bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel hydroxyapatite/niobium surface coating for endodontic dental implant
Authors: Fathi M. H. , Salehi M. , Mortazavi V. , Mousavi S. B. , Parsapour A.
Published: September 2006

Endodontic dental implants have been used for many years. Many materials have been advocated for use as endodontic implants but a few of them have shown biocompatibility and have been acceptable. The aim of this study was to design and produce a novel biomaterial by producing a new surface coating on metallic substrate in order to achieve two goals, namely, an improvement in the corrosion behaviour of metallic endodontic dental implant and the bone osteointegration simultaneously. Stainless steel (SS) 316L was used as the metallic substrate and a novel double layer hydroxyapatite/niobium (HA/Nb) composite coating was prepared on it. X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques were utilised to characterise the coating. Electrochemical tests were performed in physiological solutions in order to determine the corrosion behaviour of the coated and uncoated specimens. Two types of endodontic implants were used, including SS with and without novel HA/Nb coating, which were prepared and subsequently implanted in the mandibular canine of 22 cats after completion of root canal treatment and osseous preparation. After a healing period of 4 months, osteointegration evaluation and histopathological interpretation were carried out using SEM and optical microscopy. In vitro tests indicated that the novel HA/Nb composite coating could improve the corrosion resistance and therefore the biocompatibility of SS endodontic dental implant. The clinical evaluation results showed that the average bone osteointegration of coated implants was more than for uncoated implants. The histopathological results and bone tissue response to the coated endodontic dental implants were acceptable. It can be concluded that HA/Nb composite coated SS could be used as an endodontic dental implant material.
Effect of gas tungsten arc welding process variables on dilution and bead geometry of Stellite 6 hardfaced valve seat rings
Authors: Shanmugam R. , Murugan N.
Published: September 2006

Hardfacing is one of the surfacing methods most widely employed in valve manufacturing industries to deposit Stellite 6, a cobalt based alloy, on low carbon steel valve seat rings to enhance specific properties such as wear and corrosion resistance. Gas tungsten arc welding (GTAW) process is used for hardfacing smaller size valves. The quality of the hardfaced deposits depends on the degree of dilution. The control of dilution will result in better metallurgical and mechanical properties of hardfaced deposits. Mathematical models have been developed in this paper to study the effects of GTAW process parameters on dilution and other important hardfacing parameters, namely, penetration, reinforcement and bead width. Models have been tested for their adequacy by regression methods. The direct and interaction effects are presented in graphical form which can be used not only for the prediction of geometry but also for controlling weld bead quality.
C20 clusters formation by laser ablation of graphite at 308 nm
Authors: Rumianowski R. T. , Płóciennik P.
Published: September 2006

Carbon cluster ions generated by pulsed laser ablation have been analysed by time of flight mass spectrometer. The observed mass spectra showed that the singly charged C20 clusters were obtained.
Commonly dysregulated genes in murine APL cells
Authors: Yuan Wenlin , Payton Jacqueline E. , Holt Matthew S. , Link Daniel C. , Watson Mark A. , DiPersio John F. , Ley Timothy J.
Published: September 2006

To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly expressed in restricted developmental “windows,” suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RARα under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid cells from the same mouse model, suggesting that dysregulation occurs as a “downstream” event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis.
Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model
Authors: Birrell M. A. , McCluskie K. , Hardaker E. , Knowles R. , Belvisi M. G.
Published: September 2006

There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic.

The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of κB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia.

Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway.

The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.
Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children
Authors: Roller C. M. , Zhang G. , Troedson R. G. , Leach C. L. , Le Souëf P. N. , Devadason S. G.
Published: September 2006

The aim of the present study was to measure airway, oropharyngeal and gastrointestinal deposition of99mTc-labelled hydrofluoroalkane-beclomethasone dipropionate after inhalationviaa pressurised metered-dose inhaler and spacer (Aerochamber PlusTM) in asthmatic children.

A group of 24 children (aged 5–17 yrs) with mild asthma inhaled the labelled drug. A total of 12 children took five tidal breaths after each actuation (tidal group). The other 12 children used a slow maximal inhalation followed by a 5–10-s breath-hold (breath-hold group). Simultaneous anterior and posterior planar γ-scintigraphic scans (120-s acquisition) were recorded.

