bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of clofazimine as salvage therapy for atypical mycobacterial infection in solid organ transplant recipients
Authors: Cariello P.F. , Kwak E.J. , Abdel‐Massih R.C. , Silveira F.P. 
Published: January 2015

AbstractBackgroundThe treatment of Mycobacterium avium complex (MAC) requires prolonged, multidrug therapy, which is often not well tolerated. In solid organ transplant (SOT) recipients, drug–drug interactions complicate treatment further. Failure or intolerance requires the use of salvage regimens, and clofazimine is one of the drugs that can be used. No data are available on the safety and tolerability of clofazimine for the treatment of MAC in SOT recipients.MethodsRetrospective review of all SOT recipients treated for MAC infection with clofazimine at a large transplant center between 2006 and 2013.ResultsFive SOT recipients received clofazimine as salvage therapy. Transplanted organs were lungs in 3 patients, and kidney and liver in 1 patient each. Infection was diagnosed at a median of 22 months (range 4–57) post transplant. Sites of infection were the lungs in 2 patients, and septic arthritis, mesenteric, and disseminated disease in 1 patient each. All patients received standard anti‐MAC therapy for a median of 26 weeks (range 18–45) before starting clofazimine. Indications for use of clofazimine included a lack of response to previous therapy (3 patients), and poor tolerance of other regimens (3 patients). All patients received at least 2 additional drugs besides clofazimine. Median duration of clofazimine‐containing regimen was 8 months (range 2–18). Clofazimine was discontinued because of gastrointestinal intolerance in 1 of the 5 patients. The most common adverse event from clofazimine was skin discoloration, in 60% of patients. No hepatotoxicity or hematologic toxicity occurred. Microbiological clearance and resolution of clinical disease was documented in 2 of 5 patients; and 2 of the 5 patients died of other causes while on therapy.ConclusionsClofazimine appears safe and may be considered as a salvage therapeutic option in SOT recipients with MAC infection who are intolerant or unresponsive to standard therapy. The small sample size does not allow conclusions regarding efficacy.
Cerebral toxoplasmosis in an adolescent post allogeneic hematopoietic stem cell transplantation: successful outcome by antiprotozoal chemotherapy and CD4+ T‐lymphocyte recovery
Authors: Kerl K. , Ehlert K. , Brentrup A. , Schiborr M. , Keyvani K. , Becker K. , Rossig C. , Groll A.H. 
Published: January 2015

AbstractToxoplasmosis is a rare opportunistic infection in pediatric allogeneic hematopoietic stem cell transplant (allo‐HSCT) recipients and associated with severe T‐cell deficiency. Here, we report the successful management of cerebral toxoplasmosis in a 15‐year‐old adolescent 4 months post allo‐HSCT for non‐Hodgkin lymphoma through rapid invasive diagnostics, long‐term antiprotozoal chemotherapy, and an hematopoietic stem cell boost for persistently poor graft function. While supportive care and antiprotozoal chemotherapy achieved stabilization, definite improvement only occurred following recovery of CD4+ T lymphocytes to >100 cells/μL. At 5 years after the diagnosis of toxoplasmosis, the patient is in continuing remission with normalized clinical and imaging findings.
The role of SDF‐1 in homing of human adipose‐derived stem cells
Authors: Stuermer Ewa K. , Lipenksy Alexandra , Thamm Oliver , Neugebauer Edmund , Schaefer Nadine , Fuchs Paul , Bouillon Bertil , Koenen Paola 
Published: January 2015

