bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathology and genetics of adipocytic tumors
Authors: Hameed M.
Published: November 2007

Adipocytic tumors are common mesenchymal neoplasms with considerable morphologic and genetic heterogeneity. The fruitful integration of morphology and cytogenetics in the past 15 years has not only enhanced the diagnostic accuracy, but also refined the various pathological classifications and subtypes in these tumors. The current WHO classification includes eleven benign subtypes, one intermediate and five categories of malignant fatty neoplasms with incorporation of relevant genetic findings. Of the benign tumors, lipomas have been extensively analyzed by chromosome banding which has shown that their cytogenetic patterns are heterogeneous. Still aberrations involving 12q13→q15, 6p23→p21 and loss of material from 13q are common and consistent findings. Among the malignant tumors, the t(12;16)(q13;p11) resulting in the fusion of DDIT3 and FUS genes is the hallmark of myxoid and round cell liposarcoma and is used as a highly specific and sensitive marker of this entity. The tumor in the intermediate group, atypical lipomatous neoplasm/well-differentiated liposarcoma which poses morphologic challenges due to close histological similarity to benign lipomas shows characteristic supernumerary rings and giant rod chromosomes due to amplification of the 12q14→q15 region often involving the MDM2 oncogene. This review will focus on the pathological features of the various adipocytic tumors and relevant genetic findings reported in the literature.
Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations
Authors: Griffin C.A. , Morsberger L. , Hawkins A.L. , Haddadin M. , Patel A. , Ried T. , Schrock E. , Perlman E.J. , Jaffee E.
Published: November 2007

Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.
Molecular mechanisms underlying the MiT translocation subgroup of renal cell carcinomas
Authors: Medendorp K. , van Groningen J.J.M. , Schepens M. , Vreede L. , Thijssen J. , Schoenmakers E.F.P.M. , van den Hurk W.H. , Geurts van Kessel A. , Kuiper R.P.
Published: November 2007

Renal cell carcinomas (RCCs) represent a heterogeneous group of neoplasms, which differ in histological, pathologic and clinical characteristics. The tumors originate from different locations within the nephron and are accompanied by different recurrent (cyto)genetic anomalies. Recently, a novel subgroup of RCCs has been defined, i.e., the MiT translocation subgroup of RCCs. These tumors originate from the proximal tubule of the nephron, exhibit pleomorphic histological features including clear cell morphologies and papillary structures, and are found predominantly in children and young adults. In addition, these tumors are characterized by the occurrence of recurrent chromosomal translocations, which result in disruption and fusion of either the TFE3 or TFEB genes, both members of the MiT family of basic helix-loop-helix/leucine-zipper transcription factor genes. Hence the name MiT translocation subgroup of RCCs. In this review several features of this RCC subgroup will be discussed, including the molecular mechanisms that may underlie their development.
The genetics of bladder cancer: a cytogeneticist’s perspective
Authors: Wolff D.J.
Published: November 2007

Cytogenetic studies of bladder cancer have helped to define two clinically distinct subtypes: benign tumors with few genetic mutations and a stable karyotype and aggressive cancers with chromosomal instability and many non-random cytogenetic aberrations. While the cytogenetic data does not provide complete information, these studies have been important for suggesting pathways for bladder carcinoma initiation and its progression. In addition, molecular cytogenetic studies have proven useful for diagnosing bladder cancer and for monitoring patients for cancer recurrence. More detailed molecular genetic studies and expression array analyses are needed to fully comprehend the biologic processes associated with urothelial cancers, but cytogenetics studies have laid the foundation for further investigation.
SNP-Array genotyping and spectral karyotyping reveal uniparental disomy as early mutational event in MSS- and MSI-colorectal cancer cell lines
Authors: Melcher R. , Al-Taie O. , Kudlich T. , Hartmann E. , Maisch S. , Steinlein C. , Schmid M. , Rosenwald A. , Menzel T. , Scheppach W. , Lührs H.
Published: November 2007

In this study nine colorectal cancer cell lines were analysed by 10K SNP-arrays and spectral karyotyping (SKY). Complex chromosomal alterations and breakpoints of deleted or translocated fragments found by SKY could further be characterized by SNP-array analysis. Interestingly many monoallelic regions identified by SNP-array analysis display no copy number alterations, representing uniparental disomy (UPD). It was demonstrated that UPD seems to be involved in activation of early-acting tumor suppressor genes in MSS- (APC, CDKN2A) and MSI- (MLH1, MSH2, APC, CDKN2A) colorectal cancer cell lines. Genes involved later on in the adenoma-carcinoma sequence (i.e. TP53/SMAD4) were not found to be inactivated by UPD. Furthermore, identified amplified monoallelic regions may include oncogenes activated by allele-specific-amplification (i.e. Cyclin D1). However, at present, the majority of the monoallelic regions located in the present study have not yet been associated with known tumor suppressor genes and oncogenes. Further studies are warranted to identify relevant genes in the respective regions and to further verify the results presented here.
FISH panels for hematologic malignancies
Authors: Sreekantaiah C.
Published: November 2007

