating with porcine liver esterase – retinol palmitate and ascorbyl palmitate were included for comparison. Freshly excised skin contained higher amounts of active proteins than previously frozen skin. RA-AsA underwent hydrolytic reduction causing the AsA moiety to disintegrate due to the presence of free radicals in the media. An intermediate was produced that seemed to be cleaved by enzymes. Addition of ascorbic acid, as antioxidant, to the media of crude protein extracts decelerated the hydrolysis rate. This was supported when RA-AsA and retinyl-2-carboxy-2-hydroxy-ethanoate were incubated separately with pure esterase. There was ∼5-fold more soluble protein per ml of cytosol in the fresh skin compared to the stored skin. Therefore, the amount of protein present within ∼1.5 cm2 of skin (average diffusion area in the Franz cells used in our skin penetration studies) was 0.06 mg cm–2 and 0.01 mg cm–2 for fresh and stored extracts, respectively.
Procyanidin Oligomers Counteract TGF-β1- and TGF-β2-Induced Apoptosis in Hair Epithelial Cells: An Insight into Their Mechanisms
Authors: Kamimura A. , Takahashi T. , Morohashi M. , Takano Y.
Published: June 2006

Procyanidin oligomers are polyphenol compounds we have identified in apples and barley which have hair growth stimulant effects, and which are able to promote hair epithelial cell growth and induce anagen induction of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of procyanidin oligomers, we examined their relationship to the TGF-β signal pathway, known to be a regulator of catagen induction, and the mitogen-activated protein kinase cascade linked to cell proliferation. Addition of TGF-β1 or TGF-β2 to hair epithelial cell cultures dose-dependently decreased cell growth and induced apoptosis; however, addition of procyanidin B-2 to the culture neutralized the growth-inhibiting effects of both TGF-β1 and TGF-β2 and protected the cells from apoptosis. The same effects were observed with procyanidin B-3. We confirmed that procyanidin B-2 upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. We speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-β1- or TGF-β2-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.
‘Keratolytic’ Properties of Benzoyl Peroxide and Retinoic Acid Resemble Salicylic Acid in Man
Authors: Waller J.M. , Dreher F. , Behnam S. , Ford C. , Lee C. , Tiet T. , Weinstein G.D. , Maibach H.I.
Published: June 2006

Objectives: Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions. Patients/Methods:Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed. Results and Conclusion: After 3 h, BP was significantly more effective in disrupting SC cohesion than SA and RA, indicating BP is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.
Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery
Authors: Takaoka Minoru , Uemura Shiro , Kawata Hiroyuki , Imagawa Kei-ichi , Takeda Yukiji , Nakatani Kimihiko , Naya Noriyuki , Horii Manabu , Yamano Shigeru , Miyamoto Yoshihiro , Yoshimasa Yasunao , Saito Yoshihiko
Published: June 2006

Objective—

Percutaneous coronary intervention (PCI) is currently the most widely accepted treatment for acute myocardial infarction (AMI). It remains unclear, however, whether post-AMI conditions might exacerbate neointimal hyperplasia and restenosis following PCI. Given that both a medial smooth muscle cell lineage and a bone marrow (BM)-derived hematopoietic stem cell lineage are now thought to contribute to neointima formation, the primary aims of the present study were to determine whether AMI augments neointimal hyperplasia at sites of arterial injury, and whether BM-derived cells contribute to that process.

Methods and Results—

We simultaneously generated models of AMI and arterial injury in the same mice, some of which had received BM transplantation. We found that AMI augments neointimal hyperplasia at sites of femoral artery injury by &35% (
P
<0.05), but that while BM-derived cells contributed to neointimal hyperplasia, they did not contribute to the AMI-related augmentation. Expression of interleukin (IL)-6 mRNA was &7-fold higher in the neointimas of mice subjected to both AMI and arterial injury than in those of mice subjected to arterial injury alone. In addition, we observed increased synthesis of tumor necrosis factor (TNF)-α within infarcted hearts and TNF-α receptor type 1 (TNFR1) within injured arteries. Chronic treatment with pentoxifylline, which mainly inhibits TNF-α synthesis, reduced levels of circulating TNF-α and attenuated neointimal hyperplasia after AMI.