AbstractOne of the putative pathophysiological mechanisms of chronic wounds is a disturbed homing of stem cells. In this project, the stromal cell‐derived factor 1 (SDF‐1)/C‐X‐C chemokine receptor (CXCR) 4 and SDF‐1/CXCR7 pathway were focused in human adipose‐derived stem cells (ASCs). ASCs were incubated with acute (AWF) or chronic wound fluid (CWF) to analyze their effects by quantitative real‐time polymerase chain reaction (SDF‐1, CXCR4, CXCR7, TIMP3), enzyme‐linked immunosorbent assay (SDF‐1 in WFs and supernatant), and transwell migration assay with/without antagonization. Whereas SDF‐1 amounted 73.5 pg/mL in AWF, it could not be detected in CWF. Incubation with AWF led to a significant enhancement (129.7 pg/mL vs. 95.5 pg/mL), whereas CWF resulted in a significant reduction (30 pg/mL vs. 95.5 pg/mL) of SDF‐1 in ASC supernatant. The SDF‐1 receptor CXCR7 was detected on ASCs. AWF but not CWF significantly induced ASC migration, which was inhibited by CXCR4 and CXCR7 antagonists. Expressions of SDF‐1, CXCR4, and CXCR7 were significantly stimulated by AWF while TIMP3 expression was reduced. In conclusion, an uncontrolled inflammation in the chronic wound environment, indicated by a reduced SDF‐1 expression, resulted in a decreased ASC migration. A disturbed SDF‐1/CXCR4 as well as SDF‐1/CXCR7 pathway seems to play an important role in the impaired healing of chronic wounds.
Does interprofessional simulation increase self-efficacy: a comparative study
Authors: Watters Colm , Reedy Gabriel , Ross Alastair , Morgan Nicola J , Handslip Rhodri , Jaye Peter 
Published: January 2015

ObjectivesIn this work, we have compared uniprofessional and interprofessional versions of a simulation education intervention, in an attempt to understand more about whether it improves trainees’ self-efficacy.BackgroundInterprofessionalism has been climbing the healthcare agenda for over 50 years. Simulation education attempts to create an environment for healthcare professionals to learn, without potential safety risks for patients. Integrating simulation and interprofessional education can provide benefits to individual learners.SettingThe intervention took place in a high-fidelity simulation facility located on the campus of a large urban hospital. The centre provides educational activities for an Academic Health Sciences Centre. Approximately 2500 staff are trained at the centre each year.ParticipantsOne hundred and fifteen nurses and midwives along with 156 doctors, all within the early years of their postgraduate experience participated. All were included on the basis of their ongoing postgraduate education.MethodsEach course was a one-day simulation course incorporating five clinical and one communication scenarios. After each a facilitated debriefing took place. A mixed methods approach utilised precourse and postcourse questionnaires measuring self-efficacy in managing emergency situations, communication, teamwork and leadership.ResultsThematic analysis of qualitative data showed improvements in communication/teamwork and leadership, for doctors and nurses undergoing simulation training. These findings were confirmed by statistical analysis showing that confidence ratings improved in nurses and doctors overall (p<0.001). Improved outcomes from baseline were observed for interprofessional versus uniprofessional trained nurses (n=115; p<0.001). Postcourse ratings for doctors showed that interprofessional training was significantly associated with better final outcomes for a communication/teamwork dimension (n=156; p<0.05).ConclusionsThis study provides evidence that simulation training enhances participants’ self-efficacy in clinical situations. It also leads to increases in their perceived abilities relating to communication/teamwork and leadership/management of clinical scenarios. Interprofessional training showed increased positive effects on self-efficacy for nurses and doctors.
Unintentional Home Injuries Across the Life Span: Problems and Solutions
Authors: Gielen Andrea C. , McDonald Eileen M. , Shields Wendy 
Published: January 2015

Home injuries cause more than 30,000 deaths and 12 million nonfatal injuries annually in the United States. They generate an estimated $222 billion in lifetime costs annually. Despite some data limitations in documenting home as the location of an injury, much progress has been made in identifying effective prevention strategies that reduce injury or mitigate risk behaviors.The current interest in public health in the role of housing in health offers unparalleled opportunities for injury prevention professionals concerned with home injuries. Sharing the science of injury prevention with the wide array of professionals—such as architects, home builders, home visitors, and fire and emergency medical services providers—who create home environments and interact with residents could be a useful approach. A collaborative national effort to reduce the burden of home injuries is needed.
DNA Measurement of Overlapping Cell Nuclei in Thick Tissue Sections
Authors: Ji Liang , Tucker James 
Published: January 2015