Cytogenetic analysis of hematological malignancies has played a crucial role in the diagnosis and clinical management of patients, as well as in providing fundamental insights into the genetic basis of the pathogenesis of these diseases. Leukemias and lymphomas have lent themselves readily to karyotypic analysis and undoubtedly represent the greatest successes of cytogenetics in human cancer. Several cytogenetic changes have been shown to have considerable prognostic significance also and are being used as measurable targets for response to therapy. Molecular characterization of the recurrent cytogenetic abnormalities has identified genes involved in leukemogenesis and formed a basis for specific treatment strategies. Fluorescence in situ hybridization (FISH) analysis, since its introduction, has revolutionized the field and enabled a more precise determination of the presence and frequency of genetic abnormalities. It is particularly indispensable where metaphase cytogenetics may be difficult in the largely quiescent cells of some hematological malignancies, particularly the lymphoid disorders. FISH probes have been used extensively to detect nonrandom abnormalities in interphase nuclei and the true incidence of chromosome abnormalities has been proven to be much higher than that detected by conventional chromosomal analysis. The avail- ability of a comprehensive line of commercial probes for rapid identification of critical genetic aberrations has contributed to the widespread use of this technique. It has also led to the current practice in most laboratories to test for genetic aberrations by using FISH panels that have been designed to detect genetic changes important not only in the diagnosis of leukemias and lymphomas, but also because of their association with prognosis, to identify high-risk populations in specific hematological cancers, so they can be targeted for aggressive therapy.
Genetic alteration associated with chronic lymphocytic leukemia
Authors: Cotter F.E. , Auer R.L.
Published: November 2007

The genetics of B-cell chronic lymphocytic leukemia (B-CLL) differ considerably from most other forms of hematologic malignancy which are usually characterized by chromosome translocations. B-CLL typically contains chromosomal deletions and chromosomes 13q14 and 11q22→q23 are the most common. These two regions appear to share a common ancestral origin (Auer et al., 2007b). Overall, chromosomal abnormalities can be found in the majority of patients with B-CLL when using sensitive techniques (Dohneret al., 2000) and possibly reflects an underlying predisposition, with a small but significant number of familial cases. Although single and consistent abnormalities are most common, multiple rearrangements can occur, often with disease progression (Feganetal., 1995; Dohner et al., 2000). Regions of recurrent deletion suggest the presence of tumor suppressor genes if following Knudson’s theoretical 2-hit model. However, despite extensive sequencing analysis over the last decade and lack of pathogenic mutations identified, there has been a move away from this suggested hypothesis and alternative mechanisms of gene inactivation involving epigenetic silencing or haploinsufficiency may be considered as more likely in this disease. This review focuses on the common genetic abnormalities in B-CLL and relates them to some of the more recent hypotheses on inactivation of genes within these regions of deletion.
Genetics and epigenetics of 1q rearrangements in hematological malignancies
Authors: Fournier A. , Florin A. , Lefebvre C. , Solly F. , Leroux D. , Callanan M.B.
Published: November 2007

Recently, we and others have described a novel class of chromosome aberrations that involves constitutive heterochromatin on human chromosome 1 (cytogenetic band 1q12). These anomalies are particularly frequent in B cell non-Hodgkins lymphoma (NHL) and multiple myeloma (MM) and, remarkably, almost invariably involve partial or total gain of chromosome 1q (including 1q12 heterochromatin) and the formation of novel heterochromatin/euchromatin junctions. This review discusses the pathological significance of these anomalies in light of i) recent integrated gene expression and array comparative genomic hybridisation (aCGH) profiling in MM and ii) increasing evidence of a key role for heterochromatin in the control of normal and pathological gene silencing.
Molecular cytogenetics in the study of cutaneous T-cell lymphomas (CTCL)
Authors: Karenko L. , Hahtola S. , Ranki A.
Published: November 2007

The etiology of primary cutaneous T-cell lymphomas (CTCL) has been poorly understood. CTCL patients show a large variety of non-clonal and clonal chromosome aberrations, but no specific aberration has been found until recently. This review describes cytogenetic and molecular cytogenetic findings and their relevance to diagnostics and etiology in two of the most common forms of CTCL, mycosis fungoides (MF) and the leukemic CTCL, Sézary syndrome (SS).
Exogenous Application of Platelet-Leukocyte Gel during Open Subacromial Decompression Contributes to Improved Patient Outcome
Authors: Everts P.A. , Devilee R.J.J. , Brown Mahoney C. , van Erp A. , Oosterbos C.J.M. , Stellenboom M. , Knape J.T.A. , van Zundert A.
Published: November 2007

Background: Platelet-leukocyte gel (PLG) is being used during various surgical procedures in an attempt to enhance the healing process. We studied the effects of PLG on postoperative recovery of patients undergoing open subacromial decompression (OSD). Methods: PLG was produced from platelet-leukocyte-rich plasma (P-LRP), prepared from a unit of whole blood. Forty patients were included in the study. Self-assessed evaluations, using the American Shoulder and Elbow Surgeons scoring system of activities of daily living (ADL), joint instability, pain levels, pain medications, and clinical evaluations for range of motion were conducted. Results: Platelet and leukocyte counts were significantly increased in the P-LRP compared to baseline counts. Treated patients demonstrated decreased visual analog scales for pain and used significantly less pain medication, had an improved range of motion during passive forward elevation, external rotation, external rotation with arm at 90° abduction, internal rotation, and cross body adduction compared to control patients (p < 0.001). No differences in the instability score were observed between the groups. Furthermore, treated patients performed more ADL (p < 0.05). Conclusion: In the PLG-treated group, recovery was faster and patients returned earlier to daily activities and also took less pain medication than control subjects.
CT Scan in Patients with Suspected Appendicitis: Clinical Implications for the Acute Care Surgeon
Authors: Petrosyan M. , Estrada J. , Chan S. , Somers S. , Yacoub W.N. , Kelso R.L. , Mason R.J.
Published: November 2007