For the tidal group, mean±sdlung deposition (% ex-actuator, attenuation corrected) was 35.4±18.3, 47.5±13.0 and 54.9±11.2 in patients aged 5–7 (n = 4), 8–10 (n = 4) and 11–17 yrs (n = 4), respectively. Oropharyngeal and gastrointestinal deposition was 24.0±10.5, 10.3±4.4 and 10.1±6.2. With the breath-hold technique, lung deposition was 58.1±6.7, 56.6±5.2 and 58.4±9.2. Oropharyngeal and gastrointestinal deposition was 12.9±3.2, 20.1±9.5 and 20.8±8.8.

Inhalation of the extrafine formulation with the breath-hold technique showed significantly improved lung deposition compared with tidal breathing across all ages. Oropharyngeal and gastrointestinal deposition was markedly decreased, regardless of which inhalation technique was applied, compared with a previous paediatric study using the same formulation deliveredviaa breath-actuated metered-dose inhaler.
Transbronchial needle aspirates: how many passes per target site?
Authors: Diacon A. H. , Schuurmans M. M. , Theron J. , Brundyn K. , Louw M. , Wright C. A. , Bolliger C. T.
Published: September 2006

Transbronchial needle aspiration is a bronchoscopic sampling method for a variety of bronchial and pulmonary lesions. The present study investigated whether and how serial needle passes contribute to the yield of transbronchial needle aspiration at specific target sites.

A total of 1,562 needle passes, performed at 374 target sites in 245 patients with neoplastic disease (82%), non-neoplastic disease (15%) or undiagnosed lesions (3%), were prospectively recorded and rated for anatomical location, size, bronchoscopic appearance and underlying disease.

Positive aspirates were obtained in 75% of patients and at 68% of target sites. A diagnosis was established with the first, second, third and fourth needle pass at 64, 87, 95 and 98% of targets, respectively. The absolute yield varied strongly with target site features, but the stepwise increment to the maximum yield provided by serial passes was similar across target sites.

In conclusion, three transbronchial needle passes per site are appropriate when only a tissue diagnosis is sought and when alternative sites or sampling modalities are available. At least four or five passes should be carried out at lymph node stations critical for the staging of lung cancer.
Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?
Authors: Chang K. C. , Leung C. C. , Yew W. W. , Tam C. M.
Published: September 2006

A nested case–control study was conducted in order to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment (standard treatment) might affect hepatotoxicity.

The present authors retrospectively identified all patients with hepatitis using biochemical criteria from a cohort of 3,007 clinic patients who commenced anti-TB treatment from January 1 to June 30, 2001. Each case with hepatitis between 1–9 weeks post-TB treatment was compared using conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by sex, age and standard treatment. Impacts of sex and age were examined by logistic regression analysis of cases and patients without hepatitis.

Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional logistic risk model identified hepatitis B surface antigen carriage as the only risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1–3.1)). Logistic regression analysis showed that sex was nonsignificant but ageing increased the odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9–3.5%) to 4.1% (3.2–5.3%) as age exceeded 49 yrs.

Dosing schedules in the first 9 weeks have little impact on hepatotoxicity. If patients at risk of both hepatitis and relapse receive standard treatment, daily dosing is preferable.
Inhibitory effects of repeated hyperoxia on breathing in newborn mice
Authors: Lofaso F. , Dauger S. , Matrot B. , Vardon G. , Gaultier C. , Gallego J.
Published: September 2006

Brief oxygen therapy is commonly used for resuscitation at birth or prevention of hypoxaemia before procedures during the neonatal period. However, O2may severely depress breathing, especially when administered repeatedly. The aim of the present study was to test the effects of repeated hyperoxia on breathing control in newborn mice.

A total of 97 Swiss mouse pups were assigned to O2or air on post-natal day 0, 1 or 2. Each pup in the O2group was subjected to four hyperoxic tests (100% O2for 3 min followed by 12 min normoxia), whereas pups in the air group were maintained in normoxia. Breathing variables were measured using flow-through barometric plethysmography.

