bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Kinase C- and Reactive Oxygen Species-Dependent Stimulation of Intracellular cAMP in Human Eosinophils
Authors: Ezeamuzie Charles I. , Taslim Najla
Published: October 2008

Objective: The objective of this study was to investigate the role of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in the signalling pathway of the novel protein kinase C (PKC)- and reactive oxygen species (ROS)-dependent stimulation of intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) production in human eosinophils. Materials and Methods: Immunomagnetically purified human eosinophils were stimulated in vitro with a PKC activator, phorbol myristate acetate (PMA), and the cAMP response in the presence of a phosphodiesterase inhibitor, rolipram, was determined. The role of ERK1/2 phosphorylation was investigated using specific inhibitors and Western blot analysis. Results: The PMA-stimulated eosinophils responded with a profound increase in intracellular levels of cAMP that was dependent on both PKC and ROS, as confirmed by the use of specific inhibitors: Ro 31-8220 for PKC and diphenyleneiodonium (DPI) for the ROS-generating enzyme NADPH oxidase. Pre-treatment of cells with the ERK1/2 inhibitor PD 98059, but not the p38-MAPK inhibitor SB203580, nor the PI3 kinase inhibitor, wortmannin, abolished the response. PMA treatment induced the phosphorylation of ERK1/2 with a time course that is consistent with a role in the cAMP response. The ERK1/2 phosphorylation was abolished by the ERK1/2 inhibitor PD 98059 and the PKC inhibitor Ro 31-8220, but not the NADPH oxidase inhibitor DPI. Conclusion: These results reveal the involvement of ERK1/2 in the signalling mechanism of PMA-stimulated, PKC- and ROS-dependent stimulation of cAMP production in human eosinophils, and show that ERK1/2 phosphorylation is upstream of ROS production in the signalling pathway.
Comparison of Inflammatory Breast Cancer and Noninflammatory Breast Cancer in Western Turkey
Authors: Karaca Saydam Birsen , Goksel Gamze , Korkmaz Esra , Zekioglu Osman , Kapkac Murat , Sanli Ulus Ali , Uslu Ruchan , Sezgin Canfeza
Published: October 2008

Objective: The study was aimed at investigating the clinical and biological features and survival outcomes of patients who were treated for metastatic inflammatory and noninflammatory breast carcinoma. Subjects and Methods: One hundred and sixty-seven metastatic breast cancer patients were enrolled into this study and divided into two groups: inflammatory (n = 46) and noninflammatory (n = 121). The clinical and hormone receptor status, c-erbB-2, Ki-67, and p53 expression, based on the immunohistochemical staining patterns, were compared between the two groups. Results: The inflammatory breast carcinoma group had a younger patient population, higher rate of adjuvant anthracycline therapy, number of lymph node metastases, rates of extranodal extension and c-erbB-2 overexpression than noninflammatory breast cancer patients (p < 0.05). With regard to survival, there were slightly better outcomes in the noninflammatory breast carcinoma group (30 months) compared to the inflammatory breast carcinoma group (23 months), but the difference was not statistically significant (p = 0.08). While survival results of p53-negative inflammatory and noninflammatory breast carcinoma patients were similar, p53-positive survival was significantly worse (p < 0.05) in inflammatory breast cancer carcinoma patients. Conclusion: Because of c-erbB-2 overexpression in inflammatory breast carcinoma patients, treatment options including trastuzumab could have given better survival outcomes. Survival of inflammatory breast carcinoma patients with a low p53 immunohistochemistry staining appeared similar to that for noninflammatory breast carcinoma. For this reason, new treatment options are needed especially in inflammatory breast carcinoma patients with high p53 positivity.
Outcome Measures and Psychomotor Skills Related to Shoulder Conditions for Clinical Orthopedic Training
Authors: Mahomed Surreya , Al-Obaidi Saud , Al-Zoabi Baker
Published: October 2008

Objective: This study was designed to assess the ability of physical therapy (PT) students to utilize selected outcome measures such as range of motion (ROM), pain and a number of psychomotor skills and to determine the efficacy of treatment they carried out during orthopedic clinical training. Materials and Methods: The clinical education booklets in orthopedics of all PT students over a 6-year period were reviewed. Students’ application of psychomotor skills such as peripheral joint mobilizations (PJM), proprioceptive neuromuscular facilitation (PNF) techniques, therapeutic exercise techniques as well as utilization of basic outcome measures such as ROM and pain were analyzed with descriptive statistics and paired t test. Results: A majority of students used PJM techniques (78.6%) and PNF techniques (58.6%). The paired t test indicated that treatment interventions used by the students were associated with improved shoulder joint ROM and decreased pain levels (p < 0.001). At the same time, therapeutic exercises were employed by the students after PJM and PNF. The most common ‘comparable joint sign’ was limitation in shoulder abduction ROM, which occurred in 44% of patients seen by the students. Conclusion: PT students’ application of PJM, PNF, and therapeutic exercise improved ROM and decreased pain in patients with shoulder pathologies.
Lymphatic Microvessel Density and the Expression of Lymphangiogenic Factors in Oral Squamous Cell Carcinoma
Authors: Ali Mohammad A.
Published: October 2008

