bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of the blastic transformation of chronic granulocytic leukemia using high dose BCNU chemotherapy and cryopreserved autologous peripheral blood stem cells
Authors: Karp Daniel D. , Parker Leroy M. , Binder Neil , Tantravahi Ramana , Smith Brian R. , Ervin Thomas J. , Canellos George P.
Published: October 2008

Seven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11–46 months prior to use. Patients received 2.9 × 108 (1.9–7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic CGL.
Anomalous neutrophil granule distribution in a patient with lactoferrin deficiency: Pertinence to the respiratory burst
Authors: Borregaard Niels , Boxer Laurence A. , Smolen James E. , Tauber Alfred I.
Published: October 2008

Neutrophils from a patient with lactoferrin deficiency were examined and the quantity and subcellular localization of protein markers were determined on Percoll density gradients. Distribution of azurophilic and specific granule markers was abnormal in that azurophilic granules were lighter than normal and appeared in the fraction of the gradient where normally the specific granules sediment. The specific granule membrane markers, cytochrome b‐235 and its associated flavoprotein, were abnormally distributed in the γ fraction, the site of the plasma membrane marker alkaline phosphatase. Thus, the b‐cytochrome‐flavoprotein complex had either been incorporated into the plasma membrane or was still present in the membranes of granules that were abnormally light and cosedimented with the plasma membranes. This is of particular interest in regard to the patient's respiratory burst oxidase function, since the b‐cytochrome/flavoprotein complex normally translocates from the specific granules to the plasma membrane to constitute the active respiratory burst oxidase. The functional consequences of this abnormal distribution are discussed, as is the importance of characterizing both intragranular enzymatic markers and granule membrane proteins to define granular disorders.
Pseudothrombocytopenia masking true thrombocytopenia
Authors: Forscher C. A. , Sussman I. I. , Friedman E. W. , Solomon V. , Spaet T. H.
Published: October 2008

Pseudothrombocytopenia owing to platelet clumping is usually associated with blood specimens anticoagulated with EDTA. It may also be seen if spcimens possessing IgM cold agglutinins are processed at room temperature. A patient with a temperature‐independent, EDTA‐independent agglutinin is reported whose pseudothrombocytopenia was masking true thrombocytopenia. A technique for blood collection when evaluating similar cases is described.
Heparin‐mediated neutralization of platelet antiaggregatory activity of prostacyclin (PGI2): Studies on mechanism
Authors: Saba Sabiha R. , Saba Hussain I.
Published: October 2008

Prostacyclin (PGI2) is a well‐known potent inhibitor of platelet aggregation. Its role has been implicated in physiological and pathological states of hemostasis. Heparin blocks the prostacyclin‐mediated antiaggregatory activity on platelets. Prior treatment of heparin with heparinase as well as with protamine destroyed heparin's ability to neutralize PGI2. Studies on the mechanism of heparin blocking of PGI2 activity suggested that heparin interacted directly with PGI2, as shown by the loss of PGI2 mobility on thin layer chromatography concomitant with the loss of PGI2‐mediated inhibition of platelet aggregation. PGI2 in this combination with heparin, nevertheless, retained its time‐dependent ability to be hydrolyzed to 6‐keto‐PGF1α. Findings of these studies may have implications in thrombosis and hemostasis, particularly in heparin‐mediated abnormalities of circulating platelets.
Case report: 1‐deamino‐8‐D‐arginine vasopressin and cryoprecipitate in variant von Willebrand disease
Authors: Hanna Wahid T. , Slywka Joseph , Dent Judith , Ruggeri Zaverio M. , Zimmerman Theodore S.
Published: October 2008

The effect of infusing DDAVP and cryoprecipitate either singly or in combination was studied in a patient with variant von Willebrand disease. Both DDAVP and cryoprecipitate caused only partial correction in the hemostatic defect when used as a single agent. A combination of DDAVP and cryoprecipitate induced a complete correction of the hemostatic defect as well as factor VIII related properties.
Contiguous gene syndrome due to a maternally inherited 8.41 Mb distal deletion of chromosome band Xp22.3 in a boy with short stature, ichthyosis, epilepsy, mental retardation, cerebral cortical heterotopias and Dandy–Walker malformation
Authors: van Steensel M.A.M. , Vreeburg M. , Engelen J. , Ghesquiere S. , Stegmann A.P.A. , Herbergs J. , van Lent J. , Smeets B. , Vles J.H.
Published: October 2008

Microdeletions of Xp22.3 are associated with contiguous gene syndromes, the extent and nature of which depend on the genes encompassed by the deletion. Common symptoms include ichthyosis, mental retardation and hypogonadism. We report on a boy with short stature, ichthyosis, severe mental retardation, cortical heterotopias and Dandy–Walker malformation. The latter two abnormalities have so far not been reported in terminal Xp deletions. MLPA showed deletion of SHOX and subsequent analysis using FISH and SNP‐arrays revealed that the patient had an 8.41 Mb distal deletion of chromosome region Xp22.31 → Xpter. This interval contains several genes whose deletion can partly explain our patient's phenotype. His cortical heterotopias and DWM suggest that a gene involved in brain development may be in the deleted interval, but we found no immediately obvious candidates. Interestingly, further analysis of the family revealed that the patient had inherited his deletion from his mother, who has a mos 46,X,del(X)(p22)/45,X/46, XX karyotype. © 2008 Wiley‐Liss, Inc.
Microcephaly, malformation of brain development and intracranial calcification in sibs: Pseudo‐TORCH or a new syndrome
Authors: Abdel‐Salam Ghada M.H. , Zaki Maha S. , Saleem Sahar N. , Gaber Khaled R.
Published: October 2008

