bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and In vivo Radiosensitization Induced by the DNA Methylating Agent Temozolomide
Authors: Kil Whoon Jong , Cerna David , Burgan William E. , Beam Katie , Carter Donna , Steeg Patricia S. , Tofilon Philip J. , Camphausen Kevin
Published: February 2008

Purpose: Temozolomide, a DNA methylating agent, is currently undergoing clinical evaluation for cancer therapy. Because temozolomide has been shown to increase survival rates of patients with malignant gliomas when given combined with radiation, and there is conflicting preclinical data concerning the radiosensitizing effects of temozolomide, we further investigated the possible temozolomide-induced enhancement of radiosensitivity.

Experimental Design: The effects of temozolomide on the in vitro radiosensitivity of U251 (a human glioma) and MDA-MB231BR (a brain-seeking variant of a human breast tumor) cell lines was evaluated using clonogenic assay. DNA damage and repair were evaluated using phosphorylated histone H2AX (γH2AX), and mitotic catastrophe was measured using nuclear fragmentation. Growth delay was used to evaluate the effects of temozolomide on in vivo (U251) tumor radiosensitivity.

Results: Exposure of each cell line to temozolomide for 1 h before irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1 ranging from 1.30 to 1.32. Temozolomide had no effect on radiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. As a measure of DNA double strand breaks, γH2AX foci were determined as a function of time after the temozolomide + irradiation combination. The number of γH2AX foci per cell was significantly greater at 24 h after the combined modality compared with the individual treatments. Mitotic catastrophe, measured at 72 h, was also significantly increased in cells receiving the temozolomide + irradiation combination compared with the single treatments. In vivo studies revealed that temozolomide administration to mice bearing U251 tumor xenografts resulted in a greater than additive increase in radiation-induced tumor growth delay with a dose enhancement factor of 2.8.

Conclusions: These results indicate that temozolomide can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an inhibition of DNA repair leading to an increase in mitotic catastrophe.
Suppression of Lung Tumor Growth and Metastasis in Mice by Adeno-Associated Virus-Mediated Expression of Vasostatin
Authors: Cai Ke Xia , Tse Lai Ying , Leung Carly , Tam Paul K.H. , Xu Ruian , Sham Mai Har
Published: February 2008

Purpose: Angiogenesis inhibitors have strong therapeutic potential as antitumor agents in suppressing tumor growth and metastatic progression. Vasostatin, the N-terminal domain of calreticulin, is a potent angiogenesis inhibitor. In this study, we determined the effectiveness of vasostatin delivered by recombinant pseudotype adeno-associated virus 2/5 (rAAV2/5-VAS) as a gene therapy approach for lung cancer treatment.

Experimental Design: We used rAAV2/5 to deliver vasostatin intratumorally or systemically in different mouse lung tumor models — subcutaneous, orthotopic xenograft, and spontaneous metastasis lung tumor models. The therapeutic efficacy of rAAV2/5-VAS was determined by monitoring tumor volume, survival rate, and degree of neovascularization after treatment in these models.

Results: Mice bearing subcutaneous tumor of rAAV2/5-VAS pretreated Lewis lung carcinoma cells showed >50% reduction in primary tumor volume and reduced spontaneous pulmonary metastases. The tumor-suppressive action of rAAV2/5-VAS in subcutaneous human lung tumor A549 xenograft correlated with a reduced number of capillary vessels in tumors. In the orthotopic xenograft model, rAAV2/5-VAS suppressed metastasis of A549 tumors to mediastinal lymph nodes and contralateral lung. Furthermore, treatment of immunocompetent mice in the spontaneous lung metastases model with rAAV2/5-VAS after primary tumor excision prolonged their median survival from 21 to 51.5 days.

Conclusion: Our results show the effectiveness of rAAV2/5-VAS as an angiogenesis inhibitor in suppressing tumor growth during different stages of tumor progression, validating the application of rAAV2/5-VAS gene therapy in treatment against lung cancer.
Activation of CCR9/CCL25 in Cutaneous Melanoma Mediates Preferential Metastasis to the Small Intestine
Authors: Amersi Farin F. , Terando Alicia M. , Goto Yasufumi , Scolyer Richard A. , Thompson John F. , Tran Andy N. , Faries Mark B. , Morton Donald L. , Hoon Dave S.B.
Published: February 2008

Purpose: Specific chemokines and their respective receptors have been implicated in distant tumor cell metastasis. Cutaneous melanoma has a distinct pattern of metastasis, preferentially targeting the submucosa of the small intestine. However, the underlying pathogenic mechanism remains unknown. Migration of CCR9(+) lymphocytes to the small intestine is known to occur in response to the chemoattractant effects of CCL25 (thymus-expressed chemokine). The integrin heterodimers αβ are also known to be important mediators of cellular adhesion. We hypothesize that the mechanism of small intestinal metastasis by melanoma is via the CCR9-CCL25 axis and specific integrins.