Objective: In this study, the expression of several lymphangiogenic growth factors was investigated to determine the mechanism underlying lymphangiogenesis in oral squamous cell carcinoma (OSCCa). Materials and Methods: An immunohistochemical study was performed to determine the lymphatic microvessel density (LMVD) and the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGF-I/II), and hepatocyte growth factor (HGF) in 25 OSCCa and 20 normal oral mucosal tissue samples. Results: Significantly higher levels of expression of VEGF, PDGF, bFGF, HGF, IGF-I, and IGF-II existed in OSCCa tissue compared to normal oral mucosal tissue (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.01, respectively; Mann-Whitney test). In OSCCa samples, significant positive correlations, based on the Spearman correlation test, existed between the LMVD and VEGF (r = 0.573; p < 0.01), PDGF (r = 0.559; p < 0.01), bFGF (r = 0.516; p < 0.01), HGF (r = 0.448; p < 0.05), and IGF-I (r = 0.6; p < 0.01), but no correlation existed between LMVD and IGF-II (r = 0.380; p > 0.05). Conclusion: These findings indicate that several growth factors may promote lymphangiogenesis in OSCCa. Future treatment for OSCCa utilizing antilymphangiogenic agents should target these different growth factor signaling pathways that are involved in lymphangiogenesis in OSCCa.
Pantoea agglomerans Bloodstream Infection in Preterm Neonates
Authors: Aly Nasser Yehia A. , Salmeen Hadeel N. , Lila Reda A. Abo , Nagaraja Prem A.
Published: October 2008

Objective: To report an uncommon incidence of sporadic bloodstream infection (BSI) caused by Pantoea agglomerans in preterm neonates. Case Presentation and Intervention: Fives cases of nosocomial BSI with P. agglomerans in preterm neonates (weight ≤1,500 g; age 8–17 days; gestational age 26–30 weeks) are presented. All cases were late onset neonatal sepsis (>7 days of age). Lethargy, skin mottling and bradycardia were often present. Although there was no evidence of pneumonia, desaturation was a common feature. Thrombocytopenia developed in 4 patients, metabolic acidosis in 2 and jaundice in 2. No bleeding tendency or disseminating intravascular coagulation was recorded. Organisms cultured from blood were identified by the Vitek-2 system (bioMérieux, France) and the findings confirmed by testing the isolate on the API 20E system. All isolates shared in vitro susceptibility to gentamicin, amikacin, ciprofloxacin, piperacillin/tazobactam and meropenem. One patient was treated with a cefotaxime/amikacin combination, 2 with meropenem and the remaining 2 with tazocin. All patients responded well to antibiotic treatment and survived. Conclusion:P. agglomerans is an unusual pathogen in the etiology of neonatal sepsis. Despite significant clinical deterioration, early detection and proper antibiotic therapy carry a favorable outcome.
Acute Lymphoblastic Leukemia Presenting as Bilateral Renal Enlargement in a Child
Authors: Ali S.H.G. , Yacoub F.M. , Al-Matar E.
Published: October 2008

Objective: To report a case with early presentation of acute lymphoblastic leukemia (ALL) as bilateral renal masses and renal failure. Clinical Presentation and Intervention: A 6-year-old boy was admitted with bilaterally enlarged kidneys and severe renal impairment. Magnetic resonance imaging (MRI) showed bilateral renal enlargement with features suggestive of an infiltrative lesion. Accordingly, bone marrow examination was performed, and diagnosis of ALL was made. The patient developed acute renal failure after initiation of chemotherapy, so he received hemodialysis. His renal function normalized and kidney enlargement regressed. Conclusion: This case demonstrates an unusual early renal involvement in ALL in a child. MRI is a valuable imaging modality in the evaluation of renal masses.
Treatment of Stable Atrial Fibrillation in the Emergency Department: A Population-Based Comparison of Electrical Direct-Current versus Pharmacological Cardioversion or Conservative Management
Authors: Dankner Rachel , Shahar Amir , Novikov Ilya , Agmon Uri , Ziv Arnona , Hod Hanoch
Published: October 2008

Objective: To compare the success rates and short-term complications of three treatment approaches, pharmacological and direct-current cardioversion (DCC), or ‘wait-and-watch’ among stable atrial fibrillation (AF) patients in the emergency department (ED). Methods: All AF-related ED admissions during a 1-year period were retrospectively reviewed, and those meeting criteria of eligibility for immediate cardioversion, based on clinical stability, AF duration and adequacy of anticoagulation, were included. The propensity score approach generalized for the three groups was used to adjust for the observational non-randomized study nature. Results: Among 374 eligible patients, the rate of successful cardioversion was higher in DCC than in pharmacological or wait-and-watch groups (78.2, 59.2 and 37.9% respectively, p < 0.001), with corresponding percentages of patients discharged from ED (52.9, 47.9 and 32.1%, p < 0.01) and respective odds ratios of 6.00, 2.47 and 1, adjusting for seniority of the treating physician, age, gender and patient comorbidities. DCC was 2.43 times more effective than pharmacological treatment in achieving sinus rhythm (95% confidence interval = 1.36–4.33, p = 0.003). Rehospitalization within 14 days due to probable AF-treatment-related complications of home-discharged patients was 3.4%. Conclusions: DCC was found to be the most effective treatment, with few short-term complications following conversion of stable AF patients to sinus rhythm in the ED.
Use of Oral Erythromycin for the Treatment of Gastrointestinal Dysmotility in Preterm Infants
Authors: Ng Pak C.
Published: October 2008