Objective: To determine the influence of computed tomography (CT) scans on diagnosis and management of patients with suspected appendicitis. Methods: Retrospective 2-year review of 1,630 patients with suspected appendicitis, categorized into three groups based on the likelihood (Alvarado scores) of having appendicitis. Group 1: low likelihood (Alvarado score ≤4); group 2: intermediate likelihood (Alvarado scores 5–7), and group 3: high likelihood (Alvarado score ≧ 8). CT scan utilization, hospital course, and final pathology were retrospectively reviewed. Results: More patients received a CT scan in 2006 as compared with 2005 (60 vs. 52%; p = 0.001). The overall appendectomy rate was similar between the 2 years (57% in 2005 vs. 57% in 2006; p = 0.995). The overall appendectomy rate in patients with a CT was significantly higher as compared with those without (60 vs. 53%; p = 0.002). The appendectomy rate in patients with Alvarado scores ≤4 and no CT scan was significantly lower than in those with a CT scan (12 vs. 48%; p < 0.0001). The overall negative appendectomy rate in patients with a CT scan was similar to that in those without: 31/546 (6%) vs. 23/383 (6%). Conclusions: CT scan utilization increased the appendectomy rate only in patients with a low clinical suspicion for appendicitis. Preoperative CT scans did not decrease the negative appendectomy rate.
Wallenberg’s Syndrome: An Unusual Case of Dysphagia
Authors: Loaeza-del Castillo Aurora , Barahona-Garrido Josué , Criales Sergio , Chang-Menéndez Sergio , Torre Aldo
Published: November 2007

A 56-year-old man presented with sudden-onset oropharyngeal dysphagia and vomiting of central etiology. Neurological evaluation showed uvula deviation to the left, paresis of the mid-right portion of the soft palate, lateralization of gaze to the right side, and dysphonia. Magnetic resonance imaging (MRI) showed an infarction in the left lateral medullary region, therefore the diagnosis of Wallenberg’s syndrome was established. The neurological issues along with the dysphagia gradually improved and the patient was discharged.
Oral Administration of Bepotastine Besilate Suppressed Scratching Behavior of Atopic Dermatitis Model NC/Nga Mice
Authors: Tanizaki Hideaki , Kambe Naotomo , Nakamura Yuumi , Tanaka Akane , Matsuda Hiroshi , Miyachi Yoshiki
Published: November 2007

Background: Pruritus is the most severe problem in atopic dermatitis. Even though its mechanism is still not fully understood, antihistamines have been prescribed for atopic dermatitis. Objective: To evaluate the effect of antihistamine on atopic dermatitis, we analyzed the scratching behavior in atopic dermatitis model NC/Nga mice. Methods: BALB/c mice, in which scratching behavior was induced by intradermal injection of compound 48/80 (100 µg/100 µl/mouse), and NC/Nga mice, housed in a conventional environment and having developed spontaneous eczematous regions, were monitored with a SCLABA system after oral administration of bepotastine besilate. The number of eosinophils in the ear skin and the serum leukotriene B4 (LTB4) levels were also evaluated. Results: Bepotastine at doses of 3 and 10 mg/kg effectively inhibited the compound 48/80-induced scratching behavior of BALB/c mice 1 h after oral administration, comparable with the blood Tmax, which was reached within 0.8–1.6 h in humans. Bepotastine also significantly inhibited the scratching behavior of NC/Nga mice 1 h after oral administration. Even though 10 mg/kg bepotastine could not influence the number of tissue eosinophils, it effectively suppressed the serum LTB4 levels, just comparable with the suppression of scratch behavior of NC/Nga mice. Conclusion: Bepotastin effectively suppressed the scratch behavior of atopic dermatitis model mice, which may not simply be explained by the suppression of histamine but also by the suppression of other mediators like LTB4. Bepotastine could be useful in the treatment of pruritus, especially early after oral administration.
Antigenic Similarity among Group 1 Allergens from Grasses and Quantitation ELISA Using Monoclonal Antibodies to Phl p 1
Authors: Duffort Oscar , Quintana Juan , Ipsen Henrik , Barber Domingo , Polo Florentino
Published: November 2007