Experimental Design: Quantitative reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to assess melanoma tumors for CCR9 and CCL25. Integrin expression was assessed using flow cytometry. CCR9 expression by quantitative reverse transcription-PCR was assessed in primary (n = 23) and metastatic (n = 198) melanomas, and melanoma lines derived from small intestinal metastases (n = 23).

Results: We showed CCR9 expression in 88 of 102 paraffin-embedded metastatic melanomas from the small intestine, 8 of 8 melanoma lines derived from metastases in the small intestine, and 0 of 96 metastatic melanomas from other sites. In vitro migration and invasion studies done on CCR9(+) melanoma lines showed migration in response to CCL25 that was inhibited by anti-CCR9 antibody or by short interfering RNA CCR9. Flow cytometric analysis confirmed CCR9 expression by melanomas to the small intestine and showed concomitant α4β1 integrin expression.

Conclusions: Our findings show that functionally active CCR9 on melanoma cells facilitates metastasis to the small intestine. The CCR9-CCL25 axis may explain the high incidence of melanoma metastasis to this specific location.
Progression and Tumor Heterogeneity Analysis in Early Rectal Cancer
Authors: Lips Esther H. , van Eijk Ronald , de Graaf Eelco J.R. , Doornebosch Pascal G. , de Miranda Noel F.C.C. , Oosting Jan , Karsten Tom , Eilers Paul H.C. , Tollenaar Rob A.E.M. , van Wezel Tom , Morreau Hans
Published: February 2008

Purpose: Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression.

Experimental Design: We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis.

Results: Five specific “malignant” events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (r = 0.807; P < 0.001).

Conclusion: Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity.
The Prognostic Significance of Serum β2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Patients
Authors: Tsimberidou Apostolia-Maria , Kantarjian Hagop M. , Wen Sijin , O'Brien Susan , Cortes Jorge , Wierda William G. , Koller Charles , Pierce Sherry , Brandt Mark , Freireich Emil J. , Keating Michael J. , Estey Elihu H.
Published: February 2008

Purpose: Serum β2 microglobulin (β2M) is prognostic in other hematologic malignancies; therefore, we evaluated its prognostic significance in acute myeloid leukemia (AML).

Experimental Design: Multivariate analyses were used to examine the effect of pretreatment serum β2M levels on clinical outcomes in patients with AML. β2M was associated with poorer survival in older but not younger patients. We thus fit separate Cox survival models in patients above and below age 60 years treated with remission induction therapy containing high-dose cytarabine (n = 1,280). In each age group, 50% of the patients were used to develop the model, which was tested in the other 50%. Resampling methods were also used to validate the independent prognostic significance of covariates.

Results: In patients 60 years or older (n = 591), poorer risk cytogenetics; poorer performance status; and higher levels of β2M, uric acid, and lactate dehydrogenase were each found to independently predict shorter survival and formed the basis of a scoring system. A similar approach was used in patients younger than 60 years (n = 589), with poorer risk cytogenetics, poorer performance status, older age, higher hemoglobin level, and higher leukocyte count predicting a shorter survival and forming the basis of the scoring system. Higher β2M levels were an adverse independent factor for response, survival, relapse-free survival, and event-free survival in older but not in younger patients.

Conclusions: Serum β2M levels can help predict outcome in patients ≥60 years with untreated AML, and their use is strongly encouraged.
Focal Adhesion Kinase: Targeting Adhesion Signaling Pathways for Therapeutic Intervention
Authors: Parsons J. Thomas , Slack-Davis Jill , Tilghman Robert , Roberts W. Gregory
Published: February 2008

The tumor microenvironment plays a central role in cancer progression and metastasis. Within this environment, cancer cells respond to a host of signals including growth factors and chemotactic factors, as well as signals from adjacent cells, cells in the surrounding stroma, and signals from the extracellular matrix. Targeting the pathways that mediate many of these signals has been a major goal in the effort to develop therapeutics.
Upper Gastrointestinal Crohn’s Disease
Authors: Mottet Christian , Juillerat Pascal , Pittet Valérie , Gonvers Jean-Jacques , Michetti Pierre , Vader John-Paul , Felley Christian , Froehlich Florian
Published: February 2008

Symptomatic gastroduodenal manifestations of Crohn’s disease are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal Crohn’s disease usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of the galenic formulation of sulfasalazine and mesalazine with pH-dependent release. The presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider.
Extraintestinal Manifestations of Crohn’s Disease
Authors: Juillerat Pascal , Mottet Christian , Pittet Valérie , Froehlich Florian , Felley Christian , Gonvers Jean-Jacques , Vader John-Paul , Michetti Pierre
Published: February 2008

In each case of extraintestinal manifestations of Crohn’s disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy – axial arthropathy – and primary sclerosing cholangitis, which have also been described in quiescent Crohn’s disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn’s disease have been developed in the past and only the role of infliximab has increased in Crohn’s disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept and cyclosporine or tacrolimus. Unfortunately, because of the paucity of data in this field, the best evidence presented and discussed in this article for the treatment of these extraintestinal manifestations is extrapolated from patients that for the most part did not suffer from Crohn’s disease.
Herpes Virus and Ménière’s Disease
Authors: Gärtner M. , Bossart W. , Linder T.
Published: February 2008