Conclusions—

Conditions after AMI could exacerbate postangioplasty restenosis, not by increasing mobilization of BM-derived cells, but by stimulating signaling via TNF-α, TNFR1 and IL-6.
Novel Effect of Oxidized Low-Density Lipoprotein
Authors: Sukhanov Sergiy , Higashi Yusuke , Shai Shaw-Yung , Itabe Hiroyuki , Ono Koichi , Parthasarathy Sampath , Delafontaine Patrick
Published: June 2006

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolytic enzyme that is involved in cellular energy production and has important housekeeping functions. We used the natural prooxidant and proatherogenic molecule oxidized low-density lipoprotein (OxLDL) to determine a potential link between OxLDL-promoted oxidative stress, GAPDH expression, and smooth muscle cell energy metabolism. OxLDL but not native LDL (nLDL) produced a 60% to 100% dose- and time-dependent reduction of GAPDH protein. OxLDL increased reactive oxygen species (ROS) formation, including rapid elevation of H
2
O
2
levels. OxLDL decreased intracellular catalase expression, likely contributing to the increase in H
2
O
2
. Antioxidants, anti-CD36 receptor antibody, NADPH oxidase, or lipoxygenase blockers decreased OxLDL-specific ROS and prevented GAPDH downregulation. 12/15-Lipoxygenase or p47phox deficiency resulted in attenuation of GAPDH downregulation, but 5-lipoxygenase suppression had no effect. OxLDL or exogenous H
2
O
2
oxidized GAPDH thiols, decreasing GAPDH protein half-life and increasing GAPDH sensitivity to proteasome-mediated protein degradation in vitro. OxLDL- or small interfering RNA–specific downregulation of GAPDH resulted in 65% reduction in glycolysis rate and 82% decrease in ATP levels. In conclusion, our data demonstrate that OxLDL downregulated GAPDH via a H
2
O
2
-dependent decrease in protein stability. GAPDH protein damage resulted in marked depletion of cellular ATP levels. Our data have important implications for understanding the metabolic effect of OxLDL on the vessel wall and mechanism of atherogenesis.
Dynamic Responses of Single Cardiomyocytes to Graded Ischemia Studied by Oxygen Clamp in On-Chip Picochambers
Authors: Ganitkevich Vladimir , Reil Sibylle , Schwethelm Brigitta , Schroeter Thomas , Benndorf Klaus
Published: June 2006

Single mouse cardiomyocytes were exposed to defined ischemia. We designed chambers on glass chips with a volume of 192 pL (picochambers). After a picochamber was loaded with a single cardiomyocyte, P
o
2
in the picochamber was equilibrated with that in the headspace, where it was controlled in the critical range between <0.2 and 10 mm Hg. Because the extracellular fluid volume in a picochamber was restricted, these conditions are close to tissue ischemia. Responses of the sarcolemmal K
ATP
-channel current (
I
KATP
), the production of reactive oxygen species (ROS), and the mitochondrial membrane potential (Δψ) of single cardiomyocytes to graded ischemia and, in particular, to rapid changes of the ischemic grade by defined oxygen steps were studied. The results show that
I
KATP
is readily activated during ischemia and that the grade of ischemia tightly controls the amplitude of
I
KATP
. Furthermore, maximal ischemia-induced
I
KATP
was similar when it followed either reoxygenation or reperfusion, suggesting that there is no major autocrine modulation of maximal
I
KATP
during ischemia. A P
o
2
staircase from <0.2 to 10 mm Hg increased the ROS signal, starting already at a P
o
2
of ≈0.3 mm Hg. With a similar P
o
2
staircase, Δψ first hyperpolarized and then, above 1 mm Hg, depolarized. The depolarizing response of Δψ at a P
o
2
of >1 mm Hg could be blocked by increasing the antioxidant defense with glutathione–monoethyl ester. It is concluded that in an ischemic cardiomyocyte
I
KATP
is essentially controlled by P
o
2
and that at low P
o
2
Δψ is balanced by oxygen-induced hyperpolarization and ROS-induced depolarization.
Complement Component C3 Mediates Inflammatory Injury Following Focal Cerebral Ischemia
Authors: Mocco J , Mack William J. , Ducruet Andrew F. , Sosunov Sergei A. , Sughrue Michael E. , Hassid Benjamin G. , Nair M. Nathan , Laufer Ilya , Komotar Ricardo J. , Claire M. , Holland H. , Pinsky David J. , Connolly E. Sander
Published: June 2006

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3
−/−
mice were protected, as demonstrated by 34% reductions in both infarct volume (
P
<0.01) and neurological deficit score (
P
<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (
P
<0.02) and reduced oxidative stress (
P
<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (
P
<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.
Critical Assessment of Microphysical Assumptions within TRMM Radiometer Rain Profile Algorithm Using Satellite, Aircraft, and Surface Datasets from KWAJEX
Authors: Fiorino Steven T. , Smith Eric A.
Published: June 2006

