bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Dermatomycoses of the Foot as Risk Factors for Acute Bacterial Cellulitis of the Leg: A Case-Control Study
Authors: Roujeau Jean-Claude , Sigurgeirsson Bardur , Korting Hans-Christian , Kerl Helmut , Paul Carle
Published: November 2004

Objective: To assess the role of foot dermatomycosis (tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. Methods: A case-control study, including 243 patients (cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (±5 years), hospital and admission date (±2 months). Results: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. Conclusions: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy.
Partial Unilateral Lentiginosis with Ipsilateral Lisch Nodules and Axillary Freckling
Authors: Chen WenChieh , Fan Po-Chyung , Happle Rudolf
Published: November 2004

A 9-year-old Taiwanese girl had an unusual combination of multiple lentigines clustered on her left face, 3 café-au-lait spots on her left arm and ipsilateral axillary freckling. Two Lisch nodules of the iris were recognized in the left eye but none in the right eye, which is why we established a diagnosis of segmental neurofibromatosis 1. No family member had any sign of neurofibromatosis 1. Moreover, the patient had a large speckled lentiginous nevus involving the left side of her trunk, and her father showed a similar skin disorder on his left buttock. These lesions were taken to be unrelated to the patient’s segmental neurofibromatosis 1. This case provides further evidence in favor of the concept that partial unilateral lentiginosis represents a mosaic manifestation of type 1 neurofibromatosis.
A Phase I and Pharmacokinetic Study of BAY59: A Novel Taxane
Authors: Ramnath N. , Hamm J. , Schwartz G. , Holden S. , Eckhardt S.G. , Vredenburg M.R. , Bernacki R.J. , Lathia C. , Kanter P. , Creaven P.J.
Published: November 2004

Purpose: To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLT) and the pharmacokinetics of BAY59, a novel taxane given as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory solid tumors. Experimental Design: Initially, 15 patients with previously treated (median of 4 prior chemotherapy regimens) refractory cancers, but with normal marrow, hepatic and renal function were treated with BAY59 at doses of 15, 30, 50, 75 and 100 mg/m2 using a standard dose escalation design. Subsequently, 11 patients were treated, 5 at 90 mg/m2 and 6 who had had prior oxaliplatin at 75 mg/m2. Results: At 75 mg/m2, grade 4 neutropenia was noted in 2/6 patients, of whom 1 had grade 4 neutropenia lasting more than 5 days (DLT). At 100 mg/m2, 2/2 patients had febrile neutropenia, with 1 fatality. At 90 mg/m2, 2/5 patients had DLTs, including grade 3 neuropathy, severe lower extremity pain, dehydration and grade 4 neutropenia. The MTD was determined to be 75 mg/m2. A cohort of 6 patients, previously exposed to oxaliplatin, were enrolled at the MTD to evaluate the incidence of neurotoxicity. While DLTs (grade 3 arthralgia, grade 4 neutropenia) were noted in 3/6 patients, there was no increase in the incidence of neurotoxicity. There were no responses. Pharmacokinetics of BAY59 was linear over the doses studied, with a median terminal half-life of 21 h. Conclusions: The recommended phase II dose for BAY59 is 75 mg/m2.
Fas Gene Mutations in Mycosis fungoides: Analysis of Laser Capture-Microdissected Specimens from Cutaneous Lesions
Authors: Nagasawa Tomohiko , Takakuwa Tetsuya , Takayama Hitoshi , Dong Zhiming , Miyagawa Sachiko , Itami Satoshi , Yoshikawa Kunihiko , Aozasa Katsuyuiki
Published: November 2004

Fas (APO-1/CD95) is a transmembrane protein which mediates programmed cell death (apoptosis). Cells with a mutated Fas gene are resistant to apoptosis and thus accumulate in lesional tissues. This might provide a basis for the development of neoplasias. Genomic DNA selectively obtained from Pautrier’s microabscesses in 16 cases of mycosis fungoides (MF) using a laser capture microdissection method was analyzed. Fas gene mutations were detected in 3 of 16 cases of MF (18.8%); 1 was silent and 2 were missense mutations located in exon 9. One of the 2 missense mutations involved the death domain of the Fas gene, which is essential for apoptotic signal transduction. The missense mutations resulted in the substitution of Ala with Asp at codon 220 and Ile with Thr at codon 314. Mouse T cell lymphoma cells transfected with mutant genes were resistant to apoptosis induced by the anti-Fas antibody, indicating that the missense mutations found in MF were loss-of-function mutations, thus causing the accumulation of cells in the cutaneous lesions. These findings suggest that the accumulation of lymphoid cells with Fas mutations provides, in part, a basis for the development or maintenance of MF.
Frequent Loss of Heterozygosity but Rare Microsatellite Instability in Oesophageal Cancer in Japanese and Chinese Patients
Authors: Araki Koshi , Wang Bing , Miyashita Kaname , Cui Qingping , Ohno Shinji , Baba Hideo , Zhang Ru Gang , Sugimachi Keizo , Maehara Yoshihiko , Oda Shinya
Published: November 2004