The paper describes an improved image analysis procedure for measuring the DNA content of cell nuclei in thick sections of liver tissue by absorption densitometry. Whereas previous methods only permitted the analysis of isolated nuclei, the new technique enables both isolated and overlapping nuclei to be measured. A 3D segmentation procedure determines whether each object is an isolated nucleus or a pair of overlapping nuclei; in the latter case the combined optical density is redistributed to the individual nuclei. A selection procedure ensures that only complete nuclei are measured.The method has been tested on specially‐prepared Feulgen‐stained 20μ sections of normal liver tissue. The overall distribution of the nuclear DNA measurements shows well‐defined diploid and tetraploid peaks, with coefficient of variations of less than 10%. Similar distributions were obtained from both the isolated nuclei and overlapped nuclei sub‐populations.
Quantitative Comparison of Immunohistochemical Staining Intensity in Tissues Fixed in Formalin and Histochoice
Authors: Vince D. Geoffrey , Tbakhi Abdelghani , Gaddipati Ajeetkumar , Cothren Robert M. , Cornhill J. Fredrick , Tubbs Raymond R. 
Published: January 2015

Formaldehyde fixatives have traditionally been used to preserve tissues as they impart excellent morphological preservation. Formaldehyde fixes tissue by cross linking, a process which can reduce the antigenicity of tissue and weakens the intensity of immunohistochemical stains. Preliminary studies have shown that Histochoice tissue fixative offers equal or greater staining intensity than neutral buffered formalin (NBF). This study compares these fixatives quantitatively and presents the results in unambiguous statistical terms.Tissue samples were collected, bisected, and fixed in NBF or Histochoice. The sections were stained with a total of 21 antibodies, and color images were collected. The hue, saturation, and value were determined for each positive pixel and an ANOVA performed. Small differences in hue were noted in 8 of 21 cases. Histochoice‐fixed tissue gave a greater mean saturation than NBF with 57.1% of the antibodies tested. No significant difference in the saturation was detected in 28.6% of the cases; NBF gave higher mean saturation levels with only 14.3% of the antibodies. Histochoice‐fixed tissue was found to give lower values in 66.7% of cases than those prepared with NBF, indicating darker staining. These results show that Histochoice produces staining intensity that is comparable, and in many cases superior, to formalin.
Correlation between p53 Status, DNA Ploidy, Proliferation Rate and Nuclear Morphology in Breast Cancer. An Image Cytometric Study
Authors: Friedrich Katrin , Dimmer Volker , Haroske Gunter , Meyer Wolfdietrich , Theissig Franz , Kunze Klaus Dietmar 
Published: January 2015

The study was designed to detect differences in the nuclear morphology of tumours and tumour cell populations with different p53 expression in correlation with DNA ploidy and proliferation rate. The paraffin sections from routinely processed samples of 88 breast cancers were immunostained with the monoclonal p53‐antibody DO‐1. After localization and evaluation with a scoring system the sections were destained and stained by the Feulgen method. The nuclei were relocated automatically and measured by means of the image cytometry workstation. Significant differences between the tumours and tumour cell populations with different p53 expression were found in the euploid tumours as well as in the aneuploid tumours and in the breast cancers with a high proliferation rate. The breast cancers with a low immunoreactive score (IRS 1–4) differ from the negative cancers as well as from the cancers with a higher immunoreactive score (IRS 5–12). Evaluating the nuclear populations of the p53 positive cancers, there were differences in the features of the chromatin amount and distribution in the groups of the euploid breast cancers and in cancer with a high proliferation rate. In contrast, the nuclear populations of the aneuploid cancers did not show any differences in their nuclear morphology.The results showed the different impacts of the p53 expression, DNA ploidy and the proliferation rate on the nuclear morphology in breast cancer.
Immunophenotypic Characterization of Human Bone Marrow Mast Cells. A Flow Cytometric Study of Normal and Pathological Bone Marrow Samples
Authors: Escribano Luis , Orfao Alberto , Villarrubia Jesús , Díaz-Agustín Beatriz , Cerveró Carlos , Rios Agustín , Velasco José L. , Ciudad Juana , Navarro José L. , San Miguel Jesús F. 
Published: January 2015