The Tropical Rainfall Measuring Mission (TRMM) Microwave Imager precipitation profile retrieval algorithm (2a12) assumes cloud model–derived vertically distributed microphysics as part of the radiative transfer–controlled inversion process to generate rain-rate estimates. Although this algorithm has been extensively evaluated, none of the evaluation approaches has explicitly examined the underlying microphysical assumptions through a direct intercomparison of the assumed cloud-model microphysics with in situ, three-dimensional microphysical observations. The main scientific objective of this study is to identify and overcome the foremost model-generated microphysical weaknesses in the TRMM 2a12 algorithm through analysis of (a) in situ aircraft microphysical observations; (b) aircraft- and satellite-based passive microwave measurements; (c) ground-, aircraft-, and satellite-based radar measurements; (d) synthesized satellite brightness temperatures and radar reflectivities; (e) radiometer-only profile algorithm retrievals; and (f) radar-only profile or volume algorithm retrievals. Results indicate the assumed 2a12 microphysics differs most from aircraft-observed microphysics where either ground or aircraft radar–derived rain rates exhibit the greatest differences with 2a12-retrieved rain rates. An emission–scattering coordinate system highlights the 2a12 algorithm's tendency to match high-emission/high-scattering observed profiles to high-emission/low-scattering database profiles. This is due to a lack of mixed-phase-layer ice hydrometeor scatterers in the cloud model–generated profiles as compared with observed profiles. Direct comparisons between aircraft-measured and model-generated 2a12 microphysics suggest that, on average, the radiometer algorithm's microphysics database retrieves liquid and ice water contents that are approximately 1/3 the size of those observed at levels below 10 km. Also, the 2a12 rain-rate retrievals are shown to be strongly influenced by the 2a12's convective fraction specification. A proposed modification of this factor would improve 2a12 rain-rate retrievals; however, fundamental changes to the cloud radiation model's ice parameterization are necessary to overcome the algorithm's tendency to produce mixed-phase-layer ice hydrometeor deficits.
Freustrated Achievers: Winners, Losers, and Subjective Well-Being in Peru’s Emerging Economy
Authors: Graham Carol , Pettinato Stefano
Published: June 2006

The literature on subjective well-being has focused primarily on the developed economies. The authors provide empirical evidence from a developing country, Peru. Their results—and in particular a strong negative skew in the assessments of the respondents with the greatest income gains—support the importance of relative rather than absolute income differences. Among other factors, they attribute their results to shifts in reference norms and to macroeconomic volatility. Relative differences seem to matter more for those in the middle of the distribution than for the very wealthy or the very poor. Respondents were more critical in assessing their progress vis-à-vis others in their country versus those in their community. The frustrations that the authors find among the upwardly mobile may have implications for the future economic and political behavior of a group that is critical to the sustainability of market policies.
Detecting Heterogeneity in Logistic Regression Models
Authors: Balázs Katalin , Hidegkuti István , De Boeck Paul
Published: June 2006

In the context of item response theory, it is not uncommon that person-by-item data are correlated beyond the correlation that is captured by the model—in other words, there is extra binomial variation. Heterogeneity of the parameters can explain this variation. There is a need for proper statistical methods to indicate possible extra heterogeneity and its location because investigating all different combinations of random parameters is not practical and sometimes even unfeasible. The ignored random person effects are the focus of this study. Considering the random weights linear logistic test model, random effects can occur as a general latent trait and as weights of covariates. A simulation study was conducted with different sources and degrees of heterogeneity to investigate and compare various methods: individual analyses (one per person), marginal modeling, principal component analysis of the raw data, DIMTEST, and DETECT. The methods are illustrated with an application on deductive reasoning.
Analysis of natural killer–cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease
Authors: Marcenaro Stefania , Gallo Federico , Martini Stefania , Santoro Alessandra , Griffiths Gillian M. , Aricó Maurizio , Moretta Lorenzo , Pende Daniela
Published: June 2006

Natural killer (NK) cells from patients with familial hemophagocytic lymphohistiocytosis because of PRF1 (FHL2, n = 5) or MUNC13-4 (FHL3, n = 8) mutations were cultured in IL-2 prior to their use in various functional assays. Here, we report on the surface CD107a expression as a novel rapid tool for identification of patients with Munc13-4 defect. On target interaction and degranulation, FHL3 NK cells displayed low levels of surface CD107a staining, in contrast to healthy control subjects or perforin-deficient NK cells. B-EBV cell lines and dendritic cell targets reveal the FHL3 NK-cell defect, whereas highly susceptible tumor targets were partially lysed by FHL3 NK cells expressing only trace amounts of Munc13-4 protein. Perforin-deficient NK cells were completely devoid of any ability to lyse target cells. Cytokine production induced by mAb-crosslinking of triggering receptors was comparable in patients and healthy control subjects. However, when cytokine production was induced by coculture with 721.221 B-EBV cells, FHL NK cells resulted in high producers, whereas control cells were almost ineffective. This could reflect survival versus elimination of B-EBV cells (ie, the source of NK-cell stimulation) in patients versus healthy control subjects, thus mimicking the pathophysiologic scenario of FHL.
Bacillus subtilis SbcC protein plays an important role in DNA inter-strand cross-link repair
Authors: Mascarenhas Judita , Sanchez Humberto , Tadesse Serkalem , Kidane Dawit , Krisnamurthy Mahalakshmi , Alonso Juan C , Graumann Peter L
Published: June 2006