Milk intolerance due to functional gastrointestinal (GI) dysmotility is a common problem in preterm infants. In the past decade, erythromycin has been used for its motilinomimetric effect to facilitate enteral feeding in preterm infants. Although earlier studies suggested that erythromycin is an effective prokinetic agent, recent randomized control trials (RCTs) reveal conflicting findings. This review assesses the evidence from all RCTs performed to date on erythromycin for preterm infants. The results suggest that oral erythromycin administered in intermediate or high doses as a rescue treatment is associated with a shorter time to attain full enteral feeding and decrease in the duration of requirement for parenteral nutrition. More importantly, the outcome study further indicates that oral erythromycin can reduce the incidence of parenteral nutrition-associated cholestasis by almost 50% and decreases the incidence of recurrent septicemia. None of the RCTs reported any sinister adverse effects, in particular, hypertrophic infantile pyloric stenosis or fatal cardiac arrhythmia. Nonetheless, as long-term outcomes have not been fully evaluated, neonatologists should use this treatment cautiously and selectively in preterm infants with moderately severe GI dysmotility.
The C242T Polymorphism of the NAD(P)H Oxidase p22phox Subunit Is Associated with an Enhanced Risk for Cerebrovascular Disease at a Young Age
Authors: Genius Just , Grau Armin J. , Lichy Christoph
Published: October 2008

Background and Purpose: Oxidative stress has been proposed as a major contributing factor for vascular disease, that acts independently from its participation in predisposing disorders such as diabetes and arterial hypertension. A functionally relevant C242T polymorphism of the CYBA gene encoding the NAD(P)H oxidase p22phox subunit, is supposed to lead to an abnormal reduction in the generation of reactive oxygen species in vascular smooth-muscle and endothelial cells. Methods: We investigated the p22phox C242T single-nucleotide polymorphism by polymerase chain reaction in consecutive patients with ischemic stroke or transient ischemic attack under the age of 50 (n = 161) and in population-based control subjects (n = 136). Results: Homozygosity for the T variant was associated with an enhanced risk for cerebral ischemia (odds ratio 3.85, confidence interval 1.39–10.64) after adjusting for classical risk factors. Risk for cerebral ischemia was not increased in heterozygous subjects. Conclusion: The p22phox C242T single-nucleotide polymorphism is associated with stroke risk. This finding supports the hypothesis that oxidative stress may contribute to stroke pathogenesis.
Brain Natriuretic Peptide as a Surrogate Marker for Cardioembolic Stroke with Paroxysmal Atrial Fibrillation
Authors: Naya Takayuki , Yukiiri Kazushi , Hosomi Naohisa , Takahashi Tsutomu , Ohkita Hiroyuki , Mukai Mao , Koziol James A. , Kohno Masakazu
Published: October 2008

Background: Cardioembolic stroke generally results in severer disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic from noncardioembolic stroke (atherothrombotic and lacunar stroke), whenever ischemic stroke patients have sinus rhythm at the time of presentation. Methods: In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic or noncardioembolic stroke and assessed whether this could provide a basis for differentiating cardioembolic stroke (especially due to paroxysmal atrial fibrillation) from noncardioembolic stroke. Our patient cohort consisted of 99 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005, to December 31, 2006. We excluded 23 patients with valve disease, heart failure, myocardial infarction or chronic renal failure. The mean age of the remaining 76 patients (51 males, 25 females) was 70.0 ± 10.1 years. Results: Thirty-six patients had cardioembolic stroke with atrial fibrillation (including permanent and paroxysmal atrial fibrillation); the remaining 40 had noncardioembolic stroke. The plasma brain natriuretic peptide was evaluated on the first morning after admission in all patients. In cardioembolic stroke with atrial fibrillation (permanent and paroxysmal atrial fibrillation), the plasma brain natriuretic peptide, ratio of peak early filling velocity to peak atrial systolic velocity (E/A) and left atrial diameter were significantly increased (p < 0.001), and the left atrial appendage flow was significantly decreased (p < 0.001), compared with noncardioembolic stroke. Analyzed in those 4 factors, cardioembolic stroke was strongly predicted with >95% accuracy assessed by plasma brain natriuretic peptide and left atrial appendage flow. Conclusion: From our results, it was suggested that the first-day brain natriuretic peptide and left atrial appendage flow measurements would be helpful in differentiating cardioembolic stroke with atrial fibrillation from noncardioembolic stroke.
Estimating the Prevalence of Sleep-Disordered Breathing in Community-Based, Long-Term Stroke Survivors Using a Validated Predictive Model
Authors: Pearce Dora C. , Cadilhac Dominique A , Pierce Robert J. , Thrift Amanda G. , Davis Stephen , Donnan Geoffrey A.
Published: October 2008

