bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective review of emergency response activations during a 13‐year period at a tertiary care children's hospital
Authors: Wang George Sam , Erwin Nicole , Zuk Jeannie , Henry Desmond B. , Dobyns Emily L.
Published: November 2010

OBJECTIVES:

Pediatric in‐hospital arrests are uncommon but are associated with poor outcomes. In preparation for implenting a Rapid Response Team (RRT) at The Children's Hospital, we reviewed our data collection of 13 years of emergency response team (ERT) activations. We describe demographic and clinical variables, including outcomes of ERT activations at a free‐standing tertiary care children's hospital.

METHODS:

Analysis was performed on data collected from January 1993 through July 2007. Variables collected included age, sex, admission diagnosis, core event, admission diagnosis and secondary diagnosis, medical division or winter/nonwinter months, day/night shifts, survival of core event, survival to discharge, and primary attending service.

RESULTS:

There were 1537 ERT activations in the database, 203 were eliminated due to missing data or were adult visitors/employees. The remaining 1334 were included for analysis. Our results showed 39%(511) of all ERT activations occurred in patients under 1 year of age. The most common admission diagnosis category was cardiac disease. There was no statistical significance between summer and winter months although more activations occurred during daytime hours (P < .001). Survival rate of an ERT was 90%, with a 78% survival rate to discharge.

CONCLUSION:

Our data support the general belief that younger children with chronic disease are at highest risk for ERT activations. These risk factors should be taken into consideration when planning patient placement, medical staffing, and the threshold for ICU consultations or admissions. More extensive multisite studies using clinical data are necessary to further identify hospitalized children at risk for sudden decompensation. Journal of Hospital Medicine 2010;. © 2010 Society of Hospital Medicine.
Computed tomography and magnetic resonance imaging of pulmonary hypertension: Pulmonary vessels and right ventricle
Authors: Ley Sebastian , Grünig Ekkehard , Kiely David G. , van Beek Edwin , Wild Jim
Published: November 2010

Pulmonary hypertension (PH) is very heterogeneous and the classification identifies five major groups including many associated disease processes. The treatment of PH depends on the underlying cause and accurate classification is paramount. A comprehensive assessment to identify the cause and severity of PH is therefore needed. Furthermore, follow‐up assessments are required to monitor changes in disease status and response to therapy. Traditionally, the diagnostic imaging work‐up of PH comprised mainly echocardiography, invasive right heart catheterization, and ventilation/perfusion scintigraphy. Due to technical advances, multidetector row computed tomography (CT) and magnetic resonance imaging (MRI) have become important and complementary investigations in the evaluation of patients with suspected PH. Both modalities are reviewed and recommendations for clinical use are given. J. Magn. Reson. Imaging 2010;32:1313–1324. © 2010 Wiley‐Liss, Inc.
Computed tomography and magnetic resonance imaging in cystic fibrosis lung disease
Authors: Eichinger Monika , Heussel Claus‐Peter , Kauczor Hans‐Ulrich , Tiddens Harm , Puderbach Michael
Published: November 2010

Computed tomography (CT) is the current “gold standard” for assessment of lung morphology and is so far the most reliable imaging modality for monitoring cystic fibrosis (CF) lung disease. CT has a much higher radiation exposure than chest x‐ray. The cumulative radiation dose for life‐long repeated CT scans has limited its use for CF patients as their life expectancy increases. Clearly, no dose would be preferable over low dose when the same or more relevant information can be obtained. Magnetic resonance imaging (MRI) is comparable to CT with regard to the detection of most morphological changes in the CF lung. It is thought to be less sensitive to detect small airway disease. At the same time, MRI is superior to CT when it comes to the assessment of functional changes such as altered pulmonary perfusion. The recommendation is to further reduce radiation dose related to the use of CT and to use MRI in the follow‐up of morphological changes where possible. J. Magn. Reson. Imaging 2010;32:1370–1378. © 2010 Wiley‐Liss, Inc.
Imaging of lung function using hyperpolarized helium‐3 magnetic resonance imaging: Review of current and emerging translational methods and applications
Authors: Fain Sean , Schiebler Mark L. , McCormack David G. , Parraga Grace
Published: November 2010

During the past several years there has been extensive development and application of hyperpolarized helium‐3 (HP 3He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation‐induced lung injury, and transplantation. This review focuses on the state‐of‐the‐art of HP 3He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion‐weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation‐induced lung injury. The strengths and challenges of the application of 3He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques. J. Magn. Reson. Imaging 2010;32:1398–1408. © 2010 Wiley‐Liss, Inc.
Recent technological and application developments in computed tomography and magnetic resonance imaging for improved pulmonary nodule detection and lung cancer staging
Authors: Sieren Jessica C. , Ohno Yoshiharu , Koyama Hisanobu , Sugimura Kazuro , McLennan Geoffrey
Published: November 2010