Background: Group 1 allergens elicit a specific IgE response in about 90% of grass pollen-allergic patients. The aim of this work was to study the antigenic similarity among group 1 allergens from different grasses and to develop a monoclonal antibody (MAb)-based quantitation ELISA. Methods: Twenty specific MAbs were produced from BALB/c mice immunized with natural Phl p 1. These MAbs were tested for specificity with thirteen different grass pollen extracts from the Poaceae family and in cross-inhibition experiments for the binding of Phl p 1. Purified group 1 allergens from Poeae grasses (Dactylis glomerata, Lolium perenne, Festuca pratensis and Poa pratensis) were tested for parallelism in quantitation ELISA. Results: Eighteen to nineteen anti-Phl p 1 MAbs recognized the homologous allergen in pollen extracts from grasses of the Poeae tribe. In contrast, only four MAbs recognized group 1 from Cynodon dactylon and Phragmites communis. Four groups of MAbs with different epitope specificity were identified. A grass group 1 quantitation ELISA was developed using a mix of three MAbs on the solid phase and a polyclonal rabbit antibody as the second antibody. The group 1 content could be measured in different batches of Phleum pratense as well as in pollen extracts from Poeae grasses, since they showed parallel dose-response curves. Conclusions: MAbs produced in this work enabled us to show the high antigenic similarity between group 1 allergens from temperate grasses. The results prove the usefulness of the ELISA method developed for standardization of grass allergen products.
Enzymatic Activity of Dermatophagoides pteronyssinus Extracts after Acidic Treatment
Authors: Fernández-Caldas Enrique , Gallego Mayte , Carnés Jerónimo , Iraola Victor
Published: November 2007

Background: Mite extracts contain potent enzymes. These enzymes, especially Der p 1, may affect the bronchial homeostasis and the amplification of the allergic response. The objectives of this study were to determine how depigmentation affects the enzymatic activity of allergen extracts of Dermatophagoides pteronyssinus and to verify if these depigmented extracts retain their in vitro allergenic properties. Methods: Four native extracts were manufactured from 4 different batches of raw material of D. pteronyssinus. Once extracted, native extracts were reconstituted and modified by adding increasing quantities of 2 M HCl to the solution and dialyzed against double-distilled water. The enzymatic activity of these 8 extracts (4 native and 4 depigmented) was evaluated using in vitro methods. The allergenic potency was evaluated by human specific IgE and IgG ELISA inhibition experiments. The major allergen content (Der p 1 and Der p 2) was measured with monoclonal antibodies. Results: Protease, phosphatase, lipase and glycosidase activity was detected in native extracts. After depigmentation, all the enzymatic activities showed a significant decrease. SDS-PAGE reveals the same protein profile in both types of extracts. The results of ELISA inhibition confirmed that depigmented extracts preserved their antigenic and allergenic capacity. Der p 2 levels increased in depigmented extracts, while the detection capacity of Der p 1 decreased. Conclusions: The depigmentation process significantly reduced the enzymatic activity of these mite extracts, while preserving their allergenicity and antigenicity. No significant differences were observed in the antigenic profile of native and depigmented extracts.
Birth Order and Cord Immunoglobulin E: Results Using a High-Sensitivity Immunoglobulin E Protocol
Authors: Wegienka Ganesa , Havstad Suzanne , Shue Leo , Zoratti Edward , Ownby Dennis R. , Johnson Christine Cole
Published: November 2007

Background: Studies have shown an inverse association between birth order and allergic disease risk; some but not all have shown an inverse association between cord blood immunoglobulin E (IgE) and birth order. We further examined the relationship between birth order and cord blood IgE in a racially diverse birth cohort. Methods: Women were interviewed about their pregnancy history, and their babies’ cord blood was collected to measure total IgE using a high-sensitivity protocol (lower detection limit 0.01 IU/ml). We analyzed cord IgE as both a continuous and categorical measure. Results: Of the 733 children, 171 (23%) were first born, 92 (13%) were first born with the mother having prior pregnancies but no live births, and 470 (64%) were born second or later. By birth order, the geometric means ± standard deviations were: first born 0.26 ± 4.2 IU/ml, first born after prior pregnancies 0.35 ± 3.9 IU/ml, second born 0.30 ± 4.8 IU/ml, third born 0.28 ± 5.1 IU/ml, and fourth born or greater 0.28 ± 4.5 IU/ml (trend p = 0.51). Other factors considered (maternal allergic disease history, age, race, exposure to smoking and cats/dogs during pregnancy, fetal gender, season of delivery) neither modified nor confounded these relationships. Conclusions: Unlike some previous reports, there was no association between total cord IgE level and birth order. Mechanisms other than cord IgE should be studied in the quest to understand the role of birth order in allergic disease risk. Categorization of a continuous measure of IgE may incorrectly create statistically significant results.
Growth Factors Temporally Associate with Airway Responsiveness and Inflammation in Allergen-Exposed Mice
Authors: Ito Wataru , Tanimoto Mitsune , Ono Katsuichiro , Mizuno Shinya , Yoshida Akio , Koga Hikari , Fuchimoto Yasuko , Kondo Naruhito , Tanimoto Yasushi , Kiura Katsuyuki , Matsumoto Kunio , Kataoka Mikio , Nakamura Toshikazu , Gelfand Erwin W. , Kanehiro Arihiko
Published: November 2007