Reported frequencies for microsatellite instability (MSI) in oesophageal cancer differ widely in the literature, perhaps due to the high incidence of loss of heterozygosity (LOH) in this cancer. Using high-resolution fluorescent microsatellite analysis (HRFMA), we analysed microsatellite alterations in detail in 50 Japanese and 50 Chinese patients with squamous cell carcinoma in the oesophagus. In HRFMA, several devices have been developed to improve the detection characteristics, reproducibility of polymerase chain reaction and the migration accuracy of electrophoresis. All the alterations observed were separable into MSI, LOH and alterations ambiguous for both. MSI was rare in these panels of oesophageal carcinomas. The frequencies of MSI in the Japanese and Chinese subjects were 8 and 4%, respectively. All the alterations were mild (within 2 base pairs) and were observed in a limited number of markers. More drastic types of MSI, such as those typical in colorectal cancer, were not observed. On the other hand, the incidence of LOH was high, reaching 50% for the Japanese and 70% for the Chinese subjects. In many of these cases, LOH was observed in multiple microsatellite markers. The frequency of LOH in each marker was not apparently biased. Although in many cases MSI and LOH were clearly distinguished with use of the sensitive and quantitative fluorescent assay, theoretically indistinguishable patterns were noted in some cases. In conclusion, MSI is rare and LOH predominates in squamous cell carcinoma in the oesophagus.
Thrombin Inhibitor, Argatroban, Prevents Tumor Cell Migration and Bone Metastasis
Authors: Asanuma Kunihiro , Wakabayashi Hiroki , Hayashi Tatsuya , Okuyama Noritaka , Seto Masashi , Matsumine Akihiko , Kusuzaki Katsuyuki , Suzuki Koji , Uchida Atsumasa
Published: November 2004

It is well known that malignant cells show procoagulant activity, which is associated with their metastatic potential. Thrombin, the key enzyme of the blood coagulation system, is generated around tumor cells, promoting the migration and metastasis of tumor cells. In this study, we evaluated the effect of argatroban, a specific thrombin inhibitor, on the migration and metastasis of B16BL6 melanoma cells. In vitro argatroban dose-dependently inhibited cell migration, the maximum inhibition being observed in the presence of 10 µM argatroban (p < 0.0001). In order to investigate the antimetastatic effect of the thrombin inhibitor, we used an animal model that we have reported previously. C57BL6 mice which had received a bone (femur or tibia) transplanted into the dorsal subcutis were injected with B16 melanoma cells into the left heart ventricle. Intraperitoneal injection of argatroban (9 mg/kg/day for 4 weeks) significantly reduced the number of limbs with metastatic lesions as compared to a placebo (p < 0.05). These results suggest that argatroban was associated with reduced melanoma metastases by inhibiting cell migration. Our results showed that argatroban is effective for treatment of bone metastasis.
Brain Metastasis Responding to Gefitinib Alone
Authors: Poon Annette N.Y. , Ho Simon S.M. , Yeo Winnie , Mok Tony S.K.
Published: November 2004

A woman with stage IIIb non-small cell lung cancer (NSCLC) developed disease progression with brain metastases during chemotherapy. Due to unusual circumstances, the patient received gefitinib alone, without the use of corticosteroid treatment or radiotherapy. There was a dramatic clinical improvement within 1 week. Follow-up magnetic resonance imaging of the brain 1 month later showed decreases in both the size and number of brain metastases. The patient remains well 9 months after initiation of gefitinib. It is proposed that gefitinib may have a role in treatment of brain metastases from NSCLC.
Effects of L-Ornithine on Metabolic Processes of the Urea Cycle in Human Keratinocytes
Authors: Höche F. , Klapperstück T. , Wohlrab J.
Published: November 2004

The complex metabolic function of L-ornithine has led to a great interest in studying its pharmacotherapeutic potential. L-Ornithine is known to be crucial for the metabolism of keratinocytes, especially in the synthesis of urea, polyamines and precursors of collagen synthesis. In this study, we investigated in vitro the cytotoxicity of L-ornithine, and its influence on urea synthesis and arginase expression in primary human keratinocytes. L-Ornithine (≧1 mM) induced a decrease in the de novo urea synthesis of keratinocytes and an increase (≧10 mM) in the expression of the urea-generating enzyme arginase. Up to 20 mM, L-ornithine showed no cytotoxic potential, whereas higher concentrations induced apoptosis in keratinocytes in a concentration- and time-dependent manner.
Basal Cell Adhesion Molecule Is Inversely Associated with Apoptosis, but Plays a Limited Role for Protection against Apoptotic Stimuli
Authors: Drewniok C. , Schön M. , Schön M.P.
Published: November 2004

