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Sample records for intracerebral murine xenografts

  1. Development of a multi-fraction radiation protocol for intracerebral human glioblastoma xenografts

    International Nuclear Information System (INIS)

    Ozawa, T.; Santos, R.A.; Hu, L.H.; Faddegon, B.A.; Lamborn, K.R.; Deen, D.F.

    2003-01-01

    Patients with malignant gliomas are typically treated by surgery, radiation therapy and chemotherapy. Fractionated radiotherapy consists of 30 daily doses of 1.8 to 2 Gy given over a 6-week period. We have investigated a multi-fraction radiation protocol in which rats bearing intracerebral tumors are irradiated once daily for 10 days with a 2-day break in the middle. This scheme simulates the first third of a typical human radiation protocol, and it is a practical scheme to conduct in the laboratory. U-87 MG or U-251 MG human glioblastoma cells were implanted into the right caudate-putamens of male athymic rats. We irradiated rats using an irradiation jig that allowed us to deliver Cesium-137 photons at a dose rate of 280 cGy/minute selectively to the portion of the head containing the tumor. This device adequately shields all other parts of rat, including the critically sensitive oropharynx. Animals received the first radiation dose when intracerebral tumors were ∼20 mg in size. Untreated U-87 MG tumor-bearing rats died with a median survival of 23 days, while tumor bearing rats that were given ten 1-Gy doses died with a median survival of 28.5 days. Untreated U-251 MG tumor-bearing rats died with a median survival of 34.5 days, while tumor-bearing rats that were given ten 1-Gy doses died with a median survival of 58 days. However, 5 of 14 of these rats had a lifespan >68 days and were considered cured. A daily dose of 0.75 Gy produced a median survival of 43 days, but again 2 rats had a lifespan >70 days. Currently, we are seeking a dose that causes reproducible tumor growth delay of 1 to 2 weeks, without curing any animals, to use in future studies that combine radiation with other anti-tumor agents

  2. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

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    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  3. Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Sakurai, Hideyuki; Mitsuhashi, Norio; Murata, Osamu; Kitamoto, Yoshizumi; Saito, Yoshihiro; Hasegawa, Masatoshi; Akimoto, Tetsuo; Takahashi, Takeo; Nasu, Sachiko; Niibe, Hideo

    1998-01-01

    Purpose: Phosphorus-31 magnetic resonance spectra ( 31 P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. Methods and Materials: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The β-ATP/Pi, PME/Pi, and β-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (%apoptosis). Results: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in β-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of β-ATP/Pi 24 hr after radiation were inversely related to radiation dose. Conclusion: The increase in β-ATP/Pi observed by 31 P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis

  4. Local control of murine melanoma xenografts in nude mice by neutron capture therapy

    International Nuclear Information System (INIS)

    Allen, B.J.; Corderoy-Buck, S.; Moore, D.E.; Mishima, Y.; Ichihashi, M.

    1992-01-01

    In recent years considerable progress has been made in the development and implementation of neutron capture therapy (NCT) for the treatment of cancer. In particular, the boron analogue of the melanin precursor phenylalanine, i.e., DL-p-boronophenylalanine (BPA), has been used to demonstrate the regression and cure of Harding-Passey (HP) melanoma in syngeneic mice. However, 18 to 25% cures were obtained for neutron irradiations without boron, suggesting that the neutron dose alone plays an important role. Neutron capture therapy of B-16 melanoma xenografts in nude mice showed substantial tumor regression over 35 days, but the survival rate of NCT treated mice after 7 weeks was only 40-60%. In this paper the authors demonstrate the equivalence of the nude mouse model with a syngeneic model, using the same Harding-Passey murine melanoma line, and delineate the conditions required for maximum differential response between neutron irradiation with and without BPA administration, with complete local control as the end point

  5. FDG small animal PET permits early detection of malignant cells in a xenograft murine model

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    Nanni, Cristina; Spinelli, Antonello; Trespidi, Silvia; Ambrosini, Valentina; Castellucci, Paolo; Farsad, Mohsen; Franchi, Roberto; Fanti, Stefano; Leo, Korinne di; Tonelli, Roberto; Pession, Andrea; Pettinato, Cinzia; Rubello, Domenico

    2007-01-01

    The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. We studied 23 nude mice, in which 7 x 10 6 rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals

  6. Intracerebral Hemorrhage

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    ... Home » Patients & Families » About Stroke » Intracerebral Hemorrhage Intracerebral Hemorrhage What is a Stroke? Ischemic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage Pediatric Stroke Warning Signs Stroke Statistics ...

  7. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

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    Valentina E Schneeberger

    Full Text Available Patient-derived xenograft (PDX mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR amplicon length (ssPAL differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS, an immunomagnetic mouse cell depletion (MCD approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors.

  8. Modeling of Chronic Myeloid Leukemia : An Overview of In Vivo Murine and Human Xenograft Models

    NARCIS (Netherlands)

    Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone

  9. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

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    Heimberger, Amy B; Archer, Gary E; Crotty, Laura E; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2002-01-01

    Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

  10. Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.

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    Dolores Hernán Pérez de la Ossa

    Full Text Available Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9-Tetrahydrocannabinol (THC and Cannabidiol (CBD - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

  11. Effects of aurothiomalate treatment on canine osteosarcoma in a murine xenograft model.

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    Scharf, Valery F; Farese, James P; Siemann, Dietmar W; Abbott, Jeffrey R; Kiupel, Matti; Salute, Marc E; Milner, Rowan J

    2014-03-01

    Osteosarcoma is a highly fatal cancer, with most patients ultimately succumbing to metastatic disease. The purpose of this study was to evaluate the effects of the antirheumatoid drug aurothiomalate on canine and human osteosarcoma cells and on canine osteosarcoma growth and metastasis in a mouse xenograft model. We hypothesized that aurothiomalate would decrease osteosarcoma cell survival, tumor cellular proliferation, tumor growth, and metastasis. After performing clonogenic assays, aurothiomalate or a placebo was administered to 54 mice inoculated with canine osteosarcoma. Survival, tumor growth, embolization, metastasis, histopathology, cell proliferation marker Ki67, and apoptosis marker caspase-3 were compared between groups. Statistical analysis was carried out using the Kaplan-Meier method with the log-rank test and one-way analysis of variance with the Tukey's test or Dunn's method. Aurothiomalate caused dose-dependent inhibition of osteosarcoma cell survival (Posteosarcoma cell survival and reduced tumor cell proliferation, growth, embolization, and pulmonary metastasis. Given aurothiomalate's established utility in canine and human medicine, our results suggest that this compound may hold promise as an adjunctive therapy for osteosarcoma. Further translational research is warranted to better characterize the dose response of canine and human osteosarcoma to aurothiomalate.

  12. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

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    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  13. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    International Nuclear Information System (INIS)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  14. Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

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    Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

    2017-09-01

    Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

  15. Reproducibility study of [{sup 18}F]FPP(RGD){sub 2} uptake in murine models of human tumor xenografts

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    Chang, Edwin; Liu, Shuangdong; Chin, Frederick; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Gowrishankar, Gayatri; Yaghoubi, Shahriar [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Wedgeworth, James Patrick [Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Berndorff, Dietmar; Gekeler, Volker [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany); Gambhir, Sanjiv S. [Stanford University, Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford, Department of Bioengineering, School of Medicine, Stanford, CA (United States); Canary Center at Stanford for Cancer Early Detection, Nuclear Medicine, Departments of Radiology and Bioengineering, Molecular Imaging Program at Stanford, Stanford, CA (United States)

    2011-04-15

    An {sup 18}F-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer [{sup 18}F]FPP(RGD){sub 2} has been used to image tumor {alpha}{sub v}{beta}{sub 3} integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin {alpha}{sub v}{beta}{sub 3}-targeted PET probe, [{sup 18}F ]FPP(RGD){sub 2} using small animal PET. Human HCT116 colon cancer xenografts were implanted into nude mice (n = 12) in the breast and scapular region and grown to mean diameters of 5-15 mm for approximately 2.5 weeks. A 3-min acquisition was performed on a small animal PET scanner approximately 1 h after administration of [{sup 18}F]FPP(RGD){sub 2} (1.9-3.8 MBq, 50-100 {mu}Ci) via the tail vein. A second small animal PET scan was performed approximately 6 h later after reinjection of the probe to assess for reproducibility. Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean or maximum activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility. The coefficient of variation (mean {+-}SD) for %ID{sub mean}/g and %ID{sub max}/g values between [{sup 18}F]FPP(RGD){sub 2} small animal PET scans performed 6 h apart on the same day were 11.1 {+-} 7.6% and 10.4 {+-} 9.3%, respectively. The corresponding differences in %ID{sub mean}/g and %ID{sub max}/g values between scans were -0.025 {+-} 0.067 and -0.039 {+-} 0.426. Immunofluorescence studies revealed a direct relationship between extent of {alpha}{sub {nu}}{beta}{sub 3} integrin expression in tumors and tumor vasculature

  16. Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.

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    GuhaSarkar, Dwijit; Neiswender, James; Su, Qin; Gao, Guangping; Sena-Esteves, Miguel

    2017-02-01

    The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models. First, we show that a single intracranial injection of AAV encoding human IFN-β eliminates invasive human GBM8 tumors and promotes long-term survival. Next, we screened five AAV-IFN-β vectors with different promoters to drive safe expression of mouse IFN-β in the brain in the context of syngeneic GL261 tumors. Two AAV-IFN-β vectors were excluded due to safety concerns, but therapeutic studies with the other three vectors showed extensive tumor cell death, activation of microglia surrounding the tumors, and a 56% increase in median survival of the animals treated with AAV/P2-Int-mIFN-β vector. We also assessed the therapeutic effect of combining AAV-IFN-β therapy with temozolomide (TMZ). As TMZ affects DNA replication, an event that is crucial for second-strand DNA synthesis of single-stranded AAV vectors before active transcription, we tested two TMZ treatment regimens. Treatment with TMZ prior to AAV-IFN-β abrogated any benefit from the latter, while the reverse order of treatment doubled the median survival compared to controls. These studies demonstrate the therapeutic potential of intracranial AAV-IFN-β therapy in a highly migratory GBM model as well as in a syngeneic mouse model and that combination with TMZ is likely to enhance its antitumor potency. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  17. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

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    Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  18. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    International Nuclear Information System (INIS)

    Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.; McFadden, Grant

    2015-01-01

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases

  19. Rapamycin targeting mTOR and hedgehog signaling pathways blocks human rhabdomyosarcoma growth in xenograft murine model

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    Kaylani, Samer Z. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Xu, Jianmin; Srivastava, Ritesh K. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, Bethesda (United States); Pressey, Joseph G. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-06-14

    Graphical abstract: Intervention of poorly differentiated RMS by rapamycin: In poorly differentiated RMS, rapamycin blocks mTOR and Hh signaling pathways concomitantly. This leads to dampening in cell cycle regulation and induction of apoptosis. This study provides a rationale for the therapeutic intervention of poorly differentiated RMS by treating patients with rapamycin alone or in combination with other chemotherapeutic agents. -- Highlights: •Rapamycin abrogates RMS tumor growth by modulating proliferation and apoptosis. •Co-targeting mTOR/Hh pathways underlie the molecular basis of effectiveness. •Reduction in mTOR/Hh pathways diminish EMT leading to reduced invasiveness. -- Abstract: Rhabdomyosarcomas (RMS) represent the most common childhood soft-tissue sarcoma. Over the past few decades outcomes for low and intermediate risk RMS patients have slowly improved while patients with metastatic or relapsed RMS still face a grim prognosis. New chemotherapeutic agents or combinations of chemotherapies have largely failed to improve the outcome. Based on the identification of novel molecular targets, potential therapeutic approaches in RMS may offer a decreased reliance on conventional chemotherapy. Thus, identification of effective therapeutic agents that specifically target relevant pathways may be particularly beneficial for patients with metastatic and refractory RMS. The PI3K/AKT/mTOR pathway has been found to be a potentially attractive target in RMS therapy. In this study, we provide evidence that rapamycin (sirolimus) abrogates growth of RMS development in a RMS xenograft mouse model. As compared to a vehicle-treated control group, more than 95% inhibition in tumor growth was observed in mice receiving parenteral administration of rapamycin. The residual tumors in rapamycin-treated group showed significant reduction in the expression of biomarkers indicative of proliferation and tumor invasiveness. These tumors also showed enhanced apoptosis

  20. Intracerebral hemorrhage (image)

    Science.gov (United States)

    Intracerebral hemorrhage may be caused by trauma (brain injury) or abnormalities of the blood vessels (aneurysm or angioma), but it is most commonly associated with high blood pressure (hypertensive intracerebral hemorrhage).

  1. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model.

    Science.gov (United States)

    Kurundkar, Deepali; Srivastava, Ritesh K; Chaudhary, Sandeep C; Ballestas, Mary E; Kopelovich, Levy; Elmets, Craig A; Athar, Mohammad

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model

    Science.gov (United States)

    2012-01-01

    Background Regardless of the availability of therapeutic options, the overall 5-year survival for patients diagnosed with pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have been used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions. Both frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit anti-neoplastic activity, and have been investigated as potential anti-cancer agents. The goals of this study are to identify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to evaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model. Methods Boswellia sacra gum resins were hydrodistilled at 78°C; and essential oil distillate fractions were collected at different durations (Fraction I at 0–2 h, Fraction II at 8–10 h, and Fraction III at 11–12 h). Hydrodistillation of the second half of gum resins was performed at 100°C; and distillate was collected at 11–12 h (Fraction IV). Chemical compositions were identified by gas chromatography–mass spectrometry (GC-MS); and total boswellic acids contents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated pancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic (subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability of Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic activities in animals were assessed by immunohistochemistry. Results Longer duration and higher temperature hydrodistillation produced more abundant high molecular

  3. Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer.

    Science.gov (United States)

    Martey, Orleans; Nimick, Mhairi; Taurin, Sebastien; Sundararajan, Vignesh; Greish, Khaled; Rosengren, Rhonda J

    2017-01-01

    Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles.

  4. Recurrent Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Schmidt, Linnea Boegeskov; Goertz, Sanne; Wohlfahrt, Jan

    2016-01-01

    BACKGROUND: Intracerebral hemorrhage (ICH) is a disease with high mortality and a substantial risk of recurrence. However, the recurrence risk is poorly documented and the knowledge of potential predictors for recurrence among co-morbidities and medicine with antithrombotic effect is limited....... OBJECTIVES: 1) To estimate the short- and long-term cumulative risks of recurrent intracerebral hemorrhage (ICH). 2) To investigate associations between typical comorbid diseases, surgical treatment, use of medicine with antithrombotic effects, including antithrombotic treatment (ATT), selective serotonin...

  5. Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Martey O

    2017-10-01

    Full Text Available Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene-1-methylpiperidine-4-one (RL71, that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles. Keywords: curcumin derivatives, nanomedicine, EGFR, biodistribution

  6. Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

    Science.gov (United States)

    Rofstad, E K; Fenton, B M; Sutherland, R M

    1988-05-01

    Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

  7. Intracerebral haemorrhage after carotid endarterectomy

    DEFF Research Database (Denmark)

    Schroeder, T; Sillesen, H; Boesen, J

    1987-01-01

    Among 662 consecutive carotid endarterectomies eight cases of postoperative ipsilateral intracerebral haemorrhage were identified, occurring into brain areas which, preoperatively were without infarction. As blood pressures across the stenosis were routinely measured during surgery, the internal...

  8. Intracerebral hemorrhage in brain tumors

    International Nuclear Information System (INIS)

    Fujita, Katsuzo; Matsumoto, Satoshi

    1980-01-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief. (author)

  9. Intracerebral hemorrhage in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, K; Matsumoto, S [Kobe Univ. (Japan). School of Medicine

    1980-10-01

    A series of 16 cases of intracerebral hemorrhage associated with brain tumors are described. The literature is reviewed and the incidence of these cases is reported to be low, but we had clinically encountered these cases more commonly than reported, since CT was introduced to the neurosurgical field as a diagnostic aid. The presenting symptoms were those of spontaneous intracerebral hemorrhage or brain tumor. The intracerebral hemorrhage associated with brain tumor may mask the cause of bleeding and confuse the diagnosis. The majority of the tumor causing the intracerebral hemorrhage are highly malignant as glioblastoma or metastatic brain tumor, but there are some benign tumors such as pituitary adenoma, hemangioblastoma, benign astrocytoma and meningioma, which would have good survival rates if discovered early. The mechanisms of massive hemorrhage with brain tumor are not clear. From pathological findings of our cases and other reports, the mechanism seems to be due to the vascular endothelial proliferation with subsequent obliteration of the lumen of the vessel. Thin walled, poorly formed vessels in tumor may also become distorted with growth of the tumor and these may easily rupture and bleed. Necrosis with subsequent loss of vessel support may be a factor in production of hemorrhage. Radiation therapy may be a predisposing factor. Children are rarely involved in these cases. The prognosis in the majority of cases would seen to be poor, since the majority of the tumor are highly malignant and most such patients are seen by the neurosurgeon some time after the hemorrhage has accomplished its fatal mischief.

  10. Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation

    OpenAIRE

    Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-01-01

    Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving...

  11. Intracerebral myiasis in a child

    Energy Technology Data Exchange (ETDEWEB)

    Pouillaude, J M; Dupont, J; Gilly, R; Lapras, C

    1980-01-01

    Larvae of Hypoderma bovis accidentally parisitize man. These larvae can penetrate into the brain by a path which remains unknown, causing an intracerebral haematoma and clinical signs. Computerized tomography shows the haematoma, and carotid angiography shows the absence of a vascular malformation, but these examinations do not allow etiological diagnosis. This is suggested by seroimmunological examinations and by the discovery of the larva during the operation. We report findings in a 6 1/4 year old boy.

  12. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  13. Tumor localization of boronated porphyrins in an intracerebral model of glioma

    International Nuclear Information System (INIS)

    Hill, J.S.; Kaye, A.H.; Gonzales, M.F.; Stylli, S.S.; Nakamura, Y.; Kahl, S.B.; Vardaxis, N.J.; Johnson, C.I.

    1992-01-01

    Treatment of the most common cerebral tumor, cerebral glioma, is unsatisfactory as the tumor recurs due to inadequate local control. Photodynamic therapy (PDT) and Boron Neutron Capture Therapy (BNCT) offer some promise as adjuvant treatments for cerebral glioma. Several clinical trials have been reported utilizing PDT and BNCT to treat the high grade glioma, glioblastoma multiforme. The authors have investigated the pharmacokinetic tissue distribution of the photosensitizer Haematoporphyrin derivative (HpD), the nido carboranyl porphyrin, boron tetraphenyl porphine (BTPP) and the closo carboranyl monomeric protoporphyrin (BOPP) in CBA mice bearing the intracerebral C6 glioma xenograft

  14. Lateral type of intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Yamagami, Tatsuhito; Gotoh, Yasunobu; Imataka, Kiyoharu; Niijima, Kyo; Handa, Hajime.

    1987-01-01

    The magnetic resonance imaging (MRI) of intracerebral hemorrhages (lateral type) was studied. The strength of the magnetic field was 0.2 Tesla. Four cases were studied with inversion recovery (IR) and saturation recovery (SR) images. The findings of the acute stage (within 1 week) were a central isointensity and a peripheral low intensity on the IR image. On the SR image we recognized a central isointensity and a peripheral high intensity holding a faintly high intensity area around the hematoma. The findings of the subacute stage (from 1 to 3 weeks) were characterized by a central isointensity and a peripheral high-intensity ring, with a low-intensity area outside the hematoma on the IR image. A widespread high-intensity area including the hematoma itself and the surrounding white matter was observed on the SR image. The findings of the chronic stage (over 3 weeks) were the disapperance of a high-intensity ring and a change to a low-intensity area on the IR image. The hematoma itself and surrounding white matter had a high intensity, which has decreased in size in comparison with that of the subacute stage. The hypointensity rim was found in the immediately adjacent part of the original hematoma on the SR image. The MRI of a small hematoma 70 days from the onset showed an almost normal brain structure. Some magnetic resonance findings of intracerebral hemorrhage were reviewed. (author)

  15. Clinical practice guidelines in intracerebral haemorrhage.

    Science.gov (United States)

    Rodríguez-Yáñez, M; Castellanos, M; Freijo, M M; López Fernández, J C; Martí-Fàbregas, J; Nombela, F; Simal, P; Castillo, J; Díez-Tejedor, E; Fuentes, B; Alonso de Leciñana, M; Alvarez-Sabin, J; Arenillas, J; Calleja, S; Casado, I; Dávalos, A; Díaz-Otero, F; Egido, J A; Gállego, J; García Pastor, A; Gil-Núñez, A; Gilo, F; Irimia, P; Lago, A; Maestre, J; Masjuan, J; Martínez-Sánchez, P; Martínez-Vila, E; Molina, C; Morales, A; Purroy, F; Ribó, M; Roquer, J; Rubio, F; Segura, T; Serena, J; Tejada, J; Vivancos, J

    2013-05-01

    Intracerebral haemorrhage accounts for 10%-15% of all strokes; however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours after onset and determines poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Various phases of intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Kino, Masao; Anno, Izumi; Yano, Yuhiko; Anno, Yasuro.

    1980-01-01

    Cases of intracerebral hemorrhage except typical putamen thalamic hemorrhage were reported. It is not difficult to diagnose typical attacks of cerebral apoplexy in patients older than 40 years with hypertension by CT. When the condition of the onset is not typical, cerebral infarction must be considered. Though conservative treatment is performed for severe cerebral hemorrhage and cerbral infarction, there is no specific medicine curing these diseases completely. On the contrary, the risk that the administration of fibrinolysis activators and STA-MCA anastomosis may induce cerebral hemorrhage is stressed. Not a few patients with cerebral apoplexy accompanied by small hemorrhagic focuses have been found, especially since CT was used widely. However, treatment for this disease has many inconsistencies. From above-mentioned facts, we recognize excellent roles of CT in an application of surgery for cerebral hemorrhage of early stage, and we, general radiologists, are under an obligation to advise most adequate theraphy for each patient. (Tsunoda, M.)

  17. Two cases of intracerebral cysticercosis

    International Nuclear Information System (INIS)

    Nakase, Hiroyuki; Kamada, Kitaro; Inui, Shoji; Hiramatsu, Ken-ichiro; Okuchi, Kazuo; Minami, Shigenori; Araki, Kouji.

    1986-01-01

    We report 2 cases of intracerebral cysticercosis. One was followed up by CT with preservative treatment, and the other, treated surgically. Case 1: A 60-year-old man who had lived in Korea until the age of 12 and who had often eaten raw pork. He had been diagnosed as having cysticercosis after the excision of facial and somatic nodules. On January 17, 1980, he visited our clinic first with a complaint of generalized convulsions. CT revealed multiple low-density areas. For the subsequent 4 years, the patient was followed-up by CT. Meanwhile, the cyst became large and was calcified; in addition, brain atrophy progressed, and a new lesion of the cyst appeared. Case 2: A 50-year-old man who had also lived in Korea and who had also eaten raw pork often. He had been diagnosed as having ''cestodiasis'' in a gastro-intestinal hospital 7 or 8 years before. He visited our clinic because of sensory aphasia which developed on January 15, 1980. CT disclosed multiple low-density areas and a calcification of the left cerebellar hemisphere. Ring enhancement was also found on enhanced CT. The patient was then surgically treated. The excised specimen contained a three-layer structure characteristic of cysticercosis. The immunoelectrophoresis of the cyst fluid gave a positive result for the disease. Postoperatively, the symptoms improved. Intracerebral cysticercosis is a very rare disease in Japan. Its incidence, however, is likely to increase on account of the development of transportation. For this reason, and because of the necessity to differentiate it from a brain tumor or abscess on CT, it seems that this disease is of concern. (author)

  18. Treatment for Supra-tentorial Intracerebral Hemorrhage

    OpenAIRE

    長島, 梧郎; 藤本, 司; 鈴木, 龍太; 浅井, 潤一郎; 松永, 篤子; 張, 智為; 永井, 美穂; Goro, NAGASHIMA; Tsukasa, FUJIMOTO; Ryuta, SUZUKI; Jun-ichiro, ASAI; Atsuko, MATSUNAGA; Tomoo, CHANG; Miho, NAGAI; 昭和大学藤が丘病院脳神経外科

    2002-01-01

    Only vague guidelines exist for the surgical management of intracerebral hemorrhage (ICH). We investigated the indications for surgical management of intracerebral hemorrhage and compared the outcomes of computed tomography (CT)-guided stereotactic hematoma aspiration with those after hematoma removal under craniotomy. Our indications for CT-guided stereotactic hematoma aspiration were an age < 80 years old, a hematoma volume ≧ 10 ml, and a Glasgow Coma Scale (GCS) score ≦ 14. Those for hemat...

  19. European research priorities for intracerebral haemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam

    2011-01-01

    Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time...... and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH....

  20. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  1. Invasive intracerebral fungal infection in a leukaemic patient.

    LENUS (Irish Health Repository)

    O'Brien, Deirdre

    2012-06-01

    Intracerebral abscesses secondary to Zygomycosis are potentially fatal. A 12-year-old girl with acute promyelocytic leukaemia was successfully treated for intracerebral abscess caused by Zygomycosis with complete surgical excision and combination antifungal therapy.

  2. Intracerebral abscess: A complication of severe cystic fibrosis lung disease

    OpenAIRE

    Fenton, Mark E; Cockcroft, Donald W; Gjevre, John A

    2008-01-01

    Intracerebral abscess is an uncommon complication of severe cystic fibrosis lung disease. The present report describes a case of fatal multiple intracerebral abscesses in a patient with a severely bronchiectatic, nonfunctioning right lung and chronic low-grade infection. The patient was previously turned down for pneumonectomy. Intracerebral abscess in cystic fibrosis and the potential role of pneumonectomy in the present patient are discussed.

  3. Aphasia caused by intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Furuya, Kazuhide; Segawa, Hiromu; Shiokawa, Yoshiaki; Hasegawa, Isao; Sano, Keiji

    1992-01-01

    It is generally accepted that cases of aphasia can be divided into several groups according to verbal fluency, auditory comprehension, and repetition abilities. Although many authors have studied aphasia and its location by means of a CT scan, the primary lesion on a CT scan with regard to the subtypes of aphasia still remains controversial. In this report we present our new CT classification for the syndromes of aphasia and the prognosis. Twenty-one patients with intracerebral hematoma (ICH) were followed up for more than 3 months after onset. ICH was classified according to the mode of the horizontal extension of the hematoma on a CT scan. Four lines were decided as follows: Line (a) is between the anterior horn of the lateral ventricle and the midpoint of the third ventricle; Line (b) is the vertical line to the saggital line which originates from the midpoint of the third ventricle; Line (c) is between the trigone of the lateral ventricle and the midpoint of the third ventricle. The CT classification consisted of 4 types: in Type A, ICH was located anterior to line (a); in Type B, ICH was located between line (a) and line (b); in Type C, ICH was located between line (b) and line (c); Type B+C, was a combination of Type B and Type C. Transcortical motor aphasia belonged to the Type A group. Transcortical sensory aphasia belonged to the Type B and Type B+C groups. Wernicke's and anomic aphasia belonged to the Type C group. Conduction and global aphasia belonged to the Type B+C group. Pure Broca's aphasia could not be observed in this series. Several relationships between the syndromes of aphasia and its CT findings were evident. On the other hand, the syndromes of aphasia and the degree of recovery were not correlated, except for global aphasia. (author)

  4. Glycemia in Spontaneous Intracerebral Hemorrhage: Clinical Implications

    Directory of Open Access Journals (Sweden)

    Alvis-Miranda Hernando

    2014-10-01

    Full Text Available Spontaneous cerebral hemorrhage or intracranial hemorrhage accounts for 10-15% of all strokes. Intracranial hemorrhage is much less common than ischemic stroke, but has higher mortality and morbidity, one of the leading causes of severe disability. Various alterations, among these the endocrine were identified when an intracerebral hemorrhage, these stress-mediated mechanisms exacerbate secondary injury. Deep knowledge of the injuries which are directly involved alterations of glucose, offers insight as cytotoxicity, neuronal death and metabolic dysregulations alter the prognosis of patients with spontaneous intracerebral hemorrhage.