This review compares the emerging technologies and approaches in the application of magnetic resonance (MR) and computed tomography (CT) imaging for the assessment of pulmonary nodules and staging of malignant findings. Included in this review is a brief definition of pulmonary nodules and an introduction to the challenges faced. We have highlighted the current status of both MR and CT for the early detection of lung nodules. Developments are detailed in this review for the management of pulmonary nodules using advanced imaging, including: dynamic imaging studies, dual energy CT, computer aided detection and diagnosis, and imaging assisted nodule biopsy approaches which have improved lung nodule detection and diagnosis rates. Recent advancements linking in vivo imaging to corresponding histological pathology are also highlighted. In vivo imaging plays a pivotal role in the clinical staging of pulmonary nodules through TNM assessment. While CT and positron emission tomography (PET)/CT are currently the most commonly clinically employed modalities for pulmonary nodule staging, studies are presented that highlight the augmentative potential of MR. J. Magn. Reson. Imaging 2010;32:1353–1369. © 2010 Wiley‐Liss, Inc.
Magnetic resonance imaging and computed tomography of respiratory mechanics
Authors: Biederer Jürgen , Hintze Christian , Fabel Michael , Dinkel Julien
Published: November 2010

Radiotherapy for organs with respiratory motion has motivated the development of dynamic volume lung imaging with computed tomography (4D‐CT) or magnetic resonance imaging (4D‐MRI). 4D‐CT can be realized in helical (continuous couch translation during image acquisition) or cine mode (translation step‐by‐step), either acquired prospectively or reconstructed retrospectively with temporal resolutions of up to 250 msec. Long exposure times result in high radiation dose and restrict 4D‐CT to specific indications (ie, radiotherapy planning). Dynamic MRI accelerated by parallel imaging and echo sharing reaches temporal resolutions of up to 10 images/sec (2D+t) or 1 volume/s (3D+t) that allow analyzing respiratory motion of the lung and its tumors. Near isotropic 4D‐MRI can be used to assess tumor displacement, chest wall invasion, and segmental respiratory mechanics. Limited temporal resolution of dynamic volume acquisitions (in their current implementation) may lead to an overestimation of tumor size, as the mass is volume averaged into many voxels during motion. Nevertheless, 4D‐MRI allows for repeated and prolonged measurements without radiation exposure and therefore appears to be appropriate for patient selection in motion‐adapted radiotherapy as well as for a broad spectrum of scientific applications. J. Magn. Reson. Imaging 2010;32:1388–1397. © 2010 Wiley‐Liss, Inc.
In vitro study on vertical transmission of the HIV‐1 gag gene by human sperm
Authors: Wang Dian , Kang Xiang‐Jin , Li Lian‐Bing , Xie Qing‐Dong , Gao Yu‐Sen , Huang Tian‐Hua
Published: November 2010

HIV/AIDS is a major public health problem worldwide. To explore the feasibility of HIV vertical transmission by human sperm, plasmid construction and transfection, interspecific in vitro fertilization of zona‐free hamster ova by human sperm, fluorescence in situ hybridization (FISH), RT‐PCR, and immunofluorescence assay (IFA) were carried out. The FISH signals for HIV‐1 gag DNA were observed in the nuclei and chromosomes of transfected human sperm, male pronuclei of zygotes, and nuclei of blastomeres of two‐cell embryos, indicating that the HIV‐1 gag gene could be transmitted via the sperm membrane and integrated into the sperm genome. In contrast, human sperm carrying the target gene achieved normal fertilization, and replication of the sperm‐mediated target gene was synchronized with the host genome. Using RT‐PCR, the positive bands for the target gene were observed in the transfected human sperm and two‐cell embryos. These results further confirm that the target gene can be transcribed into mRNA in human sperm and embryonic cells. Positive signals for the HIV‐1 p24 gag protein were shown by IFA in two‐cell embryos containing the sperm‐mediated target gene and not in the transfected human sperm, which indicated that the sperm‐mediated target gene could be translated to make HIV‐1 p24 gag protein in embryonic cells, but not in sperm cells. The results provide evidence for possible vertical transmission of the HIV‐1 gag gene to the embryo by fertilizing sperm in vitro. J. Med. Virol. 83:16–23, 2011. © 2010 Wiley‐Liss, Inc.
Low prevalence of HPV in Brazilian children with retinoblastoma
Authors: Antoneli Célia B.G. , Ribeiro Karina B. , Sredni Simone T. , Arias Victor E.A. , Andreoli Maria A. , de Camargo Beatriz , Sobrinho João S. , Prado José C.M. , Soares Fernando A. , Villa Luisa L.
Published: November 2010

Retinoblastoma is the most frequent intra‐ocular malignant tumor of the childhood, occurring in 1 of 18,000–30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin‐fixed, paraffin‐embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro‐dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro‐dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human β‐globin gene using primers PCO3+/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty‐four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm. J. Med. Virol. 83:115–118, 2011. © 2010 Wiley‐Liss, Inc.
Lymphocytopenia as a marker for pandemic influenza A/H1N1 2009 virus infection in children
Authors: Chiappini Elena , Galli Luisa , Azzi Alberta , Resti Massimo , Bonsignori Francesca , de Martino Maurizio
Published: November 2010