O2significantly decreased minute ventilation as seen in a decrease in respiratory rate. This decrease became significantly larger with repeated exposure and ranged -17– -26% for all ages combined. Furthermore, hyperoxia increased total apnoea duration, as compared with the baseline value.

In newborn mice, repeated hyperoxia increasingly depressed breathing. This finding further supports a need for stringent control of oxygen therapy, most notably repeated oxygen administration in the neonatal period for premature newborn infants and those carried to term.
Identification and characterization of the heme-binding proteins SeShp and SeHtsA of Streptococcus equi subspecies equi
Authors: Nygaard Tyler K , Liu Mengyao , McClure Michael J , Lei Benfang
Published: September 2006

Background

Heme is a preferred iron source of bacterial pathogens.Streptococcus equisubspeciesequiis a bacterial pathogen that causes strangles in horses. WhetherS. equihas a heme acquisition transporter is unknown.

Results

AnS. equigenome database was blasted with the heme binding proteins Shp and HtsA ofStreptococcus pyogenes, and found thatS. equihas the homologue of Shp (designated SeShp) and HtsA (designated SeHtsA). Tag-free recombinant SeShp and SeHtsA and 6xHis-tagged SeHtsA (SeHtsAHis) were prepared and characterized. Purified holoSeShp and holoSeHtsA bind Fe(II)-protoporphyrin IX (heme) and Fe(III)-protoporphyrin IX (hemin) in a 1:1 stoichiometry, respectively, and are designated hemoSeShp and hemiSeHtsA. HemiSeShp and hemiSeHtsAHiscan be reconstituted from apoSeShp and apoSeHtsAHisand hemin. HemoSeShp is stable in air and can be oxidized to hemiSeShp by ferricyanide. HemiSeHtsA can be reduced into hemoSeHtsA, which autoxidizes readily. HemoSeShp rapidly transfers its heme to apoSeHtsAHis. In addition, hemoSeShp can also transfer its heme to apoHtsA, and hemoShp is able to donate heme to apoSeHtsAHis.

Conclusion

The primary structures, optical properties, oxidative stability, and in vitro heme transfer reaction of SeShp and SeHtsA are very similar to those ofS. pyogenesShp and HtsA. The data suggest that the putative cell surface protein SeShp and lipoprotein SeHtsA are part of the machinery to acquire heme inS. equi. The results also imply that the structure, function, and functional mechanism of the heme acquisition machinery are conserved inS. equiandS. pyogenes.
Endovascular control of haemorrhagic urological emergencies: an observational study
Authors: Somani Bhaskar K , Nabi Ghulam , Thorpe Peter , McClinton Sam
Published: September 2006

Background

Transarterial embolisation (TAE) is an effective method in control of haemorrhage irrespective of the nature of urological emergency. As the technique and technology have evolved, it is now possible to perform highly selective embolisation. The aim of this study was to critically appraise feasibility and efficacy of therapeutic TAE in control of haemorrhagic urological emergencies using selective and non-selective embolisation. Specifically, we aimed to assess the impact of timing of embolisation on the requirement of blood transfusion and long-term morphological and functional follow-up of embolised organs.

Methods

This is a single institutional observational study carried out between March 1992 and March 2006. Records of all patients who underwent selective and non-selective angioembolisation to control bleeding in urological emergencies were reviewed. Data on success rate, periprocedural complications, timing of embolisation, requirement of blood transfusion and the long-term morphological and functional outcomes of embolised organs was recorded.

Results

Fourteen patients underwent endovascular control of bleeding as a result of trauma, iatrogenic injury and spontaneous perinephric haemorrhage during a period of 14 years. All these patients would have required emergency open surgery without the option of embolisation procedure. The mean time between the first presentation and embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation transfusion requirement was 6.8 units (range 0–22 units). None of the patients with successful embolisation required post-procedural blood transfusion. Permanent haemostasis was achieved in all but one patient, who required emergency nephrectomy. There were no serious procedure related post-embolisation complications.