  5. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  6. Cerebral microbleeds and intracerebral hemorrhages in patients on maintenance hemodialysis

    International Nuclear Information System (INIS)

    Watanabe, Akira

    2006-01-01

    Cerebrovascular diseases are important causes of death in patients on maintenance hemodialysis. Recently, it has become clear that the presence of cerebral microbleeds (MBs) on T2 * -weighted magnetic resonance imaging (MRI) is closely related to intracerebral hemorrhages. This study investigated the incidence of MBs in chronic dialysis patients and prospective hemorrhagic complications of chronic dialysis patients with old intracerebral hemorrhages. Eighty patients (34 males, 46 females) with chronic renal failure, whose mean age was 62.9±11.4 years, were examined by MRI. The mean duration of hemodialysis was 7.8±6.3 years. MBs were found in 28 patients (35%) by T2 * -weighted MRI. Old intracerebral hemorrhages were seen in seven of the patients, and MBs were found in five (71%) of these seven patients. The frequency of old intracerebral hemorrhages was significantly higher in patients with MBs than in those without (p=0.048), and the numbers of MBs were significantly larger in patients with old intracerebral hemorrhages than in those without (p=0.0065). Three of the seven patients with old intracerebral hemorrhages had new hemorrhagic complications (two intracerebral hemorrhages and one cerebral microbleed) within a year. These intracerebral hemorrhages occurred in areas without MBs on the first T2 * -weighted MRI. T2 * -weighted MRI is useful for the detection of MBs, which may be a predictor of intracerebral hemorrhage. When a patient has a large number of MBs and old intracerebral hemorrhages, the risk of intracerebral hemorrhage undoubtedly increases. (author)

  7. Continued bleeding following acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Brouwers, H.B.

    2014-01-01

    In this Ph.D. thesis, ‘Continued bleeding following acute intracerebral hemorrhage’, we have discussed the background literature, risk factors, and underlying biology of hematoma expansion, as well as the clinical applicability of the CT angiography (CTA) 'spot sign' as an imaging marker of this

  8. Error processing - evidence from intracerebral ERP recordings

    Czech Academy of Sciences Publication Activity Database

    Brázdil, M.; Roman, R.; Falkenstein, M.; Daniel, P.; Jurák, Pavel; Rektor, I.

    2002-01-01

    Roč. 146, č. 4 (2002), s. - ISSN 1432-1106 R&D Projects: GA ČR GA102/95/0467; GA ČR GA102/02/1339 Institutional research plan: CEZ:AV0Z2065902 Keywords : error processing * event-related potentials * intracerebral recordings Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  9. Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

    Science.gov (United States)

    Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

    2010-03-01

    Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

  10. Glioblastoma Multiforme Presenting as Spontaneous Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Cagatay Ozdol

    2014-06-01

    Full Text Available Brain tumors with concomitant intracerebral hemorrhage are rarely encountered. Hemorrhage as the initial presentation of a brain tumour may pose some diagnostic problems, especially if the tumour is small or the hemorrhage is abundant. We present a 47-year-old man who admitted to the emergency department with sudden onset headache, right blurred vision and gait disturbance. A non-contrast cranial computerized tomography scan performed immediately after his admission revealed a well circumscribed right occipitoparietal haematoma with intense peripheral edema causing compression of the ipsilateral ventricles. On 6th hour of his admission the patient%u2019s neurological status deteriorated and he subsequently underwent emergent craniotomy and microsurgical evacuation of the haematoma. The histopathological examination of the mass was consistent with a glioblastoma multiforme. Neoplasms may be hidden behind each case of spontaneous intracerebral hemorrhage. Histological sampling and investigation is mandatory in the presence of preoperative radiological features suggesting a neoplasm.

  11. Chronological changes in hypertensive intracerebral hemorrhages

    International Nuclear Information System (INIS)

    Takasugi, Shinsuke; Kashihara, Michiharu; Okamoto, Junji; Hondo, Hideki; Yamashita, Shigeru

    1983-01-01

    The clinical series consisted of 28 patients with hypertensive intracerebral hematoma observed in the natural course from 1976 through 1978. A total of 114 repeated computer tomographic (CT) examinations were made with an EMI-1010 or an ACTA-0100 scanner. The experimental series consisted of 26 adult mongrel dogs with intracerebral hematoma near the basal ganglia. In 20 dogs, autopsy and histological examinations were performed, and in 12 dogs a total of 31 repeated CT examinations were carried out with an EMI scanner (matrix 320 x 320, high-definition scan). In the clinical series, the time of the decrease in density beginning in the periphery of the hematoma, like the first appearance of ring enhancement and its concentric concentration toward the center of the hematoma, was not affected by the size of the hematoma. However, the time when the intracerebral hematoma was resolved did vary with the size of the hematoma. In the experimental series, the tissue reaction near the periphery of the intracerebral hematoma seemed to be a constant process. First, a necrotic layer appeared, and then this was replaced by immature connective tissue with granular cells, newly formed vessels, and reticulin fibers; finally, the immature layer was gradually transformed into mature connective tissue with collagenous fibers. Moreover, this process of change was not related to the size of the hematoma. The following correlations were suggested by a chronological observation of the CT images and the histological appearance: 1) acute stage - homogeneous high-density extending to the periphery, apperance of a necrotic layer; 2) subacute stage - decreased density spreading from the periphery and formation of ring enhancement, apperance of immature connective tissue with reticulin fibers; 3) chronic stage - concentric concentration of ring enhancement, mature connective tissue with collagenous fibers

  12. Emergency Neurological Life Support: Intracerebral Hemorrhage.

    Science.gov (United States)

    Jauch, Edward C; Pineda, Jose A; Hemphill, J Claude

    2015-12-01

    Intracerebral hemorrhage (ICH) is a subset of stroke due to bleeding within the parenchyma of the brain. It is potentially lethal, and survival depends on ensuring an adequate airway, reversal of coagulopathy, and proper diagnosis. ICH was chosen as an Emergency Neurological Life Support protocol because intervention within the first critical hour may improve outcome, and it is critical to have site-specific protocols to drive care quickly and efficiently.

  13. Delayed intracerebral hemorrhage as demonstrated by CT scanning

    International Nuclear Information System (INIS)

    Brunetti, J.; Zingesser, L.; Dunn, J.; Rovit, R.L.; Saint Vincent's Hospital and Medical Center, New York

    1979-01-01

    Three patients are presented who developed delayed intracerebral hematomas after head injury. Two patients had essentially negative CT scans on admission and developed intracerebral hematomas within 24 h after injury. They required surgical treatment and had fatal outcomes. The third patient presented with an epidural hematoma on CT scan, developed an intracerebral hematoma 48 h after evacuation of the epidural hematoma, and did well with conservative management. (orig.) [de

  14. Clinical features of multiple spontaneous intracerebral hemorrhages

    Directory of Open Access Journals (Sweden)

    Tao CHANG

    2016-01-01

    Full Text Available Objective To analyze the clinical features of multiple spontaneous intracerebral hemorrhages (MICH. Methods Conservative therapy, puncture and drainage, hematoma removal and/or decompressive craniectomy were used in the treatment of 630 intracerebral hemorrhage (ICH patients, who were divided into 2 groups: 30 cases with MICH and another 600 cases with solitary intracerebral hemorrhage (SICH. Three months after onset, modified Rankin Scale (mRS was used to evaluate the prognosis of all cases. Results Compared with patients in SICH group, the occurrence rate of hypertension > 5 years (P = 0.008, diabetes mellitus (P = 0.024, hypercholesterolemia (P = 0.050 and previous ischemic stroke (P = 0.026 were all significantly higher in MICH group. The mean arterial pressure (MAP level (P = 0.002 and the incidence of limb movement disorder (P = 0.000 were significantly higher in patients with MICH than those with SICH. Basal ganglia and thalamus were the predilection sites of hematoma (P = 0.001. Patients with MICH had worse prognosis compared to those with SICH 3 months after onset (P = 0.006. Conclusions Hypertension > 5 years, diabetes mellitus, hypercholesterolemia and ischemic stroke were identified to be the pathophysiological basis of MICH in this study. All patients with MICH had more serious clinical manifestations after onset and worse prognosis. DOI: 10.3969/j.issn.1672-6731.2016.01.008

  15. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

    Science.gov (United States)

    Heimberger, Amy B; Crotty, Laura E; Archer, Gary E; Hess, Kenneth R; Wikstrand, Carol J; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2003-09-15

    The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The

  16. Hemodynamics in patients with hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Kitahara, Tetsuhiro

    1997-01-01

    Cerebral hemodynamics in 15 patients with hypertensive intracerebral hemorrhage (HICH) were evaluated by measuring cerebral blood flow (CBF) and cerebrovascular reserve capacity, using stable xenon-enhanced computed tomography. Their hematomas were removed by stereotactic aqua stream aspiration. The hemispheric and thalamic CBFs of patients with HICH were lower than those of hypertensive patients without hematomas. However, the hemispheric CBF increased according to how much of the hematoma was removed surgically. Thus, hemodynamics in patients with HICH can be improved by surgical hematoma removal, although some adjunct therapies are necessary in order to prevent secondary edema and the delayed neuronal death. (author)

  17. Intracerebral Capillary Hemangioma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Youn, In Young; Kim, Jae Kyun; Byun, Jun Soo [Dept. of Radiology, Chung Ang University Medical Center, Chung Ang University College of Medicine, Seoul (Korea, Republic of); Park, Eon Sub [Dept. of Radiology, Chung Ang University Medical Center, Chung Ang University College of Medicine, Seoul (Korea, Republic of)

    2012-01-15

    Intracerebral capillary hemangiomas are very rare benign vascular tumors that mostly occur during infancy. We described a 69-year-old man with generalized tonic-clonic seizures who was diagnosed with an intracranial mass. Multidetector computed tomography, magnetic resonance imaging and digital subtraction angiography studies were performed for evaluation of brain, and there was a well-enhancing mass found in the right temporal lobe without a definite feeding vessel. The patient underwent surgery and the pathologic examination demonstrated marked proliferation of small vessels with a lobular pattern in the brain parenchyma, which was confirmed to be capillary hemangioma.

  18. European research priorities for intracerebral haemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam

    2011-01-01

    and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH........ No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death...

  19. Nonbacterial thrombotic endocarditis presenting as intracerebral hemorrhage.

    Science.gov (United States)

    Wigger, Olivier; Windecker, Stephan; Bloechlinger, Stefan

    2016-12-01

    Nonbacterial thrombotic endocarditis is a rare cause of valvular heart disease, most commonly associated with advanced malignancy. The morbidity of this kind of endocarditis lies in its tendency to embolize, while the valve function is usually preserved. The central nervous system is the most common site of embolization, leading to ischemic stroke. We report a case of nonbacterial thrombotic endocarditis complicated by intracerebral hemorrhage as the first manifestation of adenocarcinoma of the lung. The endocarditis led to severe aortic regurgitation. In view of the advanced stage of lung cancer, the patient refused further therapy. He passed away 3 weeks after first diagnosis of the adenocarcinoma.

  20. Chimeric anti-tenascin antibody 81C6: Increased tumor localization compared with its murine parent

    International Nuclear Information System (INIS)

    Zalutsky, Michael R.; Archer, Gary E.; Garg, Pradeep K.; Batra, Surinder K.; Bigner, Darell D.

    1996-01-01

    When labeled using the Iodogen method, a chimeric antibody composed of the human IgG 2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6

  1. Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation.

    Science.gov (United States)

    Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-03-01

    Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving NSCs in the left hemisphere and PBS in the right; group B, receiving NSCs in the right hemisphere and PBS in the left; and group C, receiving equal NSCs in both hemispheres. Murine brains were stained for morphological analysis and subsequent evaluation of infiltrated immune cells. ELISA was performed to detect neurotrophic and immunomodulatory factors in the brain. The findings indicated that brain injury and secondary inflammation in the left hemisphere were more severe than those in the right hemisphere, following NSC transplantation. In contrast to the left hemisphere, more neurotrophic factors but less pro-inflammatory cytokines were detected in the right hemisphere. In addition, increased levels of neurotrophic factors and interleukin (IL)-10 were observed in the NSC transplantation side when compared with the PBS-treated hemispheres, although lower levels of IL-6 and tumor necrosis factor-α were detected. In conclusion, the present study indicated that syringe needle skull penetration vs. drill penetration is an improved method that reduces the risk of brain injury and secondary inflammation following intracerebral NSC transplantation. Furthermore, NSCs have the potential to modulate inflammation secondary to brain injuries.

  2. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

    Directory of Open Access Journals (Sweden)

    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  3. Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Rémy Nicolle

    2017-11-01

    Full Text Available Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively. Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

  4. Glyceryl Trinitrate for Acute Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa

    2016-01-01

    if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome...... was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed...

  5. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Science.gov (United States)

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  6. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Xiaochun Duan

    2016-01-01

    Full Text Available Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH. Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

  7. A new treatment for hypertensive intracerebral hematoma

    International Nuclear Information System (INIS)

    Shiwaku, Tetsushi; Tanikawa, Tatsuya; Amano, Keiichi

    1986-01-01

    Durining the last 2 years, 46 cases of hypertensive intracerebral hemorrhage in the basal ganglia were treated by CT guided stereotactic aspiration and their outcome was evaluated in terms of the rate of hematoma removal, the change of consciousness level and the recovery of motor and sensory functions. They are aged from 45 to 79 years old, the average 56, and aspirated 1 to 24 days after the onset, two third of them being within 1 week. The whole procedure was done in the CT room under direct CT guidance and by one trial. In putaminal type hemorrhage, the removed hematoma volumes ranged from 9 to 48 ml, average being 23.7 ml, in thalamic type from 5 to 29 ml, average being 15.5 ml. The average rate of removal was 81.1 % in 30 cases within 1 week. In most cases, preoperative consciousness was not severely disturbed, in putaminal type, 19 were alert or confused, 4 somnolent, 5 stuperous and in thalamic type, 6, 6, 3 respectively and 2 were semicomatous, one of them had herniation sign. In putaminal type all but 2 cases recovered to alert or confused state, the first one had postoperative bleeding and the other was already apallic preoperatively. In thalamic type, we lost 3 cases, 2 by gastrointestinal bleeding and 1 DIC, by rehemorrhage 2 months after the operation. All but one who was semicomatous preoperatively recovered to alertness. In motor function, some cases of the putaminal bleeding with intact internal capsule remained hemiplegic. On the other hand, most of the cases with partial destruction of the internal capsule on CT recovered well in both types of hematoma. Especially in thalamic type, only 2 had inability to walk durinig the follow-up period. In sensory function, two thirds of the cases recovered to almost normal level. CT guided stereotactic aspiration, therefore, can be evaluated as less invasive and more definitive treatment for intracerebral hematoma in the basal ganglia. (author)

  8. Hyponatremia in Patients with Spontaneous Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Jaime Robenolt Gray

    2014-11-01

    Full Text Available Hyponatremia is the most frequently encountered electrolyte abnormality in critically ill patients. Hyponatremia on admission has been identified as an independent predictor of in-hospital mortality in patients with spontaneous intracerebral hemorrhage (sICH. However, the incidence and etiology of hyponatremia (HN during hospitalization in a neurointensive care unit following spontaneous intracerebral hemorrhage (sICH remains unknown. This was a retrospective analysis of consecutive patients admitted to Detroit Receiving Hospital for sICH between January 2006 and July 2009. All serum Na levels were recorded for patients during the ICU stay. HN was defined as Na <135 mmol/L. A total of 99 patients were analyzed with HN developing in 24% of sICH patients. Patients with HN had an average sodium nadir of 130 ± 3 mmol/L and an average time from admission to sodium <135 mmol/L of 3.9 ± 5.7 days. The most common cause of hyponatremia was syndrome of inappropriate antidiuretic hormone (90% of HN patients. Patients with HN were more likely to have fever (50% vs. 23%; p = 0.01, infection (58% vs. 28%; p = 0.007 as well as a longer hospital length of stay (14 (8–25 vs. 6 (3–9 days; p < 0.001. Of the patients who developed HN, fifteen (62.5% patients developed HN in the first week following sICH. This shows HN has a fairly high incidence following sICH. The presence of HN is associated with longer hospital length of stays and higher rates of patient complications, which may result in worse patient outcomes. Further study is necessary to characterize the clinical relevance and treatment of HN in this population.

  9. A study on hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Miura, Naohisa

    1982-01-01

    We studied 235 patients with hypertensive intracerebral hemorrhage by CT for about five years. An acute intracerebral hematoma is characterized by sharply delineated high density area. Repeated CT examinations demonstrate reduction in size of the high density hematoma after intervals of 20 - 40 days. And then, in general, the areas formerly occupied with hematoma show normal or reduced density. One or two days after hemorrhage, the high density is surrounded by a thin low density zone. After a few days the low density area is seen at the anterior and posterior pole of the high density in the white matter. These low density are produced by edema or resolving hematoma. About five days after hemorrhage, high density area is associated with wide surrounding low density zone of edema and then gradually diminishes in size. The wide low density zone surrounding the high density of hematoma persisting for over 15 days is probably composed not only of edema, but also of liquefied hematoma, necrotic brain tissue and so on. Enlarged hematoma and surrounding low density area extend to anterior, posterior, superior and inferior direction in the white matter. CT studies with i.v. contrast enhancement demonstrate from the 2nd to 4th weeks a ring-shaped high density around the hematoma. We classified each of the putaminal and thalamic hemorrhage into four types based on CT findings of hematoma advancement. In this study, a statistical method of Speareman's coefficients of rank correlation was utilized. According to this investigation, the important factors influencing prognosis and operative results were found to be the CT findings including the location and size of a hematoma, as well as the rapidity and the direction of its evolution. (J.P.N.)

  10. Ultraearly hematoma growth in active intracerebral hemorrhage

    Science.gov (United States)

    Coscojuela, Pilar; Rubiera, Marta; Hill, Michael D.; Dowlatshahi, Dar; Aviv, Richard I.; Silva, Yolanda; Dzialowski, Imanuel; Lum, Cheemun; Czlonkowska, Anna; Boulanger, Jean-Martin; Kase, Carlos S.; Gubitz, Gord; Bhatia, Rohit; Padma, Vasantha; Roy, Jayanta; Tomasello, Alejandro; Demchuk, Andrew M.; Molina, Carlos A.

    2016-01-01

    Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients (p 4.7 mL/h (p = 0.002) and the CTA spot sign (p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients. PMID:27343067

  11. Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Sprigg, Nikola; Robson, Katie; Bath, Philip

    2016-01-01

    RATIONALE: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. AIM: This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h...... of spontaneous intracerebral hemorrhage reduces death or dependency. DESIGN: Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h......, and institutionalization. DISCUSSION: This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial...

  12. Evaluation of Intraventricular Hemorrhage in Pediatric Intracerebral hemorrhage

    OpenAIRE

    Kleinman, Jonathan T; Beslow, Lauren A; Engelmann, Kyle; Smith, Sabrina E; Licht, Daniel J; Ichord, Rebecca N; Jordan, Lori C

    2011-01-01

    Previous studies of pediatric intracerebral hemorrhage have investigated isolated intraparenchymal hemorrhage. We investigated whether detailed assessment of intraventricular hemorrhage enhanced outcome prediction after intracerebral hemorrhage. We prospectively enrolled 46 children, full-term to 17 years, median age 2.7 years with spontaneous intraparenchymal hemorrhage and/or intraventricular hemorrhage. Outcome was assessed with the King’s Outcome Scale for Childhood Head Injury. Twenty-si...

  13. Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.

    Science.gov (United States)

    Xu, Yunhua; Zhang, Feifei; Pan, Xiaoqing; Wang, Guan; Zhu, Lei; Zhang, Jie; Wen, Danyi; Lu, Shun

    2018-05-09

    Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively. Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically. The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) gene fusion (patient/xenograft: CTC15035 EML4-ALK ) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063 EGFR L858R, T790M )). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035 EML4-ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063 EGFR L858R, T790M xenografts. We successfully developed a new method of generating

  14. Vitrification and xenografting of human ovarian tissue.

    Science.gov (United States)

    Amorim, Christiani Andrade; Dolmans, Marie-Madeleine; David, Anu; Jaeger, Jonathan; Vanacker, Julie; Camboni, Alessandra; Donnez, Jacques; Van Langendonckt, Anne

    2012-11-01

    To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model. Pilot study. Gynecology research unit in a university hospital. Ovarian biopsies were obtained from seven women aged 30-41 years. Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice. The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry. After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups. Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Computed tomographic findings of intracerebral cysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Kyo; Lee, Sun Wha; Kim, Ho Kyun; Ahn, Chi Yul [School of Medicine, Kyung-Hee University, Seoul (Korea, Republic of)

    1980-12-15

    Cysticercosis is a parasitic disease in which man serves as the intermediate host of Taenia Solium, the pork tapeworm. The computed tomographic findings of 25 cases of intracerebral cysticercosis proven by pathologic and/or clinical findings during past 2 years were analysed. The results were as follows; 1. The sex was 19 males and 6 females, and 56 percent of the patients were seen in fourth and fifth decades. The most common symptom was epilepsy (72%). 2. The C. T. findings in precontrast study were varied; such as ill defined low density (48%), cystic low density (20%), dilated ventricles (20%), ill defined low density with isodense nodule (18%), cystic low density with isodense mural nodule (12%) and calcification (8%). 3. The areas of involvement were 20 cases (80%) of parenchymal form, 3 cases (12%) of ventricular form and 2 cases (8%) of mixed form. 4. The contrast-enhanced 13 cases were 5 nodular, 5 ring or rim-like and 3 mixed type enhancements, while 12 cases were not enhanced. 5. C.T. scan demonstrated more precise location and extents of cerebral cysticercosis, especially in parenchymal form. It was considered to be important in determination of surgical feasibility and its approach.

  16. Advances in the management of intracerebral hemorrhage.

    Science.gov (United States)

    Kuramatsu, J B; Huttner, H B; Schwab, S

    2013-09-01

    Intracerebral hemorrhage (ICH) is one of the most detrimental sub-types of stroke and accounts for 10-15% of all strokes Qureshi et al. (Lancet 373(9675):1632-1644, 2009). ICH has an incidence of 10-30 cases per 100,000 people/year which is increasing and expected to double by the year 2050 Qureshi et al. (N Engl J Med 344 (19):1450-1460, 2001). Mortality rates still remain poor (30-50%) and functional dependency after ICH is high (~75%) van Asch et al. (Lancet Neurol 9 (2):167-176, 2010). Up to now, all randomized controlled trials investigating treatment approaches in ICH have failed to document improvements on clinical endpoints Mayer et al. (N Engl J Med 358 (20):2127-2137, 2008); Brouwers and Goldstein (Neurotherapeutics 9 (1):87-98, 2012). Only a specialized treatment of severely injured patients at dedicated neuro intensive care units [NICU] has been shown to be beneficial Qureshi et al. (Lancet 373(9675):1632-1644, 2009); Suarez et al. (Crit Care Med 32 (11):2311-2317, 2004). Currently, ongoing trials are investigating aggressive blood pressure lowering, hemostatic therapies, different operative strategies, intraventricular thrombolysis as well as neuroprotective approaches, and brain edema therapies. This review will summarize advanced treatment strategies and novel approaches which are currently under investigation.

  17. Hematoma Expansion Following Acute Intracerebral Hemorrhage

    Science.gov (United States)

    Brouwers, H. Bart; Greenberg, Steven M.

    2013-01-01

    Intracerebral hemorrhage, the most devastating form of stroke, has no specific therapy proven to improve outcome by randomized controlled trial. Location and baseline hematoma volume are strong predictors of mortality, but are non-modifiable by the time of diagnosis. Expansion of the initial hematoma is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for hematoma expansion have been identified, including baseline ICH volume, early presentation after symptom onset, anticoagulation, and the CT angiography spot sign. Although the biological mechanisms of hematoma expansion remain unclear, accumulating evidence supports a model of ongoing secondary bleeding from ruptured adjacent vessels surrounding the initial bleeding site. Several large clinical trials testing therapies aimed at preventing hematoma expansion are in progress, including aggressive blood pressure reduction, treatment with recombinant factor VIIa guided by CT angiography findings, and surgical intervention for superficial hematomas without intraventricular extension. Hematoma expansion is so far the only marker of outcome that is amenable to treatment and thus a potentially important therapeutic target. PMID:23466430

  18. Spontaneous Intracerebral Hemorrhage: Computed Tomographic Characteristics and Outcome

    Directory of Open Access Journals (Sweden)

    Aimara de la Caridad Vergara Santos

    2015-12-01

    Full Text Available Background: strokes are the third leading cause of death among adults and 10-15 % of them are due to spontaneous intracerebral hemorrhage. Objective: to characterize spontaneous intracerebral hemorrhage through computed tomography scan and its outcome. Methods: a case series study was conducted comprising patients diagnosed with spontaneous intracerebral hemorrhage admitted to the Arnaldo Milián Castro Provincial University Hospital in Villa Clara from January 2009 to January 2010. Tomographic variables of interest were derived from evaluation of spontaneous intracerebral hematomas. Results: fifty-nine cases of spontaneous intracerebral hemorrhage were studied, 23 were located in lobar regions, 4 had severe midline shift, and 2 showed volume greater than 80 ml. Eight out of eleven with extension into the ventricular system had an unfavorable outcome. Among those with thalamic hemorrhage, patients with diameter larger than 4cm and extension into the ventricular system died. Patients with putaminal hemorrhage larger than 4 cm and posterior fossa hematoma with hydrocephalus had a poor outcome, as well as most individuals (55 with other mass effects. Most lobar hematomas (14 out of 23 had a satisfactory outcome, unlike cerebellar and brainstem hematomas. Conclusions: tomographic variables that had a negative impact on the outcome were: volume greater than 80 ml, severe midline shift, diameter larger than 4 cm, extension into the ventricular system, hydrocephalus, other signs of mass effect and brainstem location.

  19. Brain Perfusion Changes in Intracerebral Hemorrhage

    International Nuclear Information System (INIS)

    Mititelu, R.; Mazilu, C.; Ghita, S.; Rimbu, A.; Marinescu, G.; Codorean, I.; Bajenaru, O.