Lymphocytopenia has been reported in adults with pandemic influenza A/H1N1 2009 infection, but data in children are inconclusive. Data from 76 children presented with flu‐like symptoms between July and November 2009 and tested for pandemic influenza A/H1N1 2009 virus and white blood cell (WBC) counts were analyzed. Samples from 37 (48.7%) children resulted in a positive PCR assay for pandemic influenza A/H1N1 2009 virus. When comparing data from these children with data from 39 (51.3%) children with uncomplicated flu‐like illness and negative PCR assay for pandemic influenza A/H1N1 2009 virus, no difference in disease duration, median age, red blood cell count, hemoglobin concentration, C reactive protein concentration, and absolute neutrophil count was observed, whereas significant differences were apparent when considering WBC count, relative and absolute lymphocyte count, absolute lymphocyte count z‐score, and platelet count. Receiver operating characteristic curve analysis revealed that the best absolute lymphocyte count and absolute lymphocyte count z‐score cut‐points that simultaneously maximized sensitivity and specificity were 2,256 cells/µl and −0.89, respectively, sensitivity being 0.81 (95% CI: 0.68–0.94), specificity 0.87 (95% CI: 0.77–0.98), positive predictive value 0.85 (95% CI: 0.74–0.97), and negative predictive value 0.83 (95% CI: 0.71–0.94).

In conclusion, lymphocytopenia is a marker for influenza A/H1N1 2009 virus infection in children. Absolute lymphocyte count <2,556 cells/µl or absolute lymphocyte count z‐score < −0.89 may be useful cut‐offs to discriminate against children at higher risk of infection during epidemics. Considering that the pandemic virus is highly likely to continue to circulate in the coming winter season, these findings provide direct and practical implications for the near future. J. Med. Virol. 83:1–4, 2011. © 2010 Wiley‐Liss, Inc.
Analysis of the full‐length genomes of novel hepatitis B virus subgenotypes C11 and C12 in Papua, Indonesia
Authors: Mulyanto  , Depamede Sulaiman Ngongu , Wahyono Arif , Jirintai  , Nagashima Shigeo , Takahashi Masaharu , Okamoto Hiroaki
Published: November 2010

Two novel subgenotypes (C6 and D6) of hepatitis B virus (HBV) were identified recently in Papua, a multiethnic area of Indonesia. To characterize further the HBV strains in Papua, serum samples collected from 59 viremic subjects (44 males and 15 females; mean age: 30.0 ± 15.5 years) among indigenous inhabitants in Papua, were subjected to phylogenetic analysis of an 1.6‐kb partial sequence. Forty‐five samples (76%) had genotype C HBV (HBV/C) [C5 (n = 1), C6 (n = 40), and unclassifiable (n = 4)], while seven samples (12%) were HBV/D [D1 (n = 1) and D6 (n = 6)] and six samples (10%) were HBV/B [B2 (n = 1), B3 (n = 3), B7 (n = 1), and B8 (n = 1)]; the remaining sample possessed B3 and C6. An analysis of the full‐length sequence of the four HBV/C isolates (NMB09122, NMB09124, NMB09075, and MRK89073) that were unclassifiable into any of the 10 known HBV/C subgenotypes (C1–C10) showed no significant evidence of recombination. Over the entire genome, the NMB09122 and NMB09124 isolates shared 99.8% identity and segregated into a cluster with a bootstrap value of 100%, differing from HBV/C1‐HBV/C10 by 3.8–6.9% (mean, ≥4.0%), indicating that NMB09122 and NMB09124 can be classified into a novel subgenotype within genotype C (tentatively designated C11). The NMB09075 and MRK89073 isolates were 97.4% identical to each other and differed from known HBV/C isolates, including the C11 strains, by 4.0–7.2% (mean, ≥4.5%) over the entire genome, indicating that NMB09075 and MRK89703 can be classified into another novel HBV/C subgenotype (C12). The distribution of C11 and C12 seemed to be associated with particular language speakers in Papua. J. Med. Virol. 83:54–64, 2011. © 2010 Wiley‐Liss, Inc.
Evaluation of reverse transcription loop‐mediated isothermal amplification assays for rapid diagnosis of pandemic influenza A/H1N1 2009 virus
Authors: Nakauchi Mina , Yoshikawa Tetsushi , Nakai Hidetaka , Sugata Ken , Yoshikawa Akiko , Asano Yoshizo , Ihira Masaru , Tashiro Masato , Kageyama Tsutomu
Published: November 2010

Two genetic diagnosis systems using reverse transcription‐loop‐mediated isothermal amplification (RT‐LAMP) technology were evaluated: one for detecting the HA gene of the pandemic influenza A/H1N1 2009 virus (H1pdm RT‐LAMP) and the other for detecting the matrix gene of the influenza A virus (TypeA RT‐LAMP). The competence of these two RT‐LAMP assay kits for the diagnosis of the pandemic influenza A/H1N1 2009 virus was compared using real‐time RT‐PCR assays developed recently on viruses isolated and clinical specimens collected from patients with suspected infection. TypeA RT‐LAMP and H1pdm RT‐LAMP showed almost the same sensitivity as real‐time RT‐PCR for viruses isolated. The sensitivity and specificity of TypeA RT‐LAMP and H1pdm RT‐LAMP were 96.3% and 88.9%, respectively, for clinical specimens. Considering that the ability of the two RT‐LAMP assay kits for detection of the pandemic influenza A/H1N1 2009 virus was comparable to that of the real‐time RT‐PCR assays, and that the assays were completed within 1 hr and did not require any expensive equipment, these two RT‐LAMP assays are promising rapid diagnostic tests for the pandemic influenza A/H1N1 2009 virus at the hospital bedside. J. Med. Virol. 83:10–15, 2011. © 2010 Wiley‐Liss, Inc.
Outcome in partial early virologic responders to combination therapy with peginterferon and ribavirin in patients infected with hepatitis C virus genotype 1b
Authors: Toyoda Hidenori , Kumada Takashi , Kiriyama Seiki , Tanikawa Makoto , Hisanaga Yasuhiro , Kanamori Akira , Tada Toshifumi , Hosokawa Takanori , Arakawa Takahiro , Fujimori Masashi
Published: November 2010