Background: To clarify whether growth factors play critical roles in the development of airway hyperresponsiveness (AHR) and airway inflammation in the early stages of asthma, the relationship between growth factors and AHR and airway inflammation were analyzed in a mouse model of asthma. Methods: Following ovalbumin (OVA) sensitization and challenge, airway function, inflammation, cytokine and growth factor levels were monitored. Results: AHR to inhaled methacholine increased at 6 h, peaked at 48 h, and remained elevated for 14 days. IL-4 and IL-5 levels in bronchoalveolar lavage (BAL) fluid were increased at 6 h, peaked at 24 h, but returned to baseline quickly. IL-13 levels increased up to 14 days, peaking at 48 h. Increases in BAL fluid transforming growth factor-β1 and platelet-derived growth factor were observed at 12 h, and remained elevated at 14 days. Nerve growth factor levels were increased at 24–28 days. BAL fluid hepatocyte growth factor (HGF) was detected at 12 h, peaked at 24 h, and returned to baseline by 72 h. c-Met/HGF receptor was detected in the airways at 6 h, before HGF in the BAL, and continued to be observed 96 h after the last OVA challenge. Conclusions: These data identify a temporal association between growth factor production and Th2 cytokine production and the kinetics of AHR. Growth factors may play important roles in the development of allergic airway inflammation and AHR even in the early stages of asthma, before remodeling is initiated.
Activation of Phospholipase Cγ1 Protects Renal Arteriolar VSMCs from H2O2-Induced Cell Death
Authors: Peng Zhangping , Arendshorst William J.
Published: November 2007

Background: We evaluated the effect of hydrogen peroxide (H2O2) on viability of vascular smooth muscle cells (VSMCs) of renal resistance arterioles and determined whether responses are modulated by activation of PLCγ1. Methods: Phospholipase C (PLC)-isozyme protein levels and activity were measured using Western blot analysis and enzymatic production of phosphoinositol 1,4,5-trisphosphate (IP3), respectively. Stimulation of PLCγ1 was assessed by immunoblots of tyrosine phosphorylation. Results: Cytotoxicity of H2O2 exposure was concentration-dependent (30% death with 250 µM; 87% with 500 µM at 8 h) and time-dependent (7% at 1 h; 30% at 8 h with 250 µM H2O2). Catalase abolished such relations. H2O2 increased PLCγ1 expression more than that of PLCδ1 and almost doubled total PLC enzymatic activity between 2 and 8 h, changes prevented by catalase. The PLC inhibitor U73112 (3 µM) enhanced the cytotoxic concentration and time effects of H2O2. In acute studies, H2O2 rapidly caused tyrosine phosphorylation of PLCγ1. Conclusion: H2O2 increased PLCγ1 expression and almost doubled total PLC activity, changes abolished by catalase. We conclude that H2O2 is cytotoxic to cultured VSMCs of renal preglomerular arterioles, a process that is attenuated by compensatory increases in PLCγ1 protein level, tyrosine phosphorylation of PLCγ1 and PLC enzymatic activity to generate IP3.
Severe Ticlopidine-Induced Cholestatic Syndrome
Authors: Mambelli Emanuele , Mancini Elena , Casanova Silvia , Di Felice Antonio , Santoro Antonio
Published: November 2007

A patient with chronic renal insufficiency undergoing dialysis treatment presented with a clinical picture of acute intrahepatic cholestasis and alterations in liver function indices. Liver biopsy showed a histological picture of hepatitis with cholestatic signs. A causal correlation with the recent administration of ticlopidine was hypothesized, which led to the drug being discontinued. Four months after drug withdrawal no improvement in the biochemical parameters had yet occurred and the patient’s clinical conditions were indeed worsening so we proceeded with extracorporeal selective plasmapheresis treatments to reduce the bilirubin. As the cholestatic syndrome was unresolved and owing to the progressive worsening in the clinical picture, the patient was submitted to combined liver and kidney transplant followed by a rapid functional recovery in both organs. Regular monitoring of the hepatic function indices during the therapy with ticlopidine is therefore indispensable for the early detection of unpredictably severe hepatotoxicity.
A Pilot Phase II Study of Capecitabine plus Cisplatin in the Treatment of Recurrent Carcinoma of the Uterine Cervix
Authors: Benjapibal Mongkol , Thirapakawong Chaiyod , Leelaphatanadit Chairatana , Therasakvichya Suwanit , Inthasorn Perapong
Published: November 2007

Background: To assess the efficacy and tolerability of combination therapy with capecitabine and cisplatin in patients with recurrent carcinoma of the uterine cervix. Methods: Sixteen patients were treated with oral capecitabine (1,000 mg/m2 twice daily, days 1–14) and intravenous cisplatin (50 mg/m2 on day 1 every 3 weeks) for a maximum of six cycles. Results: Their median age was 50 years (31–74 years). Ten patients (63%) had recurrent disease outside the radiation field. The overall response rate was 50% (95% confidence interval 26–75%); 4 patients had complete response (25%). The overall response rate was 33% in patients with recurrent disease within the previous irradiated field and 60% in patients with tumor outside the irradiated field. The median time to progression was 9 months, with a median overall survival of 23 months. The majority of adverse events were mild and there were no grade 4 adverse events. Hematological toxicity was the most frequent adverse event with grade 3 neutropenia in 19% of patients. Grade 2 and 3 hand-foot syndrome occurred in 38 and 6% of the patients, respectively. There were no chemotherapy-related deaths. Conclusion: The combination of capecitabine plus cisplatin is a clinically active regimen with acceptable tolerability for patients with recurrent carcinoma of the uterine cervix.
Malignant Sublingual Gland Tumors: A Retrospective Clinicopathologic Study of 28 Cases
Authors: Yu Tao , Gao Qing-Hong , Wang Xiao-Yi , Wen Yu-Ming , Li Long-Jiang
Published: November 2007