Background

Several distinct pathways for the repair of damaged DNA exist in all cells. DNA modifications are repaired by base excision or nucleotide excision repair, while DNA double strand breaks (DSBs) can be repaired through direct joining of broken ends (non homologous end joining, NHEJ) or through recombination with the non broken sister chromosome (homologous recombination, HR). Rad50 protein plays an important role in repair of DNA damage in eukaryotic cells, and forms a complex with the Mre11 nuclease. The prokaryotic ortholog of Rad50, SbcC, also forms a complex with a nuclease, SbcD, in Escherichia coli, and has been implicated in the removal of hairpin structures that can arise during DNA replication. Ku protein is a component of the NHEJ pathway in pro- and eukaryotic cells.

Results

A deletion of the sbcC gene rendered Bacillus subtilis cells sensitive to DNA damage caused by Mitomycin C (MMC) or by gamma irradiation. The deletion of the sbcC gene in a recN mutant background increased the sensitivity of the single recN mutant strain. SbcC was also non-epistatic with AddAB (analog of Escherichia coli RecBCD), but epistatic with RecA. A deletion of the ykoV gene encoding the B. subtilis Ku protein in a sbcC mutant strain did not resulted in an increase in sensitivity towards MMC and gamma irradiation, but exacerbated the phenotype of a recN or a recA mutant strain. In exponentially growing cells, SbcC-GFP was present throughout the cells, or as a central focus in rare cases. Upon induction of DNA damage, SbcC formed 1, rarely 2, foci on the nucleoids. Different to RecN protein, which forms repair centers at any location on the nucleoids, SbcC foci mostly co-localized with the DNA polymerase complex. In contrast to this, AddA-GFP or AddB-GFP did not form detectable foci upon addition of MMC.

Conclusion

Our experiments show that SbcC plays an important role in the repair of DNA inter-strand cross-links (induced by MMC), most likely through HR, and suggest that NHEJ via Ku serves as a backup DNA repair system. The cell biological experiments show that SbcC functions in close proximity to the replication machinery, suggesting that SbcC may act on stalled or collapsed replication forks. Our results show that different patterns of localization exist for DNA repair proteins, and that the B. subtilis SMC proteins RecN and SbcC play distinct roles in the repair of DNA damage.
The use of genetic programming in the analysis of quantitative gene expression profiles for identification of nodal status in bladder cancer
Authors: Mitra Anirban P , Almal Arpit A , George Ben , Fry David W , Lenehan Peter F , Pagliarulo Vincenzo , Cote Richard J , Datar Ram H , Worzel William P
Published: June 2006

Background

Previous studies on bladder cancer have shown nodal involvement to be an independent indicator of prognosis and survival. This study aimed at developing an objective method for detection of nodal metastasis from molecular profiles of primary urothelial carcinoma tissues.

Methods

The study included primary bladder tumor tissues from 60 patients across different stages and 5 control tissues of normal urothelium. The entire cohort was divided into training and validation sets comprised of node positive and node negative subjects. Quantitative expression profiling was performed for a panel of 70 genes using standardized competitive RT-PCR and the expression values of the training set samples were run through an iterative machine learning process called genetic programming that employed an N-fold cross validation technique to generate classifier rules of limited complexity. These were then used in a voting algorithm to classify the validation set samples into those associated with or without nodal metastasis.

Results

The generated classifier rules using 70 genes demonstrated 81% accuracy on the validation set when compared to the pathological nodal status. The rules showed a strong predilection for ICAM1, MAP2K6 and KDR resulting in gene expression motifs that cumulatively suggested a pattern ICAM1>MAP2K6>KDR for node positive cases. Additionally, the motifs showed CDK8 to be lower relative to ICAM1, and ANXA5 to be relatively high by itself in node positive tumors. Rules generated using only ICAM1, MAP2K6 and KDR were comparably robust, with a single representative rule producing an accuracy of 90% when used by itself on the validation set, suggesting a crucial role for these genes in nodal metastasis.