Basal cell adhesion molecule (B-CAM) is strongly upregulated in epithelial skin cancer cells in vivo and in vitro. We have tested here whether B-CAM is (1) inversely associated with or (2) functionally involved in apoptosis. Towards this end, B-CAM expression was assessed in HaCaT transfectants overexpressing murine Bcl-2 and untransfected HaCaT cells exposed to various proapoptotic stimuli. In another series of experiments, we overexpressed B-CAM in HaCaT cells and different fibroblast lines, and stimulated various apoptotic pathways in the transfectants and control cells. In addition, apoptosis was assessed after an antibody-mediated B-CAM blockade. We could demonstrate that expression of B-CAM is inversely associated with the susceptibility of cells to apoptosis. However, overexpression or antibody- mediated inhibition of B-CAM had only limited functional effects on cellular apoptosis.
Formulation of an HPMC Gel Drug Reservoir System with Ethanol-Water as a Solvent System and Limonene as a Penetration Enhancer for Enhancing in vitro Transdermal Delivery of Nicorandil
Authors: Al-Saidan S.M. , Krishnaiah Y.S.R. , Chandrasekhar D.V. , Lalla J.K. , Rama B. , Jayaram B. , Bhaskar P.
Published: November 2004

The objective of the present study was to formulate a hydroxypropyl methylcellulose (HPMC) gel drug reservoir system with ethanol-water as a solvent system and limonene as a penetration enhancer for enhancing the transdermal delivery of nicorandil so as to develop and fabricate a membrane-moderated transdermal therapeutic system (TTS). The in vitro permeation of nicorandil was determined across rat abdominal skin from a solvent system consisting of ethanol or various proportions of ethanol and water. The ethanol-water (70:30 v/v) solvent system that provided an optimal transdermal permeation was used in formulating an HPMC gel drug reservoir system with selected concentrations (0% w/w, 4% w/w, 6% w/w, 8% w/w or 10% w/w) of limonene as a penetration enhancer for further enhancement of transdermal permeation of nicorandil. The amount of nicorandil permeated in 24 h was found increased with an increase in the concentration of limonene in the drug reservoir system up to a concentration of 6% w/w, but beyond this concentration there was no further increase in the amount of drug permeated. The flux of nicorandil was 370.9 ± 4.2 µg/cm2·h from the drug reservoir system with 6% w/w of limonene, which is about 2.6 times the required flux to be obtained across rat abdominal skin for producing the desired plasma concentration for the predetermined period in humans. The results of a Fourier Transform Infrared study indicated that limonene enhanced the percutaneous permeation of nicorandil by partially extracting the stratum corneum lipids. It is concluded that the HPMC gel drug reservoir system prepared with a 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene is useful in designing and fabricating a membrane-moderated TTS of nicorandil.
Peroxisome Proliferator-Activated Receptor-Alpha and Atherosclerosis: From Basic Mechanisms to Clinical Implications
Authors: Israelian-Konaraki Zarmen , Reaven Peter D.
Published: November 2004

Atherosclerosis is an inflammatory process triggered by the presence of lipids in the vascular wall and encompasses a complex interaction between inflammatory cells, vascular elements and lipoproteins through the expression of several adhesion molecules and cytokines. Activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive and it is abundantly present in the vascular wall where it may mediate many of anti-inflammatory and antiatherogenic effects. Major clinical trials, such as the Veterans Affairs High-Density Lipoprotein Intervention Trial, the Helsinki Heart Study and the Diabetes Atherosclerosis Intervention Study, have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. In this paper, we will review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their anti-inflammatory and antithrombotic properties.
Angiotensin-Converting Enzyme Inhibitor Use in Elderly Patients Hospitalized with Heart Failure and Left Ventricular Systolic Dysfunction
Authors: Rangaswamy Chandhiran , Finn Jeannine I. , Koelling Todd M.
Published: November 2004