The course and outcome in patients infected with hepatitis C virus (HCV) genotype 1b with partial early virologic response during combination therapy with peginterferon and ribavirin, in whom serum HCV RNA is detectable but has decreased by more than 2 log10 12 weeks after the start of the therapy, has not been elucidated sufficiently. The outcome in this group of patients was investigated. Serum HCV RNA levels was measured every 4 weeks in 149 patients with HCV genotype 1b infection who underwent combination therapy for 48 weeks. In patients with partial early virologic response, the time point when serum HCV RNA became undetectable as well as the final virologic response to treatment was determined. Sixty‐three patients (42.3%) had partial early virologic response. The time when serum HCV RNA became undetectable ranged from 16 to 48 weeks after the start of therapy. Serum HCV RNA remained detectable in 17 patients. The rates of sustained virologic response decreased with the delay of the time when serum HCV RNA became undetectable; sustained virologic responder was not found in patients in whom HCV RNA was still detectable at 24 weeks after the start of treatment. The degree of decrease in serum HCV RNA levels at 12 weeks corresponded to the rate of sustained virologic response in partial early virologic responders. The outcome of partial early virologic responders varied greatly, and close monitoring of serum HCV RNA is required for predicting the outcome of treatment in these patients. J. Med. Virol. 83:101–107, 2011. © 2010 Wiley‐Liss, Inc.
Naturally occurring hepatitis B virus X deletions and insertions among Korean chronic patients
Authors: Lee Seoung‐Ae , Mun Ho‐Suk , Kim Hong , Lee Hyung‐Ki , Kim Buyng‐Jun , Hwang Eung‐Soo , Kook Yoon‐Hoh , Kim Bum‐Joon
Published: November 2010

Deletions and insertions in the hepatitis B virus (HBV) X region have been associated with severe forms of liver disease, including hepatocellular carcinoma (HCC). However, the molecular epidemiologic features of this virus have been described rarely. Deletions and insertions in the X region were determined by direct sequencing in a Korean cohort of 267 patients with different clinical statuses. Deletions and insertions were observed in two sets of six patients each (2.2%, 6/267). The prevalence of deletions or insertions was significantly higher in patients with severe liver disease, HCC, or cirrhosis of the liver (7.2%, 10/132) compared to patients who were carriers or had chronic hepatitis (1.5%, 2/135) (P = 0.017). All deletions in six strains were concentrated at the C terminal end of HBx, encompassing the 113th to 154th codons. A total of four novel types of insertions (PKLL, GM, FFN, and tt) were observed in six patients. Of particular interest, all six strains with insertions were accompanied by double mutations in the basal core promoter (BCP). In conclusion, these results suggest that deletions or insertions in the X region may contribute to disease progression in Korean patients with genotype C infection. J. Med. Virol. 83:65–70, 2011. © 2010 Wiley‐Liss, Inc.
Application of new assays for rapid confirmation and genotyping of isolates of Rubella virus
Authors: Feng Yan , Santibanez Sabine , Appleton Hazel , Lu Yiyu , Jin Li
Published: November 2010

Rubella virus (RV) isolation is recommended by the WHO Measles and Rubella Labnet for studying the etiology and epidemiology of rubella. However, the absence of cytopathologic effects (CPE) in many of the cell lines used commonly makes it difficult to confirm RV growth. In this study, two assays amplifying RV cDNA were developed and validated in order to confirm and genotype RV isolates after cell culture. A SYBR Green I‐based real‐time PCR (Rtime‐SGE317) was established for initial rapid detection of RV in Vero cells and a nested PCR (PCR‐E860) was used for amplifying further the 739 nt window of the E1 gene for the identification of RV genotype as recommended by the WHO. Sensitivities of the two assays were evaluated using eight RV isolates, two from infants with the congenital rubella syndrome (CRS) and six from patients with acute rubella. All the isolates had cycle threshold (Ct) values <37 after the third passage, which is recommended as the cut‐off for the confirmation of a viable RV isolate. Phylogenetic analysis based on the 739 nt window generated by the PCR‐E860 showed that the eight RV isolates belonged to genotypes 1E, 1G, and 2B. The Rtime‐SGE317 assay can be carried out in local public health laboratories, which would extend the molecular surveillance of rubella and contribute to the WHO goal of eradicating rubella worldwide. J. Med. Virol. 83:170–177, 2011. © 2010 Wiley‐Liss, Inc.
Identification and characterization of acute infection with parvovirus B19 genotype 2 in immunocompromised patients in Poland
Authors: Grabarczyk Piotr , Kalińska Aleksandra , Kara Mahmut , Wieczorek Renata , Ejduk Anna , Sulkowska Ewa , Gołębiowska‐Staroszczyk Sydonia , Matysiak Michał , Baylis Sally A. , Brojer Ewa
Published: November 2010