Objective: The main goal of this study was to examine the vestibular ganglia from patients with intractable classic Ménière’s disease (MD) for the presence or absence of DNA from three neurotropic viruses herpes simplex virus 1 and 2 (HSV1, HSV2) and varicella zoster virus (VZV) and to investigate the hypothesis that MD is associated with virus reactivation within Scarpa’s ganglion. Study Design: Polymerase chain reaction (PCR) was performed with nested primer sets specific for viral genomic DNA of HSV1, HSV2 and VZV in biopsies of the ganglion scarpae of patients with MD who underwent vestibular neurectomy. Included were patients with MD classified as definite MD according to American Academy of Otolaryngology/Head and Neck Surgery criteria. The ganglion scarpae and ganglion geniculi harvested at autopsy from patients without history of MD or facial palsy served as control specimens. Results: No viral DNA was detected in the vestibular ganglion of 7 patients with definite MD. In 34% of the vestibular ganglia of the control group we detected either HSV1 or VZV. Only one Scarpa’s ganglion had both viruses present at the same time. Thirty-two out of 34 ganglia from the geniculate segment of the facial nerve contained either HSV1 and/or VZV genomic DNA. Eight specimens contained both viruses simultaneously. Altogether viral DNA was found in 94% of ganglia. Viral genomic DNA of HSV2 was not detected. Conclusion: Although HSV and VZV appear to be present in many ganglion cells throughout the human body, we were unable to find genomic DNA of these viruses in patients with definite MD and disabling vertigo, who underwent vestibular neurectomy. Based on these results, reactivation of HSV1 and VZV in the vestibular ganglion does not seem to play a role in the pathogenesis of MD.
Sudden Deafness: Is It Viral?
Authors: Merchant Saumil N. , Durand Marlene L. , Adams Joe C.
Published: February 2008

A number of theories have been proposed to explain the etiopathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL), including viral infection, vascular occlusion, breaks of labyrinthine membranes, immune-mediated mechanisms and abnormal cellular stress responses within the cochlea. In the present paper, we provide a critical review of the viral hypothesis of ISSHL. The evidence reviewed includes published reports of epidemiological and serological studies, clinical observations and results of antiviral therapy, morphological and histopathological studies, as well as results of animal experiments. The published evidence does not satisfy the majority of the Henle-Koch postulates for viral causation of an infectious disease. Possible explanations as to why these postulates remain unfulfilled are reviewed, and future studies that may provide more insight are described. We also discuss other mechanisms that have been postulated to explain ISSHL. Our review indicates that vascular occlusion, labyrinthine membrane breaks and immune-mediated mechanisms are unlikely to be common causes of ISSHL. Finally, we review our recently proposed theory that abnormal cellular stress responses within the cochlea may be responsible for ISSHL.
DMD and IL1RAPL1: two large adjacent genes localized within a common fragile site (FRAXC) have reduced expression in cultured brain tumors
Authors: McAvoy S. , Ganapathiraju S. , Perez D.S. , James C.D. , Smith D.I.
Published: February 2008

Common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. Spanning the center of the two most frequently expressed CFS regions, FRA3B (3p14.3) and FRA16D (16q23.2), are the 1.5 Mb FHIT gene and the 1.0 Mb WWOX gene. These genes are frequently deleted and/or altered in many different cancers. Both FHIT and WWOX have been demonstrated to function as tumor suppressors, both in vitro and in vivo. A number of other large CFS genes have been identified and are also frequently inactivated in multiple cancers. Based on these data, several additional very large genes were tested to determine if they were derived from within CFS regions, but DCC and RAD51L1 were not. However, the 2.0 Mb DMD gene and its immediately distal neighbor, the 1.8 Mb IL1RAPL1 gene are CFS genes contained within the FRAXC CFS region (Xp21.2→p21.1). They are abundantly expressed in normal brain but were dramatically underexpressed in every brain tumor cell line and xenograft (derived from an intracranial model of glioblastoma multiforme) examined. We studied the expression of eleven other large CFS genes in the same panel of brain tumor cell lines and xenografts and found reduced expression of multiple large CFS genes in these samples. In this report we show that there is selective loss of specific large CFS genes in different cancers that does not appear to be mediated by the relative instability within different CFS regions. Further, the inactivation of multiple large CFS genes in xenografts and brain tumor cell lines may help to explain why this type of cancer is highly aggressive and associated with a poor clinical outcome.
Dicentric chromosomes and 20q11.2 amplification in MDS/AML with apparent monosomy 20
Authors: MacKinnon R.N. , Campbell L.J.
Published: February 2008