Conclusion

Endovascular control using transarterial angioembolisation is an effective method for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated, this option should be considered early in the management of these cases.
The impact of a decision aid about heart disease prevention on patients' discussions with their doctor and their plans for prevention: a pilot randomized trial
Authors: Sheridan Stacey L , Shadle John , Simpson Ross J , Pignone Michael P
Published: September 2006

Background

Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention.

Methods

We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor.

Results

We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0–5%, 25% a risk of 6–10%, 24% a risk of 11–20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions).

Conclusion

Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD.

Trial Registration: ClinicalTrials.gov NCT00315978
Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits
Authors: Luengo Gimeno Federico , Gatto Silvia , Ferro José , Croxatto Juan Oscar , Gallo Juan Eduardo
Published: September 2006

Purpose

Platelet-rich plasma (PRP) is an autologous substance with adhesive properties. We aimed at developing and testing the efficacy of a method for PRP preparation in rabbits.

Materials and methods

An in vitro study was carried out to obtain PRP from forty rabbits and to analyze the number of platelets and type of substance needed to trigger platelet activation. To induce platelet activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal graft. A control group made up of six rabbits underwent corneal transplantation without using PRP.

Results

5% CaCl was the most effective concentration in activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen 3 months after surgery. A detached corneal button was seen in all controls.

Conclusion

Our method was able to produce rabbit-derived PRP with suitable properties for soft tissue adhesion. These results could be useful for researchers of the growing fields of tissue repair and experimental transplantation.
CD97 neutralisation increases resistance to collagen-induced arthritis in mice
Authors: Kop Else N , Adriaansen Janik , Smeets Tom JM , Vervoordeldonk Margriet J , van Lier René AW , Hamann Jörg , Tak Paul P
Published: September 2006

Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and α5β1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis.
Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling
Authors: Lasunskaia Elena B , Campos Mariana N N , de Andrade Marcelle R M , DaMatta Renato A , Kipnis Thereza L , Einicker-Lamas Marcelo , Da Silva Wilmar D
Published: September 2006

Macrophage migration and adhesion are important for the control of mycobacterial infection and are critically dependent on the reorganization of the cytoskeleton. Mycobacteria elicit rapid morphological changes, such as cell spreading, a process relevant to in vivo changes of macrophage shape during extravasation and migration. In this study, we investigated the BCG mycobacteria-induced signaling events leading to macrophage cytoskeletal rearrangements employing specific pharmacological inhibitors to suppress distinct kinase pathways known to be elicited by infection. Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods, which impart radial spreading within 3 h, leading later to persistent cell polarization. BCG induced rapid activation of phosphatidylinositol 3-kinase, PI3K, activation that was recruited to the activated TLR2 receptor. TLR2- neutralizing antibody inhibited macrophage spreading and PI3K activation induced by p19. Additionally, BCG induced spreading and polarization of bone marrow-derived macrophages from TLR2- expressing mice in contrast to their TLR2-knockout counterparts. Neither MEK1/ERK, p38 MAPK, nor NF-κB activation were important for the early cytoskeletal rearrangements observed, although suppression of these pathways is known to inhibit chemokine secretion by activated macrophages. Β2-integrins blockade with a corresponding antibody inhibited macrophage spreading and polarization but had no effect on pseudopodia protrusions demonstrating the downstream position of integrin-mediated adhesion in PI3K- dependent signaling pathway leading to the motility phenotype. The obtained data demonstrate that the direct effect of mycobacteria on macrophage shape might be mediated through TLR2-dependent PI3K activation.
Genomic Prediction of Locoregional Recurrence After Mastectomy in Breast Cancer
Authors: Cheng Skye H. , Horng Cheng-Fang , West Mike , Huang Erich , Pittman Jennifer , Tsou Mei-Hua , Dressman Holly , Chen Chii-Ming , Tsai Stella Y. , Jian James J. , Liu Mei-Chin , Nevins Joseph R. , Huang Andrew T.
Published: September 2006

Purpose

This study aims to explore gene expression profiles that are associated with locoregional (LR) recurrence in breast cancer after mastectomy.

Patients and Methods

A total of 94 breast cancer patients who underwent mastectomy between 1990 and 2001 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patient should have no evidence of LR recurrence without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n = 67) and any LR recurrence (n = 27). They were randomly split into training and validation sets. Statistical classification tree analysis and proportional hazards models were developed to identify and validate gene expression profiles that relate to LR recurrence.