Parvovirus B19 (B19V) is divided into three genotypes. Genotypes 2 and 3 may cause diagnostic difficulties and their epidemiology is not well understood. In the present study the prevalence of B19V genotypes in patients with symptomatic infection in Poland was evaluated and the course of infection in patients infected with non‐genotype 1 strains is described. Real‐time PCR, able to detect all three genotypes of B19V was used to screen patient plasma samples. Sixty‐nine, mainly acute‐phase B19V DNA positive cases were identified in patients from hematological and obstetric/gynecological wards between 2004 and 2008. Thirty patients were studied in greater detail and genotyping was performed by analysis of the NS1/VP1u region. The majority of samples were genotype 1. However two (6.6%) strains were identified as genotype 2, associated with high viremia and identified in a kidney transplant recipient with anemia and a leukemia patient, following chemotherapy, with pancytopenia. A change of immunosuppression treatment in the former and treatment with intravenous immunoglobulin in latter, resulted in normalization of clinical parameters, and whilst viral loads fell, B19V DNA was still detectable. The kidney transplant recipient subsequently became pregnant with no clinical complications, although persistently infected with B19V genotype 2. This is the first description of symptomatic cases of genotype 2 B19V infection in Eastern Europe suggesting that acute infection, particularly among immunocompromised patients with these virus strains may be more prevalent than thought. J. Med. Virol. 83:142–149, 2011. © 2010 Wiley‐Liss, Inc.
JC virus DNA in the peripheral blood of renal transplant patients: A 1‐year prospective follow‐up in France
Authors: Mengelle C. , Kamar N. , Mansuy J‐M. , Sandres‐Sauné K. , Legrand‐Abravanel F. , Miédougé M. , Rostaing L. , Izopet J.
Published: November 2010

There is little information on JC virus (JCV) infection in renal transplant patients. A long‐term prospective follow‐up study was conducted to assess the incidence of JCV DNA in the blood of 103 adult renal transplant patients enrolled prospectively between 1 January and 31 December 2006. Patients were monitored until April 2008. JCV DNA was quantified by a real‐time polymerase chain reaction in whole blood samples collected regularly for at least 1 year post‐transplant. JCV was detected in seven patients (6.8%) (31/1,487 whole blood samples) at a median time of 139 days post‐transplant. The median JC virus load of the first positive DNA blood sample was 3.4 log10 copies/ml (1.9–5.7 log10 copies/ml). Induction therapy were either anti‐CD25 monoclonal antibodies (n = 5) or antithymocyte globulins (n = 2). Post‐transplant immunosuppressive treatment included steroids with tacrolimus/mycophenolate mofetil (MMF) (n = 2), or ciclosporin/MMF (n = 1), or belatacept/MMF (n = 4). Two patients were also treated with rituximab. All seven patients infected with JCV had other viral infections(s): BK virus (3), Epstein–Barr virus (2), Cytomegalovirus (1) or both BK virus and Epstein–Barr virus (1). Three patients had BKV‐associated nephropathy and decoy cells shedding. JCV infection was not associated with acute rejection episodes or nephropathy, regardless of the virus load. No patient developed progressive multifocal leukoencephalopathy during follow‐up. Thus the incidence of JCV infection in renal transplant patients was low and not associated with any specific clinical manifestations. JCV replication must still be diagnosed and differentiated from BK virus infection because of its non‐aggressive course. J. Med. Virol. 83:132–136, 2011. © 2010 Wiley‐Liss, Inc.
Association between DNA repair gene ATM polymorphisms and oral cancer susceptibility
Authors: Bau Da‐Tian , Chang Chao‐Hsiang , Tsai Ming‐Hsui , Chiu Chang‐Fang , Tsou Yung‐An , Wang Rou‐Fen , Tsai Chia‐Wen , Tsai Ru‐Yin
Published: November 2010

Objectives/Hypothesis:

The ataxia‐telangiectasia mutated (ATM) is thought to play a major role in the caretaking of the overall genome stability, and its mutations have been implicated in human cancers. However, the role of ATM polymorphisms in oral carcinogenesis is largely unexplored. Thus, the polymorphic variants of ATM were first investigated for their association with oral cancer susceptibility.

Study Design:

In this hospital‐based, case‐control study, associations of seven ATM single nucleotide polymorphisms with oral cancer risk in a Taiwanese population were investigated.

Methods:

A total of 620 patients with oral cancer and 620 healthy controls were genotyped and analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) method.

Results:

There were significant differences between oral cancer and control groups in the distributions of their genotypes (P = 3.71E‐6) and allelic frequencies (P = 5.09E‐6) in the ATM rs189037 polymorphisms. In the other six polymorphisms, there was no differential distribution between both groups. There are synergistic joint interactions of ATM genotyping with smoking, alcohol drinking, and betel quid chewing.

Conclusions:

The ATM rs189037 A allele is correlated with oral cancer susceptibility, and this polymorphism may be a useful marker for oral cancer prevention and early detection. Laryngoscope, 120:2417–2422, 2010
Affinity‐Based Drug Delivery
Authors: Wang Nick X. , von Recum Horst A.
Published: November 2010

Affinity‐based drug delivery systems utilize interactions between the therapeutic drug and the delivery system to manipulate drug loading and to control drug release. In this paper, affinity‐based drug delivery system syntheses, types of therapeutic factors delivered, and delivery system loading and release are discussed in detail. The paper is divided into three subsections, based on the type of delivery system: molecular imprinting systems, growth‐factor delivery, and cyclodextrin‐based delivery. The objective of this paper is to examine the current state of research, highlight the breakthroughs and challenges, point out potential impacts of this relatively new technology, and explore future developmental areas.