Purpose: Although angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with systolic heart failure, prior studies suggest that elderly cohorts are less likely to receive such therapy. The purpose of this study was to determine the age dependence of adherence to guideline-based medical care in hospitalized heart failure patients. Methods: We performed a multicenter observational cohort study including 613 patients admitted to participating hospitals with a primary diagnosis of heart failure with ejection fraction ≤40%. This cohort was divided into four age groups (group 1: <60, group 2: 60–69, group 3: 70–79, and group 4: 80 years) and adherence to guideline-based medical care was measured. Results: ACE inhibitors were administered to 83% of ideal heart failure patients, and this rate was similar for all age groups. Elderly patients received significantly lower ACE inhibitor dosages compared to their younger counterparts (168, 148, 125 and 117 mg captopril in groups 1, 2, 3, and 4, respectively, p = 0.001). Lower creatinine clearance (p < 0.001), prior residence in a long-term care facility (p = 0.037), intolerance to ACE inhibitors (p = 0.006), lower blood pressure (p = 0.005), absence of a history of hypertension (p = 0.005), and no prior heart failure hospitalizations within the past year (p = 0.001) were found to be independent predictors of low ACE inhibitor dosing. Conclusions: In this heart failure benchmarking project, elderly patients received guideline-based ACE inhibitor therapy at similar rates, but at lower doses, compared to their younger counterparts.
Relationship between Retinopathy and Cognitive Impairment among Hypertensive Subjects
Authors: Tekin Oğuz , Çukur Serdar , Uraldı Cem , Işık Bünyamin , Özkara Adem , Kurtaran Hanifi , Çatal Ferhat , Üstün Ihsan
Published: November 2004

Background: The relationship between hypertension and cognitive impairment has been investigated in the literature; several clinical studies suggested a relationship between hypertension and retinopathy. Methods: We examined the relationship between the retinopathy status and cognitive functions by using the Mini-Mental State Examination (MMSE) among hypertensive subjects older than 40 years who were admitted to our Family Medicine, Internal Medicine and Ophthalmology clinics. The subjects were categorized into three groups: group 1 = control subjects (n = 39), group 2 = hypertensive patients without retinopathy (n = 32), and group 3 = hypertensive patients with retinopathy (n = 25). Results: The number of patients with total MMSE scores less than 24 was distributed as follows: group 1: 3 patients (7.7%), group 2: 4 patients (12.5%), and group 3: 14 patients (56%). Hypertension was found to be related with a significant decrease in total MMSE scores in comparison with group 1 subjects (p < 0.001). Furthermore, retinopathy significantly correlated with lower MMSE scores among hypertensive patients (p = 0.001). Compared with group 1, group 3 showed a significant decrease in orientation (p = 0.001), registration (p = 0.001), attention and calculation (p = 0.004), recall (p = 0.009), and total (p < 0.001) MMSE scores. We also found a significant decrease in recall (p = 0.032) and total (p = 0.034) scores in group 3 when compared with group 2. There was a significant decrease in registration (p = 0.002) and total (p = 0.029) MMSE scores in group 2 when compared with group 1. We also observed negative correlations between duration of the disease and orientation (R = –0.597, n = 32, p = 0.001), and between duration of the disease and total (R = –0.495, n = 32, p = 0.006) scores in group 2. Conclusions: Hypertension was found to be related with a decline in MMSE scores. This relation was even more significant in the group of hypertensive patients with retinopathy. Thus, we suggest that cognitive tests be routinely used in the follow-up of hypertensive patients.
Characterization of an Active Pharmaceutical Ingredient by Its Dissolution Properties: Amoxicillin Trihydrate as a Model Drug
Authors: Horkovics-Kovats Stefan
Published: November 2004

To characterize the dissolution of particles, a dissolution rate coefficient α, consisting of a geometric factor γ and material constant µ, was introduced. The impact of the particle geometry on the initial rate of dissolution was assessed for spherical, cubic and tetrahedral particles. Additionally, a description of dissolution of samples containing multiple populations of particles was derived. A two-population model was employed to characterize sieved fractions of amoxicillin trihydrate. The investigation, using factor analysis, of the influence of dose, particle size and agitation intensity on the dissolution rate coefficient α indicated the presence of disintegrating agglomerates in larger particles. Based on the dissolution characteristics of particular particle size fractions and on the determined particle size distribution, the dissolution profile of the mixed sample containing nine sieved fractions in size was successfully predicted. Finally, the limitations of the film theory are discussed in light of the multiple-population dissolution theory.
The Emergence of Glycopeptide-Resistant Enterococcus faecium in a University Hospital in Southwestern Greece
Authors: Kolonitsiou F. , Mani V. , Parikou H. , Trakala M. , Dimitracopoulos G. , Spiliopoulou I.
Published: November 2004

Background: Enterococci and especially glycopeptide-resistant strains (GRE) are widely distributed in the hospital environment, by acquiring resistance determinants and virulence factors. Methods: The study included 48 GRE isolated during a 1-year period from different inpatients in a tertiary hospital in southwestern Greece. Antibiotic susceptibility was determined by the Etest, and the presence of resistance and virulence genes was shown by PCR. Clonal types were identified by pulsed-field gel electrophoresis of SmaI DNA digests. Results: All GRE were multi-resistant of the VanA phenotype, verified by the detection of the gene by PCR. Two major clones were distributed in all hospital wards. The majority of the strains (46 of 48) harbored the esp gene, while 27 GRE expressed also the gelE and/or as genes. Conclusions: The spread of two clones expressing the vanA gene and virulence factors were responsible for the emergence of GRE in the University Hospital of Patras.
Effect of Ceftazidime, Amikacin and Ciprofloxacin on Biofilm Formation by Some Enterobacterial Clinical Isolates
Authors: Bret Laurent , Di Martino Patrick
Published: November 2004