    2006-01-01

    Full text: Purpose: Despite the latest advances in medical treatment and neuro critical care, patients suffering spontaneous intracerebral hemorrhage (SICH) still have a very poor prognosis, with a greater mortality and larger neurological deficits at the survivors than for ischemic stroke. Many authors have shown that there are many mechanisms involved in the pathology of SICH: edema, ischemia, inflammation, apoptosis. All of these factors are affecting brain tissue surrounding hematoma and are responsible of the progressive neurological deterioration; most of these damages are not revealed by anatomical imaging techniques. The aim of our study was to asses the role of brain perfusion SPECT in demonstrating perfusion changes in SICH patients. Method: 17 SICH pts were studied. All pts underwent same day CT and brain SPECT with 99mTcHMPAO, 24h-5d from onset of stroke. Results: 14/17 pts showed a larger perfusion defect than expected after CT. In 2 pts hematoma diameter was comparable on CT and SPECT; 1pt had quasinormal aspect of SPECT study. In pts with larger defects, SPECT revealed a large cold spot with similar size compared with CT, and a surrounding hypo perfused area. 6/17 pts revealed cortical hyper perfusion adjacent to hypo perfused area and corresponding to a normal-appearing brain tissue on CT. In 3 pts we found crossed cerebellar diaskisis.In 2 pts we found cortical hypo perfused area in the contralateral cortex, with normal appearing brain tissue on CT. Conclusions: Brain perfusion SPECT revealed different types of perfusion changes in the brain tissue surrounding hematoma. These areas contain viable brain tissue that may be a target for future ne uroprotective strategies. Further studies are definitely required to demonstrate prognostic significance of these changes, but we can conclude that brain perfusion SPECT can play an important role in SICH, by early demonstrating functional changes responsible of clinical deterioration, thus allowing prompt

  20. Congenital intracerebral teratoma: a rare differential diagnosis in newborn hydrocephalus

    International Nuclear Information System (INIS)

    Storr, U.; Rupprecht, T.; Bornemann, A.; Ries, M.; Beinder, E.; Boewing, B.; Harms, D.

    1997-01-01

    Cogenital hydrocephalus is caused by a broad spectrum of underlying disorders. In the majority of cases it is due to aqueductal stenosis and other distinct congenital anomalies, like Arnold-Chiari malformation. Nevertheless, in the differential diagnosis rare conditions such as cerebral malignancies must also be considered. We present two cases of congenital intracerebral teratoma as a differential diagnosis in congenital obstructive hydrocephalus. A teratoma is suggested when a rapidly growing hydrocephalus with a central calcified and vascularized mass is found sonographically. Regular cerebral structures using cannot be detected. Early diagnosis in such cases is of clinical importance as the prognosis of congential intracerebral teratoma is generally very poor. (orig.)

  1. Congenital intracerebral teratoma: a rare differential diagnosis in newborn hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Storr, U. [Landratsamt Neuburg-Schrobenhausen, Gesundheitsamt, Neuburg an der Donau (Germany)]|[Hospital for Sick Children, Erlangen-Nuernberg Univ., Nuernberg (Germany); Rupprecht, T. [Hospital for Sick Children, Erlangen-Nuernberg Univ., Nuernberg (Germany); Bornemann, A. [Inst. for General Pathology, Erlangen-Nuernberg Univ., Nuernberg (Germany); Ries, M. [Hospital for Sick Children, Erlangen-Nuernberg Univ., Nuernberg (Germany); Beinder, E. [Dept. of Obstetrics and Gynecology, Erlangen-Nuernberg Univ., Nuernberg (Germany); Boewing, B. [Hospital for Sick Children, Erlangen-Nuernberg Univ., Nuernberg (Germany); Harms, D. [Hospital for Sick Children, Erlangen-Nuernberg Univ., Nuernberg (Germany)

    1997-03-01

    Cogenital hydrocephalus is caused by a broad spectrum of underlying disorders. In the majority of cases it is due to aqueductal stenosis and other distinct congenital anomalies, like Arnold-Chiari malformation. Nevertheless, in the differential diagnosis rare conditions such as cerebral malignancies must also be considered. We present two cases of congenital intracerebral teratoma as a differential diagnosis in congenital obstructive hydrocephalus. A teratoma is suggested when a rapidly growing hydrocephalus with a central calcified and vascularized mass is found sonographically. Regular cerebral structures using cannot be detected. Early diagnosis in such cases is of clinical importance as the prognosis of congential intracerebral teratoma is generally very poor. (orig.)

  2. Spreading depolarizations in patients with spontaneous intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Helbok, Raimund; Schiefecker, Alois Josef; Friberg, Christian

    2017-01-01

    , subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography...... was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3-5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18...

  3. Preexisting cognitive impairment in intracerebral hemorrhage.

    Science.gov (United States)

    Laible, M; Horstmann, S; Möhlenbruch, M; Schueler, S; Rizos, T; Veltkamp, R

    2017-06-01

    Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of ≥3.44; an IQCODE ≥4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. Among the 89 participants, median age was 70 years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS≥3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.

    Science.gov (United States)

    Shanmugam, Victoria K; Tassi, Elena; Schmidt, Marcel O; McNish, Sean; Baker, Stephen; Attinger, Christopher; Wang, Hong; Shara, Nawar; Wellstein, Anton

    2015-12-01

    To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  5. Genetic variants in CETP increase risk of intracerebral hemorrhage

    NARCIS (Netherlands)

    Anderson, C.D.; Falcone, G.J.; Phuah, C.L.; Radmanesh, F.; Brouwers, H.B.; Battey, T.W.; Biffi, A.; Peloso, G.M.; Liu, D.J.; Ayres, A.M.; Goldstein, J.N.; Viswanathan, A.; Greenberg, S.M.; Selim, M.; Meschia, J.F.; Brown, D.L.; Worrall, B.B.; Silliman, S.L.; Tirschwell, D.L.; Flaherty, M.L.; Kraft, P.; Jagiella, J.M.; Schmidt, H.; Hansen, B.M.; Jimenez-Conde, J.; Giralt-Steinhauer, E.; Elosua, R.; Cuadrado-Godia, E.; Soriano, C.; Nieuwenhuizen, K.M. van; Klijn, C.J.M.; Rannikmae, K.; Samarasekera, N.; Salman, R.A.; Sudlow, C.L.; Deary, I.J.; Morotti, A.; Pezzini, A.; Pera, J.; Urbanik, A.; Pichler, A.; Enzinger, C.; Norrving, B.; Montaner, J.; Fernandez-Cadenas, I.; Delgado, P.; Roquer, J.; Lindgren, A.; Slowik, A.; Schmidt, R.; Kidwell, C.S.; Kittner, S.J.; Waddy, S.P.; Langefeld, C.D.; Abecasis, G.; Willer, C.J.; Kathiresan, S.; Woo, D.; Rosand, J.

    2016-01-01

    OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

  6. Genetic variants in CETP increase risk of intracerebral hemorrhage

    NARCIS (Netherlands)

    Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W K; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J.; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M.; Klijn, Catharina J M; Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al Shahi; Sudlow, Catherine L.; Deary, Ian J.; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Kidwell, Chelsea S.; Kittner, Steven J.; Waddy, Salina P.; Langefeld, Carl D.; Abecasis, Goncalo; Willer, Cristen J.; Kathiresan, Sekar; Woo, Daniel; Rosand, Jonathan

    2016-01-01

    Objective: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

  7. Intracerebral Event-related Potentials to Subthreshold Target Stimuli

    Czech Academy of Sciences Publication Activity Database

    Brázdil, M.; Rektor, I.; Daniel, P.; Dufek, M.; Jurák, Pavel

    2001-01-01

    Roč. 112, č. 4 (2001), s. 650-661 ISSN 1388-2457 R&D Projects: GA ČR GA309/98/0490 Institutional research plan: CEZ:AV0Z2065902 Keywords : event-related potentials * intracerebral recordings * oddball paradigm Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.922, year: 2001

  8. CT guided stereotactic evacuation of hypertensive and traumatic intracerebral hematomas

    International Nuclear Information System (INIS)

    Hondo, Hideki; Matsumoto, Keizo

    1983-01-01

    Recent advancement of CT system provides not only definite diagnosis and location of intracerebral hematoma but also coordinates of the center of the hematoma. Trials of stereotactic evacuation of the hematoma have been reported by some authors in the cases of subacute or chronic stages of hypertensive intracerebral hemorrhage. In this series, similar surgery has been performed in 33 cases of hypertensive intracerebral hematoma including 22 cases in acute stage, and 2 cases of traumatic hematoma. Clinical outcomes were investigated and the results were considered to be equivalent or rather better in the conventional microsurgery with evacuation of hematoma under direct vision. However, there still remained controversial problems in the cases of threatened herniation signs, because in these cases regular surgery with total evacuation of the hematoma at one time might have been preferable. The benefits of this CT guided stereotactic approach for the evacuation of the hematoma were thought to be as follow: 1) the procedure is simple and safe, 2) operation is readily performed under local anesthesia, and 3) the hematoma was drained out totally by means of urokinase activity. It is our impression that this surgery not only is indicated as emergency treatment for the patients of high-age or in high risk, but also can institute as a routine surgery for the intracerebral hematomas in patients showing no herniation sign. (J.P.N.)

  9. Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas

    NARCIS (Netherlands)

    Behrouz, R.; Misra, V.; Godoy, D.A.; Topel, C.H.; Masotti, L.; Klijn, C.J.M.; Smith, C.J.; Parry-Jones, A.R.; Slevin, M.A.; Silver, B.; Willey, J.Z.; Vallejo, J. Masjuan; Nzwalo, H.; Popa-Wagner, A.; Malek, A.R.; Hafeez, S.; Napoli, M. Di

    2017-01-01

    BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) volume, particularly if >/=30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL. METHODS: Basic

  10. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, Adrian R.; Di Napoli, Mario; Goldstein, Joshua N.; Schreuder, Floris H B M; Tetri, Sami; Tatlisumak, Turgut; Yan, Bernard; Van Nieuwenhuizen, Koen M.; Dequatre-Ponchelle, Nelly; Lee-Archer, Matthew; Horstmann, Solveig; Wilson, Duncan; Pomero, Fulvio; Masotti, Luca; Lerpiniere, Christine; Godoy, Daniel Agustin; Cohen, Abigail S.; Houben, Rik; Al-Shahi Salman, Rustam; Pennati, Paolo; Fenoglio, Luigi; Werring, David; Veltkamp, Roland; Wood, Edith; Dewey, Helen M.; Cordonnier, Charlotte; Klijn, Catharina J M; Meligeni, Fabrizio; Davis, Stephen M.; Huhtakangas, Juha; Staals, Julie; Rosand, Jonathan; Meretoja, Atte

    2015-01-01

    Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  11. Clinical characteristics and outcome of intracerebral hemorrhage in young adults

    NARCIS (Netherlands)

    Rutten-Jacobs, L.C.A.; Maaijwee, N.A.M.M.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Dijk, E.J. van; Leeuw, F.E. de

    2014-01-01

    Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young adults are scarce. Our aim was to identify clinical determinants of prognosis after ICH in adults aged 18-50. We investigated 98 consecutive patients with an ICH, aged 18-50 years, admitted to our hospital between 1980

  12. Pattern and location of intracerebral hemorrhage in Enugu, South ...

    African Journals Online (AJOL)

    Introduction: The incidence rates and location of nontraumatic intracerebral hemorrhage (ICH) have been shown to vary between population and races. Knowledge of ICH patterns may give some insight into the etiology of ICH and help reduce its burden particularly among Africans where health infrastructure is poorly ...

  13. Intracerebral hemorrhage in children | Zidan | Alexandria Journal of ...

    African Journals Online (AJOL)

    Introduction: Intracerebral hemorrhage (ICH) in children is relatively less common as compared to adults. It could be traumatic or spontaneous. Objective: There are limited studies about ICH in children. In this study, we analyze the etiology, clinical features, management options and outcome assessment in this population.

  14. Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage

    NARCIS (Netherlands)

    Napoli, M. Di; Zha, A.M.; Godoy, D.A.; Masotti, L.; Schreuder, F.H.B.M.; Popa-Wagner, A.; Behrouz, R.

    2016-01-01

    OBJECTIVE: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. METHODS: An analysis of an international, multicenter,

  15. Prognostic Factors for Cognitive Decline After Intracerebral Hemorrhage

    NARCIS (Netherlands)

    Benedictus, M.R.; Hochart, A.; Rossi, C.; Boulouis, G.; Henon, H.; van der Flier, W.M.; Cordonnier, C.

    2015-01-01

    Background and Purpose-Stroke and dementia are closely related, but no prospective study ever focused on poststroke cognitive decline in patients with intracerebral hemorrhage (ICH). We aimed to determine prognostic factors for cognitive decline in patients with ICH. Methods-We prospectively

  16. Pheochromocytoma complicated by intracerebral hemorrhage - a case report

    International Nuclear Information System (INIS)

    Nogueira, Aline Silva; Marchiori, Edson; Almeida, Fabiola Assuncao de; Martins, Renata Romano; Sales, Anderson Ribeiro; Santos, Tereza Cristina C.R.S. dos; Reis, Simone Teixeira; Silveira, Sonia Marcelino T. da

    1999-01-01

    The authors report a case of pheochromocytoma that was complicated by intracerebral hemorrhage in a 17-year-old female patient. Computed tomography showed a solid mass, heterogeneous, on the right adrenal. The patient underwent a right adrenalectomy. She is being observed by our out-patients clinic, presenting normal blood pressure levels and a left hemiparesis. (author)

  17. Pathogenesis of lober intracerebral hemorrhage related to cerebral amyloid angiopathy

    International Nuclear Information System (INIS)

    Sakai, Naoto; Namba, Hiroki; Miura, Katsutoshi; Baba, Satoshi; Isoda, Haruo; Yokoyama, Tetsuo

    2010-01-01

    Cerebral amyloid angiopathy (CAA) is an important cause of lober intracerebral hemorrhage in the elderly. Although leptomeningeal and cortical arteries with the deposition of the amyloid β-protein (Aβ) have been thought to rupture in CAA, the pathogenesis of CAA-related hemorrhage still remains obscure. We studied 10 cases of CAA according to the Boston criteria from April 2006 to July 2009 in Omaezaki Municipal Hospital. Based on clinical data, we examined the primary site of hemorrhage and hypothesized the mechanisms of bleeding. Intracerebral hematoma evacuation was performed to alleviate neurological deteriolation in 2 patients and to make diagnosis in 3 patients. The surgical specimens were pathologically examined. The characteristic MR images of CAA related hemorrhage were characterized by microbleeds, superficial siderosis, subpial or subarachnoid hemorrhage, subcortical hemorrhage and lober intracerebral hemorrhage. Chronological images obtained in 1 patient revealed that lober intracerebral hemorrhage developed from microbleed with subpial hemorrhage without subarachnoid hemorrhage in one side of the cortex in the affected facing cerebral sulci. Operative findings showed subpial and subarachnoid hemorrhages around the cortical veins on the affected cerebral sulci in all cases. Abnormal fragile vessels existed in one side of the cortex of the affected sulci but not in the other side of the cortex. Complete hamatoma evacuation was performed in 4 cases. The surgical specimens of the hematoma and the adjacent brain parenchyma were pathologically examined by tissue staining with hematoxylin-eosin and Congo red. Many vessels in subpial, subcortical and subarachnoid space along the cerebral sulci were deposited with Aβ. From these findings, we speculated that the primary hemorrhage related to CAA occurred from the cortical arteries with Aβ deposition in the subpial space along the cerebral sulci and formed a lober intracerebral hematoma. Subarachnoid

  18. Predictors of intracerebral hemorrhage severity and its outcome in Japanese stroke patients.

    Science.gov (United States)

    Hosomi, Naohisa; Naya, Takayuki; Ohkita, Hiroyuki; Mukai, Mao; Nakamura, Takehiro; Ueno, Masaki; Dobashi, Hiroaki; Murao, Koji; Masugata, Hisashi; Miki, Takanori; Kohno, Masakazu; Kobayashi, Shotai; Koziol, James A

    2009-01-01

    The aim of this investigation was to determine the factors influencing acute intracerebral hemorrhage severity on admission and clinical outcomes at discharge. Sixty acute stroke hospitals throughout Japan participated in the Japan Standard Stroke Registry Study (JSSRS), documenting the in-hospital course of 16,630 consecutive patients with acute stroke from January 2001 to March 2004. We identified 2,840 adult patients from the JSSRS who had intracerebral hemorrhage. Intracerebral hemorrhage severity on admission was strongly related to age, previous stroke history, and hemorrhage size in a monotone fashion [chi(2)(9) = 374.5, p < 0.0001]. Drinking history was also predictive of intracerebral hemorrhage severity on admission, but the association was not monotone. Interestingly, intracerebral hemorrhage severity on admission was increased in nondrinking and heavy drinking compared to mild drinking (p < 0.05). Unsuccessful outcome (modified Rankin scale score = 3-6) was related to age, previous stroke history, hemorrhage size, and intracerebral hemorrhage severity on admission [chi(2)(9) = 830.4, p < 0.0001]. Mortality was related to hemorrhage size, intraventricular hemorrhage, intracerebral hemorrhage severity on admission, and surgical operation [chi(2)(7) = 540.4, p < 0.0001]. We could find four varied factors associated with intracerebral hemorrhage severity and its outcomes. Interestingly, intracerebral hemorrhage severity tended to be greater in nondrinking and heavy drinking than mild drinking. Additionally, surgical operation decreased intracerebral hemorrhage mortality. Copyright 2008 S. Karger AG, Basel.

  19. Contralateral delayed epidural hematoma following intracerebral hematoma surgery

    Science.gov (United States)

    Solomiichuk, Volodymyr O.; Drizhdov, Konstantin I.

    2013-01-01

    Background: Delayed epidural hematoma (EDH) is an uncommon finding in patients after intracranial hematomas evacuation. It occurs in 6.7-7.4% of cases. A total of 29 reports were found in literature. Between them were no cases of delayed contralateral EDH after intracerebral hematoma evacuation. Case Description: This paper represents a clinical case of a 28-year-old male patient with opened penetrating head injury, who underwent left frontal lobe intracerebral hematoma evacuation and one day later a contralateral EDH was found and successfully surgically treated. Conclusion: Contralateral EDH is a life-threatening neurosurgical emergency case, which can occur during first 24 hours after decompressive craniectomy. Control CT scans must be performed next day after the operation to verify and treat contralateral EDH timely. PMID:24233058

  20. Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

    Science.gov (United States)

    Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

    2018-01-01

    Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

  1. [Brazilian guidelines for the manegement of intracerebral hemorrhage].

    Science.gov (United States)

    Pontes-Neto, Octávio M; Oliveira-Filho, Jamary; Valiente, Raul; Friedrich, Maurício; Pedreira, Bruno; Rodrigues, Bruno Castelo Branco; Liberato, Bernardo; Freitas, Gabriel Rodriguez de

    2009-09-01

    Among the stroke subtypes, intracerebral hemorrhage (ICH) has the worst prognosis and still lacks a specific treatment. The present manuscript contains the Brazilian guidelines for the management of ICH. It was elaborated by the executive committee of the Brazilian Cerebrovascular Diseases Society and was based on a broad review of articles about the theme. The text aims to provide a rational for the management of patients with an acute ICH, with the diagnostic and therapeutic resources that are available in Brazil.

  2. [Traumatic intracerebral hemorrhage developing in the apparent course].

    Science.gov (United States)

    Fujiwara, S; Nishimura, A; Yanagida, Y; Nakagawa, K; Mizoi, Y; Tatsuno, Y

    1991-06-01

    The victim, 52 year old man, was thrust down and hit his left occiput against the concrete floor. He was hospitalised and his comatose state continued to the death. On admission, blood pressure was 212/110 mmHg and the computed tomography scan of the head showed only an extensive right subdural hematoma. But the intracerebral hemorrhages in the right frontal, temporal and parietal lobes were recognized 10.5 hours after the trauma. A subdural hematoma was evacuated by operation on the second hospital day. The intracerebellar hemorrhage also appeared 16 hours after the trauma. Blood pressure fluctuated between 160/80 and 200/110 mmHg. The photo of CT scan at 38.5 hours after the trauma showed little subdural hematoma and new intracerebral hemorrhage located in the left temporal lobe. On the third hospital day, he was equipped with a respirator and blood pressure was between 132/84 and 242/100 mmHg. The reaction of the pupils to light disappeared on the 8th hospital day. Blood pressure gradually decreased on the 9th and 10th hospital days and he died on the 11th day. Autopsy revealed a bruise in the left occiput, a linear fracture in the frontal and left parietal bones and a small amount of subdural hematoma on the surface of the right cerebral hemisphere. Cortical contusions were found in the right frontal, the both temporal and the left parietal lobes. Intracerebral hemorrhages were found in the right frontal, the both temporal and the right parietal lobes. Intracerebellar hemorrhage was also found. Cardiac hypertrophy and atherosclerosis of the aorta were recognized. We thought that small hemorrhages which were not clearly detectable by CT scan immediately after injury may have developed into massive intracerebral and intracerebellar hemorrhages due to high blood pressure after a hospitalization.

  3. Transcranial Duplex Sonography Predicts Outcome following an Intracerebral Hemorrhage.

    Science.gov (United States)

    Camps-Renom, P; Méndez, J; Granell, E; Casoni, F; Prats-Sánchez, L; Martínez-Domeño, A; Guisado-Alonso, D; Martí-Fàbregas, J; Delgado-Mederos, R

    2017-08-01

    Several radiologic features such as hematoma volume are related to poor outcome following an intracerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage. We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs. We correlated these data with the CT scans and assessed the prognostic value of the transcranial duplex sonography measurements. We assessed early neurologic deterioration during hospitalization and mortality at 1-month follow-up. We included 35 patients with a mean age of 72.2 ± 12.8 years. Median baseline hematoma volume was 9.85 mL (interquartile range, 2.74-68.29 mL). We found good agreement and excellent correlation between transcranial duplex sonography and CT when measuring hematoma volume ( r = 0.791; P duplex sonography measurements showed that hematoma volume was an independent predictor of early neurologic deterioration (OR, 1.078; 95% CI, 1.023-1.135) and mortality (OR, 1.089; 95% CI, 1.020-1.160). A second regression analysis with CT variables also demonstrated that hematoma volume was associated with early neurologic deterioration and mortality. When we compared the rating operation curves of both models, their predictive power was similar. Transcranial duplex sonography showed an excellent correlation with CT in assessing hematoma volume and midline shift in patients with intracerebral hemorrhage. Hematoma volume measured with transcranial duplex sonography was an independent predictor of poor outcome. © 2017 by American Journal of Neuroradiology.

  4. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

    Science.gov (United States)

    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-12-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  5. Radio-adjuvant effects of ginsan on murine breast carcinoma xenografted model

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ji Young; Son, Hyeog Jin; Kim, Hyung Doo; Han, Young Soo; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    In a number of studies, polysaccharide extracted from Panax ginseng C.A. Meyer, ginsan has been demonstrated to be a potent promising biological response modifier (BRM), including proliferation of lymphocyte, generation of lymphokine activated killer cells, and production of several cytokines. Macrophages are the first line of defense to infections or pathogens in host innate immunity. In addition, it plays a prominent role as a professional antigen presenting cells to trigger cellular immunity. In the light of that, the current study was designed to evaluate whether ginsan exhibits anti-tumor effect as well as synergistic function with chemo- or radio-therapy.

  6. A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Ryan W Carroll

    Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

  7. In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

    Science.gov (United States)

    Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

    2017-03-01

    Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

  8. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Science.gov (United States)

    2010-04-01

    ... pain relief. 882.5840 Section 882.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical current...

  9. Mortality after primary intracerebral hemorrhage in relation to post-stroke seizures

    NARCIS (Netherlands)

    Claessens, D.; Bekelaar, K.; Schreuder, F.H.B.M.; Greef, B.T.A. de; Vlooswijk, M.C.G.; Staals, J.; Oostenbrugge, R.J. van; Rouhl, R.P.W.

    2017-01-01

    Seizures after intracerebral hemorrhage are repeatedly seen. Whether the development of seizures after intracerebral hemorrhage affects survival in the long term is unknown. This study aims to determine the relation between seizures (i.e., with and without anti-epileptic therapy) and long-term

  10. Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors

    DEFF Research Database (Denmark)

    Persson, Bertil R R; Koch, Catrin Bauréus; Grafström, Gustav

    2010-01-01

    Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumor...

  11. Unclear-onset intracerebral hemorrhage: Clinical characteristics, hematoma features, and outcomes.

    Science.gov (United States)

    Inoue, Yasuteru; Miyashita, Fumio; Koga, Masatoshi; Minematsu, Kazuo; Toyoda, Kazunori

    2017-12-01

    Background and purpose Although unclear-onset ischemic stroke, including wake-up ischemic stroke, is drawing attention as a potential target for reperfusion therapy, acute unclear-onset intracerebral hemorrhage has been understudied. Clinical characteristics, hematoma features, and outcomes of patients who developed intracerebral hemorrhage during sleep or those with intracerebral hemorrhage who were unconscious when witnessed were determined. Methods Consecutive intracerebral hemorrhage patients admitted within 24 hours after onset or last-known normal time were classified into clear-onset intracerebral hemorrhage and unclear-onset intracerebral hemorrhage groups. Outcomes included initial hematoma volume, initial National Institutes of Health Stroke Scale score, hematoma growth on 24-hour follow-up computed tomography, and vital and functional prognoses at 30 days. Results Of 377 studied patients (122 women, 69 ± 11 years old), 147 (39.0%) had unclear-onset intracerebral hemorrhage. Patients with unclear-onset intracerebral hemorrhage had larger hematoma volumes (p = 0.044) and higher National Institutes of Health Stroke Scale scores (p Hematoma growth was similarly common between the two groups (p = 0.176). There were fewer patients with modified Rankin Scale (mRS) scores of 0-2 (p = 0.033) and more patients with mRS scores of 5-6 (p = 0.009) and with fatal outcomes (p = 0.049) in unclear-onset intracerebral hemorrhage group compared with clear-onset intracerebral hemorrhage as crude values, but not after adjustment. Conclusions Patients with unclear-onset intracerebral hemorrhage presented with larger hematomas and higher National Institutes of Health Stroke Scale scores at emergent visits than those with clear-onset intracerebral hemorrhage, independent of underlying characteristics. Unclear-onset intracerebral hemorrhage patients showed poorer 30-day vital and functional outcomes than clear-onset intracerebral hemorrhage patients

  12. Pathomechanism of ring enhancement in intracerebral hematomas on CT

    International Nuclear Information System (INIS)

    Takasugi, Shinsuke; Kageyama, Takefumi; Yamashita, Shigeru; Kusaka, Kazumasa; Ueda, Shin

    1980-01-01

    As a simulation of hypertensive intracerebral hematoma, about 3.5 ml of autologus venous blood were injected into an artificial cavity of a unilateral cerebral hemisphere in dogs. The cavity was made by the insertion and inflation of a balloon canula near the basal ganglia region of the dog. At the acute stage after the injection, the hematoma showed a round-shaped and homogeneous high density. 9 days later, a positive ring enhancement appeared around this high-density area in most of the cases. Subsequently, the hematoma changed into an isodensity with a tendency toward the concentric concentration of the ring enhancement and to the final low-density stage with a spotted enhancement in the center. That is our experimental intracerebral hematoma of the dog showed a pattern of the chronological course of the CT appearance quite similar to that of clinical cases of hypertensive intracerebral hematomas. At the onset of the ring enhancement, many new and immature capillaries were noted in the adjacent tissue of the hematoma, corresponding to the positive enhancement. The new capillaries were gradually shifted to the center of the hematoma; the enhancement also coincided with them. The ultrastructures of these new capillaries were examined electronmicroscopically. There was some resemblance to the capillaries of muscle with many pinocytotic vesicles and shallowed tight junctions. These experimental facts suggest that the enhancement phenomenon occurred in close relationship to the newly produced hypervascularization of the capillaries around the hematoma, which was a phenomenon of the healing process of the lesion. Therefore, the pathomechanism of the enhancement was thought to be involved the pooling of the contrast media in the increased vascular bed as well as a loss of blood brain barrier in these newly produced immature capillaries. (J.P.N.)