FISH analysis of 41 previously karyotyped cases of MDS and AML with apparent monosomy of chromosome 20 revealed a variety of dicentric abnormalities involving chromosome 20. These usually, but not always, involved a breakpoint in the long arm of chromosome 20 and loss of the common deleted region at 20q12. Not one case of true monosomy 20 was confirmed. We found evidence for dicentric chromosome formation in 21 of 24 unbalanced translocations containing chromosome 20 and that were studied in more detail. Subsequent loss of one of the centromeres had occurred in eight of these 24 cases, and was more frequent than centromere inactivation as a means of resolving the inherent instability of a dicentric chromosome. In the three cases with dicentric chromosomes from which proximal 20q had been excised along with the 20 centromere, the excised segment was retained, and in two of these it was amplified. Proximal 20q was clearly retained in all but three cases, and present in three or more copies in 17 of 41 cases. The retention and amplification of proximal 20q provides support for the hypothesis that there is an oncogene located in this region of 20q that is activated in cases of MDS/AML with del(20q). Apparent monosomy 20 in MDS/AML should be treated as evidence of unidentified chromosome 20 abnormalities, and familiarity with the typical G-banded morphology of these derivatives can help with their identification. The reported incidence of dicentric chromosomes is clearly an under-estimate but is increasing in myeloid disorders as more cases are studied with methods allowing their detection.
A chromosome inversion near the KIT gene and the Tobiano spotting pattern in horses
Authors: Brooks S.A. , Lear T.L. , Adelson D.L. , Bailey E.
Published: February 2008

Tobiano is a white spotting pattern in horses caused by a dominant gene, Tobiano(TO). Here, we report TO associated with a large paracentric chromosome inversion on horse chromosome 3. DNA sequences flanking the inversion were identified and a PCR test was developed to detect the inversion. The inversion was only found in horses with the tobiano pattern, including horses with diverse genetic backgrounds, which indicated a common genetic origin thousands of years ago. The inversion does not interrupt any annotated genes, but begins approximately 100 kb downstream of the KIT gene. This inversion may disrupt regulatory sequences for the KIT gene and cause the white spotting pattern. This manuscript is accompanied by supplemental figures S1, S2 and S3, as well as supplemental Tables S1 and S2 (www.karger.com/doi/10.1159/000112065). The DNA sequence generated in this work has been submitted to GenBank under the following accession number: EF442014.
A radiation hybrid map of river buffalo (Bubalus bubalis) chromosome 7 and comparative mapping to the cattle and human genomes
Authors: Goldammer T. , Weikard R. , Miziara M.N. , Brunner R.M. , Agarwala R. , Schäffer A.A. , Womack J.E. , Amaral M.E.J.
Published: February 2008

A preliminary radiation hybrid (RH) map containing 50 loci on chromosome 7 of the domestic river buffalo Bubalus bubalis (BBU; 2n = 50) was constructed based on a comparative mapping approach. The RH map of BBU7 includes thirty-seven gene markers and thirteen microsatellites. All loci have been previously assigned to Bos taurus (BTA) chromosome BTA6, which is known for its association with several economically important milk production traits in cattle. The map consists of two linkage groups spanning a total length of 627.9 cR5,000. Comparative analysis of the BBU7 RH5,000 map with BTA6 in cattle gave new evidence for strong similarity between the two chromosomes over their entire length and exposed minor differences in locus order. Comparison of the BBU7 RH5,000 map with the Homo sapiens (HSA) genome revealed similarity with a large chromosome segment of HSA4. Comparative analysis of loci in both species revealed more variability than previously known in gene order and several chromosome rearrangements including centromere relocation. The data obtained in our study define the evolutionarily conserved segment on BBU7 and HSA4 to be between 3.5 megabases (Mb) and 115.8 Mb in the HSA4 (genome build 36) DNA sequence.
Comparative FISH-mapping of twelve loci in river buffalo and sheep chromosomes: comparison with HSA8p and HSA4q
Authors: Perucatti A. , Di Meo G.P. , Goldammer T. , Incarnato D. , Brunner R. , Iannuzzi L.
Published: February 2008

Twelve loci (11 of type I and 1 of type II) previously FISH-mapped in cattle were comparatively FISH-mapped in both river buffalo chromosome 1p (BBU1p) and homologous chromosome 26 of sheep (OAR26), extending the cytogenetic maps in both chromosome species and providing a more precise localization of these loci in single chromosome bands than previous locations on BTA27. Bovine BAC clones containing DCTD, C4orf20, CASP3, TLR3, MSR1, FAT, LONRF1, DLC1, C8orf41, CSSM036, LSM1 and EIF4EBP1 were used for FISH on RBPI-banded chromosomes. All loci were located on the same homologous chromosome bands (R-band positive) of both species further confirming the high degree of banding and gene (order of loci) homologies among bovids. Detailed cytogenetic maps of OAR26 and BBU1p were performed and compared with that of BTA27 as well as with those of both HSA8p and HSA4q, revealing complex chromosome rearrangements differentiating OAR26/BBU1p/BTA27 from human chromosomes.
Chromosomal markers distinguish hybrids and non-hybrid accessions of mandarin
Authors: Moraes A.P. , Lemos R.R. , Brasileiro-Vidal A.C. , dos Santos Soares Filho W. , Guerra M.
Published: February 2008