We report on five sibs affected by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving and micrognathia. Generalized tonic‐clonic seizures started very early in life. Postnatal brain computerized tomography (CT) presented cortical band‐like calcification, calcification of basal ganglia and brain stem while brain magnetic resonance imaging (MRI) revealed abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, hypogenesis of corpus callosum and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton were found to be associated with this syndrome. Fetal Magnetic resonance imaging helped reaching the diagnosis in utero in one patient. Three patients died in the first years of life while the others within days after birth preceded by high fever and status epilepticus. These patients present many overlapping features with pseudo TORCH syndrome, however, the imaging findings are quite different. We propose that the distinct pattern in these sibs constitutes genetic disorder of microcephaly, developmental brain malformation and intracranial calcification of likely autosomal recessive inheritance. © 2008 Wiley‐Liss, Inc.
Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria
Authors: Lee Phillip , Treacy Eileen P. , Crombez Eric , Wasserstein Melissa , Waber Lewis , Wolff Jon , Wendel Udo , Dorenbaum Alex , Bebchuk Judith , Christ‐Schmidt Heidi , Seashore Margretta , Giovannini Marcello , Burton Barbara K. , Morris Andrew A. ,   the Sapropterin Research Group
Published: October 2008

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation, which can lead to neurocognitive and neuromotor impairment. Sapropterin dihydrochloride, an FDA‐approved synthetic formulation of tetrahydrobiopterin (6R‐BH4, herein referred to as sapropterin) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)‐responsive PKU, offering potential for improved metabolic control. Eighty patients, ≥8 years old, who had participated in a 6‐week, randomized, placebo‐controlled study of sapropterin, were enrolled in this 22‐week, multicenter, open‐label extension study comprising a 6‐week forced dose‐titration phase (5, 20, and 10 mg/kg/day of study drug consecutively for 2 weeks each), a 4‐week dose‐analysis phase (10 mg/kg/day), and a 12‐week fixed‐dose phase (patients received doses of 5, 10, or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration). Dose‐dependent reductions in plasma Phe concentrations were observed in the forced dose‐titration phase. Mean (SD) plasma Phe concentration decreased from 844.0 (398.0) µmol/L (week 0) to 645.2 (393.4) µmol/L (week 10); the mean was maintained at this level during the study's final 12 weeks (652.2 [382.5] µmol/L at week 22). Sixty‐eight (85%) patients had at least one adverse event (AE). All AEs, except one, were mild or moderate in severity. Neither the severe AE nor any of the three serious AEs was considered related to sapropterin. No AE led to treatment discontinuation. Sapropterin is effective in reducing plasma Phe concentrations in a dose‐dependent manner and is well tolerated at doses of 5–20 mg/kg/day over 22 weeks in BH4‐responsive patients with PKU. © 2008 Wiley‐Liss, Inc.
Cognitive‐behavioral features of children with Wolf–Hirschhorn syndrome: Preliminary report of 12 cases
Authors: Fisch Gene S. , Battaglia Agatino , Parrini Barbara , Youngblom Janey , Simensen Richard
Published: October 2008

As a subset of genetic abnormalities, subtelomeric deletions have been found in 7–10% of individuals with mental retardation (MR). One subtelomeric deletion, Wolf‐Hirschhorn syndrome (WHS), causes mild to severe MR, but the cognitive‐behavioral features of individuals with WHS have not been studied systematically. To that end, we administered a comprehensive cognitive‐behavioral battery to 12 children with WHS, ages 4–17 years, who also had some expressive language. Using the Stanford‐Binet (4th Edition), we found cognitive deficits ranged from mild to severe, with mean IQ = 44.1. Interviewing parents with the Vineland Adaptive Behavior Scales, we found mean adaptive behavior score (DQ) = 37.3, with females exhibiting slightly higher scores than males. Cognitive profiles indicated relative strengths in Verbal and Quantitative Reasoning. Adaptive behavior profiles noted significant relative strengths in the Socialization Domain. These cognitive‐behavioral profiles differed from children with other subtelomeric deletion syndromes, 2q37 or 8p23. Attention deficits and hyperactivity (ADHD) were observed in 7/12 (58%) of the children we tested. One child attained a score on the Child Autism Rating Scale (CARS) suggestive of mild autism. We conclude that different genetic disorders, which cause MR, produce diverse cognitive‐behavioral profiles. Consequently, cognitive‐behavioral profiles of children with MR need to be assessed more comprehensively. © 2008 Wiley‐Liss, Inc.
Rheology of 1‐butyl‐3‐methylimidazolium chloride cellulose solutions. II. Solution character and preparation
Authors: Collier J. R. , Watson J. L. , Collier B. J. , Petrovan S.
Published: October 2008