Conclusion

Our study demonstrates the use of standardized quantitative gene expression values from primary bladder tumor tissues as inputs in a genetic programming system to generate classifier rules for determining the nodal status. Our method also suggests the involvement of ICAM1, MAP2K6, KDR, CDK8 and ANXA5 in unique mathematical combinations in the progression towards nodal positivity. Further studies are needed to identify more class-specific signatures and confirm the role of these genes in the evolution of nodal metastasis in bladder cancer.
Fluoro-edenitic fibres in the sputum of subjects from Biancavilla (Sicily): a pilot study
Authors: Putzu Maria Grazia , Bruno Caterina , Zona Amerigo , Massiccio Marilena , Pasetto Roberto , Piolatto Pier Giorgio , Comba Pietro
Published: June 2006

Background

An excess of mortality for malignant neoplasms of the pleura in Biancavilla, promoted an investigation for pleural mesothelioma, disclosing 17 cases. As the absence of known sources of asbestos exposure, a local stone quarry, located near the inhabited area, used for the extraction of building materials, was investigated. Amphibolic fibres were found in the quarry and identified as fluoro-edenite "new end-member of the edenite / fluoro-edenite series" and recognized as the fluoro-edenite holotype by International Mineralogical Association – Commission on New Minerals and Mineral Names. A pilot study was performed to verify the feasibility of using spontaneous sputum as an exposure indicator for these fibres, in a context in which the use of aerosol-induced sputum technique would not be easily accepted.

Methods

Hypothesizing a behaviour of the new fibre analogous to that of asbestos, the determination of the free fibres and the ferruginous bodies in spontaneous sputum was carried out. Phase Contrast Optical Microscope and an Environmental Scanning Electron Microscope fitted with X-ray energy dispersive analysis system (micro-analysis) were used to examine the samples. The criteria for inclusion in the study were: 1) subjects hospitalized for exacerbation of chronic obstructive pulmonary disease symptoms, 2) age ≥ 45 years, 3) residence in Biancavilla for at least 30 years.

Results

The preliminary findings are related to 12 subjects (7 females and 5 males). Uncoated fibres (with length > 5 μm, diameter < 3 μm, aspect ratio 3.1) and ferruginous bodies were searched. Six out of twelve subjects (4 females, 2 males) had at least one of the three samples positive for the presence of fluoro-edenite, confirmed by micro-analysis. The fibre concentration found in the sputum ranged from 0.04 to 10 fibres/g; the length from 20 to 40 μm, the diameter was < 0.5 μm.

No ferruginous bodies were found in any of the samples. The four women with a positive sample were housewives. Of the two men with a positive sample, one was a farmer and the other a mason. Therefore, it may be assumed that the exposure to fluoro-edenitic fibres was mainly environmental.

Conclusion

The occurrence of the pleural mesothelioma cases and the presence of fluoro-edenitic fibres in spontaneous sputum, evidence the need to study the biological activity of fluoro-edenitic fibres and the implementation of epidemiological monitoring systems.
Fine needle aspiration cytology of bone tumours--the experience from the National Orthopaedic and Lagos University Teaching Hospitals, Lagos, Nigeria
Authors: Nnodu Obiageli E , Giwa S O , Eyesan Samuel U , Abdulkareem Fatima B
Published: June 2006

Background:

Due to difficulty in confirming clinical suspicions of malignancy in patients presenting with bone tumours, the cost of surgical biopsies where hospital charges are borne almost entirely by patients, competition with bone setters and healing homes with high rate of loss to follow up; we set out to find if sufficient material could be obtained to arrive at reliable tissue diagnosis in patients with clinical and radiological evidence of bone tumours in our hospitals.

Methods:

After initial clinical and plain radiographic examinations, patients were sent for fine needle aspirations. Aspirations were carried out with size 23G needles of varying lengths with 10 ml syringes in a syringe holder (CAMECO, Sebre Medical, Vellinge, Sweden). The aspirates were air dried, stained by the MGG method and examined microscopically. Histology was performed on patients who had subsequent surgical biopsy. These were then correlated with the cytology reports.

Results:

Out of 96 patients evaluated, [57 males, 39 females, Mean age 31.52 years, Age Range 4-76 years,] material sufficient for diagnosis was obtained in 90 patients. Cytological diagnosis of benign lesions was made in 40 patients and malignant in 47. Of these, 27 were metastases, osteogenic sarcoma 16, giant cell tumour 19, infection 11. Histology was obtained in 41 patients. Correct diagnosis of benignity was made in 17 out of 18 cases, malignancy in 21 out of 22 cases. One non-diagnostic case was malignant. The accuracy of specific cytological diagnosis was 36/41 (87.8%) and incorrect in 5/41 (12.2%).