Mandarin is the common name of a heterogeneous group of Citrus species with a large range of variation in morphological and molecular characters as well as in number of species. Aiming to identify chromosome markers and to clarify the relationship within this group, the karyotype of 13 mandarin accessions were analyzed using CMA/DAPI staining and in situ hybridization with 5S and 45S rDNA probes. The CMA band pattern together with the position of rDNA sites revealed that mandarins can be separated karyologically into three groups: a) C. sunki and C. reshni; b) the Mediterranean mandarin, C. deliciosa, and the closely related C. tangerina cv. Dancy and C. reticulata cv. Cravo; c) the remaining cultivars, which are cytologically heterozygous and most probably interspecific hybrids. The former two groups are assumed to be pure species together with C. medica and C. grandis. A chromosome marker for mandarin species was identified and the relationship among the pure species and some hybrids is discussed.
Meiotic loss of the B chromosomes of maize is influenced by the B univalent co-orientation and the TR-1 knob constitution of the A chromosomes
Authors: González-Sánchez M. , González-García M. , Vega J.M. , Rosato M. , Cuacos M. , Puertas M.J.
Published: February 2008

The suppression of meiotic loss when the maize B chromosomes are unpaired is genetically determined. Two genotypes were selected in 1B × 0B crosses: the H line where the B transmission rate is Mendelian (50%) and the L line where the B is present in only about 40% of the progeny. Using the ZmBs probe located at the centromere and at the distal portion of the B chromosome in FISH, we found that the centromeric and telomeric ends of the B univalent co-orient at metaphase I. This feature seems to promote proper centromere orientation causing the lack of meiotic loss of the unpaired B. The co-orientation was observed in both lines, however in the L line the B univalents were not always properly oriented, showing amphitelic orientation in about 25% of the metaphase I cells. We also studied plants of the H and L lines with FISH to test the possible relation between the knob constitution and B loss. It has been found that the plants of both lines are similarly variable for the 180-bp knob repeat, but they differ in the TR-1 350-bp repeat, the L line having more TR-1 knobs. The use of a 45S rDNA probe which labels chromosome 6, allowed us to determine that this chromosome shows the main variability between the two lines: the L line has TR-1 in both arms, showing a large TR-1 knob on the long arm. The H line has only one, generally located on the short arm besides the NOR.
The Rare Association of Truncus Arteriosus with a Cervical Double Aortic Arch Presenting with Left Main Bronchial Compression
Authors: Huang Shao-Chi , Wang Chao-Jan , Su Wen-Jen , Chu Jaw-Ji , Hwang Mao-Sheng
Published: February 2008

Truncus arteriosus, a double aortic arch, and a cervical aortic arch are all rare cardiovascular anomalies. We experienced a unique female newborn with the rare combination of truncus arteriosus with a cervical double aortic arch, which probably resulted from abnormal persistence of the bilateral 2nd or 3rd rather than the 4thembryonic aortic arches and failure of regression of the right 8th somitic segment of the right dorsal aorta. She presented with respiratory distress soon after birth, which was initially attributed to the vascular ring and hypertensive pulmonary arteries. Our inability to relieve her respiratory compromise by surgical division of the vascular ring and main pulmonary artery banding prompted the diagnosis of left main bronchial compression caused by a posteriorly displaced dilated ascending aorta that compressed the right pulmonary artery and left main bronchus against the descending aorta. The patient then underwent successful left main bronchus stent implantation. We speculate the cervical double aortic arch is redundant in nature and is a loose ring that may not cause tracheal compression. Nevertheless, a posteriorly displaced dilated ascending aorta in patients with truncus arteriosus may compress the right pulmonary artery and the main bronchus on the side of the aortic arch against the descending aorta.
The Predictive Value of Transthoracic Echocardiographic Variables for Sinus Rhythm Maintenance after Electrical Cardioversion of Atrial Fibrillation
Authors: Grundvold Irene , Tveit Arnljot , Smith Pål , Seljeflot Ingebjørg , Abdelnoor Michael , Arnesen Harald
Published: February 2008

Objectives: The recurrence rate of atrial fibrillation after electrical cardioversion is disappointingly high. The aim of the present study was to prospectively investigate if standard echocardiographic variables at the day of cardioversion could predict sinus rhythm maintenance. Methods: Transthoracic echocardiographic examination was performed within 4 h after cardioversion for all the patients in the CAPRAF (Candesartan in the Prevention of Relapsing Atrial Fibrillation) study. Results: Cardioversion was successful for 137 patients not given specific antiarrhythmic therapy, and only 41 (30%) maintained sinus rhythm at 6-month follow-up. There were significant (p = 0.05) lower transmitral A wave velocities in the group with relapsing atrial fibrillation compared with the group with sinus rhythm at 6-month follow-up. All patients with the lowest A wave velocities had an early recurrence of atrial fibrillation. There were no differences between the groups regarding atrial dimensions or left ventricular function. The use of the angiotensin II receptor antagonist candesartan had no influence on the echocardiographic variables, nor on the recurrence rate of atrial fibrillation after cardioversion. Conclusions: Transthoracic echocardiographic examination performed a short time after electrical cardioversion of atrial fibrillation showed that only A wave peak velocities were significantly predictive of sinus rhythm maintenance 6 months after the procedure.
Exercise-Induced Improvement in Atrial Depolarization Abnormality in a Patient after Treatment with Beta-Adrenergic Blockers
Authors: Ariyarajah Vignendra , Shaikh Nasir , Spodick David H.
Published: February 2008