Results

Our study demonstrates two sets of gene expression profiles (one with 258 genes and the other 34 genes) to be of predictive value with respect to LR recurrence. The overall accuracy of the prediction tree model in validation sets is estimated 75% to 78%. Of patients in validation data set, the 3-year LR control rate with predictive index more than 0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or less is 40% (P = .008). Multivariate analysis of all patients reveals that estrogen receptor and genomic predictive index are independent prognostic factors that affect LR control.

Conclusion

Using gene expression profiles to develop prediction tree models effectively identifies breast cancer patients who are at higher risk for LR recurrence. This gene expression–based predictive index can be used to select patients for PMRT.
Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database
Authors: Govindan Ramaswamy , Page Nathan , Morgensztern Daniel , Read William , Tierney Ryan , Vlahiotis Anna , Spitznagel Edward L. , Piccirillo Jay
Published: September 2006

Purpose

Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer with a distinct biology and clinical course. It has been observed that the incidence of SCLC has been decreasing over the last several years.

Methods

We used the Surveillance, Epidemiologic, and End Results (SEER) database to determine the incidence of SCLC over the last 30 years. In addition, we sought to determine sex- and stage-based differences in the incidence and survival of SCLC among a proportion of reported cases of lung cancer over the last 30 years (1973 to 2002). Joinpoint analyses were applied to test the trends in annual percentage change for statistical significance.

Results

The proportion of SCLC (among all lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of all patients with SCLC, the proportion of women with SCLC increased from 28% in 1973% to 50% in 2002. A modest but statistically significant improvement in 2- and 5-year survival was noted among both limited-stage SCLC and extensive-stage SCLC cohorts during the study period.

Conclusion

Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.
Clinical and Pharmacologic Study of the Farnesyltransferase Inhibitor Tipifarnib in Cancer Patients With Normal or Mildly or Moderately Impaired Hepatic Function
Authors: Siegel-Lakhai Wandena S. , Crul Mirjam , De Porre Peter , Zhang Steven , Chang Ilsung , Boot Henk , Beijnen Jos H. , Schellens Jan H.M.
Published: September 2006

Purpose

This study explored the feasibility of treating patients with impaired hepatic function with tipifarnib. The safety profile, pharmacokinetics, and relationship between the pharmacokinetics and toxicities were evaluated.

Patients and Methods

Patients with mildly or moderately impaired hepatic function (Child-Pugh classification) were treated with tipifarnib bid on days 1 to 5 of cycle 1. Further dosing was based on the individual day 5 pharmacokinetic data and absolute neutrophil count. For patients with normal hepatic function, tipifarnib was dosed on days 1 to 14, followed by 1 week of rest. For all patients, in subsequent cycles, tipifarnib was administered for 21 consecutive days out of every 28 days.

Results

Twenty-eight patients were included in the normal (n = 16), mild (n = 9), and moderate (n = 3) impairment groups. The most important grade 3 to 4 hematologic toxicity was leukocytopenia/neutropenia, which was mostly observed in patients with moderate impairment. Common nonhematologic toxicities were fatigue, nausea, and vomiting. The pharmacokinetic data showed higher plasma concentrations of tipifarnib in patients with liver impairment compared with patients with normal hepatic function.

Conclusion

In patients with mildly impaired hepatic function, tipifarnib can be administered safely at a starting dose of 200 mg bid, but it is not safe to treat patients with moderate hepatic impairment.
Long-Term Follow-Up of High-Dose Methotrexate-Based Therapy With and Without Whole Brain Irradiation for Newly Diagnosed Primary CNS Lymphoma
Authors: Gavrilovic Igor T. , Hormigo Adília , Yahalom Joachim , DeAngelis Lisa M. , Abrey Lauren E.
Published: September 2006

Purpose

We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity.

Patients and Methods

Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations.

Results

The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy.