The effect of sub-minimal inhibitory concentrations of antimicrobial agents on the biofilm formationto polystyrene by Escherichia coli, Proteus vulgaris, Providencia stuartii, and Morganella morganii was investigated by examining eight clinical strains. All the isolates tested were efficient biofilm-forming strains in the microtiter plate assay, with crystal violet staining (OD595nm) ranging from 0.13 ± 0.01 for P. stuartii ER21870 to 1.23 ± 0.02 for P. vulgaris ER50120. The biofilm formation of the majority of the strains was affected in the presence of ceftazidime or ciprofloxacin: biofilm formation significantly decreased for all the E. coli and P. vulgaris strains in the presence of either of the two antibiotics, it also decreased for M. morganii ER89472 in the presence of ceftazidime but increased for P. stuartii ER21870 and M. morganii ER89472 in the presence of ciprofloxacin. Amikacin decreased only the biofilm formation of P. stuartii ER08274. In addition to their antibacterial activity, ceftazidime and ciprofloxacin could be effective in preventing the biofilm formation of E. coli and P. vulgaris.
Allergenic Potency of Spices: Hot, Medium Hot, or Very Hot
Authors: Schöll Isabella , Jensen-Jarolim Erika
Published: November 2004

Spices are the most attractive ingredients to confer an authentic taste to food. As they are derived from plants, they harbour allergenic potency and can induce symptoms ranging from mild local to severe systemic reactions. Due to the content of pharmacologically active substances of spices, the diagnosis of allergy and the differentiation from intolerance reactions may be difficult. Association with inhalative allergies via IgE cross-reactivity, but also direct gastrointestinal sensitization plays a role. This article is a botanical and allergological overview of the most important spices and molecules responsible for eliciting IgE-mediated reactions or cross-reactions. As no curative treatments are known at present, strict avoidance is recommended and, therefore, accurate labelling of pre-packed food is necessary.
Weight Loss–Associated Induction of Peroxisome Proliferator–Activated Receptor-α and Peroxisome Proliferator–Activated Receptor-γ Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice
Authors: Verreth Wim , De Keyzer Dieuwke , Pelat Michel , Verhamme Peter , Ganame Javier , Bielicki John K. , Mertens Ann , Quarck Rozenn , Benhabilès Nora , Marguerie Gérard , Mackness Bharti , Mackness Mike , Ninio Ewa , Herregods Marie-Christine , Balligand Jean-Luc , Holvoet Paul
Published: November 2004

Background—

Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown.

Methods and Results—

We studied the effect of diet restriction–induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator–activated receptors (PPAR)-α and PPAR-γ expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-α and PPAR-γ, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-α and PPAR-γ expression was inversely related to plaque volume and to oxidized LDL content in the plaques.

Conclusions—

Induction of PPAR-α and PPAR-γ in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome.
Genome-Wide Scan for Blood Pressure Suggests Linkage to Chromosome 11, and Replication of Loci on 16, 17, and 22
Authors: de Lange Marlies , Spector Tim D. , Andrew Toby
Published: November 2004

Hypertension was one of the first complex traits to be studied and is thought to be influenced by polygenic and multiple environmental risk factors. Several genomic studies have found suggestive logarithm of odds (LOD) scores for either blood pressure or essential hypertension, but few loci have been replicated. In this study, we performed a genome-wide linkage analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) on 1109 white female dizygotic twin pairs from the TwinsUK registry in London. Multipoint linkage analysis replicated the locations of 3 previously reported linkage peaks: on chromosome 16 at 65 cM (LOD 0.8 for SBP and 1.8 for DBP); on chromosome 17 at 70 cM (LOD 1.8 SBP); and at 35 cM on chromosome 22 (LOD 0.97 SBP and 0.99 DBP). Results from multipoint analysis showed 1 novel suggestive linkage for SBP (multipoint LOD 2.28; 2-point
P
=0.0007) at 35 cM on chromosome 11. Results were similar when those on blood pressure medication were excluded. These are encouraging results for hypertensive research and demonstrate that despite past disappointments, linkage studies can be used to replicate regions from other studies and potentially discover new genetic risk factors of moderate to large effect size. Considering the differences in selection and ascertainment of the previous linkage studies, these results also suggest that some quantitative trait loci are likely to influence the normal range of blood pressure and clinical hypertension, whereas others will be specific to each trait. Future studies should focus on the fine mapping of these replicated regions, which include potential candidate genes.
Utility of the Mantel-Haenszel Procedure for Detecting Differential Item Functioning in Small Samples
Authors: Fidalgo AÁngel M. , Ferreres Doris , MuÑiz JosÉ
Published: November 2004