Background: Assessing sleep-disordered breathing (SDB) in aged or disabled populations is difficult. Aims: To validate a multivariable apnea risk prediction index (MAPI) in stroke survivors and estimate SDB prevalence (apnea-hypopnea index ≧10) in a community-based stroke cohort. Methods: Self-reported sleep apnea symptoms, demographic and anthropometric data were obtained from a hospital-based (SCOPES II, n = 152) and a community-based (NEMESIS, n = 431) cohort at about 3 years after stroke. Logistic regression models for prediction of SDB using the MAPI were validated with home-based nocturnal polygraphic data recordings obtained in 74 SCOPES II participants. Results: NEMESIS subjects (median age 76, females 45%) were older than SCOPES II subjects (median age 70, females 42%). SDB prevalence was 44.9% in the nocturnal polygraphy subset, and estimated as 44.1% (SCOPES II) and 50.6% (NEMESIS) using a modified MAPI. Conclusion: The MAPI can be reliably used in stroke cohorts and SDB affects about half of chronic stroke survivors.
Perinatal Exposure to Low-Dose BDE-47, an Emergent Environmental Contaminant, Causes Hyperactivity in Rat Offspring
Authors: Suvorov Alexander , Girard Sylvie , Lachapelle Sophie , Abdelouahab Nadia , Sebire Guillaume , Takser Larissa
Published: October 2008

Background: Polybrominated diphenyl ethers (PBDE) are a group of environmental contaminants increasing in North America. Few data are available on neurobehavioral effects at low-dose exposure. Objectives: Our goal in the present study was to evaluate whether low-dose BDE-47, which is the most abundant PBDE in human samples, affects the neurobehavioral development of rats. Methods: Dams were exposed to vehicle or low-dose BDE-47 (0.002, 0.02 and 0.2 mg/kg body weight) each 5 days from gestational day 15 to postnatal day (PND) 20 by intravenous injections. Spontaneous locomotor activity of pups was assessed using the open field test on PND 15, 20 and 25. Sensorimotor coordination was assessed using a RotaRod on PND 30. Results: Exposure to BDE-47 increased locomotor activity of pups. Developmental landmarks and sensorimotor coordination were not influenced by exposure to BDE-47. BDE-47 content in adipose tissue of exposed rats was similar to that known for human populations. Conclusion: These results indicate neurodevelopmental disruption induced in rats by BDE-47 at levels found in the human population.
Archived Unfrozen Neonatal Blood Spots Are Amenable to Quantitative Gene Expression Analysis
Authors: Haak Peterson T. , Busik Julia V. , Kort Eric J. , Tikhonenko Maria , Paneth Nigel , Resau James H.
Published: October 2008

Background: State laws in the USA mandate that blood be drawn from all newborn infants to screen for health-threatening conditions. These screening assays consume only a small portion of the blood samples, which are collected on filter paper (‘Guthrie’) cards. Many states archive unused blood spots, often in unrefrigerated storage. Objectives: While individual RNA transcripts have been identified from archived neonatal blood spots, no study to date has performed quantitative analysis of archived blood spot RNA. Methods: We demonstrate that RNA can be isolated and amplified from newborn blood spots stored unfrozen for as long as 9 years, and can be analyzed by microarray and qPCR. Results: Microarray assays of archived neonatal blood spots consistently detected 3,000–4,000 expressed genes with correlations of 0.90 between replicates. Blood spot mRNA is amenable to qPCR and we detected biologically relevant expression levels of housekeeping and immune-mediating genes. Conclusions: These experiments demonstrate the feasibility of using blood spots as a source of RNA which can be analyzed using quantitative microarray and qPCR assays. The application of these methods to the analysis of widely collected biological specimens may be a valuable resource for the study of perinatal determinants of disease development.
In vivo and T Cell Cross-Reactivity between Walnut, Cashew and Peanut
Authors: Kulis Michael , Pons Laurent , Burks A. Wesley
Published: October 2008

Background: Examination of IgE cross-reactivity among nuts has been limited to in vitro experiments. Cross-reactivity studies of nuts at the T cell level are difficult to interpret because of the inability to determine which cellular responses are from a true sensitization and which are due to cross-reactivity. Using a mouse model in which the sensitizing nuts are controlled may provide novel methods to investigate in vivo and T cell cross-reactivity. Methods: C3H/HeJ mice were sensitized by intraperitoneal injection of cashew alone (monosensitized mice), or cashew plus walnut, utilizing alum as an adjuvant. Both groups underwent challenges to cashew, walnut and peanut, with subsequent monitoring of anaphylactic reactions. Anaphylactic antibodies were quantified by ELISA, and protein allergens were identified by Western blotting. Cellular responses were studied via splenocyte proliferation assay and measurement of secreted cytokines. Results: The monosensitized mice reacted to cashew and walnut during challenges, with significantly weaker reactions induced on challenge with peanut. Cross-reactive IgE to walnut and peanut were detected by ELISA, and the cross-reactive allergens were identified as vicilin proteins. In cellular assays, splenocytes from the monosensitized mice proliferated and produced IL-4 and IL-5 in response to cashew, walnut and peanut. The cashew- plus walnut-sensitized mice experienced stronger clinical reactions to walnut, recognized additional walnut allergens and secreted significantly more IL-4 and IL-5 in walnut-stimulated splenocyte assays compared to the monosensitized mice. Conclusions: Cross-reactivity in vivo was found between cashew and walnut, while cross-reactivity among cashew, walnut and peanut was demonstrated at the T cell level.
Increased Surfactant Protein A and D Expression in Acute Ovalbumin-Induced Allergic Airway Inflammation in Brown Norway Rats
Authors: Schmiedl A. , Lührmann A. , Pabst R. , Koslowski R.
Published: October 2008