  13. CT-guided stereotactic evacuation of hypertensive intracerebral hematomas

    International Nuclear Information System (INIS)

    Hondo, Hideki

    1983-01-01

    Computerized tomography (CT) is now effective not only for definite diagnosis and location of intracerebral hematomas but also for coordination of the center of a hematoma. CT-guided stereotactic evacuation of hypertensive intracerebral hematoma was performed in 51 cases: 34 of basal ganglionic hematoma with or without ventricular perforation, 11 of subcortical hematoma, 3 of thalamic hematoma and 3 of cerebellar hematoma. Three dimensional CT images or biplane CT images were taken to determine the coordinates of the target point, which was the center of the hematoma. Then, a silicon tube (O.D. 3.5 phi, I.D. 2.1 phi) was inserted into the center of the hematoma through a burr-hole under local anesthesia, and the liquid or solid hematoma was aspirated as completely as possible with a syringe. Urokinase (6,000 I.U./5 ml saline) was administered through this silicon tube every 6 or 12 hours for several days until the hematoma had drained out competely. The silicon tube was taken out when repeated CT scanning revealed no hematoma. The results of clinical follow-ups indicated that this procedure is as good as, or rather better than conventional microsurgery with evacuation of hematoma under direct vision. Moreover this CT-guided stereotactic approach for evacuation of the hematoma has the following advantages: 1) the procedure is simple and safe, 2) operation can be performed under local anesthesia, and 3) the hematoma is drained out completely with the aid of urokinase. This surgery seems indicated as an emergency treatment for high-age or high risk patients and also as a routine surgery for intracerebral hematomas in patients showing no herination signs. (author)

  14. Outcomes after endoscopic port surgery for spontaneous intracerebral hematomas.

    Science.gov (United States)

    Ochalski, Pawel; Chivukula, Srinivas; Shin, Samuel; Prevedello, Daniel; Engh, Johnathan

    2014-05-01

    Spontaneous intracerebral hemorrhages (ICHs) cause significant morbidity and mortality. Traditional open surgical management strategies offer limited benefit except for the most superficial hemorrhages in select patients. Recent reports suggest that endoscopic approaches may improve outcomes, particularly for deep subcortical hemorrhages. However, the management of these patients remains controversial. We reviewed our experience using endoscopic port surgery to identify characteristics that may predict acceptable outcomes. We completed a retrospective chart and imaging review of patients who underwent endoscopic port surgery for evacuation of spontaneous ICH at a single center. Data were gathered regarding patient demographics, hemorrhage locations, operative findings, and clinical outcomes. From 2007 to 2011, 18 patients underwent evacuation of spontaneous intracerebral hematomas using an endoscopic port. The mean age in years was 62 years (range, 43-84 years). Six of 18 patients (33%) died before discharge, and 2 others (11%) died after at least 1 month of survival. Of 12 initial survivors, all were discharged to a rehabilitation or nursing facility. Complete hematoma evacuation was achieved in 7 of 18 patients, with the remaining 11 having a partial evacuation. The patients who died (n = 6) before discharge were statistically more likely to have a left-sided hemorrhage, partial evacuation, or older age than the survivors; death at least 1  month after evacuation was additionally associated with greater preoperative hematoma volumes. Our series demonstrates that endoscopic port surgery for acute intracerebral hematoma evacuation has the ability to achieve significant decompression of large and deep-seated hematomas. Patient age, extent of evacuation, laterality, and preoperative hematoma volume appear to influence patient outcome. Most overall outcomes remain poor. Future studies are necessary to determine if surgical evacuation is in fact superior to best

  15. Evaluation of intracerebral hematoma resorption dynamics with computed tomography

    International Nuclear Information System (INIS)

    Strzesniewski, P.; Lasek, W.; Serafin, Z.; Ksiazkiewicz, B.; Wanat-Slupska, E.

    2004-01-01

    High mortality and severe grade of disability observed in patients after intracerebral hemorrhage provide efforts to improve diagnostics and therapy of the hemorrhagic cerebral stroke. An aim of this paper was an evaluation of blood resorption dynamics in patients with intracerebral hematoma, performed with computed tomography of the head and an analysis of clinical significance of this process. An examined group included 133 patients with intracerebral hematoma proven by a CT exam. In 97 patients resorption of the hematoma was measured, based on control scans taken on 15 th and 30 th day on average. Volume of the hemorrhagic foci was measured as well as the width of ventricles and the displacement of medial structures. The mean hematoma volume reached 11,59 ml after 15 days, and 3,16 m after 30 days (average decrease of the volume 0,67 ml/day). There was a significant difference in the rate of resorption between the first (0-15 days) and the second (15-30 days) observation period - 0,78 and 0,62 ml/day respectively. The dynamics of the process was dependent on volume and localization of the hematoma and independent of the grade of displacement and compression of the ventricles. The calculated mean rate of the hematomas resorption enables to schedule control examinations precisely. The significant differences of the dynamics of blood resorption depending on hematomas size and the independence of compression and displacement of ventricular system suggest, that the most important factor in therapeutic decision-making should be a clinical status of the patient. (author)

  16. Calcified subdural hematoma associated with hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Ishige, Naoki; Sunami, Kenro; Sato, Akira; Watanabe, Osamu

    1984-01-01

    A case of calcified subdural hematoma associated with hypertensive intracerebral hemorrhage is reported. A left frontal subdural hematoma with left putaminal hemorrhage was incidentally found when a CT scan was performed to evaluate right hemiparesis and aphasia in a 55-year-old man. The putaminal hemorrhage was not very extensive, but his clinical symptoms were rather serious. Not only the putaminal hemorrhage, but also the presence of the calcified subdural hematoma was considered to have caused his clinical deterioration. The subtotal removal of the calcified subdural hematoma brought about a good result. (author)

  17. Early MR abnormality indicating functional recovery from spontaneous intracerebral hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Fumeya, Hiroshi; Hideshima, Hiroshi [Hideshima Hospital, Musashino, Tokyo (Japan)

    1991-10-01

    Magnetic resonance (MR) imaging as an indicator of recovery from hemiparesis was evaluated in 60 patients with spontaneous intracerebral hemorrhage. T{sub 2}-weighted MR images revealed early MR abnormality (EMA) of the corticospinal tract within 1 week of ictus. Most patients without EMA recovered beyond Brunnstrom's Recovery Stage 3 while only a few patients with EMA did so. Patients with EMA cannot regain motor function because EMA is almost always followed by complete tract degeneration. EMA in the brainstem and poor motor function recovery are closely correlated. (author).

  18. Early MR abnormality indicating functional recovery from spontaneous intracerebral hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Fumeya, Hiroshi; Hideshima, Hiroshi (Hideshima Hospital, Musashino, Tokyo (Japan))

    1991-10-01

    Magnetic resonance (MR) imaging as an indicator of recovery from hemiparesis was evaluated in 60 patients with spontaneous intracerebral hemorrhage. T{sub 2}-weighted MR images revealed early MR abnormality (EMA) of the corticospinal tract within 1 week of ictus. Most patients without EMA recovered beyond Brunnstrom's Recovery Stage 3 while only a few patients with EMA did so. Patients with EMA cannot regain motor function because EMA is almost always followed by complete tract degeneration. EMA in the brainstem and poor motor function recovery are closely correlated. (author).

  19. Brain alpha- and beta-globin expression after intracerebral hemorrhage

    OpenAIRE

    He, Yangdong; Hua, Ya; Lee, Jin-Yul; Liu, Wenquan; Keep, Richard F; Wang, Michael M.; Xi, Guohua

    2010-01-01

    Our recent study has demonstrated that hemoglobin (Hb) is present in cerebral neurons and neuronal Hb is inducible after cerebral ischemia. In the present study, we examined the effects of intracerebral hemorrhage (ICH) on the mRNA levels of the α-globin (HbA) and the β-globin (HbB) components of Hb and Hb protein in the brain in vivo and in vitro. In vivo, male Sprague-Dawley rats received either a needle insertion (sham) or an infusion of autologous whole blood into the basal ganglia and we...

  20. Aging exacerbates intracerebral hemorrhage-induced brain injury.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

    2009-09-01

    Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

  1. A case of repeated intracerebral hemorrhages secondary to ventriculoperitoneal shunt

    Directory of Open Access Journals (Sweden)

    Jinbing Zhao

    2015-03-01

    Full Text Available Ventriculoperitoneal shunt is a routinely performed treatment in neurosurgical department. Intracerebral hemorrhage, as a complication after shunt catheterization, is really rare but with high mortality. In this study, we reported a case of a 74-year-old man who suffered from repeated intracerebral hemorrhage after ventriculoperitoneal shunt. The first hemorrhage happened 63 h after the 1st surgery, and most hematomas were located in the ipsilateral occipital lobe and intraventricles, along the ventricular catheter. Fresh blood clot casts blocked the external ventricular draining catheter, which was inserted into the right front horn during the 3rd surgery, indicating new intraventricular bleeding happened. A large hematoma in ipsilateral frontal lobe was detected on the 3rd day after the removal of external ventricular draining catheter. Different hemorrhagic locations and time points were encountered on the same case. We discussed the possible causes of repeated hemorrhage for this case, and the pre-operative preparation including risk evaluation in future clinical work.

  2. Surgical Outcome in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Rendevski Vladimir

    2017-12-01

    Full Text Available The aim of the paper was to evaluate the surgical outcome in patients with spontaneous supratentorial intracerebral hemorrhage (ICH after surgical intervention, in respect to the initial clinical conditions, age, sex, hemispheric side and anatomic localization of ICH. Thirty-eight surgically treated patients with spontaneous supratentorial intracerebral hemorrhage were included in the study. The surgical outcome was evaluated three months after the initial admission, according to the Glasgow Outcome Scale (GOS. The surgical treatment was successful in 14 patients (37%, whereas it was unsuccessful in 24 patients (63%. We have detected a significant negative correlation between the Glasgow Coma Scale (GCS scores on admission and the GOS scores after three months, suggesting worse neurological outcome in patients with initially lower GCS scores. The surgical outcome in patients with ICH was not affected by the sex, the hemispheric side and the anatomic localization of ICH, but the age of the patients was estimated as a significant factor for their functional outcome, with younger patients being more likely to be treated successfully. The surgical outcome is affected from the initial clinical state of the patients and their age. The treatment of ICH is still an unsolved clinical problem and the development of new surgical techniques with larger efficiency in the evacuation of the hematoma is necessary, thus making a minimal damage to the normal brain tissue, as well as decreasing the possibility of postoperative bleeding.

  3. Hematoma Locations Predicting Delirium Symptoms After Intracerebral Hemorrhage.

    Science.gov (United States)

    Naidech, Andrew M; Polnaszek, Kelly L; Berman, Michael D; Voss, Joel L

    2016-06-01

    Delirium symptoms are associated with later worse functional outcomes and long-term cognitive impairments, but the neuroanatomical basis for delirium symptoms in patients with acute brain injury is currently uncertain. We tested the hypothesis that hematoma location is predictive of delirium symptoms in patients with intracerebral hemorrhage, a model disease where patients are typically not sedated or bacteremic. We prospectively identified 90 patients with intracerebral hemorrhage who underwent routine twice-daily screening for delirium symptoms with a validated examination. Voxel-based lesion-symptom mapping with acute computed tomography was used to identify hematoma locations associated with delirium symptoms (N = 89). Acute delirium symptoms were predicted by hematoma of right-hemisphere subcortical white matter (superior longitudinal fasciculus) and parahippocampal gyrus. Hematoma including these locations had an odds ratio for delirium of 13 (95 % CI 3.9-43.3, P delirium symptoms. Higher odds ratio for delirium was increased due to hematoma location. The location of neurological injury could be of high prognostic value for predicting delirium symptoms.

  4. Evaluation of Intraventricular Hemorrhage in Pediatric Intracerebral hemorrhage

    Science.gov (United States)

    Kleinman, Jonathan T; Beslow, Lauren A; Engelmann, Kyle; Smith, Sabrina E; Licht, Daniel J; Ichord, Rebecca N; Jordan, Lori C

    2012-01-01

    Previous studies of pediatric intracerebral hemorrhage have investigated isolated intraparenchymal hemorrhage. We investigated whether detailed assessment of intraventricular hemorrhage enhanced outcome prediction after intracerebral hemorrhage. We prospectively enrolled 46 children, full-term to 17 years, median age 2.7 years with spontaneous intraparenchymal hemorrhage and/or intraventricular hemorrhage. Outcome was assessed with the King’s Outcome Scale for Childhood Head Injury. Twenty-six (57%) had intraparenchymal hemorrhage, 10 (22%) had pure intraventricular hemorrhage, and 10 (22%) had both. There were 2 deaths, both with intraparenchymal hemorrhage + intraventricular hemorrhage volume ≥4% of total brain volume. Presence of intraventricular hemorrhage was not associated with poor outcome, but hydrocephalus showed a trend (p=0.09) toward poor outcome. In receiver operating characteristic curve analysis, combined intraparenchymal hemorrhage + intraventricular hemorrhage volume also showed a trend toward better outcome prediction than intraparenchymal hemorrhage volume alone. Although not an independent outcome predictor, future studies should assess intraventricular hemorrhage qualitatively and quantitatively. PMID:22068828

  5. Physicochemical characterization of two deproteinized bovine xenografts

    Directory of Open Access Journals (Sweden)

    Thais Accorsi-Mendonça

    2008-03-01

    Full Text Available Calcium phosphate salts, or more specifically hydroxyapatite, are products of great interest in the fields of medical and dental science due to their biocompatibility and osteoconduction property. Deproteinized xenografts are primarily constituted of natural apatites, sintered or not. Variations in the industrial process may affect physicochemical properties and, therefore, the biological outcome. The purpose of this work was to characterize the physical and chemical properties of deproteinized xenogenic biomaterials, Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland and Gen-Ox (Baumer S.A., Brazil, widely used as bone grafts. Scanning electron microscopy, infrared region spectroscopy, X-ray diffraction, thermogravimetry and degradation analysis were conducted. The results show that both materials presented porous granules, composed of crystalline hydroxyapatite without apparent presence of other phases. Bio-Oss presented greater dissolution in Tris-HCl than Gen-Ox in the degradation test, possibly due to the low crystallinity and the presence of organic residues. In conclusion, both commercial materials are hydroxyapatite compounds, Bio-Oss being less crystalline than Gen-Ox and, therefore, more prone to degradation.

  6. Diagnostic usefulness of periIesional edema around intracerebral hemorrhage in predicting underlying causes

    International Nuclear Information System (INIS)

    Yim, Nam Yeol; Seo, Jeong Jin; Yoon, Woong; Shin, Sang Soo; Lim, Hyo Soon; Chung, Tae Woong; Jeong, Gwang Woo; Kang, Heoung Keun

    2004-01-01

    We attempted to evaluate the diagnostic usefulness of the degree of perilesional edema around intracerebral hematoma in predicting the underlying cause. This study included 54 patients with intracerebral hematoma for whom the underlying cause was confirmed by biopsy, radiological or clinical methods. Cases of subarachnoid hemorrhage, hemorrhagic transformation of cerebral infarction and intraventricular hemorrhage were excluded. The lesion size was defined as the average value of the longest axis and the axis perpendicular to this. The size of the perilesional edema was defined as the longest width of the edema. In all cases, the sizes of the lesion and edema were measured on the T2 weighted image. We defined the edema ratio as the edema size divided by the lesion size. 23 cases were diagnosed as intracerebral hemorrhage due to neoplastic conditions, such as metastasis (n=17), glioblastoma (n=5), hemangioblastoma (n=1). 31 cases were caused by non-neoplastic conditions, such as spontaneous hypertensive hemorrhage (n=23), arteriovenous malformation (n=4), cavernous angioma (n=3), and moya-moya disease (n=1). In fourteen cases, which were confirmed as malignant intracerebral hemorrhage, the edema ratio was more than 100%. Of the other cases, only 8 were confirmed as malignant intracerebral hemorrhage. It was found that the larger the edema ratio, the more malignant the intracerebral hemorrhage, and this result was statistically significant (p<0.001). Measurement of perilesional edema and the intracerebral hematoma ratio may be useful in predicting the underlying causes

  7. Global Conservation of Protein Status between Cell Lines and Xenografts

    Directory of Open Access Journals (Sweden)

    Julian Biau

    2016-08-01

    Full Text Available Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.

  8. Comparison of computer tomography and magnetic resonance tomography in the diagnosis of intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Kuhn, S.; Elste, V.; Sartor, K.; Reith, W.; Ertl-Wagner, B.; Muenchen Univ.

    1999-01-01

    Background and Purpose: Stroke symptoms are caused in 10 to 15% by intracerebral hemorrhage. From the clinical examination it is often impossible to differentiate intracerebralhemorrhage from cerebral ischemia. To exclude intracerebral hemorrhage as the cause of clinical symptoms a CT is usually performed. The aim of our study was a direct comparison of the sensitivity of Computed Tomography and MRI using different MR sequences for the detection of acute intracerebral hemorrhage. Methods: In 8 male Wistar rats intracerebral hemorrhage was induced by infusion of collagenase into the caudate nucleus. After 1 hour the brains were subsequently imaged with CT and MRI using T2- and T1-weighted Spin Echo sequences, diffusion-weighted sequences, T2*-weighted gradient echo sequences and FLAIR-sequences. Visibility of the intracerebral hemorrhage was examined using a scoring system for 1=not visible to 5=excellent visible. Finally, the intracerebral hemorrhage was verified by histological staining. Results: In all animals, intracerebral hemorrhage was visible in T2*-weighted gradient echo and diffusion weighted MR images 1 h after infusion of collagenase. T2- and PD-weighted SE images were positive in 7/8 rats. T1-weighted images revealed signal changes in 5/8 rats, and FLAIR sequence was positive in 8/8 rats. In CT intracerebral hemorrhage was only visible in 3/8 rats. When measuring the increase of Hounsfield units within the suspected hemisphere we saw a mean increase of 7% compared to the normal hemisphere in 3/8 rats. Conclusions: In this animal model, T2*-weighted magnetic resonance imaging proved to be the most sensitive imaging modality in the detection of acute intracerebral hemorrhage and is by far more sensitive than CT. (orig.) [de

  9. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  10. Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

    Science.gov (United States)

    Morotti, Andrea; Paciaroni, Maurizio; Zini, Andrea; Silvestrelli, Giorgio; Del Zotto, Elisabetta; Caso, Valeria; Dell'Acqua, Maria Luisa; Simone, Anna Maria; Lanari, Alessia; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Gamba, Massimo; Ciccone, Alfonso; Ritelli, Marco; Di Castelnuovo, Augusto; Iacoviello, Licia; Colombi, Marina; Agnelli, Giancarlo; Grassi, Mario; de Gaetano, Giovanni; Padovani, Alessandro; Pezzini, Alessandro

    2016-08-01

    Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level. Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression. During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; Prisk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level. © 2016 American Heart Association, Inc.

  11. [MRI semiotics features of experimental acute intracerebral hematomas].

    Science.gov (United States)

    Burenchev, D V; Skvortsova, V I; Tvorogova, T V; Guseva, O I; Gubskiĭ, L V; Kupriianov, D A; Pirogov, Iu A

    2009-01-01

    The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.

  12. Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa

    2016-01-01

    BACKGROUND AND PURPOSE: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH...... remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were...... taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood...

  13. Bilateral hypertensive intracerebral hemorrhage diagnosed by CT scan

    International Nuclear Information System (INIS)

    Miyasaka, Yoshio; Nakayama, Kenji; Matsumori, Kuniaki

    1982-01-01

    Five (9.6%) of 52 cases of supretentorial hypertensive intracerebral hemorrhage which suffered rehemorrhage in the contralateral regions were analyzed in the present study, and the 28 cases reported since 1950 were reviewed. The literature suggests that the time between the first hemorrhage and the second was quite long. However, the present series showed that re-hemorrhage in the contralateral side developed within one month in three out of five cases. In case 1, hemorrhages developed almost simultaneously in the left thalamus and in the right putamen. Three characteristics were observed: The symptoms including hemiparesis and/or hemispheric signs related to the first hemorrhage had a tendency to exacerbate after the second attack in other the contralateral region in the second attack, symptoms excessively severe for the size of the hematoma developed. Finally, the clinical course after the second hemorrhage was poor. (author)

  14. Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

    Science.gov (United States)

    Behrouz, Réza; Misra, Vivek; Godoy, Daniel A; Topel, Christopher H; Masotti, Luca; Klijn, Catharina J M; Smith, Craig J; Parry-Jones, Adrian R; Slevin, Mark A; Silver, Brian; Willey, Joshua Z; Masjuán Vallejo, Jaime; Nzwalo, Hipólito; Popa-Wagner, Aurel; Malek, Ali R; Hafeez, Shaheryar; Di Napoli, Mario

    2017-06-01

    Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome. Among 375 cases of supratentorial ICH with volumes hematomas <30 mL expands, leading to END or death. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Prophylaxis of venous thrombosis in patients with spontaneous intracerebral bleeding

    Directory of Open Access Journals (Sweden)

    Emanuele Rezoagli

    2011-08-01

    Full Text Available Spontaneous intracerebral haemorrhage (SIH represents a severe clinical event that is associated with high rates of mortality and morbidity. Only a minority of SIH patients receive surgical treatment, whereas the majority are treated conservatively. Venous thromboembolism (VTE is one of the most common complications in SIH patients and a potential cause of death. Because of the lack of adequate evidences from the literature, the risk to benefit ratio of pharmacologic prophylaxis of VTE, represented on the one hand by hematoma enlargement and/or rebleeding and on the other hand by an expected reduction of the risk of VTE, remains controversial. Mechanical prophylaxis is a potentially safer alternative, but the efficacy of this approach is uncertain. In the absence of specific clinical guidelines containing clear-cut recommendations, physicians have insufficient tools to assist their therapeutic decisions.

  16. Causes and clinical characteristics of spontaneous intracerebral hemorrhage in children

    Directory of Open Access Journals (Sweden)

    Yan-ju MENG

    2014-01-01

    Full Text Available In this study, clinical data of 31 patients in childhood with spontaneous intracerebral hemorrhage (SICH were retrospectively analyzed. According to various imaging examinations (CT, MRI, CTA, MRA and DSA, 22 cases (70.97% had definite causes, including 9 cases (29.03% with intracranial arteriovenous malformation, 6 cases (19.35% with cavernous hemangioma, 3 cases (9.68% with hematopathy, 2 cases (6.45% with tumor apoplexy, one case (3.23% with intracranial aneurysm and one case (3.23% with moyamoya disease; 9 cases (29.03% had unclear causes. All cases were timely diagnosed and treated. Among all the patients, 23 cases (74.19% were cured with good prognosis, 6 cases (19.35% improved, and the other 2 cases (6.45% died. Therefore, primary diseases should be timely treated as hematoma was removed.

  17. CT guided stereotactic evacuation for hypertensive intracerebral hematoma

    International Nuclear Information System (INIS)

    Nakajima, Hideo

    1990-01-01

    Sixty-one cases of hypertensive intracerebral hematoma were evacuated by CT guided stereotactic method. The operation was performed in the CT room under general anesthesia using the KOMAI-NAKAJIMA STEREOTACTIC DEVICE. This instrument has a micromanipulater that can be used for various kinds of stereotactic procedures. Three dimensional position of the target point (aspiration point of the hematoma) was determined on the film obtained from CT scanning of the patient in the stereotactic system. If the hematoma was small, the target point was enough to be one point at the center of the hematoma, but in case of the large hematoma, several target points were given according to the shape of hematoma. The probe, ordinarily a steel tube 4 mm in outer diameter, was inserted through brain to the target point and the hematoma was aspirated through a silicon tube connected to a vacuum system. Among 61 cases examined, 30 cases of thalamic hemorrhage were operated upon and 36 cases were not operated. They were classified according to the volume of hematoma into 3 groups as follows: A=less than 10 ml, B=11-25 ml, C=more than 25 ml. The operated cases were compared with the non operated cases on the improvement of consciousness in each group. In the A group, the operated patients in the level I recovered more slowly than the non operated patients, but in the level II patients, this was reversed. In the B group, the operated patients improved more quickly except the level I patients. In the C group, almost all of non operated patients died. Thus, this operation was very useful in improving consciousness of level II or III patients independent of hematoma volume. It accelerated the recovery of motor function in the level I. This non inversive technique is considered effective for the removal of deep intracerebral hematoma. (author)

  18. Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II Protocol

    Directory of Open Access Journals (Sweden)

    Rowan Elise N

    2011-05-01

    Full Text Available Abstract Background Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively. There is equipoise about the management of patients between these two extremes. In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation. The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment. Methods/Design an international multicentre randomised parallel group trial. Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible. All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage (≤1 cm from the cortex surface of the brain and 10-100 ml in volume. Any clotting or coagulation problems must be corrected and randomisation must take place within 48 hours of ictus. With 600 patients, the study will be able to demonstrate a 12% benefit from surgery (2p Stratified randomisation is undertaken using a central 24 hour randomisation service accessed by telephone or web. Patients randomised to early surgery should have the operation within 12 hours. Information about the status (Glasgow Coma Score and focal signs of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days (+/- 2 days. Outcome is measured at six months via a postal questionnaire to the patient. Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale. Secondary outcomes include: Mortality, Rankin, Barthel, EuroQol, and Survival. Trial

  19. Evaluation of permselective membranes for optimization of intracerebral amperometric glutamate biosensors

    NARCIS (Netherlands)

    Wahono, N.; Qin, S.; Oomen, P.; Cremers, T. I. F.; de Vries, M. G.; Westerink, B. H. C.

    2012-01-01

    Monitoring of extracellular brain glutamate concentrations by intracerebral biosensors is a promising approach to further investigate the role of this important neurotransmitter. However, amperometric biosensors are typically hampered by Faradaic interference caused by the presence of other

  20. Time Course of Early Postadmission Hematoma Expansion in Spontaneous Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Ovesen, Christian; Christensen, Anders Fogh; Krieger, Derk W

    2014-01-01

    spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal...

  1. Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

    DEFF Research Database (Denmark)

    Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

    2016-01-01

    inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality......BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage...... and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were...