The focus of this article of a three part series is the effects of preparation and composition on the shear rheology of cellulose in the ionic liquid 1‐butyl‐3‐methylimidazolium chloride ([Bmim]Cl). Included are the effects of three different degrees of polymerization, (i.e., average molecular weight), manual versus high shear mixing, a range of cellulose concentrations, and the effects of controlled amounts of lignin and a hemicellulose. The rheology implies that a gel phase develops at higher degrees of polymerization, higher concentration, and at lower temperatures. The first article focused primarily on shear rheology of cellulose in [Bmim]Cl with a high shear preparation technique, one degree of polymerization, a narrow range of cellulose concentrations, and temperature. The third article focuses on elongational rheology of cellulose in [Bmim]Cl. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Rheological properties of recycled chlorinated polyethylene/natural rubber blends vulcanized by sulfur
Authors: Prasopnatra Preeyanuch , Saeoui Pongdhorn , Sirisinha Chakrit
Published: October 2008

Blends of elastomeric chlorinated polyethylene (CPE) and natural rubber (NR) with a blend composition ratio of 80/20 were prepared and recycled. Viscoelastic properties of the blends as a function of the recycling cycle were monitored. The results obtained revealed that, with an increase in the number of recycling cycles, a noticeable change in the viscoelastic properties of blends could be observed; that is, a decrease in the elastic contribution associated with a noticeable shift in the glass‐transition temperature of the NR phase of the blends was observed, implying a molecular change in the NR phase via a thermal chain‐scission mechanism. The influence of magnesium oxide (MgO) as an acid acceptor for CPE on the viscoelasticity of the blends was also investigated. Through a reduction of the amount of MgO, the molecular change was found to be more pronounced in NR than in CPE phases in a manner similar to the increase in the recycling cycles. An explanation of the changes in the viscoelastic properties of the blends with various MgO loadings and recycling cycles is proposed in terms of thermal degradation via a molecular chain‐scission mechanism taking place mainly in the NR phase. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
A Comparison of Methods for Adaptive Treatment Selection
Authors: Friede Tim , Stallard Nigel
Published: October 2008

Traditionally drug development is generally divided into three phases which have different aims and objectives. Recently so‐called adaptive seamless designs that allow combination of the objectives of different development phases into a single trial have gained much interest. Adaptive trials combining treatment selection typical for Phase II and confirmation of efficacy as in Phase III are referred to as adaptive seamless Phase II/III designs and are considered in this paper. We compared four methods for adaptive treatment selection, namely the classical Dunnett test, an adaptive version of the Dunnett test based on the conditional error approach, the combination test approach, and an approach within the classical group‐sequential framework. The latter two approaches have only recently been published. In a simulation study we found that no one method dominates the others in terms of power apart from the adaptive Dunnett test that dominates the classical Dunnett by construction. Furthermore, scenarios under which one approach outperforms others are described. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Identification of the Number of Best Treatments Using the Newman‐Keuls Test
Authors: Wu Samuel S. , Wang Weizhen , Annis David H.
Published: October 2008

In this paper, we provide a stochastic ordering of the Studentized range statistics under a balanced one‐way ANOVA model. Based on this result we show that, when restricted to the multiple comparisons with the best, the Newman–Keuls (NK) procedure strongly controls experimentwise error rate for a sequence of null hypotheses regarding the number of largest treatment means. In other words, the NK procedure provides an upper confidence bound for the number of best treatments. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Aesthetics and Power Considerations in Multiple Testing – A Contradiction?
Authors: Hommel Gerhard , Bretz Frank
Published: October 2008

In this paper we discuss aesthetical concepts and requirements for reasonable multiple test procedures. Aesthetical considerations lead to logical decision patterns which are conceivable and, if possible, simple to use and to communicate. Such considerations are sometimes contradictory to the ubiquitous requirement of maximizing power for a multiple test procedure. We illustrate the necessary trade‐offs with several examples. We start by considering important logical properties and then discuss three different concepts of monotonicity. Afterwards we have a closer look at the recently proposed “fallback procedure” and show that it has some less appealing properties. Finally, we investigate the distribution of the numbers of significant results with respect to both expectation and variance. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Detecting Potential Safety Issues in Clinical Trials by Bayesian Screening
Authors: Gould A. Lawrence
Published: October 2008

Patients in large clinical trials report many different adverse events, most of which will not have been anticipated in the protocol. Conventional hypothesis testing of between group differences for each adverse event can be problematic: Lack of significance does not mean lack of risk, the tests usually are not adjusted for multiplicity, and the data determine which hypotheses are tested. This paper describes a Bayesian screening approach that does not test hypotheses, is self‐adjusting for multiplicity, provides a direct assessment of the likelihood of no material drug‐event association, and quantifies the strength of the observed association. The approach directly incorporates clinical judgment by having the criteria for treatment association determined by the investigator(s). Diagnostic properties can be evaluated analytically. Application of the method to findings from a vaccine trial yield results similar to those found by methods using a false discovery rate argument and using a hierarchical Bayes approach. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
General Solutions to Multiple Testing Problems
Authors: Sonnemann Eckart
Published: October 2008

The introduction of sequentially rejective multiple test procedures (Einot and Gabriel, 1975; Naik, 1975; Holm, 1977; Holm, 1979) has caused considerable progress in the theory of multiple comparisons. Emphasizing the closure of multiple tests we give a survey of the general theory and its recent results in applications. Some new applications are given including a discussion of the connection with the theory of confidence regions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Isofagomine Induced Stabilization of Glucocerebrosidase
Authors: Kornhaber Gregory J. , Tropak Michael B. , Maegawa Gustavo H. , Tuske Steven J. , Coales Stephen J. , Mahuran Don J. , Hamuro Yoshitomo
Published: October 2008