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Design and Synthesis of Novel Polyglycerol Hybrid Nanomaterials for Potential Applications in Drug Delivery Systems
Authors: Zarrabi Ali , Adeli Mohsen , Vossoughi Manouchehr , Shokrgozar Mohammad Ali
Published: November 2010

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β‐CD core and hyperbranched PG is described. Conjugating PG branches onto β‐CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short‐term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β‐CD‐g‐PG hybrid nanomaterials are introduced as promising materials for nanomedicine, e.g., for drug delivery issues.

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Porous Scaffolds Based on Cross‐Linking of Poly(L‐glutamic acid)
Authors: Cao Bin , Yin Jingbo , Yan Shifeng , Cui Lei , Chen Xuesi , Xie Yongtao
Published: November 2010

Porous scaffolds based on water‐soluble PLGA and CS were prepared. The pores were verified to be alveolate, uniform and continuous. The effects of freezing temperature, freeze‐drying time, solid content and molecular weight of reactants on the pore structure of the scaffolds were studied. The scaffold morphology could be adjusted by changing the freezing temperature and solid content of reacting polymer. Their degradation rate can be adjusted by changing the proportion of PLGA and CS. The porosity of scaffolds was higher than 90% and the high swelling ratio showed that these scaffolds had excellent hydrophilic performance. The in vitro culture of chondrocytes indicates that the obtained PLGA/CS porous scaffolds are very promising biomaterials for tissue engineering applications.

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Adaptive black blood fast spin echo for end‐systolic rest cardiac imaging
Authors: Fernandez Brice , Oster Julien , Lohezic Maelene , Mandry Damien , Pietquin Olivier , Vuissoz Pierre‐André , Felblinger Jacques
Published: November 2010

Black Blood Fast Spin Echo imaging of the heart is usually performed during mid‐diastolic rest. This is a direct consequence of the long inversion time required to suppress the blood signal, which is constrained by the T1 of the blood, and of the heart rate. To overcome these constraints, and to acquire black blood images in the end‐systolic rest period, a new approach is introduced aiming at adaptively predicting the best time to prepare and acquire MR signals. It is based on a RR interval prediction algorithm and on a cardiac cycle model. The proposed method was applied to 14 healthy volunteers and is compared to a simple alternative method using a fixed delay and to the standard black blood imaging method for imaging in the mid‐diastolic rest period. Results show that the proposed method offers an increased robustness in terms of trigger delay error and image quality compared to the tested simple alternative. Also, it has been shown by qualitative analysis done by an experienced observer that the right ventricle, especially the thin right ventricle free wall, is better depicted with our method than with the standard mid‐diastolic rest acquisition. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Head and Neck Squamous Cell Carcinoma: New Translational Therapies
Authors: Prince Anthony , Aguirre‐Ghizo Julio , Genden Eric , Posner Marshall , Sikora Andrew
Published: November 2010

Head and neck squamous cell carcinoma includes cancers of the mouth, throat, larynx, and lymph nodes of the neck. Although early disease is amenable to single‐modality treatment with surgery or radiation, patients with advanced disease have a dramatically worse prognosis, despite potentially morbid/toxic treatment regimens involving surgery, radiation, chemotherapy, or all 3 modalities. The present review seeks to provide an overview of current understanding and treatment of head and neck squamous cell carcinoma for the nonspecialist clinician or basic/translational researcher, followed by an overview of major translational approaches to the treatment of head and neck squamous cell carcinoma. Translational research topics addressed include targeted molecular therapy, immunotherapy, minimally invasive robotic surgery, and ablation of dormant/residual tumor cells. Despite the many potentially promising avenues of head and neck squamous cell carcinoma research, only 2 new treatment approaches (antiepidermal growth factor receptor therapy and robotic surgery) have been approved by the US Food and Drug Administration in the past 30 years. Focused research programs involving integrated teams of clinicians, basic scientists, and translational clinician‐researchers have the potential to accelerate discovery and change treatment paradigms for patients with head and neck cancer. Mt Sinai J Med 77:684–699, 2010. © 2010 Mount Sinai School of Medicine
A Cross‐Cultural Perspective on Irritable Bowel Syndrome
Authors: Gerson Charles D. , Gerson Mary‐Joan
Published: November 2010

Irritable bowel syndrome is a functional gastrointestinal illness, defined by symptoms. Irritable bowel syndrome has been described as a biopsychosocial condition, in which colonic dysfunction is affected by psychological and social factors. As a result of this unusual constellation, irritable bowel syndrome may be subject to cultural variables that differ in different parts of the globe. In this article, we describe some of the ways in which irritable bowel syndrome may be experienced differently, depending on local belief systems, psychological pressures, acceptance or resistance to a mind‐body paradigm, and breakdown in support or relationship structure. Examples are given in which irritable bowel syndrome investigators from countries around the world describe various aspects of the syndrome that may affect the illness experience of their patients. We describe our own research studies that have demonstrated possible adverse effects on disease severity from relationship conflict, attribution of symptoms to physical rather than emotional cause, and the belief that irritable bowel syndrome is enduring and mysterious. Also described is our finding that symptom patterns may differ significantly between different geographic locations. Finally, we discuss the importance of “cultural competence” on the part of healthcare professionals in regard to caring for patients of diverse cultural backgrounds. Mt Sinai J Med 77:707–712, 2010. © 2010 Mount Sinai School of Medicine
Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF‐β1 blocker
Authors: Taniguti Ana Paula Tiemi , Pertille Adriana , Matsumura Cíntia Yuri , Neto Humberto Santo , Marques Maria Julia
Published: November 2010