The goal of the present paper was to define the immunophenotype of bone marrow mast cells (BMMC) from healthy controls and patients with hematologic malignancies (HM) based on the use of multiple stainings with monoclonal antibodies analyzed by flow cytometry. Our results show that BMMC from both groups of individuals display a similar but heterogenous immunophenotype. The overall numbers of BMMC are higher in the HM group of individuals (p = 0.08). Three patterns of antigen expression were detected: (1) markers constantly positive in all cases analyzed (CD9, CD29, CD33, CD43, CD44, CD49d, CD49e, CD51, CD71, CD117, and FcεRI), (2) antigens that were constantly negative (CD1a, CD2, CD3, CD5, CD6, CD11a, CD14, CD15, CD16, CD19, CD20, CD21, CD23, CD25, CD30, CD34, CD38, CD41a, CD42b, CD65, CD66b, HLA‐DR, and CD138), and (3) markers that were positive in a variable proportion of cases – CD11b (50%), CD11c (77%), CD13 (40%), CD18 (20%), CD22 (68%), CD35 (27%), CD40 (67%), CD54 (88%) and CD61 (40%). In addition, BMMC from all cases explored were CD45+, and this antigen was expressed at an intensity similar to that of mature granulocytes.In summary, our results show that BMMC from both healthy controls and HM patients display a relatively heterogenous immunophenotype. Interestingly, we have observed clear differences between the immunophenotype of BMMC and MC from other tissues. This could be due either to the heterogeneity of human MC according to their tissue localization or to the sensitivity of the method used for antigen detection.
p53 Mutations and DNA Ploidy in Colorectal Adenocarcinomas
Authors: Campomenosi Paola , Assereto Paola , Bogliolo Massimo , Fronza Gilberto , Abbondandolo Angelo , Capasso Antonella , Bellomo Patrizia F. , Monaco Roberto , Rapallo Anna , Sciutto Andrea , Orecchia Roberto , Geido Elio , Giaretti Walter 
Published: January 2015

The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases.Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher’s exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild‐type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation.The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis.
Preliminary Characterization of a Monoclonal Antibody (AS‐2) against Cell Cycle Related Proteins
Authors: Nigro Stefano , Rapallo Anna , Di Vinci Angela , Geido Elio , Orecchia Roberto , Giaretti Walter 
Published: January 2015

A monoclonal antibody (AS‐2) raised by using isolated nuclei from a human erythroleukemia cell line as immunogen is described.AS‐2 was of IgM type and recognized proteins present in both isolated cytoplasms and nuclei. The molecular weight of the AS‐2 recognized proteins in the cytoplasm was 200 kDa and 70 and 60 kDa in the nucleus. The relative amount of these proteins were measured simultaneously with DNA content by flow cytometry. We found the highest protein content (or stainability) for both cells and nuclei in late‐G1, S and G2, at approximately the same level, and the lowest content in M and early‐G1. Sorting based on DNA content and AS‐2 associated fluorescence helped identifying the staining pattern of cells and nuclei. Interphase isolated nuclei and cell cytoplasms were characterized by interdispersed staining over the entire surfaces while mitoses showed two dots only. The present preliminary data indicate that the proteins recognized by the AS‐2 monoclonal are cell cycle related and suggest that in mitoses they are associated with the centrosomes.
In situ Apoptotic and Proliferation Index in Laryngeal Squamous Cell Carcinomas
Authors: Hagedorn Hjalmar G. , Tübel Jutta , Wiest Irmgard , Nerlich Andreas G. 
Published: January 2015