Structurally destabilizing mutations in acid β‐glucosidase (GCase) can result in Gaucher disease (GD). The iminosugar isofagomine (IFG), a competitive inhibitor and a potential pharmacological chaperone of GCase, is currently undergoing clinical evaluation for the treatment of GD. An X‐ray crystallographic study of the GCase‐IFG complex revealed a hydrogen bonding network between IFG and certain active site residues. It was suggested that this network may translate into greater global stability. Here it is demonstrated that IFG does increase the global stability of wild‐type GCase, shifting its melting curve by ∼15 °C and that it enhances mutant GCase activity in pre‐treated N370S/N370S and F213I/L444P patient fibroblasts. Additionally, amide hydrogen/deuterium exchange mass spectroscopy (H/D‐Ex) was employed to identify regions within GCase that undergo stabilization upon IFG‐binding. H/D‐Ex data indicate that the binding of IFG not only restricts the local protein dynamics of the active site, but also propagates this effect into surrounding regions.
Impact of opening an acute palliative care unit on administrative outcomes for a general oncology ward
Authors: Rigby Andrew , Krzyzanowska Monika , Le Lisa W. , Swami Nadia , Coe Gary , Rodin Gary , Moore Malcolm , Zimmermann Camilla
Published: October 2008

BACKGROUND.

Acute palliative care units (APCUs) are gaining popularity in tertiary care centers. In this study, the authors examined the impact of opening an APCU on administrative outcomes for a general oncology ward (GOW) at a comprehensive cancer center.

METHODS.

The GOW database was reviewed for 3 periods: June 2000 through May 2002 (before the APCU opened), June 2002 through May 2004 (transitional period, including APCU opening in a temporary location), and June 2004 through May 2006 (after opening of the APCU). Data were extracted on demographics, reasons for admission, admission type, waiting time for admission, length of stay (LOS), overstay (>2 days over expected LOS), death rate, and discharge destination. Linear regression analysis and the Cochran‐Armitage test were used for data analysis.

RESULTS.

There were 5340 admissions: The median patient age was 60 years, and 55% of patients were women. The most common primary cancers were head and neck (22%), gynecologic (21%), gastrointestinal (13%), and lung (12%). There were significant trends on the GOW in decreased admissions for palliative care (12.2%, 9.6%, and 7.9%, respectively, for the 3 periods; P < .0001), fewer inpatient deaths (11.4%, 8.6%, and 6.1%, respectively; P < .0001), and fewer patients with prolonged waits for a bed on a palliative care unit (3.4%, 3%, and 1.7%, respectively; P = .002). Admissions increased for interventions (10.4%, 17.3%, and 22.5%, respectively, for the 3 periods; P < .0001) and for chemotherapy (6.8%, 6.6%, and 9.7%, respectively; P = .001).

CONCLUSIONS.

After the opening of an APCU at the authors' cancer center, the GOW experienced a decrease in administrative endpoints related to palliative and end‐of‐life care and an increase in endpoints related to cancer‐directed interventions. Prospective studies with clinical endpoints will be required to determine whether this specialization of inpatient care improves quality of life, quality of death, and psychosocial well being. Cancer 2008. © 2008 American Cancer Society.
The American Cancer Society guidelines for breast screening with magnetic resonance imaging
Authors: Murphy Colleen D. , Lee Janie M. , Drohan Brian , Euhus David M. , Kopans Daniel B. , Gadd Michele A. , Rafferty Elizabeth A. , Specht Michelle C. , Smith Barbara L. , Hughes Kevin S.
Published: October 2008

BACKGROUND.

The American Cancer Society (ACS) guidelines for screening with breast magnetic resonance imaging (MRI) recommend MRI for women who have a lifetime risk ≥20% of developing breast cancer. Genetic testing for breast cancer gene (BRCA) mutations is offered to women who have a risk ≥10% of carrying a mutation. The objectives of the current study were 1) to identify the number of women in a breast cancer screening population who had ≥20% lifetime breast cancer risk and, thus, were candidates for screening MRI; and 2) to determine the number of women who had ≥10% risk of BRCA mutation yet had <20% lifetime risk of breast cancer and, thus, may not have been identified as candidates for MRI screening.

METHODS.

From 2003 to 2005, women who underwent screening mammography completed a self‐administered questionnaire regarding breast cancer risk factors. For each patient, the lifetime breast cancer risk and the risk of BRCA mutation was determined by using the computerized BRCAPRO breast cancer risk‐assessment model.

RESULTS.

Of 18,190 women, 78 (0.43%) had ≥20% lifetime risk of breast cancer, all of whom had ≥10% risk of carrying a BRCA mutation. An additional 374 women (2.06%) had <20% lifetime breast cancer risk but ≥10% risk of mutation. Overall, there were 183 (1%) predicted mutation carriers, 27 women (0.15%) who had ≥20% lifetime risk of breast cancer, and 62 women (0.34%) who had ≥10% risk of mutation but <20% lifetime breast cancer risk.

CONCLUSIONS.

The ACS guidelines for breast MRI screening may systematically exclude MRI screening for many women who have a substantial risk for BRCA mutation. The current results demonstrated a need for greater awareness of breast cancer risk factors in the screening mammography population, so that high‐risk women can be identified and given access to genetic testing and counseling regarding all risk‐reducing interventions. Cancer 2008. © 2008 American Cancer Society.
Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications
Authors: Wu Chun‐Chieh , Hsu Hui‐Yu , Liu Hui‐Ping , Chang John Wen‐Cheng , Chen Ya‐Ting , Hsieh Wen‐Yu , Hsieh Jia‐Juan , Hsieh Meng‐Shu , Chen Yi‐Rong , Huang Shiu‐Feng
Published: October 2008

BACKGROUND.