Conclusion:

We conclude that FNAC can be useful in the pre-operative assessment of bone tumours especially where other diagnostic modalities are unavailable.
Community-acquired pneumonia on the intensive care unit: secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database
Authors: Woodhead Mark , Welch Catherine A , Harrison David A , Bellingan Geoff , Ayres Jon G
Published: June 2006

Introduction

This paper describes the case mix, outcome and activity for admissions to intensive care units (ICUs) with community-acquired pneumonia (CAP).

Methods

We conducted a secondary analysis of a high quality clinical database, the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, of 301,871 admissions to 172 adult ICUs across England, Wales and Northern Ireland, 1995 to 2004. Cases of CAP were identified from pneumonia admissions excluding nosocomial pneumonias and the immuno-compromised. It was not possible to review data from the time of hospital admission; therefore, some patients who developed hospital-acquired/nosocomial pneumonia may have been included.

Results

We identified 17,869 cases of CAP (5.9% of all ICU admissions). There was a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to only a 24% rise in total ICU admissions (p < 0.001). Eighty-five percent of admissions were from within the same hospital. Fifty-nine percent of cases were admitted to the ICU <2 days, 21.5% between 2 and 7 days, and 19.5% >7 days after hospital admission. Between 1995 and 1999 and 2000 and 2004 there was a rise in admissions from accident and emergency (14.8% to 16.8%; p < 0.001) and high dependency units (6.9% to 11.9%; p < 0.001) within the same hospital, those aged >74 (18.5 to 26.1%; p < 0.001), and mean APACHE II score (6.83 to 6.91; p < 0.001). There was a fall in past history of severe respiratory problems (8.7% to 6.4%; p < 0.001), renal replacement therapy (1.6% to 1.2%; p < 0.01), steroid treatment (3.4% to 2.8%; p < 0.05), sedation/paralysis (50.2% to 40.4%; p < 0.001), cardiopulmonary resuscitation prior to admission (7.5% to 5.5%; p < 0.001), and septic shock (7.3% to 6.6%; p < 0.001). ICU mortality was 34.9% and ultimate hospital mortality 49.4%. Mortality was 46.3% in those admitted to the ICU within 2 days of hospital admission rising to 50.4% in those admitted at 2 to 7 days and 57.6% in those admitted after 7 days following hospital admission.

Conclusion

CAP makes up a small, but important and rising, proportion of adult ICU admissions. Survival of over half of all cases vindicates the use of ICU facilities in CAP management. Nevertheless, overall mortality remains high, especially in those admitted later in their hospital stay.
Use and Outcomes of Adjuvant Chemotherapy in Older Women With Breast Cancer
Authors: Giordano Sharon H. , Duan Zhigang , Kuo Yong-Fang , Hortobagyi Gabriel N. , Goodwin James S.
Published: June 2006

Purpose

This study was undertaken to determine patterns and outcomes of adjuvant chemotherapy use in a population-based cohort of older women with primary breast cancer.

Patients and Methods

Women were identified from the Surveillance, Epidemiology, and End Results–Medicare-linked database who met the following criteria: age ≥ 65 years, stage I to III breast cancer, and diagnosis between 1991 and 1999. Adjuvant chemotherapy use was ascertained by Common Procedural Terminology J codes. Logistic regression analysis was performed to determine factors associated with chemotherapy use. Multivariate Cox proportional hazards models were used to calculate the hazard of death for women with and without chemotherapy.

Results

A total of 41,390 women met study criteria, of whom 4,500 (10.9%) received chemotherapy. The use of adjuvant chemotherapy more than doubled during the 1990s, from 7.4% in 1991 to 16.3% in 1999 (P < .0001), with a significant shift toward anthracycline use. Women who were younger, white, with lower comorbidity scores, more advanced stage disease, and estrogen receptor (ER) –negative disease were significantly more likely to receive chemotherapy. Chemotherapy was not associated with improved survival among women with lymph node–negative (LN) disease or LN-positive, ER-positive disease (hazard ratio [HR], 1.05; 95% CI, 0.85 to 1.31). However, among women with LN-positive, ER-negative breast cancer, chemotherapy was associated with a significant reduction in breast cancer mortality (HR, 0.72; 95% CI, 0.54 to 0.96). A similar significant benefit of chemotherapy was seen in the subset of women age 70 years or older (HR, 0.74; 95% CI, 0.56 to 0.97).