Fibrosis is a pathological feature observed in patients with Duchenne muscular dystrophy (DMD) and in mdx mice, the experimental model of DMD. We evaluated the effect of suramin, a transforming growth factor‐beta 1 (TGF‐β1) blocker, on fibrosis in mdx mice. mdx mice (6 months old) received suramin for 7 weeks. Suramin‐ and saline‐treated (control) mdx mice performed exercise on a treadmill to worsen disease progression. Immunoblotting showed an increase of TGF‐β1 in mdx diaphragm, limb, and cardiac muscles. Suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle. Suramin protected limb muscles against damage and reduced the exercise‐induced loss of strength over time. These findings support a role for TGF‐β1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice. Suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies. Muscle Nerve, 2011
Turns–amplitude analysis in normal and myopathic facial muscles
Authors: Karandreas Nikos , Kararizou Evangelia , Papagianni Aikaterini , Zambelis Thomas , Kokotis Panagiotis
Published: November 2010

The purpose of this study was to assess turns/amplitude analysis (TAA) as an objective alternative to conventional qualitative electromyography (EMG) for detection of myopathy in facial muscles. Normal values of TAA parameters were calculated in the frontalis and mentalis muscles of 26 control subjects. We estimated the slope of the regression line of mean amplitude/turn values (MA) plotted against the number of turns/second (NT) and the resulting clouds. The 95% confidence limits of the cloud data were drawn as an ellipse. The sensitivity of TAA was determined from a group of 35 myopathic patients and specificity from a second group of 25 control subjects. Significant differences for every TAA parameter were found between frontalis and mentalis. Cumulative sensitivity and specificity of TAA for frontalis and mentalis were 74.6%, 56.5%, and 73.3%, 70.8%, respectively. With at least two of the aforementioned criteria abnormal, the sensitivity and specificity for frontalis and mentalis were 61.3%, 82.6%, and 56.7%, 100.0%, respectively. Muscle Nerve, 2011
Accuracy of diagnoses delivered by an automated hand‐held nerve conduction device in comparison to standard electrophysiological testing in patients with unilateral leg symptoms
Authors: Schmidt Kevin , Chinea Nataly Montes , Sorenson Eric J. , Strommen Jeffrey A. , Boon Andrea J.
Published: November 2010

Introduction: Automated hand‐held nerve conduction study (NCS) devices are being marketed for use in the diagnosis of lumbosacral radiculopathy (LSR). In this study we compared the specificity and sensitivity of a hand‐held NCS device for the detection of LSR with standard electrodiagnostic study (EDX). Methods: Fifty patients referred to a tertiary referral electromyography (EMG) laboratory for testing of predominantly unilateral leg symptoms (weakness, sensory complaints, and/or pain) were included in the investigation. Twenty‐five normal “control” subjects were later recruited to calculate the specificity of the automated protocol. All patients underwent standard EDX and automated testing. Results: Raw NCS data were comparable for both techniques; however, computer‐generated interpretations delivered by the automated device showed high sensitivity with low specificity (i.e., many false positives) in both symptomatic patients and normal controls. Conclusions: The automated device accurately recorded raw data, but the interpretations provided were overly sensitive and lacked the specificity necessary for a screening or diagnostic examination. Muscle Nerve, 2011
Children with acute leukemia: A comparison of outcomes from allogeneic blood stem cell and bone marrow transplantation
Authors: Lin Yu‐Feng , Lairson David R. , Chan Wenyaw , Du Xianglin L. , Leung Kathryn S. , Kennedy‐Nasser Alana A. , Martinez Caridad A. , Heslop Helen E. , Brenner Malcolm K. , Krance Robert A.
Published: November 2010

Background

The relative merits of peripheral blood stem‐cell transplantation (PBSCT) versus bone marrow transplantation (BMT) for children with standard and high‐risk hematologic malignancies remain unclear. In a retrospective study, we compared allogeneic PBSCT (n = 30) with BMT (n = 110) in children with acute leukemia between January 2001 and September 2006.

Procedure

Median age for PBSCT was 9 years versus 8 years for BMT. Descriptive statistics were used to summarize the demographic and medical variables. The unadjusted probabilities of disease‐free survival were estimated using the Kaplan–Meier method. The association of graft‐source and time to each of the study endpoints was estimated by Cox's regression model and the occurrence of graft‐versus‐host disease (GvHD) was included as a time‐dependent covariate.