Abnormal atrial depolarization, characterized by P waves ≧110 ms on the electrocardiogram, can manifest as partial or advanced interatrial conduction delay or interatrial block (IAB). Progression from partial to advanced IAB has been shown to be altered by the use of angiotensin-converting enzyme inhibitors and β-adrenergic blockers. We previously reported that advanced IAB, denoted by biphasic P waves in leads II, II and aVF, can revert intermittently to its partial counterpart. However, potential factors that could induce such resolution remain unknown. We present the first known case of resolution of advanced IAB to partial IAB occurring during graded exercise, following treatment with a β-adrenergic blocker. Only continued study of these and other novel factors will help us understand the exact pathophysiology of both, partial and advanced IAB.
Postoperative Pulmonary Function in Open versus Laparoscopic Cholecystectomy: A Meta-Analysis of the Tiffenau Index
Authors: Damiani Gianfranco , Pinnarelli Luigi , Sammarco Annalisa , Sommella Lorenzo , Francucci Marsilio , Ricciardi Walter
Published: February 2008

Background: Available scientific literature about open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) does not show univocal results in terms of postoperative pulmonary function. A meta-analysis was carried out to evaluate the postoperative pulmonary function after OC and LC focusing on the Tiffenau index. Methods: Electronic databases were consulted (Cochrane Library, Embase and Pubmed). Standardized mean difference (SMD) with 95% CI was calculated for the Tiffenau Index. The kappa test was performed to evaluate agreement between the reviewers regarding the quality of the selected studies. A sensitivity analysis was carried out to assess the robustness of our study. Heterogeneity among studies was tested by using a χ2 test at 0.05 significance level. A random effects model meta-analysis was performed. Results: Meta-analysis of the 13 articles included, resulted in a SMD of 53% (95% CI 0.04, 1.02) for the Tiffenau Index in favor of laparoscopic cholecystectomy. The χ2 test analysis showed the presence of heterogeneity among studies (Tiffenau index χ2 = 99.97, p = 0.03). The sensitivity analysis confirms the validity of our results. Conclusions: Postoperative pulmonary function is better preserved after laparoscopic cholecystectomy than open cholecystectomy.
Management of Descending Duodenal Injuries Secondary to Laparoscopic Cholecystectomy
Authors: Testini Mario , Piccinni Giuseppe , Lissidini Germana , Di Venere Beatrice , Gurrado Angela , Poli Elisabetta , Brienza Nicola , Biondi Antonio , Greco Luigi , Nacchiero Michele
Published: February 2008

Aim: To report our experience of managing patients affected by descending duodenal injuries secondary to laparoscopic cholecystectomy and to review the literature. Methods: Analysis of 5 cases of descending duodenal injury as a consequence of laparoscopic cholecystectomy managed between June 1992 and September 2006. Results: The median age was 59 (range 49–67) years.In all cases an emergency laparotomy showed an injury to the descending duodenum. Two patients underwent direct suture of the duodenum and external biliary drainage through a T-tube, 1 case underwent a duodenojejunostomy and in another a duodenopancreatectomy. The latter patient underwent drainage of the duodenum with a Petzer tube, followed 5 days later by gastric resection, closure of the duodenal stump and repair of the duodenal wound by suture. The median postoperative stay was 45 days and 1 patient died. Conclusion: Descending duodenal injuries are extremely rare complications of laparoscopic cholecystectomy with potentially fatal consequences if not promptly recognized and treated. The site of the descending duodenal injury is important for determining the surgical approach.
Feeding Potato Flakes Affects Cecal Short-Chain Fatty Acids, Microflora and Fecal Bile Acids in Rats
Authors: Han Kyu-Ho , Hayashi Naoto , Hashimoto Naoto , Shimada Ken-ichiro , Sekikawa Mitsuo , Noda Takahiro , Fukushima Michihiro
Published: February 2008