Sample-size restrictions limit the contingency table approaches based on asymptotic distributions, such as the Mantel-Haenszel (MH) procedure, for detecting differential item functioning (DIF) in many practical applications. Within this framework, the present study investigated the power and Type I error performance of empirical and inferential criteria for DIF detection in small samples. Sample sizes (50/50, 100/50, 200/50, and 100/100 for the reference and focal groups, respectively), ability distributions (equal and unequal), and amount of DIF (moderate and high) were manipulated. The results show the advantages of employing theMHchi-square statistic using high levels of significance (• = .20) as opposed to the empirical criteria (cutoffs for categorizing DIF based on the magnitude of the MH common odds ratio estimator and the standardized p-difference statistic). Some considerations concerning Type I and Type II errors are made.
Teaching under High-Stakes Testing
Authors: Sutton Rosemary E.
Published: November 2004

In this article, the author reports on the curricular changes and testing focus that have occurred in her teaching since PRAXIS II: Principles of Learning and Teaching (PLT) tests were mandated in Ohio, where she teaches at an urban, open admissions, commuter university. Classroom dilemmas are analyzed as they relate to changes in assessments, curriculum content, and instructional strategies when teaching educational psychology to preservice teachers. The benefits and costs of the increased importance of educational psychology in the teacher education program and the advantages and disadvantages of trying to ensure that the students do well on someone else’s examination are also discussed. The author’s experiences are compared with published reports on teachers’ reactions to high-stakes testing, and the author considers how the context in which she teaches and her personal teaching biography influenced her decisions.
Spirituality, Religion, and Globalization
Authors: Kale Sudhir H.
Published: November 2004

Issues of spirituality and religion are seldom discussed in the globalization context. Spirituality and religion affect the globalization phenomenon and are, in turn, significantly influenced by globalization. This article explores the interplay between spirituality and religion, and the forces of economics, technology, and globalization. Contemporary globalization exhibits five main trends in spirituality and religion: increasing attempts to harness religion and spirituality as means toward reterritorialization, the integration of spirituality in all aspects of life, a greater thrust toward the individualization of spirituality among consumers, the enhanced role of cyberspace in the spiritual domain, and the syncretization of spirituality. These five trends affect quality of life as well as the relationship between governments and markets, two areas of interest to macromarketers.
Globalization and Development: An Expanded Macromarketing View
Authors: Kilbourne William E.
Published: November 2004

Macromarketing has expanded inquiry regarding globalization and development since its inception. It has included quality of life (QOL) and environmental measures, and argued that economic development should improve these variables. This article argues that an expanded view of development should also consider QOL, environment, and substantive freedoms as inputs to the development process because of the nature of the globalization process characterized as the spread of Western capitalist neoliberalism. Current global capitalism is an inadequate approach to development because of its focus on economic market relations. The relation among globalization, development, and neoliberalism is examined, showing that the process has economic, political, cultural, and environmental implications that must be addressed from a macromarketing perspective. The development process is unstable and can be problematic if a single model, neoliberalism, is applied to all lesser developed countries. As Russia’s experience suggests, development approaches that ignore nation-specific factors are likely to be problematic.
The Role of Consumer Agency in the Globalization Process in Emerging Markets
Authors: Eckhardt Giana M. , Mahi Humaira
Published: November 2004

In emerging markets, the main actors in the globalization process are widely considered to be governments and multinational corporations (MNCs). The authors examine the role of a key player that has largely been left out of the globalization debate—the consumer. Viewed through a lens of consumer agency, the authors outline important factors that influence whether new foreign goods that enter the marketplace are accepted, rejected, or transformed by consumers. This is investigated in the context of the Indian marketplace, an emerging market that has only recently had access to foreign goods. The authors’analysis suggests that consumers are not merely pawns of MNCs or governments. The framework developed to understand the complexities of consumer agency in an emerging market provides the first such effort to guide future empirical consumer globalization research.
The Persistence of Customer Profitability: Empirical Evidence and Implications From a Financial Services Firm
Authors: Campbell Dennis , Frei Frances
Published: November 2004

This study addresses three research questions related to persistence in customer profitability. How well does current customer profitability explain future customer profitability? Does current customer profitability fully reflect the future customer profitability implications of demographics and other customer characteristics? How do different components of customer profitability affect its persistence over time? The authors find that a substantial amount of variation in 1-year ahead customer profitability is left unexplained by current customer profitability. They also find that different components of customer profitability have vastly different levels of persistence and that data on customer demographics and other characteristics have little incremental value relative to current profitability in explaining future profitability. Segmenting customers based on how their profitability is generated within a profit tier reveals that the efficacy of predicting future profit tier based on current profit tier varies greatly even among customers in the same current profit tier.
Reconceptualizing Service Encounter Quality in a Non-Western Context
Authors: Raajpoot Nusser
Published: November 2004