  2. The analysis of initial cranial CT of early hematoma enlargement in spontaneous intracerebral hemorrhage

    OpenAIRE

    BEI Yu-zhang; CHEN Ben-yang; QI Hao-bo; ZHOU Zheng-ping; LI Yu-bo

    2012-01-01

    Objective To investigate the predictive effect of initial cranial CT on early hematoma enlargement in spontaneous intracerebral hemorrhage. Methods Three hundred patients with spontaneous intracerebral hemorrhage within 6 hours after onset were studied. Chi-square test and logistic regression analysis were used to detect the related factors which may indicate hematoma enlargement. Results Sixty-one (20.33% ) patients presented hematoma enlargement on cranial CT. Single factor and multivariate...

  3. Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design.

    Science.gov (United States)

    Liu, Liping; Wang, Yilong; Meng, Xia; Li, Na; Tan, Ying; Nie, Ximing; Liu, Dacheng; Zhao, Xingquan

    2017-04-01

    Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

  4. Analysis of angiographic findings in cerebral arteriovenous malformation with hemorrhage: comparison between intracerebral and intraventricular hemorrhage

    International Nuclear Information System (INIS)

    Kim, Jae Kyun; Kim, Joon Hyung; Kwon, Jin Sook; Yoon, Soo Woong; Lee, Ho Kyu; Choi, Choong Gon; Suh, Dae Chul

    1998-01-01

    The purpose of this study was to analyze the angioarchitectures of cerebral arteriovenous malformation (AVM) and to determine whether there was correlation between angioarchitectures and patterns of intracranial hemorrhage (intracerebral, intraventricular, and both) in cerebral AVM. One hundred and twenty-eight patients who between November 1989 and December 1994 suffered supratentorial AVM with intracranial hemorrhage were studied retrospectively. Among 128 patients, intracerebral and intraventricular hemorrhage were seen in 68(53%) and 24 patients(19%), respectively, while both types were seen in the remaining 36 (28%). We analyzed the angioarchitectual characteristics of AVM, namely nidi, feeding arteries and draining veins, in three hemorrhagic groups of patients with intracerebral hemorrhage, intraventricular hemorrhage and both. The X 2 test or Fisher's exact test was used for statistical analysis. A cortically located nidus was most common in patients with intracerebral hemorrhage, while a periventricular location was most common in those with intraventricular hemorrhage (p<0.001). Location in the corpus callosum, choroid plexus, or intraventricular area was more frequent in the intraventricular than the intracerebral hemorrhagic group (p<0.05). Superficial venous drainage was most common in patients with intracerebral hemorrhage (p<0.001), and deep venous drainage in those with intraventricular hemorrhage (p=3D0.001). The angioarchitectual characteristics of cerebral arteriovenous malformation correlate significantly with patterns of intracranial hemorrhage, and awareness of the type of hemorrhage could help to manage patients and determine prognosis.=20

  5. Murine and human leukemias.

    Science.gov (United States)

    Burchenal, J H

    1975-01-01

    Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).

  6. Experimental radioimmunotherapy of a xenografted human glioma using [sup 131]I-labeled monoclonal antibody to epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hiroshi; Nakazawa, Shozo [Nippon Medical School, Tokyo (Japan); Herlyn, D

    1993-09-01

    [sup 131]I-labeled F (ab')[sub 2] fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 [mu]Ci [sup 131]I-labeled 425 F(ab')[sub 2] achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')[sub 2] was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')[sub 2]. These studies suggest that [sup 131]I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author).

  7. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

    Energy Technology Data Exchange (ETDEWEB)

    Santamaria-Martinez, Albert [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat de Barcelona, Barcelona (Spain); Barquinero, Jordi [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Banc de Sang i Teixits, Barcelona (Spain); Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Seoane, Joan [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Medical Oncology program, Vall d' Hebron Institute of Oncology, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Poupon, Marie-France [Institut Curie, Paris (France); Morote, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Servei d' Urologia. Hospital Vall d' Hebron, Barcelona (Spain); Reventos, Jaume [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Munell, Francina, E-mail: fmunell@ir.vhebron.net [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain)

    2009-10-15

    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  8. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Energy Technology Data Exchange (ETDEWEB)

    Stagg, Brian C., E-mail: briancstagg@gmail.com; Uehara, Hironori; Lambert, Nathan; Rai, Ruju; Gupta, Isha; Radmall, Bryce; Bates, Taylor; Ambati, Balamurali K. [John A Moran Eye Center, University of Utah, Salt Lake City, UT, 65 Mario Capecchi Drive, Salt Lake City, UT 84132 (United States)

    2014-11-26

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

  9. Allografts versus Equine Xenografts in Calcaneal Fracture Repair.

    Science.gov (United States)

    Sonmez, Mehmet Mesut; Armagan, Raffi; Ugurlar, Meric; Eren, Tugrul

    Displaced intra-articular calcaneal fractures are difficult to treat. We determined the functional results and complications of using allografts or equine xenografts in treating these fractures. We reviewed patients seen at our center from May 2011 to December 2014 with Sanders type III or IV unilateral calcaneal fractures treated with locking plates and an additional bone allograft or equine xenograft. A minimum of 1 year after surgery, a history of infection and functional outcomes were assessed using the American Orthopaedic Foot and Ankle Society clinical rating system. Changes in the Gissane angle (GA) and Böhler angle were assessed from radiographs. Of the 91 eligible patients, 15 were lost to follow-up, leaving a sample of 76 patients (42 males): 45 received allografts (19 for type III and 26 for type IV fractures) and 31 received xenografts (20 for type III and 11 for type IV fractures). The mean age was about 40 years in both groups. After ≥1 year of follow-up, the proportion of patients in the American Orthopaedic Foot and Ankle Society scoring categories did not differ significantly between the 2 groups (mean ankle score, 86.5 in the allograft group and 85.1 in the xenograft group), and the American Orthopaedic Foot and Ankle Society functional outcomes were good or excellent in 69% and 68%, respectively (p = .986). The groups did not differ in the incidence of superficial or deep infection (p = 1.000). The Böhler angles were significantly decreased in the xenograft group. Xenografts might be preferred for repairing intra-articular calcaneal fractures because they can perform as well as allografts, avoid donor site morbidities, and are more available and less expensive than allografts. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

    2011-01-01

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

  11. Spontaneous intracerebral hemorrhage: the clinical neuroradiological view; Die spontane intrazerebrale Blutung aus klinisch-neuroradiologischer Sicht

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W. [Technische Hochschule Aachen (Germany). Klinikum

    1999-10-01

    Intracerebral hemorrhage is a common cause of acute neurological deterioration and a frequent indication for emergency neuroimaging. Stroke symptoms are caused in 10 to 15% by intracerebral hemorrhage. It is often not possible to differentiate intracerebral hemorrhage from cerebral ischemia by clinical examination. The therapeutic decision between thrombolysis or conservative therapy is comprised by the etiology. To exclude intracerebral hemorrhage as the cause of clinical symptoms, a CT is usually performed. Localisation and extension of the acute intracerebral hemorrhage are easy to detect. Subacute and chronic intracerebral hemorrhage are better delineated with magnetic resonance imaging. The different signal of the hemorrhage can be used for the age of the intracerebral hemorrhage. The cause of a non-traumatic intracerebral hemorrhage is in over 60% hypertony, less frequent alcoholism, malformation, or amyloid angiopathy. Uncommon causes of hemorrhage are head trauma, blood dyscrasia, tumor or venous thrombosis. Non-traumatic intracerebral hemorrhage are most common in patients between 50 and 70 years. In younger patients a malformation should be excluded with a cerebral angiography. Intracerebral hemorrhages are usually conservatively treated, in some cases an operative decompression is performed. (orig.) [German] Die intrazerebrale Blutung ist eine haeufige Ursache akut auftretender neurologischer Symptome und fuehrt oft zu einer notfallmaessigen neuroradiologischen Untersuchung. Etwa 15% der 'Schlaganfaelle' sind auf eine intrazerebrale Blutung zurueckzufuehren. Intrazerebrale Blutungen sind klinisch oft nicht von ischaemischen Infarkten zu unterscheiden. Eine Computertomographie ist zur Zeit fuer die Diagnosesicherung - und damit auch zur weiterfuehrenden Therapie - unerlaesslich. Ausdehnung und Lokalisation der akuten intrazerebralen Blutung koennen damit schnell und sicher erfasst werden. Subakute und chronische Blutungen sind dagegen

  12. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Dietmar Abraham

    2013-09-01

    Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

  13. Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model

    Directory of Open Access Journals (Sweden)

    Jae Gwang Park

    2017-01-01

    Full Text Available Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.

  14. Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')/sub 2/ fragments

    Energy Technology Data Exchange (ETDEWEB)

    Herlyn, D.; Munz, D.L.; Herlyn, M.; Koprowski, H.; Powe, J.; Alavi, A.; Meinken, G.E.; Srivastava, S.C.

    1986-01-01

    Procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice compared to experimentally immunosuppressed mice due to the higher tumor viability. MAb localization in tumor tissue was greatly enhanced when F(ab')/sub 2/ fragments rather than intact antibody molecules were used. Although tumors could be visualized with /sup 131/I-, /sup 123/I-or /sup 111/In-labeled MAb fragments without background subtraction, tumor-to-background ratios of radioactivity were highest for /sup 131/I-labeled fragments. /sup 131/I-labeled F(ab')/sub 2/ fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by ..gamma..-scintigraphy. Some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')/sub 2/ fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone.

  15. Prospective Study of Fasting Blood Glucose and Intracerebral Hemorrhagic Risk.

    Science.gov (United States)

    Jin, Cheng; Li, Guohong; Rexrode, Kathryn M; Gurol, Mahmut E; Yuan, Xiaodong; Hui, Ying; Ruan, Chunyu; Vaidya, Anand; Wang, Yanxiu; Wu, Shouling; Gao, Xiang

    2018-01-01

    Although diabetes mellitus is an established independent risk factor for ischemic stroke, the association between fasting blood glucose and intracerebral hemorrhage (ICH) is limited and inconsistent. The objective of the current study was to examine the potential impact of long-term fasting blood glucose concentration on subsequent risk of ICH. This prospective study included 96 110 participants of the Kailuan study, living in Kailuan community, Tangshan city, China, who were free of cardiovascular diseases and cancer at baseline (2006). Fasting blood glucose concentration was measured in 2006, 2008, 2010, and 2012. Updated cumulative average fasting blood glucose concentration was used as primary exposure of the current study. Incident ICH from 2006 to 2015 was confirmed by review of medical records. During 817 531 person-years of follow-up, we identified 755 incident ICH cases. The nadir risk of ICH was observed at fasting blood glucose concentration of 5.3 mmol/L. The adjusted hazard ratios and their 95% confidence intervals (CIs) of ICH were 1.59 (95% CI, 1.26-2.02) for diabetes mellitus or fasting blood glucose ≥7.00 mmol/L, 1.31 (95% CI, 1.02-1.69) for impaired fasting blood glucose (fasting blood glucose, 6.10-6.99 mmol/L), 0.98 (95% CI, 0.78-1.22) for fasting blood glucose 5.60 to 6.09 mmol/L, and 2.04 (95% CI, 1.23-3.38) for hypoglycemia (fasting blood glucose, fasting blood glucose 4.00 to 5.59 mmol/L. The results persisted after excluding individuals who used hypoglycemic, aspirin, antihypertensive agents, or anticoagulants, and those with intracerebral hemorrhagic cases occurred in the first 2 years of follow-up. In this large community-based cohort, low (fasting blood glucose concentrations were associated with higher risk of incident ICH, relative to fasting blood glucose concentrations of 4.00 to 6.09 mmol/L. © 2017 American Heart Association, Inc.

  16. A Case of Hypertensive Intracerebral Hemorrhage Accompanying Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Dae Wui Yoon

    2013-12-01

    Full Text Available Stroke is very common in patients with sleep disordered breathing, especially in the elderly. We report the case of a 26-year-old man who had been referred to us with a sudden left side motor weakness of the body, headache, chronic fatigue, and witnessed sleep apneas. Intracerebral hemorrhage in the right external capsule and putamen was identified upon brain computed tomography. He had hypertension which had not been diagnosed previously. On polysomnography, apnea-hypopnea index was 73.0/h and arousal index was 74.7/h, indicating severe sleep apnea. Continuous positive airway pressure titration was conducted to determine the optimal pressure to alleviate the respiratory disturbances. Treatment with antihypertensive medication reduced blood pressure (BP from 197/145 mm Hg to 130/80 mm Hg after 10 days of use. Co-treatment with the medication and auto-adjustable positive airway pressure additionally decreased BP to 110/60 mm Hg and normalized respiratory disturbances. In addition to BP, left hemiparesis, morning headache, daytime sleepiness, and chronic fatigue were all improved. Early treatment of OSA could help facilitate the rehabilitation of or recovery of weakness in such patients.

  17. Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

    Directory of Open Access Journals (Sweden)

    Anna Rosell

    Full Text Available BACKGROUND: Spontaneous intracerebral hemorrhage (ICH represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. METHODOLOGY/PRINCIPAL FINDINGS: Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH and the corresponding contralateral white (CW and grey (CG matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed. The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results. CONCLUSIONS: The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.

  18. CT-guided stereotactic operation for hypertensive intracerebral hematoma

    International Nuclear Information System (INIS)

    Takahashi, Shinichiro; Sonobe, Makoto; Koshu, Keiji; Kusunose, Mutsuo; Tsumura, Kotaro

    1989-01-01

    CT-guided stereotactic operation was performed in 55 patients with hypertensive intracerebral hematoma. Location of the hematoma was putamen in 28 cases, thalamus in 14 cases, subcortical area in 9 cases, cerebellum in 3 cases and pons in one case. Ages ranged from 36 to 85 years (mean 59.5). The mean timing of the surgery after bleeding was 4.2 days. The estimated volume of the hematoma on CT was 8 ml to 57 ml in putaminal, 9 ml to 40 ml in thalamic, 18 ml to 77 ml in subcortical, 17 ml to 26 ml in cerebellar and 5 ml in pontine hemorrhage. Aspiration rate at surgery was 60.4% in putaminal, 37.9% in thalamic, 41.7% in subcortical, 45.2% in cerebellar and 30% in pontine hemorrhage. In addition, we evaluated ADL at 6 months postoperatively in patients with putaminal and thalamic hamorrhage. It is concluded that stereotactic operation is advisable in those cases with 10 to 50 ml hematoma volumes in putamen or thalamus. On the other hand, in cases with over 50ml volume, hematoma should be evacuated by craniotomy. (author)

  19. Thirty-day readmission after spontaneous intracerebral hemorrhage.

    Science.gov (United States)

    Bjerkreim, Anna Therese; Khanevski, Andrej Netland; Glad, Solveig Bergliot; Thomassen, Lars; Naess, Halvor; Logallo, Nicola

    2018-03-01

    Intracerebral hemorrhage (ICH) is the most severe form of stroke, but data on readmission after ICH are sparse. We aimed to determine frequency, causes, and predictors of 30-day readmission after ICH. This retrospective cohort study includes all spontaneous ICH survivors admitted to the stroke unit at Haukeland University Hospital in Bergen in Norway from July 2007 to December 2013. Patients were followed by review of electronic medical charts, and the first unplanned readmission within 30 days after discharge was used as final outcome. Cox regression analysis was performed to identify predictors of 30-day readmission. We identified 226 patients with spontaneous ICH, 70 (31.0%) of whom died before discharge or were discharged to palliative care. Of the remaining 156 ICH survivors, 28 (18.0%) were readmitted within 30 days. Median time to readmission was 12 days (IQR 4.5 - 18.5). Most patients were readmitted due to infections ( N  = 13). None of the patients were readmitted with recurrent stroke. Pneumonia and enteral feeding during the index hospitalization were associated with readmission for infections (both p  readmission (HR 1.06, 95% CI 1.02 - 1.11, p  =   .006). Almost one in five of our spontaneous ICH survivors was readmitted within 30 days, and most readmissions were caused by infections.

  20. Ruptured aneurysms of the middle cerebral artery with intracerebral hematoma

    International Nuclear Information System (INIS)

    Inomori, Shigeo; Kim, Ilu; Ueda, Shinsuke; Pak, Shinsa

    1984-01-01

    Twenty-one cases of ruptured middle cerebral artery aneurysm with intracerebral hematoma were studied. The age distribution ranged from 16 to 68, with an average of 48 years. Fifteen were female, 6 male. Computerized tomography (CT) scans were performed within 24 hours after the onset in 19. Diagnosis was established by angiography or surgery. Seventeen patients were operated on, whereas 4 were not because their condition was too poor. CT showed hematoma in the Sylvian fissure and the temporal lobe in a section 30 mm above the orbitomeatal line. Extension of the hematoma was to the frontal lobe anteriorly and/or the temporal lobe posterosuperiorly. The site of hematoma was related to the direction of the aneurysmal projection. Cases were divided into the following three groups: Group I; cases with the temporal lobe hematoma. Group II; cases with hematoma extending to both the frontal and temporal lobes. Group III; cases with hematoma in the frontal lobe. All of the 14 cases in Group I underwent operation. Mortality was 14%. Morbidity was correlated to the size of hematoma. The outcome was good in cases with hematoma less than 40 mm in diameter. Four out of 6 cases of Group II were not operated on and died within 3 days after onset. Uncal herniation was suspected early in their course. Of two operated cases, one died and the other was severely disabled. Outcome in one case of Group III was good. This study suggests that outcome can be anticipated from CT findings. (author)

  1. Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage

    Science.gov (United States)

    Dang, Ge; Yang, Yuefan; Wu, Gang; Hua, Ya; Keep, Richard F.; Xi, Guohua

    2016-01-01

    Erythrolysis occurs in the clot after intracerebral hemorrhage (ICH) and the release of hemoglobin causes brain injury but it is unclear when such lysis occurs. The present study examined early erythrolysis in rats. ICH rats had an intra-caudate injection of 100 µl autologous blood and sham rats had a needle insertion. All rats had T2 and T2* MRI scanning and brains were used for histology and CD163 (a hemoglobin scavenger receptor) and DARPP-32 (a neuronal marker) immunohistochemistry. There was marked heterogeneity within the hematoma on T2* MRI, with a hyper- or isointense core and a hypointense periphery. Hematoxylin and eosin staining in the same animals showed significant erythrolysis in the core with the formation of erythrocyte ghosts. The degree of erythrolysis correlated with the severity of perihematomal neuronal loss. Perihematomal CD163 was increased by day 1 after ICH and may be involved in clearing hemoglobin caused by early hemolysis. Furthermore, ICH resulted in more severe erythrolysis, neuronal loss and perihematomal CD163 upregulation in spontaneously hypertensive rats compared to Wistar Kyoto rats. In conclusions, T2*MRI detectable early erythrolysis occurred in the clot after ICH, and activated CD163. Hypertension is associated with enhanced erythrolysis in the hematoma. PMID:27783383

  2. Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages

    Science.gov (United States)

    ARUMUGAM, Ananda; A RAHMAN, Noor Azman; THEOPHILUS, Sharon Casilda; SHARIFFUDIN, Ashraf; ABDULLAH, Jafri Malin

    2015-01-01

    Background: Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. Methods: We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. Results: Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). Conclusions: This study showed a significant hematoma volume expansion in the control group compared to the treatment group. PMID:27006639

  3. Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

    Science.gov (United States)

    Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito

    2018-01-01

    Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. PMID:29490916

  4. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    Science.gov (United States)

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  5. Robot-assisted intracerebral hemorrhage evacuation: an experimental evaluation

    Science.gov (United States)

    Burgner, Jessica; Swaney, Philip J.; Lathrop, Ray A.; Weaver, Kyle D.; Webster, Robert J.

    2013-03-01

    We present a novel robotic approach for the rapid, minimally invasive treatment of Intracerebral Hemorrhage (ICH), in which a hematoma or blood clot arises in the brain parenchyma. We present a custom image-guided robot system that delivers a steerable cannula into the lesion and aspirates it from the inside. The steerable cannula consists of an initial straight tube delivered in a manner similar to image-guided biopsy (and which uses a commercial image guidance system), followed by the sequential deployment of multiple individual precurved elastic tubes. Rather than deploying the tubes simultaneously, as has been done in nearly all prior studies, we deploy the tubes one at a time, using a compilation of their individual workspaces to reach desired points inside the lesion. This represents a new paradigm in active cannula research, defining a novel procedure-planning problem. A design that solves this problem can potentially save many lives by enabling brain decompression both more rapidly and less invasively than is possible through the traditional open surgery approach. Experimental results include a comparison of the simulated and actual workspaces of the prototype robot, and an accuracy evaluation of the system.

  6. Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage.

    Science.gov (United States)

    Di Napoli, Mario; Zha, Alicia M; Godoy, Daniel A; Masotti, Luca; Schreuder, Floris H B M; Popa-Wagner, Aurel; Behrouz, Réza

    2016-01-01

    Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge. © 2016 S. Karger AG, Basel.

  7. Spontaneous Intracerebral Hemorrhage Image Analysis Methods: A Survey

    Science.gov (United States)

    Pérez, Noel; Valdés, Jose; Guevara, Miguel; Silva, Augusto

    Spontaneous intracerebral hemorrhages (ICH) account for 10-30% of all strokes and are a result of acute bleeding into the brain due to ruptures of small penetrating arteries. Despite major advancements in the management of ischemic strokes and other causes of hemorrhagic strokes, such as ruptured aneurysm, arteriovenous malformations (AVMs), or cavernous angioma, during the past several decades, limited progress has been made in the treatment of ICH, and the prognosis for patients who suffer them remains poor. The societal impact of these hemorrhagic strokes is magnified by the fact that affected patients typically are a decade younger than those afflicted with ischemic strokes. The ICH continues to kill or disable most of their victims. Some studies show that those who suffer ICH have a 30-day mortality rate of 35-44% and a 6-month mortality rate approaching 50%. Approximately 700,000 new strokes occur in the United States annually and approximately 15% are hem-orrhagic strokes related to ICH. The poor outcome associated with ICH is related to the extent of brain damage. ICH produces direct destruction and compression of surrounding brain tissue. Direct compression causes poor perfusion and venous drainage to surrounding penumbra at risk, resulting in ischemia to the tissues that most need perfusion [16].

  8. Necrostatin-1 Reduces Neurovascular Injury after Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Melanie D. King

    2014-01-01

    Full Text Available Intracerebral hemorrhage (ICH is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

  9. Radiosensitivity of drug-resistant human tumour xenografts

    International Nuclear Information System (INIS)

    Mattern, J.; Bak, M. Jr.; Volm, M.; Hoever, K.H.

    1989-01-01

    The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation. (orig.) [de

  10. Cryopreservation of human colorectal carcinomas prior to xenografting

    International Nuclear Information System (INIS)

    Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

    2010-01-01

    Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

  11. Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins

    NARCIS (Netherlands)

    F.H. Jansen (Flip); J. Krijgsveld (Jeroen); A.L. Rijswijk (Angelique); G.J.C.M. van den Bemd (Gert-Jan); M.S. van den Berg (Mirella); W.M. van Weerden (Wytske); R. Willemsen (Rob); L.J.M. Dekker (Lennard); T.M. Luider (Theo); G.W. Jenster (Guido)

    2009-01-01

    textabstractNovel markers for prostate cancer (PCa) are needed because current established markers such as prostate-specific antigen lack diagnostic specificity and prognostic value. Proteomics analysis of serum from mice grafted with human PCa xenografts resulted in the identification of 44

  12. Next-generation sequence analysis of cancer xenograft models.

    Directory of Open Access Journals (Sweden)

    Fernando J Rossello

    Full Text Available Next-generation sequencing (NGS studies in cancer are limited by the amount, quality and purity of tissue samples. In this situation, primary xenografts have proven useful preclinical models. However, the presence of mouse-derived stromal cells represents a technical challenge to their use in NGS studies. We examined this problem in an established primary xenograft model of small cell lung cancer (SCLC, a malignancy often diagnosed from small biopsy or needle aspirate samples. Using an in silico strategy that assign reads according to species-of-origin, we prospectively compared NGS data from primary xenograft models with matched cell lines and with published datasets. We show here that low-coverage whole-genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. Exome capture sequencing revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene expression experiments, whereas mouse-specific transcript profiles correlated with published datasets from human cancer stroma. We conclude that primary xenografts represent a useful platform for complex NGS analysis in cancer research for tumours with limited sample resources, or those with prominent stromal cell populations.

  13. Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis.

    Science.gov (United States)

    Jackson, D P; Percy, D H; Morris, V L

    1984-09-01

    When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1-2.4 X 10(6)-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.

  14. Relationship of cerebral microbleeds with hematoma growth in elderly patients with acute hypertensive intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Shou-feng LIU

    2015-01-01

    Full Text Available Objective To investigate whether cerebral microbleeds (CMBs can predict hematoma growth in elderly patients with acute hypertensive intracerebral hemorrhage.  Methods The clinical records of 98 elderly patients with acute hypertensive intracerebral hemorrhage who underwent initial CT within 6 h and repeated CT and susceptibility-weighted imaging (SWI within 24 h of onset were analyzed. Based on the performance of SWI, patients were divided into microbleeds group and non-microbleeds group. Forward multivariate Logistic regression analysis was used to evaluate the predicting value of CMBs on the growth of intracerebral hematoma.  Results Among 98 patients, hematoma growth was found in 25 cases in the second CT scan. The ratio in microbleeds group was significantly higher than that in non-microbleeds group (43.75% vs 16.67%; χ2 = 8.319, P = 0.004. Multivariate Logistic regression showed that CMBs was independent risk factor for intracerebral hematoma (OR = 0.241, 95%CI: 0.065-0.861; P = 0.017.  Conclusions CMBs in patients with acute intracerebral hematoma can predict high risk of hemotoma growth, and effective treatment should be taken to improve the prognosis of patients. DOI: 10.3969/j.issn.1672-6731.2015.01.012

  15. Pathogenesis of traumatic intracerebral hematoma with a sequential study of computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ohmori, H; Miyazaki, S; Munekata, K; Fukushima, H [Hitachi General Hospital, Hitachi, Ibaraki (Japan); Shohji, A

    1981-04-01

    A sequential study with computerized tomography (CT scan) of two cases of traumatic intracerebral hematoma is reported. Case 1 was a 69-year-old man who had a head injury. The initial CT scan, taken 1 hour after his injury, showed a left temporal salt-and-pepper appearance, which proved to be a cerebral contusion. The CT scan 4.5 hours after his injury showed a left temporal high density area instead. An operation was performed, and a massive intracerebral hematoma was observed. Case 2 was a 61-year-old man who was also admitted because of a head injury. The initial CT scan, taken 1 hour after his injury, revealed several bifrontal intracerebral hemorrhagic spots in the low-density areas, suggesting contusion. A secondary CT scan (23 hours) demonstrated that the traumatic intracerebral hematoma had developed into a posttraumatic cerebral contusion. The operation disclosed a hematoma surrounded by contusion. These cases prove that traumatic intracerebral hematoma is often caused by cerebral contusion.

  16. On the pathogenesis of traumatic intracerebral hematoma with a sequential study of computerized tomography

    International Nuclear Information System (INIS)

    Ohmori, Hidetoshi; Miyazaki, Shinichiro; Munekata, Katsuharu; Fukushima, Hiromi; Shohji, Akira.