Results

Time to neutrophil engraftment and platelet independence was faster after PBSCT than BMT (neutrophils 15.0 days vs. 17.0 days,P < 0.001; platelets, 21.0 days vs. 27.0 days,P = 0.034). The cumulative incidence of grades II–IV acute GvHD at 100 days was 10.4% (SE 5.6%) after PBSCT and 15.1% (SE 3.5%) after BMT (P = NS). The cumulative incidence of chronic GvHD was 13.8% (SE 6.3%) after PBSCT and 11.3% (SE 3.1%) after BMT (P = NS). One‐year disease‐free survival was 37.9% (SE 9.0%) for PBSCT recipients versus 65.1% (SE 4.6%) after BMT (P = 0.005) but this difference was not sustained in multivariate analysis. Thus, only disease risk and pre‐transplant CMV seropositivity were significant predictors of disease‐free survival.

Conclusions

We conclude that PBSCT for children produces faster engraftment without increased risk of acute or chronic GvHD. Pediatr Blood Cancer. 2010;56:143–151. © 2010 Wiley‐Liss, Inc.
A phase II study of metronomic oral topotecan for recurrent childhood brain tumors
Authors: Minturn Jane E. , Janss Anna J. , Fisher Paul G. , Allen Jeffrey C. , Patti Ratnakar , Phillips Peter C. , Belasco Jean B.
Published: November 2010

Background

The prognosis for recurrent or refractory brain tumors in children is poor with conventional therapies. Topotecan is a topoisomerase I inhibitor with good central nervous system (CNS) penetration following oral administration. Increased efficacy of topotecan has been demonstrated with prolonged low‐dose daily treatment in pre‐clinical models. To investigate further this drug delivered orally in pediatric CNS malignancies, a phase II study in children with recurrent or refractory brain tumors was performed.

Procedure

Patients ≤21 years of age at diagnosis with a recurrent, progressive, or refractory primary CNS malignancy and measurable disease, were eligible. Patients enrolled into four strata: ependymoma (N = 4), high‐grade glioma (HGG) (N = 6), brainstem glioma (BSG) (N = 13), and primitive neuroectodermal tumor (PNET) (N = 8). Oral topotecan was administered once daily at a dose of 0.8 mg/m2/day for 21 consecutive days repeated every 28 days. Response and toxicity profiles were evaluated.

Results

Twenty‐six patients were evaluable (median age 9.2 years; 10 males). Two objective responses were observed in PNET patients with disseminated tumor at study entry. These two patients remain alive and in remission 7 and 9.5 years off study. Four other patients (two BSG, one PNET, and one HGG) had stable disease (median 4.6 months). The most common toxicities were hematologic.

Conclusions

Daily oral topotecan at a dose of 0.8 mg/m2/day can be safely administered to children with recurrent or refractory brain tumors. This regimen identified activity in recurrent PNET. The prolonged progression free survival (PFS) in two PNET patients justifies consideration of this regimen in more advanced clinical trials. Pediatr Blood Cancer. 2010;56:39–44. © 2010 Wiley‐Liss, Inc.
Delay and causes of delay in the diagnosis of childhood cancer in Africa
Authors: Stefan Daniela Cristina , Siemonsma Femke
Published: November 2010

Background

Although a few studies have investigated delays in diagnosis and treatment among children and adolescents with cancer, this has never been subject of study in South Africa. Early diagnosis is fundamental as it allows timely treatment and prevents unnecessary complications.

Procedures

Combined prospective and retrospective study of 194 children with cancer at Tygerberg Hospital, Cape Town, diagnosed between 2000 and 2009: 126 patients were included through review of the medical charts and 68 through interviews with the parents.

Results

The median total diagnosis delay was 34 days (2–1,826). The median patient delay was 5 days (0–457). The median physician delay was 20 days (0–924). Gender, age or ethnicity of the children, as well as parental level of education did not have a significant influence on the total time to diagnosis. Initial misdiagnoses were frequent (58%).

Conclusions

There is considerable delay in diagnosing childhood cancer in the area served by Tygerberg Hospital, due mostly to a physician delay of 20 days on average. The findings of our unit should be correlated with other South African centers. There is a clear need to increase parental awareness of childhood cancer and to intensify the education of nurses and doctors with regard to the warning signs of the disease. Pediatr Blood Cancer. 2010;56:80–85. © 2010 Wiley‐Liss, Inc.
Retrospective analysis of pediatric cancer patients diagnosed with the pandemic H1N1 influenza infection
Authors: Amayiri Nisreen , Madanat Faris
Published: November 2010

Background

Limited data are available on disease characteristics and outcome of children with cancer who contracted the H1N1 influenza infection during the 2009 pandemic.

Methods

All 76 pediatric patients with cancer and documented H1N1 infection who presented to the Pediatric Department at King Hussein Cancer Center (KHCC) between October 1 and December 1, 2009 were reviewed for clinical characteristics and course of the disease.

Results

Two‐thirds of the patients had hematological malignancies and half were receiving non‐intensive chemotherapy at the time of infection. With the exception of two patients who needed pediatric intensive care unit admission, the course of the remaining patients was uneventful whether they were hospitalized or not. No deaths related to H1N1 influenza infection were reported. Sixty‐three percent of patients became afebrile within 48 hr of receiving oseltamivir. One‐third of hospitalized patients were discharged in <3 days.

Conclusion

The course of H1N1 influenza infection in children with cancer appears to be mild in most cases. Pediatr Blood Cancer. 2010;56:86–89. © 2010 Wiley‐Liss, Inc.