Conclusion

In this observational cohort, chemotherapy was associated with a significant reduction in mortality among older women with ER-negative, LN-positive breast cancer.
Phase III Trial of Chemotherapy Plus Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402
Authors: Cairncross Gregory , Berkey Brian , Shaw Edward , Jenkins Robert , Scheithauer Bernd , Brachman David , Buckner Jan , Fink Karen , Souhami Luis , Laperierre Normand , Mehta Minesh , Curran Walter
Published: June 2006

Purpose

Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss.

Patients and Methods

Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization.

Results

Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P ≤ .001); longer progression-free survival was most apparent in this subset.

Conclusion

For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.
Detection of Occult Lymph Node Metastases in Locally Advanced Node-Negative Prostate Cancer
Authors: Pagliarulo Vincenzo , Hawes Debra , Brands Frank H. , Groshen Susan , Cai Jie , Stein John P. , Lieskovsky Gary , Skinner Donald G. , Cote Richard J.
Published: June 2006

Purpose

The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation.

Methods

Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN−), and with the 94 N+ patients.

Results

A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN− patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease.

Conclusion

The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.
Phase III Randomized Trial of Very Accelerated Radiation Therapy Compared With Conventional Radiation Therapy in Squamous Cell Head and Neck Cancer: A GORTEC Trial
Authors: Bourhis Jean , Lapeyre Michel , Tortochaux Jacques , Rives Michel , Aghili Mehdi , Bourdin Sylvain , Lesaunier François , Benassi Toufik , Lemanski Claire , Geoffrois Lionel , Lusinchi Antoine , Verrelle Pierre , Bardet Etienne , Julieron Morbize , Wibault Pierre , Luboinski Monique , Benhamou Ellen
Published: June 2006

Purpose

With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC).

Patients and Methods

Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid).

Results

The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a median overall time of 22 days and 48 days, respectively. Acute mucositis was markedly increased in the accelerated-RT arm (P < .001). The locoregional control rate was improved by 24% at 6 years with accelerated RT. In contrast, disease-free survival and overall survival were not significantly different between the two arms. There was no difference in late effects between the two arms.

Conclusion

The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival.
Regulation, Competition, and Liberalization
Authors: Armstrong Mark , Sappington David E. M
Published: June 2006

In many countries throughout the world, regulators are struggling to determine whether and how to introduce competition into regulated industries. This essay examines the complexities involved in the liberalization process. While stressing the importance of case-specific analyses, this essay distinguishes liberalization policies that generally are procompetitive from corresponding anticompetitive liberalization policies.
Purple America
Authors: Ansolabehere Stephen , Rodden Jonathan , Snyder James M
Published: June 2006

America, we are told, is a nation divided. The cartographers who draw up the maps of U.S. election results have branded a new division in American politics: Republican red versus Democratic blue. What is the source of this division? Most observers point not to the bread-and-butter economic issues of the New Deal alignment but to a “culture war.” In this paper, we draw on data from three decades of survey research to see how the electorate divides along economic and moral issues. While showing that moral values are not irrelevant, the survey data roundly reject the basic claims of the culture war thesis: that voters are polarized over moral issues, and this division maps onto important demographic categories like religious affiliation; that moral issues have more salience or weight in the minds of voters than economic issues; and that this division accounts for red and blue cartography (because red-state voters are moral conservatives who vote on moral issues without regard for their economic interests or preferences.) We put issue cleavages and electoral maps into historical perspective and demonstrate that over the course of the twentieth century there has been a noteworthy political convergence between the states. Compared to the past, the political geography of the United States today is purple.
Prognostic value of homocysteinemia in patients with congestive heart failure
Authors: Gibelin Pierre , Serre Stephanie , Candito Mirande , Houcher Bakhouche , Berthier Frederic , Baudouy Marcel
Published: June 2006

Clin Chem Lab Med 2006;44:813–6.
Evaluation and quality assessment of glucose concentration measurement in blood by point-of-care testing devices
Authors: Wehmeier Michael , Arndt Burkhard T. , Schumann Gerhard , Külpmann Wolf R.
Published: June 2006

Clin Chem Lab Med 2006;44:888–93.
Hypothesis on interferences in kinetic interaction of microparticles in solution (KIMS) technology
Authors: Giovanni Nadia De , Fucci Nadia
Published: June 2006

The present paper describes an evaluation of the interferences found with an immunochemical drug test performed during a workplace control. During the period 1993–2003 more than 200,000 urine samples from workers were examined by the Italian Air Force. Samples were screened for drugs of abuse (opiates, cocaine, cannabinoids, amphetamines, methadone) using an immunochemical technique (Roche, kinetic interaction of microparticles in solution, KIMS). A total of 520 positive samples were sent to the Forensic Toxicology Laboratory for confirmation by gas chromatography/mass spectrometry (GC/MS). Approximately 39% of these were found to be true positives. For the remaining samples, pharmacological therapy in subjects was estimated to evaluate possible interferences due to medicine intake. Our study showed a high frequency of false-positive results with this immunochemical technique, mainly for the cannabinoid and amphetamine groups. Recurrent references to some medicines during subject anamnesis were noted.