Conclusion

Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.
Preoperative Radiotherapy With or Without Concurrent Fluorouracil and Leucovorin in T3-4 Rectal Cancers: Results of FFCD 9203
Authors: Gérard Jean-Pierre , Conroy Thierry , Bonnetain Franck , Bouché Olivier , Chapet Olivier , Closon-Dejardin Marie-Thérèse , Untereiner Michel , Leduc Bernard , Francois Éric , Maurel Jean , Seitz Jean-François , Buecher Bruno , Mackiewicz Rémy , Ducreux Michel , Bedenne Laurent
Published: September 2006

Purpose

In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy.

Patients and Methods

Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival.

Results

A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ.

Conclusion

Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.
Early Response Evaluation in Malignant Pleural Mesothelioma by Positron Emission Tomography With [18F]Fluorodeoxyglucose
Authors: Ceresoli Giovanni L. , Chiti Arturo , Zucali Paolo A. , Rodari Marcello , Lutman Romano F. , Salamina Silvia , Incarbone Matteo , Alloisio Marco , Santoro Armando
Published: September 2006

Purpose

Response evaluation with conventional criteria based on computed tomography (CT) is particularly challenging in malignant pleural mesothelioma (MPM) due to its diffuse pattern of growth. There is growing evidence that therapy-induced changes in tumor [18F]fluorodeoxyglucose (FDG) uptake as measured by positron emission tomography (PET) may predict response and patient outcome early in the course of treatment.

Patients and Methods

Patients with histologically proven MPM, not candidates to curative surgery, scheduled to undergo palliative chemotherapy with a pemetrexed-based regimen were eligible for this study. Patients were evaluated by FDG-PET and CT at baseline and after two cycles of therapy. A decrease of 25% or more in tumor FDG uptake as measured by standardized uptake value was defined as a metabolic response (MR). Best overall response from CT scans was determined according to previously published criteria.

Results

Twenty-two patients were included in the study, and 20 were assessable for early metabolic response with FDG-PET. Of these, eight were classified as responders (40%) and 12 as nonresponders (60%). Early MR was significantly correlated to median time-to-tumor progression (TTP) with a median TTP for metabolic responders of 14 months versus 7 months for nonresponders (P = .02). No correlation was found between TTP and radiologic response evaluated by CT. Patients with a MR had a trend toward longer overall survival.

Conclusion

The use of MR evaluated by FDG-PET in the assessment of treatment efficacy in MPM appears promising. Our observations need to be validated in a larger prospective series.
Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia
Authors: Shanafelt Tait D. , Witzig Thomas E. , Fink Stephanie R. , Jenkins Robert B. , Paternoster Sarah F. , Smoley Stephanie A. , Stockero Kimberly J. , Nast Danielle M. , Flynn Heather C. , Tschumper Renee C. , Geyer Susan , Zent Clive S. , Call Tim G. , Jelinek Diane F. , Kay Neil E. , Dewald Gordon W.
Published: September 2006

Purpose

Retrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH.

Patients and Methods

Between 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/I) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years.

Results

Chromosomal abnormalities detected by FISH at study entry predicted overall survival. Eighteen patients experienced clonal evolution during follow-up. The rate of clonal evolution increased with duration of follow-up with only one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63; 27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of ZAP-70–negative and 42% of ZAP-70–positive patients at 5+ years (P = .008).

Conclusion

This clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.
Characterization and function of the bHLH-O protein XHes2: insight into the mechanisms controlling retinal cell fate decision
Authors: Sölter Marion , Locker Morgane , Boy Sébastien , Taelman Vincent , Bellefroid Eric J. , Perron Muriel , Pieler Tomas
Published: September 2006

Neurons and glial cells differentiate from common multipotent precursors in the vertebrate retina. We have identified a novel member of the hairy/Enhancer of split [E(spl)] gene family in Xenopus,XHes2, as a regulator to bias retinal precursor cells towards a glial fate. XHes2 expression is predominantly restricted to sensory organ territories, including the retina. Using in vivo lipofection in the optic vesicle, we found that XHes2 overexpression dramatically increases gliogenesis at the expense of neurogenesis. This increase in glial cells correlates with a delayed cell cycle withdrawal of some retinal progenitors. In addition, birthdating experiments suggest that XHes2 deviates some early born cell types towards a glial fate that would normally have given rise to neurons. Conversely, a significant inhibition of glial differentiation is observed upon XHes2 loss of function. The gliogenic activity of XHes2 relies on its ability to inhibit neuronal differentiation by at least two distinct mechanisms: it not only negatively regulates XNgnr1 and NeuroD transcription, but it also physically interacts with a subset of proneural bHLH proteins.
The bHLH transcription factorhand2is essential for noradrenergic differentiation of sympathetic neurons
Authors: Lucas Marsha E. , Müller Frank , Rüdiger Roland , Henion Paul D. , Rohrer Hermann
Published: September 2006