In western countries, the Kirsten ras oncogene homolog gene (KRAS) mutation rate is high in patients with nonsmall cell lung cancer (NSCLC), especially in those with adenocarcinoma (30%‐50%), but the epidermal growth factor receptor gene (EGFR) mutation rate is very low (3%‐8%). In addition, KRAS mutations reportedly were associated with EGFR tyrosine kinase inhibitor (EGFR‐TKI) resistance. In Taiwan, high EGFR mutation rates associated with high EGFR‐TKI response rates in patients with NSCLC have been reported; however, KRAS mutation data are limited and have not been correlated with TKI response.

METHODS.

KRAS mutation analysis was performed on 237 NSCLC specimens, and the results were correlated with clinicopathologic features. All but 2 tumors also underwent EGFR mutation analysis.

RESULTS.

KRAS mutations were identified in only 9 of 237 patients (3.80%). Five patients were women who were nonsmokers, and 4 patients were men who were ever‐smokers. The mutation rate was 5.03% in patients with adenocarcinoma (8 of 159 patients) and 1.56% in patients with squamous cell carcinoma (1 of 64 patients). Four mutations were G12V, 3 mutations were G12D, 1 mutation was L19F, and 1 was the duplication insertion mutation dupT50_M72. In contrast, EGFR mutations were detected in 96 of 235 patients (40.8%) and in 90 of 157 adenocarcinomas (57.3%). None of the KRAS mutations coexisted with EGFR mutations. KRAS mutations were not associated significantly with any clinicopathologic characteristics, including smoking status. Among the 53 patients who had received TKI monotreatment, only 1 patient had a KRAS mutation and had progressive disease.

CONCLUSIONS.

The KRAS mutation rate was too low to play a significant role in TKI resistance or tumorigenesis among Taiwanese patients with NSCLC, which was the complete reverse of the results reported in western countries. Cancer 2008. © 2008 American Cancer Society.
Head and neck squamous cell carcinoma in patients aged ≥80 years
Authors: Italiano Antoine , Ortholan Cecile , Dassonville Olivier , Poissonnet Gilles , Thariat Juliette , Benezery Karen , Vallicioni Jacques , Peyrade Frédéric , Marcy Pierre‐Yves , Bensadoun René‐Jean
Published: October 2008

BACKGROUND.

Scarce data exist concerning the outcome of very elderly patients with head and neck squamous cell carcinoma (HNSCC).

METHODS.

The clinical files of 316 patients aged ≥80 years with HNSCC who were included in the authors' hospital database between 1987 and 2006 were reviewed retrospectively.

RESULTS.

Approximately 88% of patients received locoregional treatment, 31% of patients underwent surgery, and 57% of patients received definitive radiotherapy. The median disease‐specific survival (DSS) was 21.3 months, and a plateau was observed after 5 years. The median overall survival (OS) was 13.0 months. Both the median DSS and the median OS were longer for patients with stage I/II HNSCC than for patients with stage III/IV HNSCC (median DSS, not reached vs 11.4 months; P < .001; median OS, 41.9 months vs 7.9 months; P < .001). On multivariate analysis, stage I/II disease, treatment with curative intent, and evidence of locoregional control were independent predictors of improved survival.

CONCLUSIONS.

The outcome of patients with stage I/II HNSCC aged ≥80 years was similar to that of younger patients, and the current results indicated that age should not be used to deny them optimal treatment. Elderly patients with stage III/IV HNSCC had poor survival. Geriatric tools should be used to identify elderly patients who are eligible for optimal locoregional treatment. Cancer 2008. © 2008 American Cancer Society.
Das Bundesgerichtshof‐Urteil zum Schallschutz vom 14. 6. 2007 (VII ZR 45/06) – welche Klarheit zum Thema hat es bislang für die Praxis gebracht?
Authors: Locher‐Weiß Susanne
Published: October 2008

Tragfähiger Untergrund ist die Basis allen Bauens, wobei es unsicheren Baugrund nicht nur in geologischem Sinne gibt – auch die Vereinbarungen zum Bausoll der verschiedenen Vertragsparteien sind häufig “auf Sand gebaut“. Dies gilt insbesondere im Bereich der vertraglichen Regelungen zum Schallschutz, wie sie auch dem Sachverhalt (vgl. nachstehenden Abschn. 2.1.), den der Bundesgerichtshof in seiner die Bauwirtschaft aufrüttelnden Entscheidung vom 14. 6. 2007 (Aktenzeichen: VII ZR 45/06) zu beurteilen hatte, zugrunde lagen. Das Urteil hat viel Staub aufgewirbelt, der sich noch nicht wieder gelegt hat. Dies schon allein deshalb, weil der Bundesgerichtshof etliche Fragen angerissen und angedacht hat, letztendlich aber die Sache zur weiteren Sachverhaltsaufklärung und Entscheidung an das Oberlandesgericht Hamm zurückverwiesen hat. Die dortige Entscheidung steht noch aus.
A New‐Keynesian DSGE model for forecasting the South African economy
Authors: Liu Guangling ‘Dave’ , Gupta Rangan , Schaling Eric
Published: October 2008