    1981-01-01

    A sequential study with computerized tomography (CT scan) of two cases of traumatic intracerebral hematoma is reported. Case 1 was a 69-year-old man who had a head injury. The initial CT scan, taken 1 hour after his injury, showed a left temporal salt-and-pepper appearance, which proved to be a cerebral contusion. The CT scan 4.5 hours after his injury showed a left temporal high density area instead. An operation was performed, and a massive intracerebral hematoma was observed. Case 2 was a 61-year-old man who was also admitted because of a head injury. The initial CT scan, taken 1 hour after his injury, revealed several bifrontal intracerebral hemorrhagic spots in the low-density areas, suggesting contusion. A secondary CT scan (23 hours) demonstrated that the traumatic intracerebral hematoma had developed into a posttraumatic cerebral contusion. The operation disclosed a hematoma surrounded by contusion. These cases prove that traumatic intracerebral hematoma is often caused by cerebral contusion. (author)

  17. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Hematology Research Center, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: karimim@sums.ac.ir; Rasekhi, A.R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: rasekhia@sums.ac.ir; Rasekh, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: Rasekhm@sums.ac.ir; Nabavizadeh, S.A. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: nabavia@gmail.com; Assadsangabi, R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: assadsangabi@yahoo.com; Amirhakimi, G.H. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: amirhakimig@sums.ac.ir

    2009-06-15

    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  18. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

    International Nuclear Information System (INIS)

    Karimi, M.; Rasekhi, A.R.; Rasekh, M.; Nabavizadeh, S.A.; Assadsangabi, R.; Amirhakimi, G.H.

    2009-01-01

    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  19. Effect of dexamethasone in primary intracerebral hemorrhage in the south west of iran

    International Nuclear Information System (INIS)

    Sharafadinzadeh, N.; Baghebanian, S.M.; Pipelzadeh, M.; Moravej, A. A.; Ghanavatiz, P.

    2008-01-01

    Previous study revealed the value of dexamethasone in the treatment of vasogenic edema associated with brain tumor and abscess. However there are poor documented studies about its usefulness in primary intracerebral hemorrhage. In this study we evaluated dexamethasone effects in primary intracerebral hemorrhage. In a double blind randomized placebo-controlled clinical trial we evaluated 200 intracerebral hemorrhage cases between 40 to 80 years old whom were admitted at Golestan Hospital (Ahwaz, IR) between March 2002 and March 2003. They were divided in two groups dexamethasone (N=100) and placebo (N=100). Then mortality, GI bleeding, fever, electrolytes disturbances, hypertension and hyperglycemic status were analyzed in two groups. Ethical considerations were employed and subjects were followed by appropriate statistical methods for 21 days to assess the major outcomes. Mortality was much higher in the dexamethasone group; Dexamethasone group (49.3%) and placebo (23.4%) and also fever was higher seen in the dexamethasone group; dexamethasone group (40.2%) and placebo group (24.7%) but there was not any significant statistical difference between two groups as regards other complications. Dexamethasone is widely used for cerebral edema associated conditions but in this study we saw that it's complications in intracerebral hemorrhage such as increasing fever and mortality are significantly higher. Hence it use for treatment of primary intracerebral hemorrhage should be reconsidered. (author)

  20. Increase in the fraction of necrotic, not apoptotic, cells in SiHa xenograft tumours shortly after irradiation

    International Nuclear Information System (INIS)

    Olive, P.L.; Vikse, C.M.; Vanderbyl, S.

    1999-01-01

    Background and purpose: Approximately 18% of the cells recovered by rapid mechanical dissociation of SiHa xenograft tumours contain large numbers of DNA strand breaks. The number of damaged cells increases to 30-40% 4-6 h after exposure to 5 or 15 Gy, returning to normal levels by 12 h. This observation is reminiscent of the rate of production of apoptotic cells in other murine and human xenograft tumours. The nature of this damage, rate of development and relation to cell proliferation rate were therefore examined in detail.Materials and methods: SiHa human cervical carcinoma cells were grown as xenograft tumours in SCID mice. Single-cell suspensions were prepared as a function of time after irradiation of the mouse and examined for DNA damage using the alkaline comet assay. Cell cycle progression was measured by flow cytometry evaluation of anti-bromodeoxyuridine-labelled tumour cells.Results: Significant numbers of apoptotic cells could not be detected in irradiated SiHa tumours using an end-labelling assay, electron microscopy, or histological examination of thin sections. Instead, xenograft cells exhibiting extensive DNA damage in the comet assay were predominantly necrotic cells. The increase in the proportion of heavily damaged cells 4-6 h after irradiation could be the result of an interplay between several factors including loss of viable cells and change in production or loss of necrotic cells. Analysis of the progression of BrdUrd-labelled cells confirmed that while 35% of cells from untreated SiHa tumours had divided and entered G 1 phase by 6 h after BrdUrd injection, none of the labelled cells from tumours exposed to 5 or 15 Gy had progressed to G 1 .Conclusions: The increase in the percentage of SiHa tumour cells with extensive DNA damage 4-6 h after irradiation is attributable to necrosis, not apoptosis. Cell cycle progression and cell loss are likely to influence the kinetics of appearance of both apoptotic and necrotic cells in irradiated tumours

  1. Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2.

    Science.gov (United States)

    Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Hirakawa, Yoichiro; Wang, Xia; Woodward, Mark; Robinson, Thompson; Stapf, Christian; Parsons, Mark; Lavados, Pablo M; Huang, Yining; Wang, Jiguang; Chalmers, John; Anderson, Craig S

    2015-02-03

    To investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH). INTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150-220 mm Hg) who were allocated to receive intensive (target SBP <140 mm Hg within 1 hour, with lower limit of 130 mm Hg for treatment cessation) or guideline-recommended (target SBP <180 mm Hg) BP-lowering treatment. Outcome was physical function across all 7 levels of the modified Rankin Scale at 90 days. Analysis of the randomized comparisons showed that intensive BP lowering produced comparable benefits on physical function at 90 days in 5 subgroups defined by baseline SBP of <160, 160-169, 170-179, 180-189, and ≥190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1-24 hours) and acute (2-7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg. Intensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130-139 mm Hg is likely to provide maximum benefit in acute ICH. This study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP. © 2014 American Academy of Neurology.

  2. Acute intracerebral haemorrhage: grounds for optimism in management.

    Science.gov (United States)

    Delcourt, Candice; Anderson, Craig

    2012-12-01

    Spontaneous intracerebral haemorrhage (ICH) is one of the most devastating types of stroke, which has considerable disease burden in "non-white" ethnic groups where the population-attributable risks of elevated blood pressure are very high. Since the treatment of ICH remains largely supportive and expectant, nihilism and the early withdrawal of active therapy influence management decisions in clinical practice. However, approaches to management are now better defined on the basis of evidence that both survival and speed (and degree) of recovery are critically dependent on the location, size, and degree of expansion and extension into the intraventricular system of the haematoma of the ICH. Although no medical treatment has been shown to improve outcome in ICH, several promising avenues have emerged that include haemostatic therapy and intensive control of elevated blood pressure. Conversely, there is continued controversy over the role of evacuation of the haematoma of ICH via open craniotomy. Despite being an established practice for several decades, and having undergone evaluation in multiple randomised trials, there is uncertainty over which patients have the most to gain from an intervention with clear procedural risk. Minimally invasive surgery via local anaesthetic applied drill-puncture of the cranium and infusion of a thrombolytic agent is an attractive option for patients requiring critical management of the haematoma, not just in low resource settings but arguably also in specialist centres of western countries. With several ongoing clinical trials nearing completion, these treatments could enter routine practice within the next few years, further justifying the urgency of "time is brain" and that active management within well-organized, comprehensive acute stroke care units includes patients with ICH. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Putative role of prostaglandin receptor in intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Shekher eMohan

    2012-10-01

    Full Text Available Each year, approximately 795,000 people experience a new or recurrent stroke. Of all strokes, 84% are ischemic, 13% are intracerebral hemorrhage (ICH strokes and 3% are subarachnoid hemorrhage (SAH strokes. Despite the decreased incidence of ischemic stroke, there has been no change in the incidence of hemorrhagic stroke in the last decade. ICH is a devastating disease 37-38% of patients between the ages of 45-64 die within 30 days. In an effort to prevent ischemic and hemorrhagic strokes we and others have been studying the role of prostaglandins and their receptors. Prostaglandins are bioactive lipids derived from the metabolism of arachidonic acid. They sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. Most prostaglandins are produced from specific enzymes and act upon cells via distinct G-protein coupled receptors. The presence of multiple prostaglandin receptor’s cross-reactivity and coupling to different signal transduction pathways allow differentiated cells to respond to prostaglandins in a unique manner. Due to the number of prostaglandin receptors, prostaglandin-dependent signaling can function either to promote neuronal survival or injury following acute excitotoxicity, hypoxia, and stress induced by ICH. To better understand the mechanisms of neuronal survival and neurotoxicity mediated by prostaglandin receptors, it is essential to understand downstream signaling. Several groups including ours have discovered unique roles for prostaglandin receptors in rodent models of ischemic stroke, excitotoxicity, and Alzheimer disease, highlighting the emerging role of prostaglandin receptor signaling in hemorrhagic stroke with a focus on cyclic-adenosine monophosphate (cAMP and calcium (Ca2+ signaling. We review current ICH data and discuss future directions notably on prostaglandin receptors, which may lead to the development of unique therapeutic targets against hemorrhagic stroke and

  4. Regional cerebral blood flow in patients with hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Kuroda, Kiyoshi

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 36 patients with hypertensive intracerebral hemorrhage (putaminal hemorrhage) treated surgically, using the Xenon-133 intracarotid injection method. The correlations between CBF in four regions, (the hemisphere, the frontal region, the sensori-motor area and the focal area) and the duration from the operation, the conscious level, the hematoma volume and motor function were investigated. Mean cerebral blood flow (MCBF), rCBF in sensori-motor area and in the focal area showed a value below 30 ml/100g/min. for any duration after the operation within one year. However, in the frontal region rCBF tends to increase from 4 months after the operation. There was a close correlation between the conscious level and CBF, especially in the frontal region. The higher CBF was noted in the better consciousness group. In hematoma cases the larger the hematoma volume (especially those over 31 ml)the lower the CBF in all three regions. In the focal area rCBF showed the lowest value among these three regions and was dependent on the hematoma volume, while frontal region revealed the highest flow value of them all, even in cases with a hematoma volume over 81 ml. There was a significant difference in rCBF between cases with severe motor disturbance and cases with moderate motor disturbance, except in the focal area. In the frontal region rCBF coincides rather well to the degree of motor disturbance. While, rCBF in the focal area was less than 30 ml/100g/min., and showed no correlation to motor function. (J.P.N.)

  5. Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage.

    Science.gov (United States)

    Liotta, Eric M; Prabhakaran, Shyam; Sangha, Rajbeer S; Bush, Robin A; Long, Alan E; Trevick, Stephen A; Potts, Matthew B; Jahromi, Babak S; Kim, Minjee; Manno, Edward M; Sorond, Farzaneh A; Naidech, Andrew M; Maas, Matthew B

    2017-08-22

    We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH). Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months. We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate ( p = 0.02), parsimoniously adjusted ( p = 0.002), and fully adjusted models ( p = 0.006), as well as greater hematoma growth ( p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes ( p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth. These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH. © 2017 American Academy of Neurology.

  6. Cerebral blood flow in patients with hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Sugiyama, Hirotaka

    1984-01-01

    Cerebral blood flow (CBF) is usually decreased in patients with hypertensive intracerebral hemorrhage. A total of 81 regional CBF measurements were performed using an Anger-type dynamic gamma camera with the Xe-133 intracarotid injection technique in 23 patients with thalamic hemorrhage, 18 with small putaminal hemorrhage, and 5 with large putaminal hemorrhage. The results were as follows: Bilateral CBF in thalamic hemorrhages was markedly reduced from 1 week to 2 or 3 weeks after onset; it then showed a tendency to increase from 4 weeks to 3 months. In putaminal hemorrhages, however, CBF in the affected hemisphere did not tend to increase despite increased CBF in the contralateral hemisphere. CBF of the affected hemisphere was plotted against the hematoma volume, and the biphasic curve showed an initial steep and subsequent gentle slope in both putaminal and thalamic hemorrhages. The degree of CBF reduction in the affected hemisphere was more evident in thalamic than in putaminal hemorrhages. However, the flow reduction in the contralateral hemisphere was more obvious in thalamic than in putaminal hemorrhages. Factors such as mean arterial blood pressure, partial pressure of arterial carbon dioxide, cerebrospinal fluid pressure, hematocrit and the degree of involvement of the internal capsule, as shown on CT scan were not directly related to CBF reduction. In conclusion, it is unlikely that the mass effect of the hematoma plays an important role in the discrepancy between CBF reduction in putaminal and thalamic hemorrhages. Rather, the discrepancy may result from the impairment of respective anatomical sites in the thalamic and putaminal regions. It is also suggested that ipsilateral as well as contralateral CBF reduction is probably caused by the decreased cortical metabolic demand. This may be based on the disruption of the transneural fiber pathways, which connect both the thalamus and putamen to the cerebral cortex. (author)

  7. Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin.

    Science.gov (United States)

    Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito; Iihara, Koji

    2018-03-27

    This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)-associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  8. Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study.

    Directory of Open Access Journals (Sweden)

    Danni Zheng

    Full Text Available Rates of acute intracerebral hemorrhage (ICH increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2 participants on an hourly timescale.INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset and elevated systolic blood pressure (SBP, 150-220 mmHg assigned to intensive (target SBP <140 mmHg or guideline-recommended (SBP <180 mmHg BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs and 95% CI.Low ambient temperature (≤10°C was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99-1.91 for 10°C, 1.92 (1.31-2.81 for 0°C, 3.13 (1.89-5.19 for -10°C, and 5.76 (2.30-14.42 for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses.Exposure to low ambient temperature within several hours increases the risk of ICH.ClinicalTrials.gov NCT00716079.

  9. Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study

    Science.gov (United States)

    Zheng, Danni; Arima, Hisatomi; Sato, Shoichiro; Gasparrini, Antonio; Heeley, Emma; Delcourt, Candice; Lo, Serigne; Huang, Yining; Wang, Jiguang; Stapf, Christian; Robinson, Thompson; Lavados, Pablo; Chalmers, John; Anderson, Craig S.

    2016-01-01

    Background Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. Methods INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150–220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI. Results Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99–1.91) for 10°C, 1.92 (1.31–2.81) for 0°C, 3.13 (1.89–5.19) for -10°C, and 5.76 (2.30–14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses. Conclusions Exposure to low ambient temperature within several hours increases the risk of ICH. Trial Registration ClinicalTrials.gov NCT00716079 PMID:26859491

  10. Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage.

    Science.gov (United States)

    Zhao, Xiurong; Sun, Guanghua; Zhang, Han; Ting, Shun-Ming; Song, Shen; Gonzales, Nicole; Aronowski, Jaroslaw

    2014-10-01

    Polymorphonuclear neutrophils (PMNs) infiltration into brain parenchyma after cerebrovascular accidents is viewed as a key component of secondary brain injury. Interestingly, a recent study of ischemic stroke suggests that after ischemic stroke, PMNs do not enter brain parenchyma and as such may cause no harm to the brain. Thus, the present study was designed to determine PMNs' behavior after intracerebral hemorrhage (ICH). Using the autologous blood injection model of ICH in rats and immunohistochemistry for PMNs and vascular components, we evaluated the temporal and spatial PMNs distribution in the ICH-affected brain. We found that, similar to ischemia, there is a robust increase in presence of PMNs in the ICH-injured tissue that lasts for at least 1 to 2 weeks. However, in contrast to what was suggested for ischemia, besides PMNs that stay in association with the vasculature, after ICH, we found abundance of intraparenchymal PMNs (with no obvious association with vessels) in the ICH core and hematoma border, especially between 1 and 7 days after the ictus. Interestingly, the increased presence of intraparenchymal PMNs after ICH coincided with the massive loss of microvascular integrity, suggesting vascular disruption as a potential cause of PMNs presence in the brain parenchyma. Our study indicates that in contrast to ischemic stroke, after ICH, PMNs target not only vascular compartment but also brain parenchyma in the affected brain. As such, it is possible that the pathogenic role and therapeutic implications of targeting PMNs after ICH could be different from these after ischemic stroke. Our work suggests the needs for more studies addressing the role of PMNs in ICH.

  11. Application of the FOUR Score in Intracerebral Hemorrhage Risk Analysis.

    Science.gov (United States)

    Braksick, Sherri A; Hemphill, J Claude; Mandrekar, Jay; Wijdicks, Eelco F M; Fugate, Jennifer E

    2018-06-01

    The Full Outline of Unresponsiveness (FOUR) Score is a validated scale describing the essentials of a coma examination, including motor response, eye opening and eye movements, brainstem reflexes, and respiratory pattern. We incorporated the FOUR Score into the existing ICH Score and evaluated its accuracy of risk assessment in spontaneous intracerebral hemorrhage (ICH). Consecutive patients admitted to our institution from 2009 to 2012 with spontaneous ICH were reviewed. The ICH Score was calculated using patient age, hemorrhage location, hemorrhage volume, evidence of intraventricular extension, and Glasgow Coma Scale (GCS). The FOUR Score was then incorporated into the ICH Score as a substitute for the GCS (ICH Score FS ). The ability of the 2 scores to predict mortality at 1 month was then compared. In total, 274 patients met the inclusion criteria. The median age was 73 years (interquartile range 60-82) and 138 (50.4%) were male. Overall mortality at 1 month was 28.8% (n = 79). The area under the receiver operating characteristic curve was .91 for the ICH Score and .89 for the ICH Score FS . For ICH Scores of 1, 2, 3, 4, and 5, 1-month mortality was 4.2%, 29.9%, 62.5%, 95.0%, and 100%. In the ICH Score FS model, mortality was 10.7%, 26.5%, 64.5%, 88.9%, and 100% for scores of 1, 2, 3, 4, and 5, respectively. The ICH Score and the ICH Score FS predict 1-month mortality with comparable accuracy. As the FOUR Score provides additional clinical information regarding patient status, it may be a reasonable substitute for the GCS into the ICH Score. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Wen-jing Xie

    2016-01-01

    Full Text Available Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL. Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.

  13. Subarachnoid and Intracerebral Hemorrhage in Patients with Churg-Strauss Syndrome: Two Case Reports

    Science.gov (United States)

    Go, Myeong Hoon; Park, Jeong Un; Kang, Jae Gyu

    2012-01-01

    Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia, and asthma. The exact etiology of CSS is unknown. This syndrome commonly affects the lungs, peripheral nerves, skin, heart, and gastrointestinal tract, but rarely the central nervous system. Subarachnoid and intracerebral hemorrhage in CSS patients is extremely rare; however, clinicians should consider that CSS may be a cause of intracranial hemorrhage and its high rate of mortality and morbidity. The authors report on two cases of subarachnoid and intracerebral hemorrhage with CSS and discuss a brief review of CSS. PMID:23210058

  14. High precision localization of intracerebral hemorrhage based on 3D MPR on head CT images

    Science.gov (United States)

    Sun, Jianyong; Hou, Xiaoshuai; Sun, Shujie; Zhang, Jianguo

    2017-03-01

    The key step for minimally invasive intracerebral hemorrhage surgery is precisely positioning the hematoma location in the brain before and during the hematoma surgery, which can significantly improves the success rate of puncture hematoma. We designed a 3D computerized surgical plan (CSP) workstation precisely to locate brain hematoma based on Multi-Planar Reconstruction (MPR) visualization technique. We used ten patients' CT/MR studies to verify our designed CSP intracerebral hemorrhage localization method. With the doctor's assessment and comparing with the results of manual measurements, the output of CSP WS for hematoma surgery is more precise and reliable than manual procedure.

  15. Human reconstructed skin xenografts on mice to model skin physiology.

    Science.gov (United States)

    Salgado, Giorgiana; Ng, Yi Zhen; Koh, Li Fang; Goh, Christabelle S M; Common, John E

    Xenograft models to study skin physiology have been popular for scientific use since the 1970s, with various developments and improvements to the techniques over the decades. Xenograft models are particularly useful and sought after due to the lack of clinically relevant animal models in predicting drug effectiveness in humans. Such predictions could in turn boost the process of drug discovery, since novel drug compounds have an estimated 8% chance of FDA approval despite years of rigorous preclinical testing and evaluation, albeit mostly in non-human models. In the case of skin research, the mouse persists as the most popular animal model of choice, despite its well-known anatomical differences with human skin. Differences in skin biology are especially evident when trying to dissect more complex skin conditions, such as psoriasis and eczema, where interactions between the immune system, epidermis and the environment likely occur. While the use of animal models are still considered the gold standard for systemic toxicity studies under controlled environments, there are now alternative models that have been approved for certain applications. To overcome the biological limitations of the mouse model, research efforts have also focused on "humanizing" the mice model to better recapitulate human skin physiology. In this review, we outline the different approaches undertaken thus far to study skin biology using human tissue xenografts in mice and the technical challenges involved. We also describe more recent developments to generate humanized multi-tissue compartment mice that carry both a functioning human immune system and skin xenografts. Such composite animal models provide promising opportunities to study drugs, disease and differentiation with greater clinical relevance. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  16. Temporal morphologic changes in human colorectal carcinomas following xenografting.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  17. High prevalence of cognitive impairment after intracerebral hemorrhage.

    Directory of Open Access Journals (Sweden)

    Mélanie Planton

    Full Text Available Cognitive impairment seems to be frequent in intracerebral hemorrhage (ICH survivors, but remains widely understudied. In this study, we investigated the frequency and patterns of vascular cognitive disorders (VCDs in patients with cerebral amyloid angiopathy (CAA-related and deep ICH compared to patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD and healthy controls.We prospectively recruited 20 patients with CAA-related lobar ICH, 20 with deep ICH, 20 with MCI-AD and 17 healthy controls. Patients with cognitive decline pre-ICH were excluded from the analysis. Each participant underwent a comprehensive neuropsychological assessment and a structural brain MRI. Cognitive assessment was performed at a median delay of 4 months after the acute phase in ICH patients, and more than 6 months after the first complaint in MCI-AD patients. Cognitive profiles were compared between groups. The prevalence of VCDs in the ICH groups was estimated using the recent VASCOG criteria."Mild" and "major VCDs" were respectively observed in 87.5% and 2.5% of all ICH patients. Every patient in the CAA group had mild VCDs. No significant difference was observed in cognitive functioning between CAA-related and deep ICH patients. The most impaired process in the CAA group was naming, with a mean (±standard deviation z-score of -5.2 ±5.5, followed by processing speed (-4.1±3.3, executive functioning (-2.6 ±2.5, memory (-2.4 ±3.5 and attention (-0.9 ±1.3. This cognitive pattern was different from the MCI-AD patients, but the groups were only different in gestural praxis, and by construction, in memory processes.VCDs are frequent after ICH. Cognitive patterns of patients with deep or CAA-related ICH did not differ, but there was impaired performance in specific domains distinct from the effects of Alzheimer's disease.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01619709.

  18. Boron neutron capture therapy of intracerebral rat gliosarcomas

    International Nuclear Information System (INIS)

    Joel, D.D.; Fairchild, R.G.; Laissue, J.A.; Saraf, S.K.; Kalef-Ezra, J.A.; Slatkin, D.N.

    1990-01-01

    The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation

  19. Pediatric intracerebral hemorrhage: acute symptomatic seizures and epilepsy.

    Science.gov (United States)

    Beslow, Lauren A; Abend, Nicholas S; Gindville, Melissa C; Bastian, Rachel A; Licht, Daniel J; Smith, Sabrina E; Hillis, Argye E; Ichord, Rebecca N; Jordan, Lori C

    2013-04-01

    Seizures are believed to be common presenting symptoms in neonates and children with spontaneous intracerebral hemorrhage (ICH). However, few data are available on the epidemiology of acute symptomatic seizures or the risk for later epilepsy. To define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous ICH. Our a priori hypotheses were that younger age at presentation, cortical involvement of ICH, acute symptomatic seizures after presentation, ICH due to vascular malformation, and elevated intracranial pressure requiring urgent intervention would predict remote symptomatic seizures and epilepsy. Prospective cohort study conducted between March 1, 2007, and January 1, 2012. Three tertiary care pediatric hospitals. Seventy-three pediatric subjects with spontaneous ICH including 20 perinatal (≥37 weeks' gestation to 28 days) and 53 childhood subjects (>28 days to Acute symptomatic seizures (clinically evident and electrographic-only seizures within 7 days), remote symptomatic seizures, and epilepsy. Acute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 perinatal (60%) and 19 childhood (36%) subjects (P = .07). Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9 of 32 subjects (28%) with continuous electroencephalogram monitoring. One-year and 2-year remote symptomatic seizure-free survival rates were 82% (95% CI, 68-90) and 67% (95% CI, 46-82), respectively. One-year and 2-year epilepsy-free survival rates were 96% (95% CI, 83-99) and 87% (95% CI, 65-95), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for seizures after presentation (P = .01; Fisher exact test), remote symptomatic seizures, and epilepsy (P = .03, and P = .04, respectively; log-rank test). Presenting seizures are common in perinatal and childhood ICH. Continuous

  20. Ecotropic murine leukemia virus-induced fusion of murine cells

    International Nuclear Information System (INIS)

    Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

    1986-01-01

    Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [ 3 H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells

  1. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis.

    Science.gov (United States)

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol

    2014-06-10

    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

  2. Antitumor activity of the multikinase inhibitor regorafenib in patient-derived xenograft models of gastric cancer.

    Science.gov (United States)

    Huynh, Hung; Ong, Richard; Zopf, Dieter

    2015-10-29

    Unresectable gastric cancer is associated with poor outcomes, with few treatment options available after failure of cytotoxic chemotherapy. Clinical trials of targeted therapies have generally shown no survival benefit in gastric cancer, with the exceptions of the antibodies ramucirumab (anti-VEGFR2) and trastuzumab (anti-HER2/neu). Given the efficacy of the multikinase inhibitor regorafenib in other gastrointestinal tumors, we investigated its potential in gastric cancer. The antitumor activity of oral regorafenib was assessed in eight murine patient-derived gastric cancer xenograft models. Dose-response experiments assessed the efficacy and tolerability of oral regorafenib 5, 10, and 15 mg/kg/day in two models, with 10 mg/kg/day selected for further investigation in all eight models. Tumor weight and volume was monitored during treatment; tumor cell proliferation, angiogenesis, apoptosis, and intracellular signaling were assessed using immunohistochemistry and Western blotting of total tumor lysates at the end of treatment. Regorafenib showed dose-dependent inhibition of tumor growth and was well tolerated, with no significant decreases in bodyweight or evident toxicity. Regorafenib 10 mg/kg/day significantly inhibited tumor growth in all eight models (72 to 96 %; all p Regorafenib reduced tumor angiogenesis 3- to 11-fold versus controls in all models (all p Regorafenib was effective in patient-derived models of gastric cancer of different histological subtypes, with inhibition of tumor growth, angiogenesis, and tumor-cell proliferation observed in almost all models. These findings are consistent with the observed activity of regorafenib in preclinical models of other gastrointestinal tumors, and support further clinical investigation in gastric cancer.