Background: The surfactant proteins SP-A and SP-D, components of the innate immune system, are involved in host defence. Objective: We tested the hypothesis that ovalbumin (OVA) challenge leads to an upregulation of both proteins in alveolar epithelial type II cells (AEII) and Clara cells and to an enhanced uptake by macrophages. Methods: After sensitization with OVA and heat-killed Bordetella pertussis challenge followed intratracheally with 0.5% OVA on day 13. One day after challenge lung tissue and bronchoalveolar lavage fluid (BALF) of sensitized NaCl- and OVA-challenged Brown Norway rats were compared with home cage controls using qRt-PCR, Western blot and immunohistochemistry. Results: After OVA challenge (1) eosinophils increased significantly in the BALF, (2) the total amount of SP-A and SP-D was significantly increased in lung tissue, (3) the amount of SP-A was significantly and the amount of SP-D was remarkably elevated in BALF, and (4) the levels of SP-A and SP-D mRNA in lung tissue were significantly elevated. Using quantitative immunohistochemistry, we found (5) significantly higher surface fractions of SP-A- and SP-D-labelled AEII, (6) no differences in the surface fractions of SP-A- and SP-D-labelled bronchial Clara cells, and (7) a significantly increased cell density of unlabelled and SP-A-labelled macrophages. Conclusions: Thus, combining molecular biological and histological methods we suggest that after OVA challenge (1) AEII but not Clara cells show a significantly higher expression of SP-A and SP-D leading also to higher amounts of both SPs in BALF and (2) macrophages gather predominantly SP-A.
A Common Exonic Variant of Interleukin21 Confers Susceptibility to Atopic Asthma
Authors: Chatterjee Rajshekhar , Batra Jyotsna , Ghosh Balaram
Published: October 2008

Background: Interleukin (IL)-21, an IL-2 family multifunctional cytokine, is produced by activated CD4+ T cells and is known to potentially affect growth, survival and function of numerous immune cells. As IL-21 regulates IgE production, a key mediator of various allergic disorders and asthma, it is a prime candidate gene for studying atopic asthma. Methods: In atopic asthma, analyses of four single nucleotide polymorphisms (SNP; C1455T, G1472T, C5250T and C8381T), a tetranucleotide microsatellite repeat (GAAT)n and their haplotypes were performed, and serum total IgE (TsIgE) was determined in ethnically matched unrelated patients (n = 255), unrelated controls (n = 245) and nuclear families (n = 140). Correlation between an exonic SNP C5250T in the asthmatics with serum IL-21 levels was also made. Results: In both the case-control and family study groups, the exon-3 polymorphism C5250T of the IL21 gene was significantly associated with atopic asthma and TsIgE. The C5250T polymorphism was found to affect the concentration of serum IL-21 levels in atopic asthmatics. Also, this observation was supported by the structural alteration in IL21 mRNA as predicted by mfold software. Further, our haplotypic studies indicated that while minor haplotypes 4_C_T_C_C and two locus haplotype T_C were associated with asthma in the case-control cohort, none of the major haplotypes was found to be associated with either asthma or TsIgE levels. Conclusion: Our study provides evidence that IL21 is associated with atopic asthma, TsIgE and serum IL-21 levels. Thus, it may initiate further research to elucidate the role of the IL21 gene in asthma pathogenesis.
Cysteinyl Leukotrienes Induce Macrophage Inflammatory Protein-1 in Human Monocytes/Macrophages
Authors: Ichiyama Takashi , Hasegawa Masanari , Hashimoto Kunio , Matsushige Takeshi , Hirano Reiji , Furukawa Susumu
Published: October 2008

Background: Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β are known for their chemotactic and proinflammatory effects on monocytes/macrophages which have a cysteinyl leukotriene 1 (CysLT1) receptor. Methods: We examined MIP-1α and MIP-1β production stimulated by CysLTs (LTC4, LTD4, and LTE4) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT1 receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1α and MIP-1β production by CysLTs. Results: ELISA demonstrated that CysLTs induced MIP-1α and MIP-1β production in THP-1 cells and PBMCs. PCR demonstrated that LTD4 increased MIP-1α and MIP-1β mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1α and MIP-1β production promoted by LTD4 in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1α and MIP-1β production by LTD4 in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not. Conclusion: CysLTs induce MIP-1α and MIP-1β production mediated by ERK via binding to the CysLT1 receptor in human monocytes/macrophages.
Comparative Study of Cluster and Conventional Immunotherapy Schedules with Dermatophagoides pteronyssinus in the Treatment of Persistent Allergic Rhinitis
Authors: Zhang Luo , Wang Chengshuo , Han Demin , Wang Xiangdong , Zhao Yan , Liu Jianhui
Published: October 2008

Background and Objectives: Allergy to house dust mite is one of the most common causes of allergic rhinitis (AR) in China. We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR. Methods: The trial was a prospective and randomized study involving 96 patients with persistent AR, aged 14–60 years, who were allergic to Dermatophagoides pteronyssinus. While 48 patients were randomly assigned to the cluster schedule reaching the maintenance dose within 6 weeks, the other 48 were randomly assigned to the conventional schedule reaching the maintenance dose within 14 weeks. Eighty-nine patients completed a 1-year treatment course. While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment, quality of life, cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment. Results: The cluster schedule reduced the time to reach the maintenance dose by 57% and caused mild systemic adverse reactions after 1.0% of injections (6.7% of patients), with no differences in comparison with the conventional schedule. Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule. Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year. Conclusions: The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner.
Cerebral Vasculitis and Stroke in Lyme Neuroborreliosis
Authors: Topakian Raffi , Stieglbauer Karl , Nussbaumer Karin , Aichner Franz T.
Published: October 2008