Objectives: To evaluate the clinicopathologic features and therapeutic efficacy of malignant sublingual gland tumors. PatientsandMethods: From 1955 to 2005, the clinicopathologic data of 28 patients treated in our hospital were obtained from their medical records and histopathologic slides. Results: There were 16 males and 12 females, with a mean age of 50.3 years. Eighteen cases (64.3%) were adenoid cystic carcinoma; 16 (57.1%) cases were clinically staged as III–IV. Adenoid cystic carcinoma was mainly of the histologic type, and the other histologic classifications included mucoepidermoid carcinoma, myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, adenocarcinoma and malignant pleomorphic adenoma. Pulmonary metastasis and tumor recurrence were the main death reasons. Eleven patients remain alive and well 34–312 months (median 108) after treatment. Conclusions: Malignant sublingual gland tumors are extremely rare and most are adenoid cystic carcinoma. Surgery is the main treatment option. For adenoid cystic carcinoma, hematogenous spread is common, and pulmonary metastasis is a common pathway of the distant metastasis. For some patients having lung metastasis, regional control is also important as there are some examples of patients surviving many years with asymptomatic pulmonary metastases. Postoperative radiation therapy may be adjuvant for selected patients with high-stage and high-grade tumors, or when there is concern about the inadequacy of the resection. The effect of chemotherapy remains elusive.
A Dose Escalation Study of the Biweekly Administration of Paclitaxel, Oxaliplatin and Capecitabine in Patients with Advanced Solid Tumors
Authors: Saridaki Zacharenia , Bozionelou Vasiliki , Kentepozidis Nikolaos , Kotsakis Athanasios , Vardakis Nikolaos , Kalykaki Antonia , Gioulbasanis Ioannis , Karampeazis Athanasios , Vamvakas Lambros , Georgoulias Vassilis , Mavroudis Dimitris
Published: November 2007

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors. Patients and Methods: Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1–7 and 15–21 every 28 days. DLTs were evaluated in the first cycle. Results: Sixteen patients were treated at four dose-escalating levels. Eleven (68.7%) patients had received two or more prior chemotherapy regimens. The DLT level was reached at paclitaxel 110 mg/m2, LOHP 50 mg/m2 and capecitabine 1,000 mg/m2/day. DLTs due to grade 2–3 neutropenia resulted in treatment delays. No febrile neutropenia or treatment-related death occurred. Grade 2–3 neutropenia occurred in 3 (19%) patients each, grade 2–4 fatigue affected 6 (37.5%) patients, and grade 2–3 neurotoxicity was observed in 2 (12.5%) and 1 (6%) patients, respectively. Two partial responses and four disease stabilizations were achieved. Conclusion: The recommended doses for phase II studies are paclitaxel 100 mg/m2 and LOHP 50 mg/m2 on days 1 and 15 and capecitabine 1,000 mg/m2/day on days 1–7 and 15–21 every 4 weeks. This regimen is well tolerated and merits further evaluation.
Perceptions of Americans and the Iraq Invasion
Authors: Terracciano Antonio , McCrae Robert R.
Published: November 2007

This study examines perceptions of the “typical American” from 49 cultures around the world. Contrary to the ethnocentric bias hypothesis, a strong agreement was found between in-group and out-group ratings on the American profile (assertive, open-minded, but antagonistic). In fact, Americans had a somewhat less desirable view of Americans than did others. Within cultures, in-group ratings were not systematically more favorable than out-group ratings. The Iraq invasion had a slight negative effect on perceptions of the typical American, but people around the world seem to draw a clear distinction between U.S. foreign policy and the character of the American people. National character stereotypes appear to have a variety of sources and to be perpetuated by both cognitive mechanisms and sociocultural forces.
Acute Hypoxia, Diabetes, and Neuroimmune Dysregulation: Converging Mechanisms in the Brain
Authors: Johnson Daniel R. , Sherry Christina L. , York Jason M. , Freund Gregory G.
Published: November 2007

Acute hypoxia is experienced by a variety of individuals (neonates to the elderly) and in an assortment of conditions and diseases (terrorist bomb attack to decompensated heart failure). Increasingly, elaboration of inflammatory cytokines appears key to the brain-based response to hypoxia, as evidenced by the biobehaviors of malaise, fatigue, lethargy, and loss of interest in the physical and social environment. These sickness symptoms implicate hypoxia-dependent activation of the neuroimmune system as a key component of acute hypoxia. Type 2 diabetes (T2D) is associated with increased incidence, severity, and delayed recovery from hypoxic events. Why T2D negatively affects acute hypoxia is not well understood. Recent work, however, reveals that anti-inflammatory pathways tied to the interleukin (IL)-1β arm of the neuroimmune system may be critical. In this review, the authors examine the link between acute hypoxia, T2D, and neuroimmunity. NEUROSCIENTIST 14(3):235–239, 2008. DOI: 10.1177/1073858407309544
Could Interviews Be Epistemic?
Authors: Brinkmann Svend
Published: November 2007