This article seeks to explore the domain of service encounter quality as it exists in a non-Western culture and proceeds to develop a culturally sensitive multiple-item scale, PAKSERV. Both classical testing methods and item response theory measures were used for scale purification. The scale shows high internal reliability, convergent and discriminant validity at the scale level, and moderate to high category discrimination and information content at the item level. Multiple antecedents of encounter quality are discussed to explain the variation in encounter quality evaluations. Hypotheses are developed about the impact of a personal value system, national culture orientation, and consumer context variables on how consumers assign the importance weights to the dimensions of encounter quality. Using conjoint analysis, hypotheses are tested and quality management guidelines for service managers are developed.
Determining Attribute Importance in a Service Satisfaction Model
Authors: Gustafsson Anders , Johnson Michael D.
Published: November 2004

Determining the importance that customers place on the product and service attributes that drive their satisfaction with, and loyalty to, service providers is an essential part of a firm’s resource allocation process. An unsettled issue is whether importance measures should come directly from customers or be derived statistically and, if so, how. The authors compare direct importance ratings with a variety of methods for statistically deriving attribute importance in a customer satisfaction model. Using three data sets, the methods are compared on criteria that include their ability to explain variation in satisfaction, to identify customers’more important attributes, and to be interpretable. The findings suggest that because each of the tested methods has its strengths and weaknesses, it is essential to choose a method that is compatible with the research goals and context.
Tongue lesions in psoriasis: a controlled study
Authors: Daneshpazhooh Maryam , Moslehi Homayoon , Akhyani Maryam , Etesami Marjan
Published: November 2004

Background

Our objective was to study tongue lesions and their significance in psoriatic patients.

Methods

The oral mucosa was examined in 200 psoriatic patients presenting to Razi Hospital in Tehran, Iran, and 200 matched controls.

Results

Fissured tongue (FT) and benign migratory glossitis (BMG) were the two most frequent findings. FT was seen more frequently in psoriatic patients (n = 66, 33%) than the control group (n = 19, 9.5%) [odds ratio (OR): 4.69; 95% confidence interval (CI): 2.61–8.52] (p-value < 0.0001). BMG, too, was significantly more frequent in psoriatic patients (28 cases, 14%) than the control group (12 cases, 6%) (OR: 2.55; 95% CI: 1.20–5.50) (p-value < 0.012). In 11 patients (5.5%), FT and BMG coexisted.

FT was more frequent in pustular psoriasis (7 cases, 53.8%) than erythemato-squamous types (56 cases, 30.4%). On the other hand, the frequency of BMG increased with the severity of psoriasis in plaque-type psoriasis assessed by psoriasis area and severity index (PASI) score.

Conclusions

Nonspecific tongue lesions are frequently observed in psoriasis. Further studies are recommended to substantiate the clinical significance of these seemingly nonspecific findings in suspected psoriatic cases.
A survey of relationship between anxiety, depression and duration of infertility
Authors: Ramezanzadeh Fatemeh , Aghssa Malek Mansour , Abedinia Nasrin , Zayeri Farid , Khanafshar Navid , Shariat Mamak , Jafarabadi Mina
Published: November 2004

Background

A cross sectional study was designed to survey the relationship between anxiety/depression and duration/cause of infertility, in Vali-e-Asr Reproductive Health Research Center, Tehran, Iran.

Methods

After obtaining their consents, 370 female patients with different infertility causes participated in, and data gathered by Beck Depression Inventory(BDI) and Cattle questionnaires for surveying anxiety and depression due to the duration of infertility. This was studied in relation to patients' age, educational level, socio-economic status and job (patients and their husbands).

Results

Age range was 17–45 years and duration and cause of infertility was 1–20 years. This survey showed that 151 women (40.8%) had depression and 321 women (86.8%) had anxiety. Depression had a significant relation with cause of infertility, duration of infertility, educational level, and job of women. Anxiety had a significant relationship with duration of infertility and educational level, but not with cause of infertility, or job. Findings showed that anxiety and depression were most common after 4–6 years of infertility and especially severe depression could be found in those who had infertility for 7–9 years.

Conclusions

Adequate attention to these patients psychologically and treating them properly, is of great importance for their mental health and will improve quality of their lives.
Insulin expressing hepatocytes not destroyed in transgenic NOD mice
Authors: Tabiin Muhammad T , White Christopher P , Morahan Grant , Tuch Bernard E
Published: November 2004

Background

The liver has been suggested as a suitable target organ for gene therapy of Type 1 diabetes. However, the fundamental issue whether insulin-secreting hepatocytes in vivo will be destroyed by the autoimmune processes that kill pancreatic β cells has not been fully addressed. It is possible that the insulin secreting liver cells will be destroyed by the immune system because hepatocytes express major histocompatibility complex (MHC) class I molecules and exhibit constitutive Fas expression; moreover the liver has antigen presenting activity. Together with previous reports that proinsulin is a possible autoantigen in the development of Type 1 diabetes, the autoimmune destruction of insulin producing liver cells is a distinct possibility.