  3. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

  4. Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view.

    Science.gov (United States)

    Mathon, Bertrand; Nassar, Mérie; Simonnet, Jean; Le Duigou, Caroline; Clemenceau, Stéphane; Miles, Richard; Fricker, Desdemona

    2015-12-01

    Intracerebral injections of tracers or viral constructs in rodents are now commonly used in the neurosciences and must be executed perfectly. The purpose of this article is to update existing protocols for intracerebral injections in adult and neonatal mice. Our procedure for stereotaxic injections in adult mice allows the investigator to improve the effectiveness and safety, and save time. Furthermore, for the first time, we describe a two-handed procedure for intracerebral injections in neonatal mice that can be performed by a single operator in a very short time. Our technique using the stereotaxic arm allows a higher precision than freehand techniques previously described. Stereotaxic injections in adult mice can be performed in 20 min and have >90% efficacy in targeting the injection site. Injections in neonatal mice can be performed in 5 min. Efficacy depends on the difficulty of precisely localizing the injection sites, due to the small size of the animal. We describe an innovative, effortless, and reproducible surgical protocol for intracerebral injections in adult and neonatal mice.

  5. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mayer, Stephan A; Brun, Nikolai C; Begtrup, Kamilla

    2008-01-01

    BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes. METHODS: We randomly assigned 841...

  6. Aspirin in Alzheimer's Disease Increased Risk of Intracerebral Hemorrhage: Cause for Concern?

    NARCIS (Netherlands)

    Thoonsen, Hanneke; Richard, Edo; Bentham, Peter; Gray, Richard; van Geloven, Nan; de Haan, Rob J.; van Gool, Willem A.; Nederkoorn, Paul J.

    2010-01-01

    Background and Purpose-In a randomized controlled trial in Alzheimer's disease (AD), we found a higher number of intracerebral hemorrhages (ICHs) in patients randomized to aspirin treatment. Here, we evaluate the literature on the risk of ICH as a complication in patients with AD treated with

  7. Black Hole Sign: Novel Imaging Marker That Predicts Hematoma Growth in Patients With Intracerebral Hemorrhage.

    Science.gov (United States)

    Li, Qi; Zhang, Gang; Xiong, Xin; Wang, Xing-Chen; Yang, Wen-Song; Li, Ke-Wei; Wei, Xiao; Xie, Peng

    2016-07-01

    Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting hematoma growth in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth. A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; Phole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model. The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage. © 2016 American Heart Association, Inc.

  8. Diffusion-weighted MR imaging of ring-enhancing intracerebral lesions

    International Nuclear Information System (INIS)

    Li Youcheng; Li Jiance; Tian Wei; Li Zongfang

    2005-01-01

    Objective: To assess the diagnostic value of diffusion-weighted echo-planar MR Imaging (DWI) in ring-enhancing intracerebral lesions. Methods: Magnetic resonance diffusion-weighted images of ninty-three patients presenting with ring-ehancing intracerebral lesions diagnosed by clinical or histopathologic findings were studied retrospectively, including 21 gliomas, 26 metastases, 13 pyogenic abscesses, 18 neurocysticercoses and 15 subacute intracerebral hematomas. The signal intensity ratio on diffusion-weighted images and exponential diffusion coefficient images was calculated respectively in ring walls, central contents, and perilesional edemas of ring-enhancing lesions, and normal contralateral cerebral parenchyma was used for comparison. ADC values of interest of lesions, contralateral cerebral parenchyma and CFS were calculated as well. Results: In pyogenic abscesses and subacute intracerebral hematomas, the central content was always extremely hyperintense on diffusion-weighted images, and showed low ADCs [(0.56 ± 0.20) x 10 -3 mm 2 /s, (0.69 ± 0.16) x 10 -3 mm 2 /s, respectively]. On the other hand the central content of gliomas, metastases and neurocysticercoses was hypointense, and showed high ADCs [(2.76 ± 0.41 ) x 10 -3 mm 2 /s, (2.31 ± 0.39 ) x 10 -3 mm 2 /s, (2.10 ± 0.32) x 10 -3 mm 2 /s, respectively]. The ADCs of the first two lesions were significantly lower than of the last three lesions (P 2 -weighted images should be reviewed in daily clinical practice. (authors)

  9. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review

    DEFF Research Database (Denmark)

    Thompson, B B; Béjot, Y; Caso, V

    2010-01-01

    Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH....

  10. Water dissection technique of Toth for the treatment of hypertensive intracerebral putamen hemorrhage

    International Nuclear Information System (INIS)

    Wu Jiandong; Qian Surong; Lin Liqing; Wang Chenqiu; Wang Jianren; Wang Chen; Ying Guangzhong; Hui Guozhen

    2008-01-01

    Objective: To investige the possibility of water dissection technique of Toth for craniotomy with small bone flap through lateral fissure approach for the treatment of hypertensive intracerebral putamen hemorrhage. Methods: Twenty consecutive patients with hypertensive intracerebral putamen hemorrhage were treated by making a incision on sclap long about 6 cm across sylvian fissure, making a small bone flap about 3 cm x 3 cm, After opening dual, we injected water under microscopic control by a handheld syringe with a blunt needle applying repeated injection of physiological saline into the sylvian fissure to open it, opening the insular cortex, evacuation of intracerebral hematoma. Results: There was no further mortality. Patients who returned to ADL 1 and 2 (good recovery) after surgical treatment were 10, ADL 3 were 5, ADL 4 were 4, ADL 5 were 1. Conclusion: A method of water dissection technique of Toth for craniotomy with small bone flap through lateral fissure approach for the treatment of hypertensive intracerebral putamen hemorrhage is a method of convenient, safe, and with effective result. (authors)

  11. [Traumatic intracerebral pneumocephalus communicating with two different paranasal sinuses: a case report].

    Science.gov (United States)

    Wakamoto, H; Miyazaki, H; Hayashi, T; Shimamoto, Y; Ishiyama, N

    1998-02-01

    We report a case of a 17-year-old male who had hit the front of his head in a traffic accident. CT scan revealed contusional hemorrhage and pneumocephalus of the left frontal lobe 10 hours after the accident. A month later he complained of rhinorrhea and CT scan revealed intracerebral pneumocephalus. One day he complained of headache and began to vomit after he sneezed. CT scan revealed that the pneumocephalus had become worse and air had spread throughout the subarachnoid space. Bone CT scan revealed the air communicated from the frontal sinus to the intracerebral air cavity. 3D-CT scan revealed bone defect in the roof of the ethmoid sinus. The intraoperative findings revealed that the intracerebral air cavity communicated with the frontal sinus and ethmoid sinus. Though the brain which dropped into the paranasal sinus, adhered to the dura mater around the bone defect, a part of the brain had come off from the dura mater around the frontal sinus. We suspected that the intracerebral air cavity communicated with the frontal sinus initially. When the air cavity communicated with the ethmoid sinus secondarily, intracranial pressure abated and air came into the subarachnoid space from the frontal sinus.

  12. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry

    2006-01-01

    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin...

  13. CT and SPECT in bilateral hypertensive intracerebral hemorrhages of simultaneous onset

    International Nuclear Information System (INIS)

    Kikuchi, Kenji; Kojima, Hisashi; Kowada, Masayoshi; Ogayama, Hiroyuki; Watanabe, Kazuo.

    1988-01-01

    A 59-year-old woman was admitted to the hospital on November 6, 1983, after she suddenly lost consciousness. She was semicomatous, and the level of consciousness was evaluated as 100 according to the Japan Coma Scale. There were left hemiparesis and conjugate deviation to the right. CT scans obtained one hour after onset demonstrated bilateral intracerebral hemorrhages involving the right basal ganglia and the left posterior temporal region. Carotid angiograms failed to demonstrate the presence of either cerebral aneurysms or arteriovenous malformations which might be responsible for the intracerebral hemorrhages. A right fronto-temporal craniotomy was performed, and about 50 ml of intracerebral blood clots were evacuated by the transcortical approach. The patient was discharged with left hemiparesis, disorientation, and pseudobulbar palsy. A 57-year-old man was transferred to the hospital on February 22, 1986, with an episode of cerebral stroke. On admission he was free of symptoms except for mild hemiparesis on the right side. CT scan was performed nine days after onset, revealing bilateral intracerebral hemorrhages involving the right putamen and the left thalamus. Bilateral carotid angiograms showed an avascular mass lesion medial to the left insula, displacing both the left lenticulostriate arteries and the insular segment of the left middle cerebral artery laterally. No abnormal vascular lesions, such as cerebral aneurysms and arteriovenous malformations, were demonstrated. SPECT was performed using the continuous inhalation of Xe-133, and a prolonged decrease in the cerebral blood flow was demonstrated in the vicinity of the bilateral intracerebral hematomas, in contrast to the gradual alleviations shown on CT images. (J.P.N.)

  14. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Alejo A. Morales; Duconge, Jorge; Alvarez-Ruiz, Daniel; Becquer-Viart, Maria de Los Angeles; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Caballero-Torres, Idania; Iznaga-Escobar, Normando

    2000-02-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG{sub 1}), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 {mu}g/100 {mu}Ci of {sup 99m}Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of {sup 99m}Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significant accumulation was found in tumor (6.14{+-}2.50 %ID/g, 5.06{+-}2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy.

  15. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies

    International Nuclear Information System (INIS)

    Morales, Alejo A. Morales; Duconge, Jorge; Alvarez-Ruiz, Daniel; Becquer-Viart, Maria de Los Angeles; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Caballero-Torres, Idania; Iznaga-Escobar, Normando

    2000-01-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG 1 ), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 μg/100 μCi of 99m Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of 99m Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significant accumulation was found in tumor (6.14±2.50 %ID/g, 5.06±2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy

  16. Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

    International Nuclear Information System (INIS)

    Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L.

    1990-01-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively

  17. Aortic valve replacement with the Biocor PSB stentless xenograft.

    Science.gov (United States)

    Bertolini, P; Luciani, G B; Vecchi, B; Pugliese, P; Mazzucco, A

    1998-08-01

    The midterm clinical results after aortic valve replacement with the Biocor PSB stentless xenograft on all patients operated between October 1992 and October 1996 were reviewed. One hundred six patients, aged 70+/-6 years, had aortic valve replacement for aortic stenosis (67%), regurgitation (11%), or both (22%). Associated procedures were done in 49 patients (46%), including coronary artery bypass in 30 patients, mitral valve repair/replacement in 16, and ascending aorta replacement in 5 patients. Aortic cross-clamp and cardiopulmonary bypass times were 96+/-24 and 129+/-31 minutes, respectively. There were 3 (3%) early deaths due to low output (2 patients) and cerebrovascular accident (1 patient). Follow-up of survivors ranged from 6 to 66 months (mean, 39+/-14 months). Survival was 94%+/-2% and 90%+/-3% at 1 and 5 years. There were 5 late deaths due to cardiac cause (2), cancer (2), and pulmonary embolism (1 patient). No patient had structural valve deterioration, whereas 100% and 95%+/-3% were free from valve-related events at 1 and 5 years. There were two reoperations due to narrowing of the left coronary ostium and endocarditis, with an actuarial freedom from reoperation of 99%+/-1% and 98+/-1% at 1 and 5 years, respectively. Functional results demonstrated a mean peak transprosthetic gradient of 16+/-12 mm Hg, with only 1 patient (1%) with a 55 mm Hg gradient. No cases of valve regurgitation greater than mild were recorded at follow-up. Assessment of New York Heart Association functional class demonstrated a significant improvement (2.9+/-0.6 versus 1.4+/-0.7; p=0.01). All patients were free from anticoagulation. Aortic valve replacement using the Biocor PSB stentless xenograft offers excellent midterm survival, negligible valve deterioration, and a very low rate of valve-related events, which are comparable to estimates reported with other models of stentless xenografts and currently available stented xenografts. Hemodynamic performance is favorable and

  18. Patient-Derived Xenografts of Non Small Cell Lung Cancer: Resurgence of an Old Model for Investigation of Modern Concepts of Tailored Therapy and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Massimo Moro

    2012-01-01

    Full Text Available Current chemotherapy regimens have unsatisfactory results in most advanced solid tumors. It is therefore imperative to devise novel therapeutic strategies and to optimize selection of patients, identifying early those who could benefit from available treatments. Mouse models are the most valuable tool for preclinical evaluation of novel therapeutic strategies in cancer and, among them, patient-derived xenografts models (PDX have made a recent comeback in popularity. These models, obtained by direct implants of tissue fragments in immunocompromised mice, have great potential in drug development studies because they faithfully reproduce the patient’s original tumor for both immunohistochemical markers and genetic alterations as well as in terms of response to common therapeutics They also maintain the original tumor heterogeneity, allowing studies of specific cellular subpopulations, including their modulation after drug treatment. Moreover PDXs maintain at least some aspects of the human microenvironment for weeks with the complete substitution with murine stroma occurring only after 2-3 passages in mouse and represent therefore a promising model for studies of tumor-microenvironment interaction. This review summarizes our present knowledge on mouse preclinical cancer models, with a particular attention on patient-derived xenografts of non small cell lung cancer and their relevance for preclinical and biological studies.

  19. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    NARCIS (Netherlands)

    Verhoeff, Joost J. C.; Stalpers, Lukas J. A.; Coumou, Annet W.; Koedooder, Kees; Lavini, Cristina; van Noorden, Cornelis J. F.; Haveman, Jaap; Vandertop, William P.; van Furth, Wouter R.

    2007-01-01

    BACKGROUND: High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models- high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a

  20. Targeting Secondary Hematoma Expansion in Spontaneous Intracerebral Hemorrhage—State of the Art

    Directory of Open Access Journals (Sweden)

    Jian Guan

    2016-10-01

    Full Text Available Spontaneous intracerebral hemorrhage (SICH, defined broadly as intracerebral hemorrhage not related to trauma, results in long-term disability or death in a large proportion of afflicted patients. Current management of this disease is predominantly supportive, including airway protection, optimization of hemodynamic parameters, and management of intracranial pressure. No active treatments that demonstrate beneficial effects on clinical outcome are currently available. Animal models of SICH have allowed for the elucidation of multiple pathways that may be attractive therapeutic targets. A minority of these, such as aggressive blood pressure management and recombinant activated factor VII administration, have lead to large-scale clinical trials. There remains a critical need for further translational research in the realm of SICH.

  1. Application of electronic endoscopy and CT-guided stereotactic aspiration to intracerebral hematoma

    International Nuclear Information System (INIS)

    Kusaka, Masahiko

    1991-01-01

    According to the development of computer technology and operative instruments, stereotactic neurosurgery became more precise, and extended as its indication. CT-guided stereotactic aspiration of intracerebral hematoma is superior operative procedure with rare complications. Using Stereotactic Aqua-Stream and Aspirator at the same time, hematoma was removed sufficiently. However, stereotactic neurosurgery had a major weak points, it was a blind operation. An endoscope (FVS-1000, M and M Co.) and SASA (Marui Medical Co.) were applied in 5 cases of intracerebral hematoma. In physiological saline, the endoscope had 32.9 deg angle of visual field, 1 mm - 25 mm depth of vision, and 16 pair/mm resolution. It was excellent ability for neurosurgery. Using for clinical cases, the bloody fluid in the hematoma cavity disturbed visibility. It was a difficult problem. Influence of bloody fluid concentration to depth of vision and resolution was investigated, and method of making clear visibility was described. (author)

  2. Treatment of intracerebral haemorrhage with tranexamic acid – A review of current evidence and ongoing trials

    DEFF Research Database (Denmark)

    Law, Zhe Kang; Meretoja, Atte; Engelter, Stefan T

    2017-01-01

    Purpose Haematoma expansion is a devastating complication of intracerebral haemorrhage (ICH) with no established treatment. Tranexamic acid had been an effective haemostatic agent in reducing post-operative and traumatic bleeding. We review current evidence examining the efficacy of tranexamic acid...... in improving clinical outcome after ICH. Method We searched MEDLINE, EMBASE, CENTRAL and clinical trial registers for studies using search strategies incorporating the terms ‘intracerebral haemorrhage’, ‘tranexamic acid’ and ‘antifibrinolytic’. Authors of ongoing clinical trials were contacted for further...... details. Findings We screened 268 publications and retrieved 17 articles after screening. Unpublished information from three ongoing clinical trials was obtained. We found five completed studies. Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n = 54...

  3. Benign Sphenoid Wing Meningioma Presenting with an Acute Intracerebral Hemorrhage – A Case Report

    Directory of Open Access Journals (Sweden)

    Radek Frič

    2016-01-01

    Full Text Available Background and Study Object We report an unusual case of a benign lateral sphenoid wing meningioma that presented with, and was masked by, an acute intracerebral hemorrhage. Case Report A 68-year-old woman was admitted after sudden onset of coma. Computed tomography (CT revealed an intracerebral hemorrhage, without any underlying vascular pathology on CT angiography. During the surgery, we found a lateral sphenoid wing meningioma with intratumoral bleeding that extended into the surrounding brain parenchyma. Results We removed the hematoma and resected the tumor completely in the same session. The histopathological classification of the tumor was a WHO grade I meningothelial meningioma. The patient recovered very well after surgery, without significant neurological sequelae. Conclusions Having reviewed the relevant references from the medical literature, we consider this event as an extremely rare presentation of a benign sphenoid wing meningioma in a patient without any predisposing medical factors. The possible mechanisms of bleeding from this tumor type are discussed.

  4. Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury

    OpenAIRE

    Fang, Huang; Wang, Peng-Fei; Zhou, Yu; Wang, Yan-Chun; Yang, Qing-Wu

    2013-01-01

    Intracerebral hemorrhage (ICH) is a common type of fatal stroke, accounting for about 15% to 20% of all strokes. Hemorrhagic strokes are associated with high mortality and morbidity, and increasing evidence shows that innate immune responses and inflammatory injury play a critical role in ICH-induced neurological deficits. However, the signaling pathways involved in ICH-induced inflammatory responses remain elusive. Toll-like receptor 4 (TLR4) belongs to a large family of pattern recognition ...

  5. CD36-Mediated Hematoma Absorption following Intracerebral Hemorrhage: Negative Regulation by TLR4 Signaling

    OpenAIRE

    Fang, Huang; Chen, Jing; Lin, Sen; Wang, PengFei; Wang, YanChun; Xiong, XiaoYi; Yang, QingWu

    2014-01-01

    Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic defic...

  6. Natural and synthetic retinoids afford therapeutic effects on intracerebral hemorrhage in mice.

    Science.gov (United States)

    Matsushita, Hideaki; Hijioka, Masanori; Hisatsune, Akinori; Isohama, Yoichiro; Shudo, Koichi; Katsuki, Hiroshi

    2012-05-15

    We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we further addressed the effects of retinoids as potential therapeutic drugs, using a collagenase-induced model of intracerebral hemorrhage. Daily oral administration of all-trans retinoic acid (ATRA; 5 and 15 mg/kg), a naturally occurring NR1B agonist, from 1 day before collagenase injection significantly inhibited loss of neurons within the hematoma. ATRA in the same treatment regimen also decreased the number of activated microglia/macrophages around the hematoma but did not affect the hematoma volume. ATRA (15 mg/kg) as well as Am80 (5mg/kg) rescued neurons in the central region of hematoma, even when drug administration was started from 6h after induction of intracerebral hemorrhage. However, in this post-treatment regimen, only Am80 significantly decreased the number of activated microglia/macrophages. With regard to neurological deficits, both ATRA (15 mg/kg) and Am80 (5mg/kg) given in the post-treatment regimen improved performance of mice in the beam-walking test and the modified limb-placing test. ATRA and Am80 also significantly attenuated damage of axon tracts as revealed by amyloid precursor protein immunohistochemistry. These results underscore potential therapeutic values of NR1B agonists for intracerebral hemorrhage. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare differential diagnosis in Central Europe

    International Nuclear Information System (INIS)

    Sabel, M.; Weber, F.; Neuen-Jacob, E.; Vogt, C.

    2001-01-01

    A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/μl) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis. (orig.)

  8. Recent advances in the management of post-operative intracerebral vasospasm

    Directory of Open Access Journals (Sweden)

    Harihar Dash

    2017-01-01

    Full Text Available Postoperative intracerebral vasospasm is one of the leading causes of morbidity and mortality following clipping of intra cranial aneurysm. Early diagnosis, prompt and effective management helps in salvaging these patients. Umpteen modalities of treatment strategies are available to achieve good neurologic recovery. Intraarterial nimodipine, nicardipine and milrinon provide good neurologic recovery. Stellate ganglion block on the affected side is also a treatment modality which needs to be investigated.

  9. Chronological changes in hypertensive intracerebral hemorrhages. An experimental and clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Takasugi, Shinsuke; Kashihara, Michiharu; Okamoto, Junji; Hondo, Hideki; Yamashita, Shigeru [Tokushima Univ. (Japan). School of Medicine

    1983-04-01

    The clinical series consisted of 28 patients with hypertensive intracerebral hematoma observed in the natural course from 1976 through 1978. A total of 114 repeated computer tomographic (CT) examinations were made with an EMI-1010 or an ACTA-0100 scanner. The experimental series consisted of 26 adult mongrel dogs with intracerebral hematoma near the basal ganglia. In 20 dogs, autopsy and histological examinations were performed, and in 12 dogs a total of 31 repeated CT examinations were carried out with an EMI scanner (matrix 320 x 320, high-definition scan). In the clinical series, the time of the decrease in density beginning in the periphery of the hematoma, like the first appearance of ring enhancement and its concentric concentration toward the center of the hematoma, was not affected by the size of the hematoma. However, the time when the intracerebral hematoma was resolved did vary with the size of the hematoma. In the experimental series, the tissue reaction near the periphery of the intracerebral hematoma seemed to be a constant process. First, a necrotic layer appeared, and then this was replaced by immature connective tissue with granular cells, newly formed vessels, and reticulin fibers; finally, the immature layer was gradually transformed into mature connective tissue with collagenous fibers. Moreover, this process of change was not related to the size of the hematoma. The following correlations were suggested by a chronological observation of the CT images and the histological appearance: 1) acute stage - homogeneous high-density extending to the periphery, apperance of a necrotic layer; 2) subacute stage - decreased density spreading from the periphery and formation of ring enhancement, apperance of immature connective tissue with reticulin fibers; 3) chronic stage - concentric concentration of ring enhancement, mature connective tissue with collagenous fibers.

  10. Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

    International Nuclear Information System (INIS)

    Nakajima, Y.; Lie, T.S.; Nakauo, H.; Nakagawa, K.; Segawa, M.

    1984-01-01

    Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by 51 Cr release assay

  11. Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Y; Lie, T S [Bonn Univ. (Germany, F.R.). Chirurgische Klinik und Poliklinik; Nakauo, H; Nakagawa, K; Segawa, M [Nara Women' s Univ. (Japan). Dept. of Physics

    1984-01-01

    Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by /sup 51/Cr release assay.

  12. Dynamic modulation of phosphoprotein expression in ovarian cancer xenograft models

    International Nuclear Information System (INIS)

    Koussounadis, Antonis; Langdon, Simon P.; Um, Inhwa; Kay, Charlene; Francis, Kyle E.; Harrison, David J.; Smith, V. Anne

    2016-01-01

    The dynamic changes that occur in protein expression after treatment of a cancer in vivo are poorly described. In this study we measure the effect of chemotherapy over time on the expression of a panel of proteins in ovarian cancer xenograft models. The objective was to identify phosphoprotein and other protein changes indicative of pathway activation that might link with drug response. Two xenograft models, platinum-responsive OV1002 and platinum-unresponsive HOX424, were used. Treatments were carboplatin and carboplatin-paclitaxel. Expression of 49 proteins over 14 days post treatment was measured by quantitative immunofluorescence and analysed by AQUA. Carboplatin treatment in the platinum-sensitive OV1002 model triggered up-regulation of cell cycle, mTOR and DDR pathways, while at late time points WNT, invasion, EMT and MAPK pathways were modulated. Estrogen receptor-alpha (ESR1) and ERBB pathways were down-regulated early, within 24 h from treatment administration. Combined carboplatin-paclitaxel treatment triggered a more extensive response in the OV1002 model modulating expression of 23 of 49 proteins. Therefore the cell cycle and DDR pathways showed similar or more pronounced changes than with carboplatin alone. In addition to expression of pS6 and pERK increasing, components of the AKT pathway were modulated with pAKT increasing while its regulator PTEN was down-regulated early. WNT signaling, EMT and invasion markers were modulated at later time points. Additional pathways were also observed with the NFκB and JAK/STAT pathways being up-regulated. ESR1 was down-regulated as was HER4, while further protein members of the ERBB pathway were upregulated late. By contrast, in the carboplatin-unresponsive HOX 424 xenograft, carboplatin only modulated expression of MLH1 while carboplatin-paclitaxel treatment modulated ESR1 and pMET. Thirteen proteins were modulated by carboplatin and a more robust set of changes by carboplatin-paclitaxel. Early changes included

  13. Spot Sign in Acute Intracerebral Hemorrhage in Dynamic T1-Weighted Magnetic Resonance Imaging.

    Science.gov (United States)

    Schindlbeck, Katharina A; Santaella, Anna; Galinovic, Ivana; Krause, Thomas; Rocco, Andrea; Nolte, Christian H; Villringer, Kersten; Fiebach, Jochen B

    2016-02-01

    In computed tomographic imaging of acute intracerebral hemorrhage spot sign on computed tomographic angiography has been established as a marker for hematoma expansion and poor clinical outcome. Although, magnetic resonance imaging (MRI) can accurately visualize acute intracerebral hemorrhage, a corresponding MRI marker is lacking to date. We prospectively examined 50 consecutive patients with acute intracerebral hemorrhage within 24 hours of symptom onset. The MRI protocol consisted of a standard stroke protocol and dynamic contrast-enhanced T1-weighted imaging with a time resolution of 7.07 s/batch. Stroke scores were assessed at admission and at time of discharge. Volume measurements of hematoma size and spot sign were performed with MRIcron. Contrast extravasation within sites of the hemorrhage (MRI spot sign) was seen in 46% of the patients. Patients with an MRI spot sign had a significantly shorter time to imaging than those without (Pspot sign compared with those without (P≤0.001). Hematoma expansion was observed in the spot sign group compared with the nonspot sign group, although the differences were not significant. Spot sign can be detected using MRI on postcontrast T1-weighted and dynamic T1-weighted images. It is associated with worse clinical outcome. The time course of contrast extravasation in dynamic T1 images indicates that these spots represent ongoing bleeding. © 2015 American Heart Association, Inc.