The author explores using qualitative research interviews to gain knowledge rather than mere opinions about a given topic. Current interviews typically aim to probe the respondents' experiences and opinions— doxa in Greek. An implicit model for much doxastic interviewing is client-centered therapy, in which the respondent—client is the only authority concerning his or her experiences and opinions. The author argues that doxastic interviews do not take advantage of the knowledge-producing potentials inherent in human conversations. Instead, the author examines the Socratic dialogue as an interview form that addresses not opinions but knowledge ( episteme). In epistemic interviewing, both parties are engaged in dialectically examining a topic, with the aim of gaining knowledge in a normative—epistemic sense. The author presents examples from different interview studies that illustrate the epistemic interview in practice. Finally, the author asks whether epistemic interviews are suitable only for “elite interviews” and whether they are particularly ethically problematic.
Qualitative Inquiry, Ethics, and Politics of Evidence
Authors: Cheek Julianne
Published: November 2007

Just as qualitative research is “endlessly creative and interpretative,” qualitative researchers find themselves in the position of having to be endlessly creative and interpretive with respect to the various spaces they move in and out of as they conceptualize, conduct, write, and report their research. Some of these spaces are shaped by new and mutated forms of “old” regimes of truth based in audit culture, others by refracted forms of methodological fundamentalism and imperialism emanating from without but significantly also increasingly from within, writing and talking about qualitative research. Navigating and moving in and out of these spaces creates tensions but also possibilities for qualitative researchers. This article aims to encourage a focus on better understanding these spaces.
By Their Own Hand
Authors: Isaac Carol A.
Published: November 2007

The word suicide takes on a life of its own. People are both repulsed and intrigued by the word and the silence it brings. Those who survive a loved one's suicide face the inherent contradictions that exist in society: a mixture of sympathy and disgust, spectacle and removal. The author's sister was a clinical neurologist working at a well-known, top-tier medical institution who committed suicide in reaction to thwarted efforts to obtain a tenured position. As a result, the author faced within herself a mixture of horror and wonder, isolation and community, and anger and stillness. A survivor's grief has no structure, and feelings and thoughts meander without rhyme or reason like the primitive rhizome as an uncovered memory constantly stops in the middle and unfolds to another. This autoethnographic article explores Deleuze and Guattari's oppositional binaries and the author's compelling need to search the silence.
The Technologies of Normalization and Self
Authors: Koro-Ljungberg Mirka , Gemignani Marco , Brodeur Cheri Winton , Kmiec Cheryl
Published: November 2007

In this article, the authors discuss the technologies of normalization and self in relation to ethics and the problematization of extrinsic research ethics. They argue that institutional review boards (IRBs) and other similar institutional mechanisms promote extrinsic forms of ethics that are exemplified through institutionalized structures such as (a) the Belmont Report, (b) IRB protocol, (c) informed consent, and (d) localized interpretations of IRB rules and regulations. However, at the same time, institutional normalization enables researchers and participants to construct themselves as ethically responsible participants through resistance and critical reflection. Such “care of the self” and critical awareness of dominant discourses and regimes of power and knowledge are essential to the development and practice of research that is ethical, free, and responsive. Finally, the authors conclude that the discussions about researchers' ethical decision making and freedom of choice need to be separate from discussions related to researchers' compliance, duties, and institutional responsibilities.
Cochlear Implants Special Issue Article: Vocal Emotion Recognition by Normal-Hearing Listeners and Cochlear Implant Users
Authors: Luo Xin , Fu Qian-Jie , Galvin John J.
Published: November 2007

The present study investigated the ability of normal-hearing listeners and cochlear implant users to recognize vocal emotions. Sentences were produced by 1 male and 1 female talker according to 5 target emotions: angry, anxious, happy, sad, and neutral. Overall amplitude differences between the stimuli were either preserved or normalized. In experiment 1, vocal emotion recognition was measured in normal-hearing and cochlear implant listeners; cochlear implant subjects were tested using their clinically assigned processors. When overall amplitude cues were preserved, normal-hearing listeners achieved near-perfect performance, whereas listeners with cochlear implant recognized less than half of the target emotions. Removing the overall amplitude cues significantly worsened mean normal-hearing and cochlear implant performance. In experiment 2, vocal emotion recognition was measured in listeners with cochlear implant as a function of the number of channels (from 1 to 8) and envelope filter cutoff frequency (50 vs 400 Hz) in experimental speech processors. In experiment 3, vocal emotion recognition was measured in normal-hearing listeners as a function of the number of channels (from 1 to 16) and envelope filter cutoff frequency (50 vs 500 Hz) in acoustic cochlear implant simulations. Results from experiments 2 and 3 showed that both cochlear implant and normal-hearing performance significantly improved as the number of channels or the envelope filter cutoff frequency was increased. The results suggest that spectral, temporal, and overall amplitude cues each contribute to vocal emotion recognition. The poorer cochlear implant performance is most likely attributable to the lack of salient pitch cues and the limited functional spectral resolution.
Auditory and Visual Lexical Neighborhoods in Audiovisual Speech Perception
Authors: Tye-Murray Nancy , Sommers Mitchell , Spehar Brent
Published: November 2007