Background/Aims: Feeding rats potato resistant starch improves large bowel health; however, there is little information on the physiological effects of preprocessed starch like potato flakes in animal experiments. The present study was designed to investigate the effects of the consumption of various colored potato (white, red and purple) flakes on cecal fermentation and fecal bile acid excretions in rats. Methods: The control group was fed a basal diet (BD) containing α-cornstarch for 4 weeks. The potato flake-treated groups were fed one of the following diets containing a mixture of 299.5 g/kg α-cornstarch plus 250 g/kg Hokkai kogane flakes (HK, white), Hokkai No. 91 flakes (H91, red) or Hokkai No. 92 flakes (H92, purple). Results: There were no significant differences in the body weight, food intake and cecum weight among the groups. Cecal pH values in the HK, H91 and H92 groups were significantly lower than that in the BD group, and matter excretion in the H91 group was significantly higher than in the BD and HK groups. Cecal short-chain fatty acid (SCFA) concentrations in the HK, H91 and H92 groups were significantly higher than in the BD group, and the molar ratio of butyrate to total SCFA in the HK, H91 and H92 groups was greatly increased compared with the BD group. Rats fed the HK, H91 and H92 potato flake diets presented significantly higher counts of total anaerobes in the cecum than rats fed the BD. The cecal Lactobacillus count in the H91 group was significantly increased compared to the BD group and the Bifidobacterium count was similar for all groups. Fecal total bile acid excretion in the H92 flake group and secondary bile acid excretions in the H91 and H92 groups were significantly greater than those in the other groups and in the BD and HK groups, respectively. Conclusion: The results indicate that potato flakes act like resistant starch and raise bowel SCFA, probably through anaerobic bacterial activities and fermentation of residual starch. These actions are helpful for the improvement of the colonic environment.
Is a Specialised Training of Phonological Awareness Indicated in Every Preschool Child?
Authors: Keilmann Annerose , Wintermeyer Monika
Published: February 2008

Objective and Methods: In a prospective study 218 preschool children were enrolled (stratified in 2 training programs, one specialized for phonologic awareness in order to prevent dyslexia, the other consisting in training of general perception) during the last year of kindergarten. After finishing the first grade 131 children were compared in their reading and writing abilities. Results: In the whole group only a slight difference was found between both training modalities concerning their writing abilities. However, children with a history of hearing loss, actual hearing loss or pathologic middle ear findings profited most from the specialized training program compared to the control in their reading abilities. Conclusion:  A specialized training program to improve phonologic awareness as a basis for reading and writing in every kindergarten and preschool child seems to be unnecessary. However, children with temporary hearing deficits benefit from such a program. For all other children general perception training may be sufficient.
Postural Dynamics and Vocal Effort: Preliminary Experimental Analysis
Authors: Giovanni Antoine , Akl Leslie , Ouaknine Maurice
Published: February 2008

Objectives: One postural characteristic of increased vocal effort is stiffening of the whole body, which in turn induces some postural instability. The study of postural instability can shed some insight into behavior or causes associated with vocal hyperfunction. Patients and Methods: A posturography platform was used to measure the root mean square of the velocity of variation of the center of pressure (VCOP rms) of control subjects standing upright on the platform. Four conditions were analyzed: (1) standing with eyes open versus eyes closed (n: 9); (2) standing at rest versus holding a 3-kg weight (n: 15); (3) standing while reading a dialogue at normal voice level versus loud voice (n: 17), and (4) standing while reading a dialogue in a calm versus noisy (Lombard effect) ambiance (n: 19). Results: Conditions leading to a stiffening of the body (eyes closed and weight holding) were associated with an increased instability assessed by the VCOP rms. In phonatory conditions leading to vocal effort, the mean VCOP rms was significantly increased: in 19 subjects reading a dialogue in a calm ambiance the mean VCOP rms was at 11.19 mm/s, and the VCOP rms raised 16.69 mm/s with surrounding noise at 82 db (Lombard effect). Conclusion: Increased vocal effort is associated with increased VCOP rms in most subjects studied. The effects of VCOP rms as a postural index allowing noninvasive assessment of the voice in pathology warrants further study.
The Interobserver and Test-Retest Variability of the Dysphonia Severity Index
Authors: Hakkesteegt Marieke M. , Wieringa Marjan H. , Brocaar Michael P. , Mulder Paul G.H. , Feenstra Louw
Published: February 2008

Objective: The purpose of this study was to investigate the interobserver variability and the test-retest variability of the Dysphonia Severity Index (DSI), a multiparametric instrument to assess voice quality. Methods: The DSI was measured in 30 nonsmoking volunteers without voice complaints or voice disorders by two speech pathologists. The subjects were measured on 3 different days, with an interval of 1 week. Results: The difference in DSI between two observers (interobserver difference) was not significant. The intraclass correlation coefficient for the DSI was 0.79. The standard deviation of the difference between two duplicate measurements by different observers was 1.27. Conclusion: Differences in measurements between different observers were not significant. The intraclass correlation coefficient of the DSI was 0.79, which is to be considered good. Differences in DSI within one patient need to be larger than 2.49 to be significant.
Medialization Thyroplasty with a Customized Silicone Implant: Clinical Experience
Authors: Chrobok Viktor , Pellant Arnošt , Šram František , Frič Marek , Praisler Jaroslav , Prymula Roman , Švec Jan G.
Published: February 2008