This paper develops a New‐Keynesian Dynamic Stochastic General Equilibrium (NKDSGE) model for forecasting the growth rate of output, inflation, and the nominal short‐term interest rate (91 days Treasury Bill rate) for the South African economy. The model is estimated via maximum likelihood technique for quarterly data over the period of 1970:1–2000:4. Based on a recursive estimation using the Kalman filter algorithm, out‐of‐sample forecasts from the NKDSGE model are compared with forecasts generated from the classical and Bayesian variants of vector autoregression (VAR) models for the period 2001:1–2006:4. The results indicate that in terms of out‐of‐sample forecasting, the NKDSGE model outperforms both the classical and Bayesian VARs for inflation, but not for output growth and nominal short‐term interest rate. However, differences in RMSEs are not significant across the models. Copyright © 2008 John Wiley & Sons, Ltd.
Prevalence of chronic liver disease in the general population of northern Italy: The dionysos study
Authors: Bellentani Stefano , Tiribelli Claudio , Saccoccio Gioconda , Sodde Marino , Fratti Nicoletta , De Martin Christina , Christianini Giovanni
Published: October 2008

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, γ-glutamyl-transpeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%. Other factors which predisposed subjects to chronic liver disease were age older than 35 yr, male sex, body mass index higher than 27, history of blood transfusion, drug addiction and presence of chronic liver disease in the subject's family. Cirrhosis was due to hepatitis B virus or hepatitis C virus in 37%, and alcohol was the cause in 26%. In those subjects with alcohol abuse, viral infection, especially hepatitis C virus, played an important role in the deterioration of chronic liver disease and its progression to hepatocellular carcinoma. We conclude that the Dionysos study, the first study of the prevalence of chronic liver disease in a general population of northern Italy, found a much higher prevalence of chronic liver disease than reported previously in selected populations from Western countries. Hepatitis viral infections and alcoholism were the most important causative agents. (Hepatology 1994;20:1442-1449).
Selective enhancement of metastatic capacity in mouse bladder carcinoma cells after transfection with dna from liver metastases of human colon carcinoma
Authors: Radler‐Pohl Adriana , Schirrmacher Jens Pohl Volker
Published: October 2008

To identify sequences associated with a metastatic pheno‐type, DNA fragments isolated from 2 separate human colon carcinoma metastases were transfected into a mouse bladder carcinoma cell line together with the neoR gene as selectable marker. It was found that bulk populations of neomycin resistant cells carrying these human sequences caused more metastases in syngeneic mice than did control cells transfected with calf thymus DNA. Cells isolated from metastases retained the highly metastases phenotype when transferred to secondary hosts.
Steroidumwandelnde Enzyme aus Mikroorganismen. XIII. Beziehungen zwischen Steroidstruktur und Induktion der 4‐En‐3‐oxosteroid: (Akzeptor)‐l‐en‐oxidoreduktase in Nocardia opaca
Authors: Hörhold C. , Hüller E. , Rose G.
Published: October 2008

The induction of the 4‐ene‐3‐oxosteroid: (acceptor)‐1‐ene‐oxidoreductase in Nocardia opaca has been shown to be dependent on both hydrophilic and hydrophobic structural features of the steroid molecule, i. g. the nature of the oxygen function in positions 11 and 20 and the presence of the methyl group in position 10 influence the induction of the enzyme drastically. In this connection the metabolism of the steroid inductors being degradated during the induction process has been considered.
Thermoviscoelastic Behavior of Film‐Insert‐Molded Parts Prepared under Various Processing Conditions
Authors: Kim Seong Yun , Lee Seung Hwan , Baek Soo Jin , Youn Jae Ryoun
Published: October 2008

Film‐insert‐molded (FIM) tensile specimens were prepared under various molding conditions to investigate the effects of wall temperature and packing pressure on the residual stress distribution and thermoviscoelastic deformation. The warpage of the specimen increased with increasing mold‐wall temperature difference and decreased with increasing packing pressure. The FIM specimens produced with unannealed films showed the warpage reversal phenomenon (WRP) during annealing and the degree of WRP was affected significantly by the molding conditions and thermal shrinkage of the film. The warpage of the specimen was predicted by three‐dimensional flow and stress analyses and the prediction was in good agreement with the experimental results.

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Question effects on information processing in advertising
Authors: Howard Daniel J. , Burnkrant Robert E.
Published: October 2008

This research reports the results of a study in which pre‐questions and post‐questions are employed in a radio commercial. Responses of subjects exposed to questions are compared to responses of other subjects exposed to content equivalent statements. Also manipulated in this research is the length of a pause after commercial arguments. Post‐questions were found to be more effective in facilitating information processing than post‐statements. However, pre‐questions and combined (both pre‐ and post‐) questions were not more effective than pre‐statements and combined statements respectively. Further, the length of the pause did not affect outcomes. Results are discussed in terms of the conditions under which questions may and may not be expected to increase message processing. Different theoretical views are presented in explaining the pattern of results observed.
The proximal promoter governs germ cell‐specific expression of the mouse glutathione transferase mGstm5 gene
Authors: Dehari Hironari , Tchaikovskaya Tatyana , Rubashevsky Eugeny , Sellers Rani , Listowsky Irving
Published: October 2008