We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided.
Assessment of Feasibility of Endovascular Treatment of Ruptured Intracranial Aneurysms with 16-Detector Row CT Angiography
Authors: van der Jagt Mathieu , Flach H. Zwenneke , Tanghe Hervé L.J. , Bakker Stef L.M. , Hunink M.G. Myriam , Koudstaal Peter J. , van der Lugt Aad
Published: October 2008

Background: It is unclear whether 16-detector row CT angiography (CTA) can replace digital subtraction angiography (DSA) to assess the feasibility of endovascular treatment (EVT) in the acute phase after aneurysmal subarachnoid hemorrhage. Methods: We studied 80 consecutive patients with aneurysmal subarachnoid hemorrhage, who underwent both CTA and DSA. Two interventional neuroradiologists independently scored CTA and, immediately thereafter, DSA with respect to feasibility of EVT. We determined whether CTA without DSA was sufficient for a definite judgment. We also assessed interobserver agreement. Results: The 2 readers judged EVT to be feasible in 24 and 37 patients with CTA alone and not feasible in 34 and 20 patients. In these patients, DSA yielded additional information in 6 (reader 1) and 5 patients (reader 2), which did not affect treatment decision. In 19 and 7 patients, DSA was considered inferior to CTA. In the remaining patients (n = 22 and 23, respectively), feasibility of EVT could not be judged with CTA alone, and DSA results were required in addition for a treatment decision. Interobserver agreement on feasibility of EVT was just fair (ĸ <0.40). Conclusions: In our series of patients, 16-detector row CTA was a reliable investigation to assess feasibility of EVT of ruptured intracranial aneurysms in most patients. Further, we found that interobserver disagreement on feasibility of EVT was considerable.
Prognosis of Symptomatic and Asymptomatic Middle Cerebral Artery Occlusion
Authors: Kang Bong-Su , Kwon Hyung-Min , Ryu Wi-Sun , Lee Yong-Seok
Published: October 2008

Background: The annual risk of stroke or cardiovascular events has been reported to be over 10% in middle cerebral artery stenosis. However, the prognosis of patients with middle cerebral artery occlusion (MCAO) remains unclear. We investigated the risk of cardiovascular events or death in patients with symptomatic or asymptomatic MCAO. Methods: Consecutive patients with MCAO demonstrated by transcranial Doppler sonography and magnetic resonance angiography were enrolled. Medical records were reviewed during the follow-up period and a telephone interview was conducted using a preformed questionnaire, comparing asymptomatic and symptomatic patients who had a history of ischemic stroke or transient ischemic attack in the same vascular territory. The composite outcome of ipsilateral stroke, hemorrhagic stroke, overall stroke, myocardial infarction (MI), any vascular death and nonvascular death was evaluated during the follow-up period. Results: Thirty-seven of the 48 patients were symptomatic and 11 were asymptomatic. During the mean follow-up period of 2.8 years, cardiovascular events or death occurred in a total of 13 patients: 1 from the asymptomatic group and 12 from the symptomatic group (overall stroke, 6; MI, 2; vascular death, 1; nonvascular death, 5). The annual rates of composite outcome (2.2 vs. 13.2%, p = 0.041) and overall stroke (0.0 vs. 6.6%, p = 0.048) were significantly lower in the asymptomatic group. Conclusion: These results suggest that the overall prognosis of MCAO is not worse than previously reported for patients with middle cerebral artery stenosis or internal carotid artery stenosis. Asymptomatic MCAO seems to be a benign condition associated with a low risk of subsequent stroke, MI or death under the optimal medical therapy.
Spinal Cord Infarction in Chinese Patients
Authors: Cheng Mei-Yun , Lyu Rong-Kuo , Chang Yeu-Jhy , Chen Rou-Shayn , Huang Chin-Chang , Wu Tony , Lee Tsong-Hai , Lu Chin-Song , Ro Long-Sun
Published: October 2008

Background: The clinical presentations, MRI findings and outcomes for spinal cord infarction (SCI) are well documented in the West but scarce in the East. We investigated the clinical characteristics of SCI patients and further analyzed etiologies and prognostic factors in Chinese subjects. Methods: We reviewed all SCI patients from March 1993 to March 2007. Clinical symptoms, laboratory and imaging findings as well as outcomes were retrospectively analyzed. Results: Twenty-two patients (12 female) were identified; their mean age was 57.6 years. Nine patients (40.9%) had probable etiologies, while 13 were cryptogenic (59.1%). The primary etiologies were aortic diseases. Hypertension was the most common vascular risk factor (50%). Most patients (10/22 = 45.5%) had thoracolumbar lesions (mainly at T9–L1), while cervical lesions (9/22 = 40.9%) were the second most common (mainly at C4–C7). ‘Owl’s eyes’ signs were common with the anterior spinal artery (93.8%) and central cord infarctions (50%) but not in the posterior spinal artery or transverse spinal infarctions. After a mean follow-up of 18 months, only 10 patients (10/22 = 45%) had good outcomes (independent walking or walking with 1 aid). Conclusion: Most SCI patients had acute, monophasic symptoms, reaching nadir in <24 h. The subjects frequently had acute pain near their lesions before SCI signs/symptoms (16/22 = 72.7%). Initial severe weakness (Medical Research Council score ≤2) and a young age at onset (55 years old) are correlated with poor recovery of motor functions.
Serum Urate Predicts Long-Term Risk of Acute Coronary Events in Women after a Transient Ischaemic Attack and Stroke
Authors: Koton Silvia , Howard Sally C. , Warlow Charles P. , Murphy Michael F.G. , Rothwell Peter M.
Published: October 2008