Methods

To address this question, transgenic Non-Obese Diabetic (NOD) mice which express insulin in the liver were made using the Phosphoenolpyruvate Carboxykinase (PEPCK) promoter to drive the mouse insulin I gene (Ins).

Results

The liver cells were found to possess preproinsulin mRNA, translate (pro)insulin in vivo and release it when exposed to 100 nmol/l glucagon in vitro. The amount of insulin produced was however significantly lower than that produced by the pancreas. The transgenic PEPCK-Ins NOD mice became diabetic at 20–25 weeks of age, with blood glucose levels of 24.1 ± 1.7 mmol/l. Haematoxylin and eosin staining of liver sections from these transgenic NOD PEPCK-Ins mice revealed the absence of an infiltrate of immune cells, a feature that characterised the pancreatic islets of these mice.

Conclusions

These data show that hepatocytes induced to produce (pro)insulin in NOD mice are not destroyed by an ongoing autoimmune response; furthermore the expression of (pro)insulin in hepatocytes is insufficient to prevent development of diabetes in NOD mice. These results support the use of liver cells as a potential therapy for type 1 diabetes. However it is possible that a certain threshold level of (pro)insulin production might have to be reached to trigger the autoimmune response.
Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro co-culture
Authors: Sadlonova Andrea , Novak Zdenek , Johnson Martin R , Bowe Damon B , Gault Sandra R , Page Grier P , Thottassery Jaideep V , Welch Danny R , Frost Andra R
Published: November 2004

Background

Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breast-associated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed.

Methods

NAF and CAF were grown with the nontumorigenic MCF10A epithelial cells and their more transformed, tumorigenic derivative, MCF10AT cells, in direct three-dimensional co-cultures on basement membrane material. The proliferation and apoptosis of MCF10A cells and MCF10AT cells were assessed by 5-bromo-2'-deoxyuridine labeling and TUNEL assay, respectively. Additionally, NAF and CAF were compared for expression of insulin-like growth factor II as a potential mediator of their effects on epithelial cell growth, by ELISA and by quantitative, real-time PCR.

Results

In relatively low numbers, both NAF and CAF suppressed proliferation of MCF10A cells. However, only NAF and not CAF significantly inhibited proliferation of the more transformed MCF10AT cells. The degree of growth inhibition varied among NAF or CAF from different individuals. In greater numbers, NAF and CAF have less inhibitory effect on epithelial cell growth. The rate of epithelial cell apoptosis was not affected by NAF or CAF. Mean insulin-like growth factor II levels were not significantly different in NAF versus CAF and did not correlate with the fibroblast effect on epithelial cell proliferation.

Conclusion

Both NAF and CAF have the ability to inhibit the growth of pre-cancerous breast epithelial cells. NAF have greater inhibitory capacity than CAF, suggesting that the ability of fibroblasts to inhibit epithelial cell proliferation is lost during breast carcinogenesis. Furthermore, as the degree of transformation of the epithelial cells increased they became resistant to the growth-inhibitory effects of CAF. Insulin-like growth factor II could not be implicated as a contributor to this differential effect of NAF and CAF on epithelial cell growth.
Outcome of Induction and Postremission Therapy in Younger Adults With Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study
Authors: Farag Sherif S. , Ruppert Amy S. , Mrózek Krzysztof , Mayer Robert J. , Stone Richard M. , Carroll Andrew J. , Powell Bayard L. , Moore Joseph O. , Pettenati Mark J. , Koduru Prasad R.K. , Stamberg Judith , Baer Maria R. , Block AnneMarie W. , Vardiman James W. , Kolitz Jonathan E. , Schiffer Charles A. , Larson Richard A. , Bloomfield Clara D.
Published: November 2004

Purpose

Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML).

Patients and Methods

In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide ± PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV).

Results

Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis.

Conclusion

In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.
Wall thickness variations in single-point incremental forming
Authors: Young D , Jeswiet J
Published: November 2004

Single-point incremental forming is an innovative sheet metal forming method employing a standard computer numerical controlled (CNC) vertical milling machine and basic tooling. Traditionally the part is formed with a single-pass tool-path technique. A double-pass technique has been proposed as a way to modify the final thickness profile of steep geometry. Wall thickness profiles of a series of test cones have been measured and have shown that the formation of the characteristic thinning band present in single-pass forming can be delayed. Double-pass forming can allow the production of parts that thin to failure with single-pass techniques.