The authors implemented medialization thyroplasty with a customized silicone implant in a total of 43 operations (36 patients) in 1999–2003. In 5 of these patients, the medialization thyroplasty was combined with cricothyroid subluxation (3 cases) or adduction of arytenoid cartilage (3 cases). One patient received medialization thyroplasty, cricothyroid subluxation and adduction of arytenoid cartilage. Postoperatively 36 patients reported substantial reduction of their complaints, 5 patients found their voice improved and only 2 patients (5.6%) stated that their voice had not changed. The subjective evaluation was consistent with the findings of laryngoscopy and the preoperative and postoperative phonation parameters (maximum phonation time, maximum sound pressure level, jitter and shimmer). Average maximum phonation time was 6.5 s before surgery and 12.5 s after surgery. Maximum vocal sound pressure level was, on average, about 4 dB higher after surgery. Jitter was reduced from 5.3 to 3.7% and shimmer from 32.3 to 18.6%. The differences between presurgical and postsurgical parameters in our study were all statistically significant, indicating voice improvement. Medialization thyroplasty with a silicone implant was proven to be a successful and safe surgical method for the treatment of vocal fold paralysis.
Clinical Intervention for Bilingual Children: An International Survey
Authors: Jordaan Heila
Published: February 2008

This paper reports on the results of an international survey undertaken by the Multilingual Affairs Committee of the IALP, to investigate the intervention provided to bilingual children. Information pertaining to 157 children was obtained from 99 speech-language therapists in 13 countries. The survey addressed biographical details and language background of the children, the diagnosed communication disorder, language competence of the therapists, issues pertaining to the language of intervention, use of interpreters, advice given to parents regarding the use of each language, and possible results of intervention. The findings are specific to each country and related to the sociolinguistic context. Very few therapists provide bilingual intervention, although many have strategies for ensuring the development of both languages, such as advising parents to speak only the home language. Therapists were generally unable to provide quantifiable intervention results due to a paucity of assessment materials for bilinguals. The IALP Multilingual Affairs Committee used the results of this survey to develop guidelines for working with multilingual populations with communication disorders.
Low-Dose Local Kidney Irradiation Inhibits Progression of Experimental Crescentic Nephritis by Promoting Apoptosis
Authors: Liu Diange , Nazneen Arifa , Taguchi Takashi , Razzaque M. Shawkat
Published: February 2008

Background: Crescentic glomerulonephritis is a rapidly progressive form of nephritis and is usually resistant to therapeutic intervention. Apoptosis plays a role in the resolution of glomerulonephritis. We investigated the effects of local kidney irradiation on the progression of experimental crescentic glomerulonephritis. Methods: The following three experimental rat groups were generated: (1) Group I, sham-operated control (n = 12); (2) Group II, rats injected intravenously with rabbit anti-rat GBM antibody (nephrotoxic serum, NTS) (n = 23), and (3) Group III, a single low-dose irradiation of 0.5 Gy X-ray to both kidneys at days 6, 13, 20, and 27 after NTS injection (n = 55). Renal function and blood leukocyte count were examined in different groups of rats at various time points. Kidneys obtained at various time points were analyzed to determine the effects of radiation in experimental nephritis. Results: Radiation of the kidneys reduced the levels of blood urea nitrogen and serum creatinine compared with Group II nephritic rats of similar age (p < 0.05 or 0.001). No apparent changes in blood leukocyte counts were noted in various experimental groups. Glomerular hypercellularity, crescents, global sclerosis and tubulointerstitial damage developed gradually in Group II rats, but were decreased (p < 0.05 or 0.001) after radiation treatment. The extent of tubulointerstitial damage was also reduced, and radiation-associated histological improvements were accompanied by reduced infiltration of macrophages in the glomeruli and interstitium. The numbers of PCNA- and ED1-positive cells were reduced in the kidneys at 1 day post-irradiation, of rats irradiated at 6 and 13 days after NTS injection, compared with Group II at similar time intervals (p < 0.05). A larger numbers of TUNEL-positive cells were noted at 1 day post-irradiation in rats irradiated at 6 and 13 days after NTS injection, compared with Group II at similar time intervals (p < 0.05). Immunostaining for macrophages ED1 and TUNEL staining of serial sections of irradiated nephritic kidneys showed few ED1-positive macrophages stained for TUNEL. Overexpression of active caspases 3 and 7 was noted in irradiated kidneys, compared with the corresponding Group II rats at similar time intervals. Western blot analysis showed marked increase in active caspase 3 and active caspase 7 expression in irradiated kidneys compared with NTS injection only. A marked increase in the expression of p53 protein, which is closely related to radiation-induced apoptosis, was also observed in irradiated kidneys compared with NTS injection only. Conclusion: Our study showed that renal radiation can alter acute glomerular inflammation by inducing apoptosis of intrinsic and infiltrating cells in the kidney in a rat model of crescentic glomerulonephritis. Low-dose kidney irradiation can inhibit the progression of experimental nephritis through inducing apoptosis.