The basic helix-loop-helix transcription factor Hand2, together with Ascl1, Phox2a, Phox2b and Gata2/Gata3, is induced by bone morphogenetic proteins in neural crest-derived precursor cells during sympathetic neuron generation. Hand2 overexpression experiments and the analysis of its function at the Dbh promotor implicated Hand2 in the control of noradrenergic gene expression. Using the zebrafish hand2deletion mutant hands off, we have now investigated the physiological role of hand2 in the development of sympathetic ganglia. In hands off mutant embryos, sympathetic precursor cells aggregate to form normal sympathetic ganglion primordia characterized by the expression of phox2b,phox2a and the achaete-scute family member zash1a/ascl1. The expression of the noradrenergic marker genes th and dbh is strongly reduced, as well as the transcription factors gata2 and tfap2a (Ap-2α). By contrast, generic neuronal differentiation seems to be unaffected, as the expression of elavl3(HuC) is not reduced in hands off sympathetic ganglia. These results demonstrate in vivo an essential and selective function of hand2 for the noradrenergic differentiation of sympathetic neurons,and implicates tfap2a and gata2 as downstream effectors.
Adsorptive Removal of Pb(II) Ions from Aqueous Solution Using a Coir-Based Product (Puresorbe)
Authors: Nityanandi D. , Subbhuraam C.V.
Published: September 2006

The effectiveness of Pb(II) ion removal from wastewater by adsorption methods has made this an ideal alternative to other expensive treatment options. This paper describes an investigation using a coir-based adsorbent (Puresorbe) for the removal of Pb(II) ions from aqueous solution. The adsorption of Pb(II) ions was studied varying parameters such as the agitation time, the metal ion concentration, the adsorbent dose, the temperature and the pH of the aqueous solution. The experimental isotherm data were analyzed using the Langmuir, Freundlich, Dubinin–Radushkevich (D–R) and Tempkin isotherms. For a particle size of 250–500 μm at pH 3.0, the adsorption process followed second-order kinetics. The monolayer adsorption capacity at 30°C was 55.81 mg Pb(II) ion/g Puresorbe. The thermodynamic parameters showed the endothermic nature of Pb(II) ion adsorption. Desorption studies carried out using distilled water adjusted to a pH value of 2.0–7.0 suggested that the adsorption mode could be ion exchange. As the adsorbent raw material is discarded as waste during coir processing, usage of this material is expected to be economically viable.
Adsorption and Migration of Poly(Vinyl Pyrrolidone) at a Fumed Silica Surface
Authors: Gun'ko V.M. , Voronin E.F. , Nosach L.V. , Pakhlov E.M. , Guzenko N.V. , Leboda R. , Skubiszewska-Zięba J.
Published: September 2006

A series of poly(vinyl pyrrolidone) (PVP)/fumed silica powder samples were studied using adsorption, FT-IR and AFM methods. Mild treatment (293 K for several hours) of PVP/A-300 powder with an added additional portion of A-300 in a glass reactor (2 dm3) using a mixer (> 500 rpm which provided the powder as a pseudo-liquid state, PLS) led to the redistribution (migration) of the PVP molecules between silica particles previously covered by PVP and free of PVP. This time-dependent rearrangement of the adsorbed PVP molecules caused the formation of a denser polymer layer at the silica surface. The aggregate size of the primary silica particles with adsorbed PVP molecules decreased after treatment. The volume of macropores with a pore radius Rp > 25 nm increased due to the decrease in the distances between aggregates in agglomerates because of the adhesive effect of the PVP molecules. However, the volume of micropores at Rp < 1 nm decreased because of the penetration of the PVP molecules into the primary silica particle aggregates and the filling of gaps between adjacent particles. A decrease occurred in the amount of adsorbed water in the PVP layer exhibiting a maximum density.
Adsorption Kinetics for the Removal of Nitrite Ions from Aqueous Solutions by an Ion-Exchange Resin
Authors: Kobya Mehmet , Demirbaş Erhan , Yeşilot Serkan , Başkaya Ruhtan
Published: September 2006