To explain the tissue‐selective expression patterns of a distinct subclass of glutathione S‐transferase (GST), transgenic mice expressing EGFP under control of a 2 kb promoter sequence in the 5′‐flanking region of the mGstm5 gene were produced. The intent of the study was to establish whether the promoter itself or whether posttranscriptional mechanisms, particularly at the levels of mRNA translation and stability or protein targeting, based on unique properties of mGSTM5, determine the restricted expression pattern. Indeed, the transgene expression was limited to testis as the reporter was not detected in somatic tissues such as brain, kidney or liver, indicating that the mGstm5 proximal promoter is sufficient to target testis‐specific expression of the gene. EGFP expression was also more restricted vis‐a‐vis the natural mGstm5 gene and exclusively found in germ but not in somatic cells. Real‐time quantitative PCR (qPCR) data were consistent with alternate transcription start sites in which the promoter region of the natural mGstm5 gene in somatic cells is part of exon 1 of the germ cell transcript. Thus, the primary transcription start site for mGstm5 is upstream of a TATA box in testis and downstream of this motif in somatic cells. The 5′ flanking sequence of the mGstm5 gene imparts germ cell‐specific transcription. Mol. Reprod. Dev. 76: 379–388, 2009. © 2008 Wiley‐Liss, Inc.
Manual stimulation of the orbicularis oculi muscle improves eyelid closure after facial nerve injury in adult rats
Authors: Bischoff Anna , Grosheva Maria , Irintchev Andrey , Skouras Emmanouil , Kaidoglou Katerina , Michael Joern , Angelova Srebrina K. , Kuerten Stefanie , Sinis Nektarios , Dunlop Sarah A. , Angelov Doychin N.
Published: October 2008

We have shown that manual stimulation of rat whisker‐pad muscles following facial–facial‐anastomosis (FFA) restores normal whisking by lowering the proportion of polyinnervated motor endplates. Here we examined whether manual stimulation of the orbicularis oculi muscle (OOM) after FFA would also improve outcome. Blink responses to standardized air puffs were analyzed using video‐based motion analysis. Two months after FFA, blink capacity was impaired, as indicated by a largely increased minimum distance between the eyelids after air‐puff stimulation compared with intact rats (2.7 ± 0.4 vs. 0.2 ± 0.01 mm). Manual stimulation reduced this deficit by a factor of two (1.3 ± 0.5 mm). The functional improvement after manual stimulation was associated with a 2‐fold decrease in the proportion of polyinnervated OOM endplates (21 ± 10% vs. 42 ± 10% without manual stimulation, 0% in intact rats). We conclude that manual stimulation is a noninvasive and simple procedure with immediate potential for clinical rehabilitation of eyelid closure following facial nerve injury. Muscle Nerve, 2008
An animal model of chemotherapy‐induced vagal neuropathy
Authors: Weissman‐Fogel Irit , Dashkovsky Arkadi , Rogowski Zeev , Yarnitsky David
Published: October 2008

In this study we establish an animal model of chemotherapy‐induced autonomic neuropathy. Rats were injected with vincristine (30 and 100 μg/kg/day) for 2 weeks while cardiovascular parameters were collected telemetrically. Vincristine caused a dose‐dependent decrease in vagal activity expressed by decreased parasympathetic parameters of heart rate variability, without expression of damage to the cardiac sympathetic innervation. This model can serve in assessing the potential contribution of chemotherapy‐induced vagal neuropathy to morbidity and mortality. Muscle Nerve, 2008
Test–retest reliability of pelvic floor muscle contraction measured by 4D ultrasound
Authors: Brækken Ingeborg Hoff , Majida Memona , Engh Marie Ellström , BØ Kari
Published: October 2008

Aims

The aim of the present study was to evaluate test‐retest measurements of functional aspects of pelvic floor muscle (PFM) contraction using four dimensional (4D) ultrasound.

Methods

Seventeen females preformed three maximal PFM contractions in standing, recorded by 4D real time ultrasound, on two separate occasions.

Results

Very good and good reliability was fond for measurement of: Levator hiatus (LH) area, LH antero‐posterior dimension, LH transverse dimension, puborectal muscle length and LH narrowing. Shortening of LH transverse distance and muscle length during contraction showed poor and fair reliability, respectively. In the mid sagittal plane the displacement of bladder neck, rectal ampulla and back sling of the poborectal muscle measured with on screen vector assessment demonstrated good reliability. During contraction the LH area was reduced 25% from resting area of 19.7 cm2 (95% CI = 16.8‐‐22.7) to 14.70 cm2 (95% CI = 12.82‐‐16.58). The muscle length shortened 21%, from 12.5 cm (95% CI = 11.1‐‐13.8) to 9.70 cm (95% CI = 8.73‐‐10.67). The mid urethra moved 1.1 mm (95% CI = 0.1‐‐2.2) towards the pubic bone during contraction. The back sling of the puborectal muscle and the rectal ampulla had a greater displacement than the bladder neck (P > .004). The displacement of the pelvic organs was two times, or more, greater in the cranial versus anterior direction.