Clin Chem Lab Med 2006;44;894–7.
Hypoadiponectinemia is associated with symptomatic atherosclerotic peripheral arterial disease
Authors: Dieplinger Benjamin , Poelz Werner , Haltmayer Meinhard , Mueller Thomas
Published: June 2006

There is growing evidence that adiponectin, an adipocytokine with anti-inflammatory and antiathero-genic properties, is involved in the development of atherosclerosis. The aim of the present study was to examine whether serum levels of adiponectin were associated with symptomatic atherosclerotic peripheral arterial disease (PAD). Serum concentrations of adiponectin were measured in 433 patients with symptomatic PAD and 433 controls from the Linz Peripheral Arterial Disease (LIPAD) study. Cases and controls were matched for age, sex and diabetes mellitus. The median serum level of adiponectin was significantly lower in PAD patients than in control subjects (9.5 vs. 10.8mg/L; p=0.014). After adjustment for several possible confounding variables using multivariable logistic regression, odds ratios for symptomatic PAD were 0.95 (95% CI, 0.64–1.42; p=0.080) and 0.59 (95% CI, 0.36–0.97; p=0.037) in the second and third tertiles for adiponectin serum concentrations, respectively, compared with the first tertile. Low serum levels of adiponectin were associated with the presence of symptomatic atherosclerotic PAD, independent of traditional and non-traditional risk factors, suggesting that hypoadiponectinemia may be a marker for systemic atherosclerotic disease.

Clin Chem Lab Med 2006;44:830–3.
Evaluation of clinical markers of atherosclerosis in young and elderly Japanese adults
Authors: Hara Takanobu , Takamura Noboru , Akashi Saori , Nakazato Mio , Maeda Takahiro , Wada Mitsuhiro , Nakashima Kenichiro , Abe Yasuyo , Kusano Yosuke , Aoyagi Kiyoshi
Published: June 2006

Clin Chem Lab Med 2006;44:824–9.
Fluorimetric determination of activity and isoenzyme composition of N-acetyl-β-D-hexosaminidase in seminal plasma of fertile men and infertile patients with secretory azoospermia
Authors: Tassi Carmelo , Angelini Antonio , Beccari Tommaso , Capodicasa Enrico
Published: June 2006

Clin Chem Lab Med 2006;44:843–7.
Incentive Instruments in Fruit and Vegetable Contracts: Input Control, Monitoring, Measuring, and Price Risk
Authors: Hueth Brent , Ligon Ethan , Wolf Steven , Wu Steven
Published: June 2006

This article examines the structure of contractual relations between growers and first handlers in California fruit and vegetable markets. Evidence on existing structures is collected from on‐site interviews and from a small mail survey of market intermediaries who contract with independent growers. Four generic instruments are identified—input control, field visits, quality measurement, and residual price risk—which are used to coordinate relations between growers and first handlers and which help to alleviate information asymmetries and align incentives between contracting parties. Drawing from our interviews and survey, we offer examples of how each of these instruments are employed.
Site‐Specific Crop Management: Adoption Patterns and Incentives
Authors: Khanna Madhu , Epouhe Onesime Faustin , Hornbaker Robert
Published: June 2006

This article examines the current level and likely trends in adoption of a variety of technologies for site‐specific crop management in four north‐central states. It also explores the extent to which farmers are jointly adopting multiple components. Technology adoption theories are applied to rationalize the observed selectivity in adoption. Farmer responses reveal that uncertainty in returns due to adoption, high costs of adoption, and lack of demonstrated effects of the advanced site‐specific technologies on yields and input‐use are some of the major reasons for current low rates of adoption and for the piecemeal approach to site‐specific crop management.
Value‐at‐Risk Analysis: A Review and the Potential for Agricultural Applications
Authors: Manfredo Mark R. , Leuthold Raymond M.
Published: June 2006

Value‐at‐risk (VaR) determines the probability of a portfolio of assets losing a certain amount in a given period at a particular level of confidence. Value‐at‐risk is receiving considerable attention in the finance literature for its use in reporting the risks of derivatives. This article provides a state‐of‐the‐art review of VaR estimation techniques and empirical findings. The ability of VaR estimates to represent large losses varies among procedure, confidence levels, and data used. To date no consensus exists regarding the most appropriate estimation technique. Potential applications of VaR are suggested in the context of agricultural risk management.