The rate of cellular growth is mainly influenced by the balance between cell proliferation and cellular decay. Since to our knowledge, no study so far has analysed the rate of proliferation and apoptosis in the normal laryngeal mucosa and in invasive laryngeal carcinomas, we performed a morphological analysis on both parameters in biopsies from 30 patients with laryngeal carcinoma. We applied the TUNEL end labelling technique for the investigation of apoptosis and immunohistochemistry (Ki‐67 antigen) for the determination of the cell proliferation.In our study we demonstrated that invasive tumour growth of the larynx coincides with an increase of both cellular proliferation and apoptosis. Both parameters, however, affected various tumour areas differently. While there was a preferential expression of the Ki‐67 antigen at the tumour–stroma interface, apoptotic figures could be found randomly distributed in the tumour. This indicates that the replication of tumour cells and tumour cell decay are differently distributed and possibly independently regulated. Since we observed a particularly strong increase of cell proliferation at the tumour–stroma interface which outnumbered the corresponding rate of apoptosis by far, the enhanced cell proliferation at the tumour border seems to be a main factor for tumour growth.A statistical evaluation revealed significant correlation between the apoptotic index and the degree of tumour cell differentiation, indicating that a high rate of apoptosis coincides with a high level of tumour cell differentiation.There was, however, no statistically significant correlation between prognostic clinical parameters and the rate of apoptosis or that of proliferation.
Comparison of Different Telepathology Solutions for Primary Frozen Section Diagnostic
Authors: Hufnagl P. , Bayer G. , Oberbarnscheidt P. , Wehrstedt K. , Guski H. , Hauptmann S. , Dietel M. 
Published: January 2015

In a retrospective study on a set of 125 cases we compared the following three telepathology solutions for primary frozen section diagnosis: ATM‐TP (connection via ATM), TPS 1.0 (connection via LAN) and TELEMIC (connection via Internet), which represent different concepts of telepathological procedures.A set of 125 routine frozen sections (breast) was selected from the Charité cases of the year 1999. Four experienced pathologists diagnosed retrospectively all of these cases.Using the ATM‐TP and TPS systems and 53 of them with the TELEMIC system. Using the ATM‐TP we recorded no false positive (0%), 4 false negative (3.2%) and 4 deferred (3.2%) cases. Using the TPS we recorded no false positive (0%), 4 false negative (3.2%) and 4 deferred (3.2%) cases. Using the TELEMIC we recorded in 53 cases no false positive (0%), no false negative (0%) and 16 deferred (30.2%) cases.The average time of 2.2 minutes per case using ATM‐TP is also short enough for routine frozen section diagnostic. This is also true for the TPS system with 7.2 minutes per case.
EBV-Infection in Cardiac and Non-Cardiac Gastric Adenocarcinomas is Associated with Promoter Methylation ofp16,p14andAPC, but nothMLH1
Authors: Geddert Helene , Hausen Axel zur , Gabbert Helmut E. , Sarbia Mario 
Published: January 2015

Background: Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV.Methods: One hundred GC were tested by RNA-in situ hybridization for the presence of EBV by EBV-encoded small RNA (EBER). Aberrant promoter methylation was investigated by methylation-specific real-time PCR for p16, p14, APC and hMLH1. P16 protein expression was assessed by immunohistochemistry.Results: In our selected study cohort, EBER-transcripts were detected in 19.6% (18/92) of GC. EBV-positive GC revealed significantly more often gene hypermethylation of p16, p14 and APC (p < 0.0001, p < 0.0001 and p = 0.02, respectively) than EBV-negative GC. The majority of GC with p16 hypermethylation showed a p16 protein loss (22/28). In contrast, no correlation between the presence of EBV and hMLH1 hypermethylation was found (p = 0.7). EBV-positive GC showed a trend towards non-cardiac location (p = 0.06) and lower stages (I/II) according to the WHO (p = 0.05).Conclusion: Hypermethylation of tumor suppressor genes is significantly more frequent in EBV-associated GC compared to EBV-negative GC. Our data add new insights to the role of EBV in gastric carcinogenesis and underline that EBV-associated GC comprise a distinct molecular-pathologic as well as a distinct clinicopathological entity of GC.