Background: Several studies have shown serum urate to be an independent risk factor for vascular disease, but others have not, although a stronger association in women than in men has been a consistent finding. Studies of stroke patients have shown possible associations between urate level and stroke severity, but there have been no large cohort studies of the effect of urate on the long-term risk of future vascular events in patients with a transient ischaemic attack (TIA) or stroke. We studied this relationship in 2 independent cohorts. Methods: Individual data on 15,483 patient-years of follow-up from the UK-TIA trial (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the risks of stroke and acute coronary events (ACE) were obtained from Cox models stratified by study, with and without adjustment for potential confounders. Potential interactions between urate and baseline characteristics were also assessed. Results: Linear associations between urate and risk of ACE were found in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06–1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous myocardial infarction or angina were effect modifiers, but only the effect of sex remained after adjustment for other risk factors (p = 0.002), with a 5th:1st quintile hazard ratio of 4.23 (1.97–9.07, p < 0.0001) in women and 1.09 (0.70–1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No associations were found between urate level and either risk or severity of stroke. Conclusions: High urate levels were independent predictors of long-term risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent studies. Urate levels could be useful in identifying women at high risk of coronary events in routine practice.
Co-Expression of HSV2 and Chlamydia trachomatis in HPV-Positive Cervical Cancer and Cervical Intraepithelial Neoplasia Lesions Is Associated with Aberrations in Key Intracellular Pathways
Authors: Paba Pierpaolo , Bonifacio Daniela , Di Bonito Luigi , Ombres Domenico , Favalli Cartesio , Syrjänen Kari , Ciotti Marco
Published: October 2008

Objective: Oncogenic human papillomaviruses (HPVs) are the etiological agents of cervical cancer. Different cofactors might be needed for malignant transformation, but they still remain elusive. Methods: To delineate the role of Chlamydia trachomatis (CT) and herpes simplex virus type 2 (HSV2) in HPV-positive cervical intraepithelial neoplasia (CIN) lesions and cervical carcinoma a series of 149 cervical cancer and CIN biopsies were analyzed for CT and HSV2 DNA by PCR, and HPV genotyped by InnoLipa. Monitoring of aberrations in key intracellular pathways due to CT/HSV2 and HPV co-expression were analyzed with 13 biomarkers. Results: Of the 149 samples tested, 136 were HPV DNA positive; 32/136 contained also CT DNA and 29 HSV2 DNA. Detection of CT was significantly (p = 0.0001) related to multiple-type HPV infections, while HSV2 was of borderline significance (p = 0.053). Of the 13 biomarkers tested, cytoplasmic and nuclear NF-ĸB and VEGF-C were significantly increased in CT+/HPV+ lesions; p = 0.023, p = 0.045, and p = 0.020 as well as survivin, p = 0.026. Survivin was the only marker that was overexpressed also in HSV2+/HPV+ lesions, p = 0.027. Conclusions: CT infection favors the entry and persistence of multiple HR-HPV types, which leads to viral integration, inhibition of apoptosis, overexpression of E6/E7 oncogenes and cell transformation.
Genotyping of Hepatitis B Virus – Genotypes A to G by Multiplex Polymerase Chain Reaction
Authors: Liu Wen-Chun , Lindh Magnus , Buti Maria , Phiet Pham Hoang , Mizokami Masashi , Li Hsi-Hsien , Sun Koun-Tem , Young Kung-Chia , Cheng Pin-Nan , Wu I-Chin , Chang Ting-Tsung
Published: October 2008

Objectives: Eight genotypes (A–H) of hepatitis B virus (HBV) are known with variations in nucleotide sequences greater than 8%. Several recent publications found that the clinical course and outcome of antiviral therapy depended on the genotype of the infecting HBV strain. Large epidemiological studies will require the availability of a system which is rapid, reliable and can be performed on a large number of samples. Methods: To establish a simple and accurate genotyping method, the study collected 369 HBV complete genomic sequences from the GenBank database. Type-specific primers were also designed that separated HBV genotypes A to G by multiplex polymerase chain reaction. Results: By comparison with the traditional restriction fragment length polymorphism method, over 93% of 441 samples were accurately genotyped by current assay, with a higher detection rate and sensitivity to detect mixed HBV infections. Conclusions: This methodology can be applied only to areas prevalent with HBV genotypes A to G. However, it provides an efficient alternative for clinical diagnosis and large-scale studies.
The Anaesthetic Steroid Alphaxalone Positively Modulates α1-Glycine Receptor Function
Authors: Ahrens Jörg , Leuwer Martin , Demir Reyhan , Krampfl Klaus , Foadi Nilufar , Haeseler Gertrud
Published: October 2008

Inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the processing of nociceptive signals, and mainly involves glycine. We have studied the effects of alphaxalone on α1 homomeric glycine receptors expressed in a mammalian expression system (HEK 293 cells) using the whole-cell patch-clamp technique. Our experiments showed a coactivating effect of alphaxalone with a concentration for half-maximum activation (EC50) of the effect of a low glycine concentration (EC20) of 70.9 ± 21.5 µmol/l. Taking into account the results of other groups, our study suggests that neuroactive steroids might be an interesting class of compounds to probe subunit-specific effects of glycine receptors.
Orally Administered Rapamycin, Dacarbazine or Both for Treatment of Human Melanoma Evaluated in Severe Combined Immunodeficiency Mice
Authors: Thallinger Christiane , Skorjanec Sophie , Soleiman Afschin , Tzaneva Stanislava , Griss Johannes , Rous Wolfgang , Poeppl Wolfgang , Weinlich Georg , Karimian-Teherani Daniela , Joukhadar Christian
Published: October 2008

Objective: In this experimental study, the antineoplastic potential of orally administered rapamycin in human melanoma was evaluated and compared with dacarbazine (DTIC) as well as with the antineoplastic effect of the combination of both drugs. Methods: The substances were tested using 2 human melanoma cell lines, 518A2, which is highly susceptible to DTIC, and 607B, which is moderately susceptible. A human melanoma severe combined immunodeficiency mouse xenotransplantation model was used. After development of palpable tumors, mice received oral rapamycin or saline over 18 days. Additionally, from treatment day 4 to 8, mice were randomly chosen to receive either DTIC or saline treatment. Results: The oral rapamycin treatment (1.5, 7.5, 15 and 30 mg/kg body weight) had an antineoplastic effect, ranging from 35 to 78% tumor weight reduction compared with the saline group. In DTIC less sensitive 607B tumors, rapamycin treatment (15 and 30 mg/kg body weight) was superior to DTIC treatment (p < 0.05). DTIC monotreatment reduced tumor weight in 518A2 tumors by 85% on average, whereas in 607B xenografts, no significant tumor weight reduction was observed compared with the saline group (p > 0.05). The combination of rapamycin and DTIC was not superior to rapamycin monotreatment in any cell line. Conclusion: These data indicate that oral rapamycin exerts a relevant antineoplastic effect on human melanoma cells. This effect appeared to be more pronounced in DTIC less sensitive melanoma xenografts.
Urinary Iodine in 24 h Is Associated with Natriuresis and Is Better Reflected by an Afternoon Sample
Authors: Vanacor Roberta , Soares Rosane , Manica Denise , Furlanetto Tania W.
Published: October 2008

Aims: We aimed to assess the extent of variability in urinary iodine (UI) within a day, to determine the period of the day when UI was better associated with the UI in 24 h, and to study the relationship between UI and urinary sodium. Methods: This cross-sectional study included 60 volunteers. Four urine samples were collected from each participant (A: from breakfast to lunch; B: from lunch to dinner; C: from dinner to bedtime, and D: from bedtime to breakfast) and were compared with the 24-hour sample (calculated from samples A–D ). UI, creatinine and Na+ levels were measured in the partial samples and in the 24-hour sample. Results: The content of iodine and sodium in urine varied during the day (p < 0.001). The UI concentration from lunch to dinner was closest to the 24-hour UI concentration using the method of Bland and Altman. There were correlations between the UI content in the different periods of the day and in 24 h: A (r = 0.54; p < 0.000), B (r = 0.78; p < 0.000), C (r = 0.37; p = 0.004) and D (r = 0.77; p < 0.000). UI and urinary sodium content were strongly correlated in all periods of the day (samples A and B: r = 0.69, p < 0.000; sample C: r = 0.85, p < 0.000, and sample D: r = 0.78, p < 0.000). Conclusions: There was a within-day variation in UI content, which was strongly associated with urinary sodium content. Iodine concentration in the afternoon urine sample better reflected the 24-hour UI concentration. Therefore, urine collected in the afternoon is probably the best to evaluate iodine sufficiency in subjects with similar dietary habits.
Chemoembolization Combined with Pravastatin Improves Survival in Patients with Hepatocellular Carcinoma
Authors: Graf Hannah , Jüngst Christoph , Straub Gundula , Dogan Selin , Hoffmann Ralf-Thorsten , Jakobs Tobias , Reiser Maximilian , Waggershauser Tobias , Helmberger Thomas , Walter Andreas , Walli Autar , Seidel Dietrich , Göke Burkhard , Jüngst Dieter
Published: October 2008

Background/Aims: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to inhibit growth and to induce apoptosis in human hepatocellular carcinoma (HCC) cells. However, the potential benefit of pravastatin in HCC patients has still not been characterized, which prompted us to test the efficacy of pravastatin in patients with advanced HCC. Methods: We investigated prospectively a cohort of 183 HCC patients who had been selected for palliative treatment by transarterial chemoembolization (TACE). Fifty-two patients received TACE combined with pravastatin (20–40 mg/day) and 131 patients received chemoembolization alone. Six independent predictors of survival according to the Vienna survival model for HCC were equally distributed in both groups. Results: During the observation period of up to 5 years, 31 (23.7%) out of 131 patients treated by TACE alone and 19 (36.5%) out of 52 patients treated by TACE and pravastatin survived. Median survival was significantly longer in HCC patients treated by TACE and pravastatin (20.9 months, 95% CI 15.5–26.3, p = 0.003) than in HCC patients treated by TACE alone (12.0 months, 95% CI 10.3–13.7). Conclusion: Combined treatment of chemoembolization and pravastatin improves survival of patients with advanced HCC in comparison to patients receiving chemoembolization alone.