Much evidence suggests that the mental lexicon is organized into auditory neighborhoods, with words that are phonologically similar belonging to the same neighborhood. In this investigation, we considered the existence of visual neighborhoods. When a receiver watches someone speak a word, a neighborhood of homophenes (ie, words that look alike on the face, such as pat and bat) is activated. The simultaneous activation of a word's auditory and visual neighborhoods may, in part, account for why individuals recognize speech better in an auditory–visual condition than what would be predicted by their performance in audition-only and vision-only conditions. A word test was administered to 3 groups of participants in audition-only, vision-only, and auditory–visual conditions, in the presence of 6-talker babble. Test words with sparse visual neighborhoods were recognized more accurately than words with dense neighborhoods in a vision-only condition. Densities of both the acoustic and visual neighborhoods as well as their intersection overlap were predictive of how well the test words were recognized in the auditory–visual condition. These results suggest that visual neighborhoods exist and that they affect auditory–visual speech perception. One implication is that in the presence of dual sensory impairment, the boundaries of both acoustic and visual neighborhoods may shift, adversely affecting speech recognition.
Dual Sensory Loss: Overview of Problems, Visual Assessment, and Rehabilitation
Authors: Brabyn John A. , Schneck Marilyn E. , Haegerstrom-Portnoy Gunilla , Lott Lori A.
Published: November 2007

This article provides an overview of some of the problems and possible solutions surrounding the neglected issue of combined vision and hearing deficits. The subject is treated by considering each subpopulation, ranging from those who have no residual vision or hearing to those with mild coexisting vision and hearing losses. An attempt is made to relate the different types of visual deficit to the likely problems encountered in real-life activities, such as communication and travel, among individuals who also have a hearing impairment. The assessment and appropriate referral of patients with these combined deficits is discussed, including the interpretation of visual test results and the importance of factors other than standard visual acuity. Speculation is offered on potential strategies and solutions for rehabilitation as well as the need for future research and improvements in service delivery.
Implications of Deafblindness on Visual Assessment Procedures: Considerations for Audiologists, Ophthalmologists, and Interpreters
Authors: Hyvärinen Lea
Published: November 2007

Visual assessment of deaf persons presents a challenge to the ophthalmologist and the optometrist. At the time they want to measure visual function, the interpreter uses visual communication, competing for the patient's attention. Important rules of good assessment of visual functioning include taking turns and giving the interpreter sufficient time to convey the questions related to each test. This has implications for audiologists working with this population as well. Communication should be tailored to the varying needs of people who may have long-standing deafness and good sign language, may have lost their hearing at an advanced age and have limited or no sign language, or may be young persons or children who have congenital or progressive loss of hearing combined with congenital or progressive vision loss. Individuals with sudden hearing and vision loss, as well as those with intellectual disabilities and limited language, are particularly challenging groups for the assessment of vision and require special communication skills for ophthalmologists and audiologists. The ophthalmologist usually knows the nature of vision changes typical of disorders that the patient has. For the clinical follow-up of a condition, a few measurements are usually taken. For a comprehensive assessment of visual functioning for rehabilitation and education, many more measurements, observations, and questions are needed so that vision for communication, orientation in the environment, and performance of near-vision tasks can be reported and the effects of the environment can be evaluated. Testing should cover ocular disorders and vision loss caused by brain damage.
Multicentric Castleman disease is associated with polyfunctional effector memory HHV-8–specific CD8+ T cells
Authors: Guihot Amélie , Oksenhendler Eric , Galicier Lionel , Marcelin Anne-Geneviève , Papagno Laura , Bedin Anne-Sophie , Agbalika Félix , Dupin Nicolas , Cadranel Jacques , Autran Brigitte , Carcelain Guislaine
Published: November 2007

Multicentric Castleman disease (MCD) is a devastating human herpesvirus 8 (HHV-8)–related lymphoproliferative disorder that occurs in immunocompromised persons. To determine the role of immune responses in MCD, we studied the frequency, antigenic repertoire, differentiation, and functional profile of HHV-8–specific CD8+ T cells in MCD patients and in human immunodeficiency virus–coinfected asymptomatic HHV-8 carriers (AC). Screening CD8+ T-cell responses with ELISpot interferon-γ (IFN-γ) assays using 56 peptides on 6 latent and lytic HHV-8 proteins showed that MCD and AC patients had responses of similar magnitude and antigenic repertoire and identified a new 10-mer human leukocyte antigen B7 CD8 epitope in K15. Intracellular IFN-γ staining showed significantly more CD45RA−CCR7−CD27− CD8+IFN-γ+ cells (late phenotype) and significantly fewer CCR7−CD27+CD45RA− cells (early and intermediate phenotype) in MCD than in AC patients. This phenotypic shift was not found for Epstein-Barr virus–specific CD8+ T cells tested as controls. HHV-8 viral loads were negatively correlated with early and intermediate effector memory cells. HHV-8–specific T cells were polyfunctional (secretion of IFN-γ, tumor necrosis factor-α, macrophage inflammatory protein-1β, and/or CD107a) in both MCD and AC patients. In conclusion, MCD is not associated with a lack of HHV-8–specific CD8+ T cells or limitation of their functional profile. Their differentiation increases with HHV-8 viral load. These results offer new insight into the pathophysiology of MCD.