Conclusions

4D ultrasound can reliable assess muscle length, narrowing of LH area, reduction of LH antero‐posterior dimension and lift of BN, rectal ampulla and back sling of the puborectal muscle. Hence, both squeeze and lift can be quantified during PFM contraction. Neurourol. Urodynam. 28:68–73, 2009. © 2008 Wiley‐Liss, Inc.
On the Origin of Lateral Fringes on Crystals Grown from the Melt
Authors: de Grinberg D. K.
Published: October 2008

Alkali halide single crystals were grown by the Kyropoulos method, using rotatory and fixed seeds. In both techniques, horizontal fringes appear on the lateral surface of the crystals, which are parallel to the interface. The interfringe distance was found to be related with the thermodynamical constants of the material. From the analysis of heat transfer during the growth an expression was deduced which relates the thermodynamical constants, and the crystal and seed dimensions with the rate of growth. This formula is in good agreement with the experimental results. A mechanism of discontinuous growth, based on the effect of impurities at the moving interface, is suggested to explain the appearance of the fringes in both rotatory or fixed seed techniques. This mechanism is also used to interpret the results of other authors, which were not explained by other proposed mechanisms.
Strahlensättigung und Defektstruktur in Festkörpern Von
Authors: Balarin M. , Hauser O.
Published: October 2008

Ausgehend von Arbeiten von Lück und Sizmann [2, 3] über das sättigungsartige Anwachsen der Defektkonzentration bei der Bestrahlung von Festkörpern wird eine einfache analytische Möglichkeit zur Bestimmung der Sättigungskonzentration und des Einzugsvolumens α für die spontane Rekombination angegeben. Es wird berücksichtigt, daß je nach Defektstruktur zwei Fälle auftreten: Im Falle der statistischen Erzeugung von isolierten Punktdefekten ist das Einzugsvolumen von der erreichten Defektkonzentration abhängig, im Falle von Defektkaskaden ergibt sich ein konstanter effektiver Wert für das Einzugsvolumen. Aus verschiedenen Bestrahlungsexperimenten werden für einige Metalle die Einzugsvolumina berechnet.
The Fundamental Absorption Edge of Doped CdS Single Crystals
Authors: Brodin M. S. , Vitrikhovskii N. I. , Kurik M. V.
Published: October 2008

An investigation is made of the fundamental absorption edge of single crystals of CdS at 300, 77, and 20.4 °K. The crystals have In and Ga donors, and Cu and Ag acceptors. It is shown that for donor concentrations between 1018 and 1019 cm−3 the absorption edge is shifted towards longer wavelengths. The acceptors do not lead to any changes in the absorption edge. The shift of the absorption edge by the donors and its effect on the exciton spectrum is discussed. The effect is thought to be associated with the deformation of the valence band and the formation of the “tail” of the density of states.
Accomplishment of the Analysis of an Edge Dislocation for a Simple Cubic Lattice
Authors: Gallina V. , Galotto C. P. , Omini M.
Published: October 2008

An edge type dislocation in a simple cubic lattice is studied with the inclusion of a new double row of forces confined to the core. Particular emphasis is given to the distortion in the neighbourhood of the dislocation line. The theory is based on a new formula which gives the lattice distortion arising from the introduction into the crystal of a point force, the discrete structure of the medium being taken into consideration. The resulting displacements are linear functions of some matrices whose values are tabulated for the core atoms. At greater distances from the dislocation line the present solutions are substantially the same as the classical ones.
Damping of the Electron Spectrum and Quantum Theory of Galvanomagnetic Phenomena
Authors: Askerov B. M. , Gashimzade F. M.
Published: October 2008

The components of the conductivity tensor in the presence of a magnetic field are calculated, the quantization of the electron orbits being taken into account. The interaction between the electrons and lattice imperfections is included in the one‐particle Green's function of the electron, and the response of the latter on the external perturbation is studied. A linear approximation is used for the external field. The interactions of the electrons with the impurities (infinitely localized, ionized) and phonons (acoustical, optical) is based on the Born approximation.
Elektronenmikroskopische Beobachtung der Strukturänderung von K2PdCl4 Von
Authors: Demny J.
Published: October 2008

In dünnen Schichten von K2PdCl4 bilden sich bei etwas erhöhter Elektronenbestrahlung lammellenartige Ausscheidungen, die zu neuen Reflexen im Elektronenbeugungsdiagramm führen. Aus Hell‐ und Dunkelfeldabbildungen sowie Beugungsdiagrammen kann geschlossen werden, daß es sich bei den Lamellen um eine neue Struktur des K2PdCl4 mit raumzentrierter tetragonaler Elementarzelle handelt.
Ein Modell für die Keimbildung der Stapelfehlertetraeder in abgeschrecktem Gold Von
Authors: Chik K.‐P.
Published: October 2008

Die Keimbildung von Stapelfehlertetraedern in abgeschrecktem Gold wird auf Grund eines Modells erklärt, wonach die Keime durch einen Dreierstoß von Einfach‐, Doppel‐ und Dreifachleerstellen gebildet werden. Die Keime wirken nach ihrer Bildung als effektive Senken für die beweglichen Leerstellen. Es werden Gleichungen für die Variation der Tetraederdichte mit Leerstellenkonzentration und Temperatur und für die Kinetik der Keimbildung gegeben. Ein quantitativer Vergleich zwischen Theorie und Experiment ergibt als Bindungsenergie und als Assoziationsentropie von Dreifachleerstellen 0,3 eV bzw. 3,5 k. Die Vierfach‐ und Fünffachleerstellen sind wahrscheinlich instabil, während die Wanderungsenergie der Dreifachleerstellen vermutlich zwischen den entsprechenden Energien der Einfach‐ und der Doppelleerstellen liegt.