The adsorption kinetics of nitrite ions in aqueous solutions onto an anion-exchange resin A-250 was explored in a well-stirred tank. The capacity of the ion-exchange resin for the removal of nitrite ions from aqueous solution was investigated under different conditions, viz. initial concentration (10–50 mg/l), pH (2–8), particle size (565–850 μm) and resin dosage (2–8 g/l). A number of kinetic models such as those of external and intraparticle diffusion were applied to the results from this study in order to identify the adsorption mechanism.

The results correlated well with the intraparticle diffusion model. The experimental parameters had an effect on the effective pore and surface diffusivities. Adsorption of nitrite ions onto the resin showed that the latter could be used as an efficient adsorbent material for the removal of nitrite ions from aqueous solutions.
The cytologic diagnosis of primary bronchogenic carcinoma
Authors: O'Keefe John J.
Published: September 2006

SUMMARY. Primary bronchogenic carcinoma is reviewed. A summation of its characteristics is presented, and the generally accepted methods of diagnosis are examined. The most recently developed diagnostic procedure, cytologic study of bronchoscopically removed secretions, is clinically evaluated

An effort is made to show that this method is efficient in obtaining a positive diagnosis of lung cancer in a large percentage of cases, and that it adds an appreciable margin of positive results in otherwise negative cases

Further, it is shown that diagnoses obtained before bronchial deformities occur increase the possibility of operability and indicate a more favorable prognosis
Role of the Single Assessment Process in the Care of Older People. How Will Primary Dental Care Practitioners be Involved?
Authors: Lane Elizabeth A , Gallagher Jennifer E
Published: September 2006

Following the publication of the National Service Framework for Older People, there have been developments across health and social care to facilitate holistic assessment of older people's needs, through what is called a ‘single assessment process’ or ‘SAP’. In this paper, readers are introduced to the SAP. The process can be seen as a ‘one-stop’ approach to the assessment of vulnerable older people that facilitates cross-referral between the agencies involved and triggers access to dental care. The paper explores the benefits of this new way of working in support of older people and how it will provide an opportunity for innovative dental practitioners to integrate oral healthcare for people with complex health and social care needs into the SAP. In concludes that as local commissioning evolves, opportunities for practitioners to develop targeted services for this important patient group should be expanded to improve the uptake of healthcare and oral healthcare.
Developing identities and attitudes in musicians and classroom music teachers
Authors: Hargreaves David J. , Purves Ross M. , Welch Graham F. , Marshall Nigel A.
Published: September 2006

Background.The Western classical training of many secondary music specialist teachers may be inappropriate for the demands of the contemporary secondary school classroom, leading to a conflict between their self‐concepts as ‘musicians’ and as ‘teachers’.

Aims.To undertake a short‐term longitudinal comparison of the developing identities and the attitudes of a group of intending specialist secondary music teachers, during the transition into their first teaching post, with a group of music students from university and conservatory backgrounds.

Sample.Twenty‐nine trainee music teachers completed Phases 1 and 2 of the study during their final weeks of training and during the second term of their teaching career, and a comparison group of 29 final‐year undergraduate music students did so in the first and last terms of their final year.

Method.A specially devised composite Musical Careers Questionnaire gathered information in both phases about self‐efficacy in music and in teaching, identification with professional groups in these two domains, and attitudes towards important skills for musicians and teachers.

Results.A series of ANOVAs comparing the student groups' scores in each of the two phases revealed no significant main effects or interactions for either of the self‐efficacy measures, a significant group effect for professional group identification, and some changes in the attitude measures.

Conclusion.Although participants' views of their own general effectiveness as teachers and as musicians changed very little over the period of the study, their attitudes towards music teaching and perceptions of the skills required showed some changes.