  14. Symptomatic Intracerebral Hemorrhage Secondary to Ventriculoperitoneal Shunt in Adults without Bleeding Tendency.

    Science.gov (United States)

    Hou, Kun; Suo, Shihuan; Gao, Xianfeng; Zhu, Xiaobo; Zhang, Yang; Li, Guichen

    2017-10-01

    Ventriculoperitoneal shunt (VPS) is a common procedure in daily neurosurgical practice. According to some reports, the rate of intracerebral hemorrhage secondary to VPS in patients with no bleeding tendency can be 43.1%; however, symptomatic intracerebral hemorrhage (SICH) secondary to VPS is rare with only sporadic cases reported in adults. To further elucidate the characteristics, mechanism, management, and prognosis of SICH secondary to VPS, we performed a retrospective study in our institution and a systematic review of the literature. A retrospective review of the medical records of patients admitted for VPS was performed. We also performed a systematic PubMed search of published studies. Of 5 patients identified at our institution, 3 experienced a favorable recovery. Including our case series, there were 16 (8 female) patients. The time interval from the termination of VPS procedure to SICH was 4 hours to 15 days. All but 1 patient experienced intracerebral hemorrhage adjacent to cannulation. Of 11 patients in whom a Glasgow Outcome Scale score could be obtained, the score was 5 in 4 patients, 4 in 1 patient, 3 in 1 patient, and 1 in 5 patients. SICH is a rare complication after VPS in adults without bleeding tendency. The mechanism is obscure, management is challenging, and prognosis is dismal. Future prospective study is anticipated. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Intracerebral haemorrhage associated with hourly concentration of ambient particulate matter: case-crossover analysis.

    Science.gov (United States)

    Yamazaki, S; Nitta, H; Ono, M; Green, J; Fukuhara, S

    2007-01-01

    To examine the association of hourly time lagged concentration of ambient particulate matter and death due to stroke. Mortality data for five years (January 1990 to December 1994) were obtained from the Ministry of Health, Labour, and Welfare of Japan. Data were used only if the deceased was 65 years old or older at the time of death, if death was attributed to intracerebral haemorrhage or ischaemic stroke, and if the deceased lived in one of 13 major urban areas. Hourly mean concentrations of PM7, NO2, and photochemical oxidants were measured at monitoring stations in the 13 areas. Time stratified case-crossover analysis was used to examine the data for evidence of triggering stroke mortality. The 1-hour mean concentration of PM7 measured about 2 hours before death was associated with the risk of death due to intracerebral haemorrhage from April to September (odds ratio = 2.40, 95% CI 1.48 to 3.89, for exposure to PM7 of more than 200 microg/m3 (threshold)). The higher risk was independent of the 24-hour mean concentration of PM7. PM7 was not associated with death due to ischaemic stroke. Transiently high concentrations of PM7 are associated with death due to intracerebral haemorrhage. Air quality standards or guidelines for particulate matter should be based not only on 24-hour mean concentrations, but also on hourly data.

  16. Intracerebral haemorrhage associated with hourly concentration of ambient particulate matter: case‐crossover analysis

    Science.gov (United States)

    Yamazaki, S; Nitta, H; Ono, M; Green, J; Fukuhara, S

    2007-01-01

    Aims To examine the association of hourly time lagged concentration of ambient particulate matter and death due to stroke. Methods Mortality data for five years (January 1990 to December 1994) were obtained from the Ministry of Health, Labour, and Welfare of Japan. Data were used only if the deceased was 65 years old or older at the time of death, if death was attributed to intracerebral haemorrhage or ischaemic stroke, and if the deceased lived in one of 13 major urban areas. Hourly mean concentrations of PM7, NO2, and photochemical oxidants were measured at monitoring stations in the 13 areas. Time stratified case‐crossover analysis was used to examine the data for evidence of triggering stroke mortality. Results The 1‐hour mean concentration of PM7 measured about 2 hours before death was associated with the risk of death due to intracerebral haemorrhage from April to September (odds ratio = 2.40, 95% CI 1.48 to 3.89, for exposure to PM7 of more than 200 μg/m3 (threshold)). The higher risk was independent of the 24‐hour mean concentration of PM7. PM7 was not associated with death due to ischaemic stroke. Conclusions Transiently high concentrations of PM7 are associated with death due to intracerebral haemorrhage. Air quality standards or guidelines for particulate matter should be based not only on 24‐hour mean concentrations, but also on hourly data. PMID:16847037

  17. Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report

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    Karamadoukis Lazarus

    2008-06-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and young adolescence. Case presentation We describe a 42-year-old man with Henoch-Schönlein purpura who developed an acute intracerebral haemorrhage that coincided with a reactivation of his vasculitis and the development of renal failure following discontinuation of steroids. In this patient, both the Henoch-Schönlein purpura and his neurological symptoms were successfully treated with intravenous cyclophosphamide and methylprednisolone, followed by a short course of oral cyclophosphamide and long-term oral prednisolone. His renal function also recovered sufficiently not to require renal replacement therapy. Conclusion The management of Henoch-Schönlein nephritis remains unclear, especially in the presence of severe complications such as intracerebral haemorrhage. We describe a successful outcome in such a patient.

  18. Clinical application of three dimensional ultrafast MR imaging to intracerebral traumatic lesions

    International Nuclear Information System (INIS)

    Enomoto, Kyoko; Amanuma, Makoto; Hasegawa, Makoto; Watabe, Tsuneya; Heshiki, Atsuko

    1994-01-01

    We applied a T1-weighted three-dimensional (3D) magnetization-prepared rapid gradient-echo sequence (MPRAGE) for the detection of intracerebral lesions associated with closed head injuries. Thirty-four patients underwent brain MR imaging on a 1.5 Tesla superconducting MR unit. We applied an MPRAGE sequence, together with spin echo (SE) and gradient echo (GRE) sequences, and evaluated the detectability of lesions with each sequence. A total of 100 intracerebral traumatic lesions (33 cortical contusion, 56 diffuse axonal injury, 11 subcortical gray matter injury) were found. Ninety-seven percent of all lesions were detected on MPRAGE images, and 67% on SE and GRE images. The detectability of lesions in each category was 91%, 98%, and 100% on MPRAGE images, and 88%, 54%, and 73% on either SE or GRE images. 3D MPRAGE is a promising method to detect intracerebral traumatic lesions, particularly those associated with diffuse axonal injury, because of its high quality of contrast and spatial resolution and the capability of image reconstruction in any plane. (author)

  19. Delayed angiography in the investigation of intracerebral hematomas caused by small arteriovenous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Willinsky, R.A. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada)); Fitzgerald, M. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada)); TerBrugge, K. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada)); Montanera, W. (Dept. of Radiology, Toronto Hospital, Western Div., Toronto, ON (Canada)); Wallace, M. (Div. of Neurosurgery, Dept. of Surgery, Toronto Hospital, Western Div., ON (Canada) Univ. of Toronto, Brain Vascular Malformation Study Group, ON (Canada))

    1993-04-01

    We reviewed the clinical and radiological features of ten patients with small arteriovenous malformations that caused intracerebral hematomas. In six patients, angiography showed a small nidus (less than 1 cm in diameter) with a shunt at the site of the hematoma, and in four only an early-filling vein was evident. Six patients had only delayed angiography (4 weeks or more after the ictus). In three, angiography within 2 days of the ictus failed to reveal the cause of the bleed, but repeat angiography showed an early-filling vein in two, and a nidus with shunting in one. In only one patient did early angiography reveal the malformation. MRI was obtained in eight patients, and in two prominent vessels were evident in the wall of the hematoma cavity. In investigation of an unexplained intracerebral hematoma, MRI may be useful to exclude a neoplasm or cavernoma, although the latter may be not be evident in the presence of a recent hematoma. We suggest early MRI and angiography for investigation of an unexplained, nonhypertensive intracerebral bleed, with follow-up MRI and dealyed angiography if the initial studies fail to reveal the cause. (orig.)

  20. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith

    2000-10-01

    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  2. Imported rickettsioses : think of murine typhus

    NARCIS (Netherlands)

    van der Kleij, FGH; Gansevoort, RT; Kreeftenberg, HG

    Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur,

  3. Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology.

    Science.gov (United States)

    Hölsken, Annett; Schwarz, Marc; Gillmann, Clarissa; Pfister, Christina; Uder, Michael; Doerfler, Arnd; Buchfelder, Michael; Schlaffer, Sven; Fahlbusch, Rudolf; Buslei, Rolf; Bäuerle, Tobias

    2018-01-01

    Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

  4. The use of lyophilised bovine bone xenograft in mandibular reconstructive surgery - an animal experimental surgery

    International Nuclear Information System (INIS)

    Samsudin, A.R.; Meor Kamal, M. Z.; Afifi Abu Bakar

    1999-01-01

    The aim of this study is to look at the effectiveness of using lyophillised bovine bone xenograft in mandibular reconstructive surgery. Six adult merino sheep underwent bilateral marginal block resection of the mandible under general anaesthesia. The defect on the right body of mandible was left alone while the similar mandibulectomy defect on the left body of mandible was reconstructed using a cortico-cancellous block of radiosterilised lyophillised bovine bone xenograft which was procured from a calve femur. The bone xenograft was fixed and immobilized using titanium mini plates and screws. All the sheep returned to the controlled grazing ground on the 7th. Postoperative day. One sheep was sacrificed every month and the mandible was retrieved for postmortem gross and microscopical histological examination. Clinical results showed no evidence of tissue rejection in the mandible of the sheep and all the wounds healed well. All sheep showed no problem with normal eating habits. Histological examination showed resorption of the xenograft very early at one month postoperative and xenograft resorption together with new host bone deposition started at 2 months postoperative and maximise at 6 months postoperative. There is also evidence showing that the cancellous portion resorp more than the cortical portion of the xenograft. In conclusion, cortico-cancellous blocks of bovine bone xenograft may be use in mandibular reconstructive surgery giving esthetically acceptable, functional, biocompatible and overall clinically predictable results

  5. A human lung xenograft mouse model of Nipah virus infection.

    Directory of Open Access Journals (Sweden)

    Gustavo Valbuena

    2014-04-01

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

  6. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-01-01

    AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W2) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm3; 30 mg/kg per day, 612 ± 46 mm3; 50 mg/kg per day, 563 ± 38 mm3; and 70 mg/kg per day, 221 ± 26 mm3. Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2

  7. Abdominal sacrocolpopexy with Pelvicol xenograft and concomitant Burch colposuspension

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    Hijazi S

    2017-09-01

    Full Text Available Sameh Hijazi,1,2 Dieter Echtle,3 Omar M Aboumarzouk,4 Elmar Heinrich2,5 1Department of Urology, Klinikum Ibbenbüeren, Ibbenbüeren, 2Department of Urology, University Medical Center, Goettingen, 3Department of Urology, Städtische Kliniken Mönchengladbach, Mönchengladbach, Germany; 4Urology Department, Newport, Wales, UK; 5Department of Urology, Klinikum Wels-Grieskirchen, Standort Wels, Austria Purpose: To evaluate the efficacy of Pelvicol xenograft use during abdominal sacrocolpopexy to repair pelvic organ prolapse (POP.Patients and methods: A total of 27 consecutive women with symptomatic POP were included in this study. A POP-quantification system and International Continence Society classification were used. Functional and anatomical outcomes were assessed. Subjective outcomes and physical activity after surgery were evaluated due to modified quality of life questionnaire.Results: Median follow-up was 21 months (range: 16 to 41 months. Twenty-four (89% patients were available for anatomical and subjective evaluation. Preoperative POP- quantification classification was: stage I: 11.1%, stage II: 25.9%, stage III: 48.2%, and stage IV: 14.8%. Overall, pad usage significantly decreased (mean 4.8 vs 1 pads, P=0.001. Stress urinary incontinence significantly improved after surgery in nine women (P=0.001. An additional five women were completely continent. No de-novo incontinence developed. Six women with preoperative urinary retention improved in the amount of residual urine postoperative (mean 35 vs 165 mL. Failure rate was 8.3% at 3 and 11 months after surgery, requiring a second reconstruction. There was no graft related complications or graft rejections necessitating removal occurring. Response rate of the questionnaire was 67%. Two women reported no interference in physical activity after 2 postoperative months, five women after 5 months, and five women 1 year later. Pelvic pain (vaginal pain was partly improved in eight patients

  8. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-09-28

    To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which

  9. Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig

    DEFF Research Database (Denmark)

    Bjarkam, Carsten R; GLUD, AN; Margolin, Lee

    2010-01-01

    Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig......Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig...

  10. Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan

    DEFF Research Database (Denmark)

    Ovesen, Christian; Jakobsen, Janus Christian; Gluud, Christian

    2018-01-01

    OBJECTIVE: We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared...... to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid...... versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status. RESULTS: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma...

  11. Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

    Science.gov (United States)

    Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

    2015-01-01

    It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

  12. Curcumin-Artemisinin Coamorphous Solid: Xenograft Model Preclinical Study

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    M. K. Chaitanya Mannava

    2018-01-01

    Full Text Available Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR, we evaluated Curcumin-Pyrogallol (CUR-PYR cocrystal and Curcumin-Artemisinin (CUR-ART coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose. Moreover, in simulated gastric and intestinal fluids (SGF and SIF, CUR-ART is stable up to 3 and 12 h, respectively. In addition, CUR-PYR and CUR-ART showed no adverse effects in toxicology studies (10 times higher dose at 2000 mg/kg. CUR-ART showed higher therapeutic effect and inhibited approximately 62% of tumor growth at 100 mg/kg oral dosage of CUR in xenograft models, which is equal to the positive control drug, doxorubicin (2 mg/kg by i.v. administration.

  13. Src controls castration recurrence of CWR22 prostate cancer xenografts

    International Nuclear Information System (INIS)

    Su, Bing; Gillard, Bryan; Gao, Lingqiu; Eng, Kevin H; Gelman, Irwin H

    2013-01-01

    Recurrence of prostate cancer (CaP) after androgen-deprivation therapy continues to have the greatest impact on patient survival. Castration-recurrent (CR)-CaP is likely driven by the activation of androgen receptor (AR) through multiple mechanisms including induction of AR coregulators, AR mutants or splice variants, and AR posttranslational modification such as phosphorylation by Src-family and Ack1 tyrosine kinases. Here, we address whether Src is required for the CR growth of human CWR22 CaP xenografts. The shRNA-mediated Src knockdown or treatment with the Src inhibitors, dasatinib or KXO1, reduced CaP recurrence over controls and increased time-to-recurrence following castration. Moreover, CR-CaP [Src-shRNA] tumors that recurred had similar Src protein and activation levels as those of parental cells, strengthening the notion that Src activity is required for progression to CR-CaP. In contrast, the ability of dasatinib or KXO1 to inhibit Src kinase activity in vitro did not correlate with their ability to inhibit serum-driven in vitro proliferation of CR and androgen-dependent stable cell lines derived from CWR22 tumors (CWR22Rv1 and CWR22PC, respectively), suggesting that the in vitro proliferation of these CaP lines is Src independent. Taken together, these findings strongly suggest that Src is a potent and specific therapeutic target for CR-CaP progression

  14. Vascular abnormalities associated with acute hypoxia in human melanoma xenografts

    International Nuclear Information System (INIS)

    Simonsen, Trude G.; Gaustad, Jon-Vidar; Leinaas, Marit N.; Rofstad, Einar K.

    2012-01-01

    Background and purpose: The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts. Materials and methods: Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy. Results: R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells. Conclusion: The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.

  15. Hypoxia and metastasis in an orthotopic cervix cancer xenograft model

    International Nuclear Information System (INIS)

    Chaudary, Naz; Mujcic, Hilda; Wouters, Bradly G.; Hill, Richard P.

    2013-01-01

    Background: Hypoxia can promote tumor metastasis by mechanisms that are believed to result from changes in gene expression. The current study examined the role of putative metastatic genes regulated by cyclic hypoxia in relation to metastasis formation in orthotopic models of cervix cancer. Methods: Orthotopic tumors derived from ME180 human cervix cancer cells or from early generation human cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth in vivo and tumor growth and lymphnode metastases were monitored. Expression of the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth. Results: As reported previously, exposure of tumor bearing mice to cyclic hypoxia caused a reduction of tumor growth but a large increase in metastasis. Inhibition of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor size and reduced lymphatic metastasis to levels below those seen in control mice exposed to normoxic conditions. Conclusion: Blocking CXCR4 or Hh gene expression are potential therapeutic pathways for improving cervix cancer treatment

  16. Evolution of blood pressure management in acute intracerebral hemorrhage [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Stacy Chu

    2017-11-01

    Full Text Available Intracerebral hemorrhage (ICH remains a prevalent and severe cause of death and disability worldwide. Control of the hypertensive response in acute ICH has been a mainstay of ICH management, yet the optimal approaches and the yield of recommended strategies have been difficult to establish despite a large body of literature. Over the years, theoretical and observed risks and benefits of intensive blood pressure reduction in ICH have been studied in the form of animal models, radiographic studies, and two recent large, randomized patient trials. In this article, we review the historical and developing data and discuss remaining questions surrounding blood pressure management in acute ICH.

  17. An update on surgical and medical management strategies for intracerebral hemorrhage.

    Science.gov (United States)

    Kreitzer, Natalie; Adeoye, Opeolu

    2013-11-01

    Intracerebral hemorrhage (ICH) accounts for ∼ 10 to 15% of all strokes and is one of the major causes of stroke-related death and disability. After the initial hemorrhage, further bleeding and edema contribute to secondary damage and worsened outcomes. As such, goals of previous and ongoing trials are to prevent continued bleeding, as well as mitigate the impact of cerebral edema. Although no trials have shown a definite functional outcome benefit with a given intervention, much progress has been made recently. This review focuses on recent developments that inform the acute management of ICH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Progress in translational research on intracerebral hemorrhage: Is there an end in sight?

    Science.gov (United States)

    Xi, Guohua; Strahle, Jennifer; Hua, Ya; Keep, Richard F.

    2013-01-01

    Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension. PMID:24139872

  19. Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement

    International Nuclear Information System (INIS)

    Volpe, J.J.; Herscovitch, P.; Perlman, J.M.; Raichle, M.E.

    1983-01-01

    Positron emission tomography (PET) now provides the capability of measuring regional cerebral blood flow with high resolution and little risk. In this study, we utilized PET in six premature infants (920 to 1,200 g) with major intraventricular hemorrhage and hemorrhagic intracerebral involvement to measure regional cerebral blood flow during the acute period (5 to 17 days of age). Cerebral blood flow was determined after intravenous injection of H 2 O, labeled with the positron-emitting isotope, 15 O. Findings were similar and dramatic in all six infants. In the area of hemorrhagic intracerebral involvement, little or no cerebral blood flow was detected. However, in addition, surprisingly, a marked two- to fourfold reduction in cerebral blood flow was observed throughout the affected hemisphere, well posterior and lateral to the intracerebral hematoma, including cerebral white matter and, to a lesser extent, frontal, temporal, and parietal cortex. In the one infant studied a second time, ie, at 3 months of age, the extent and severity of the decreased cerebral blood flows in the affected hemisphere were similar to those observed on the study during the neonatal period. At the three autopsies, the affected left hemisphere showed extensive infarction, corroborating the PET scans. These observations, the first demonstration of the use of PET in the determination of regional cerebral blood flow in the newborn, show marked impairments in regional cerebral blood flow in the hemisphere containing an apparently restricted intracerebral hematoma, indicating that the hemorrhagic intracerebral involvement is only a component of a much larger lesion, ischemic in basic nature, ie, an infarction. This large ischemic lesion explains the poor neurologic outcome in infants with intraventricular hemorrhage and hemorrhagic intracerebral involvement

  20. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  1. Radiosensitivity and repair capacity of two xenografted human soft tissue sarcomas to photons and fast neutrons

    International Nuclear Information System (INIS)

    Budach, V.; Stuschke, M.; Budach, W.; Krause, U.; Streffer, C.; Sack, H.

    1989-01-01

    The radiation response, the relative biological effectiveness (RBE) and sublethal damage repair of two xenografted human soft tissue sarcomas after single doses and fractionated irradiation with 60 Co and 5.8 MeV fast neutrons are presented. (author)

  2. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Science.gov (United States)

    Miao, Hongsheng; Choi, Bryan D; Suryadevara, Carter M; Sanchez-Perez, Luis; Yang, Shicheng; De Leon, Gabriel; Sayour, Elias J; McLendon, Roger; Herndon, James E; Healy, Patrick; Archer, Gary E; Bigner, Darell D; Johnson, Laura A; Sampson, John H

    2014-01-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  3. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Hongsheng Miao

    Full Text Available Glioblastoma (GBM is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  4. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.

    Science.gov (United States)

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina

    2004-03-15

    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  5. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-01-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA

  6. Comparison of Two Xenograft Materials Used in Sinus Lift Procedures: Material Characterization and In Vivo Behavior

    Directory of Open Access Journals (Sweden)

    María Piedad Ramírez Fernández

    2017-06-01

    Full Text Available Detailed information about graft material characteristic is crucial to evaluate their clinical outcomes. The present study evaluates the physico-chemical characteristics of two xenografts manufactured on an industrial scale deproteinized at different temperatures (non-sintered and sintered in accordance with a protocol previously used in sinus lift procedures. It compares how the physico-chemical properties influence the material’s performance in vivo by a histomorphometric study in retrieved bone biopsies following maxillary sinus augmentation in 10 clinical cases. An X-ray diffraction analysis revealed the typical structure of hydroxyapatite (HA for both materials. Both xenografts were porous and exhibited intraparticle pores. Strong differences were observed in terms of porosity, crystallinity, and calcium/phosphate. Histomorphometric measurements on the bone biopsies showed statistically significant differences. The physic-chemical assessment of both xenografts, made in accordance with the protocol developed on an industrial scale, confirmed that these products present excellent biocompatibilitity, with similar characteristics to natural bone. The sintered HA xenografts exhibited greater osteoconductivity, but were not completely resorbable (30.80 ± 0.88% residual material. The non-sintered HA xenografts induced about 25.92 ± 1.61% of new bone and a high level of degradation after six months of implantation. Differences in the physico-chemical characteristics found between the two HA xenografts determined a different behavior for this material.

  7. Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

    Science.gov (United States)

    Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

    2014-07-01

    Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

  8. Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

    Science.gov (United States)

    Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

    2016-10-01

    Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

  9. Clinical application of CT-controlled stereotactic aspiration for intracerebral hematoma

    International Nuclear Information System (INIS)

    Chen Weijian; Zhuge Qichuan; Zheng Rongyuan; Guo Xianzhong; Zhong Ming; Wu Jinsen; Qu Xuanxing

    2002-01-01

    Objective: To evaluate the clinical application of CT-controlled stereotactic aspiration for intracerebral hematoma. Methods: CT-guided stereotactic system was installed on the CT bed, and checked against a standard of the coordinate. According to controlled CT scan, the target can be adjusted at any time in the operation. 860 patients with cerebral hematoma underwent CT-controlled stereotactic aspiration. Of the 860 cases, basal ganglion hematoma was present in 408, thalamus and posterior limb of internal capsule hematoma in 136, cerebral lobe hematoma in 261, cerebellar hematoma in 5, ventricular hemorrhage in 10, midbrain and pons hemorrhage in 37, and medulla hemorrhage in 3. Results: Easy drainage of hematoma by aspiration was achieved in 586 cases, stickiness of hematoma with clearing away more than 50% was performed in 202 and less than 50% in 68. The operation duration ranged from 25 to 120 minutes (average 45 minutes). 693 cases survived and 167 cases died. According to the evaluation by active day life (ADL) after 3 months in survivors, ADL 1-2, ADL 3, ADL 4 and ADL 5 results were achieved in 378 cases, 166 cases, 107 cases, and 28 cases, respectively. In addition, 14 cases were lost beyond recall. Conclusion: CT-controlled stereotactic aspiration for intracerebral hematoma is a handy, less invasive, and safe procedure with high accuracy and curative effect, it is worth while popularizing the procedure

  10. Predictive Value of CTA Spot Sign on Hematoma Expansion in Intracerebral Hemorrhage Patients

    Directory of Open Access Journals (Sweden)

    Wen-Jie Peng

    2017-01-01

    Full Text Available Hematoma expansion (HE occurs in approximately one-third of patients with intracerebral hemorrhage and leads to high rates of mortality and morbidity. Currently, contrast extravasation within hematoma, termed the spot sign on computed tomography angiography (CTA, has been identified as a strong independent predictor of early hematoma expansion. Past studies indicate that the spot sign is a dynamic entity and is indicative of active hemorrhage. Furthermore, to enhance the spot sign’s accuracy of predicting HE, spot parameters observed on CTA or dynamic CTA were used for its quantification. In addition, spot signs detected on multiphase CTA and dynamic CTA are shown to have higher sensitivity and specificity when compared with simple standardized spot sign detection in recent studies. Based on the spot sign, novel methods such as leakage sign and rate of contrast extravasation were explored to redefine HE prediction in combination with clinical characteristics and spot sign on CTA to assist clinical judgment. The spot sign is an accepted independent predictor of active hemorrhage and is used in both secondary intracerebral hemorrhage and the process of surgical assessment for hemorrhagic risk in patients with ischemic stroke. Spot sign predicts patients at high risk for hematoma expansion.

  11. Spontaneous intracerebral haematomas - the influence of computerized tomography on the results of surgery

    International Nuclear Information System (INIS)

    Kolodziejczyk, D.

    1981-01-01

    The report covers 30 patients of 10 to 74 years of age who has hard spontaneous intracerebral haematomas in the time from 1975 to 1980 and had been operated on after diagnosing by means of computerized tomography. The total mortality rate was 40% and was not significantly different from the total operative result obtained by other authors in the CT-period, but it compares poor to the pre-CT-aera. This deterioration despite improved diagnoses might be an effect of computerized tomography on the operating surgeon. Out of 18 survivors, 8 were completely healed. 4 patients kept some neurological symptoms, but could manage everyday life on their own. 6 patients kept serious neurological defects needing care. The influence of neurological-clinical parameters on the final operation result hasn't lost its importance in the CT-aera. The value of CT for the therapy of intracerebral haematomas lies in course control which often justifies a conservative proceeding with good absorption tendency taking into consideration the clinical-neurological picture, despite the persistence of growing and displacing processes. (orig./MG) [de

  12. Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

    Science.gov (United States)

    Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

    2014-11-01

    Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  14. A Xenograft Model of Vestibular Schwannoma and Hearing Loss.

    Science.gov (United States)

    Dinh, Christine T; Bracho, Olena; Mei, Christine; Bas, Esperanza; Fernandez-Valle, Cristina; Telischi, Fred; Liu, Xue-Zhong

    2018-03-19

    Microsurgical implantation of mouse merlin-deficient Schwann cells (MD-SC) into the cerebellopontine angle of immunodeficient rats will initiate tumor formation, hearing loss, and vestibular dysfunction. The progress in identifying effective drug therapies for treatment of Neurofibromatosis type II (NF2) is limited by the availability of animal models of VS that develop hearing loss and imbalance. A microsurgical technique for implanting MD-SCs onto the cochleovestibular nerve of rats was developed. Ten Rowett Nude rats were implanted with either ∼10 MD-SCs expressing luciferase (N = 5) or vehicle (N = 5). Rats received bioluminescence imaging, auditory brainstem response testing, and were observed for head tilt every 2 weeks after surgery, for a total of 6 weeks. Tumors were harvested and processed with hematoxylin & eosin staining and immunohistochemistry was performed for S100. Rats implanted with MD-SCs developed significantly higher tumor bioluminescence measurements and hearing threshold shifts at multiple frequencies by the 4th and 6th weeks post-implantation, compared with control rats. Rats implanted with MD-SCs also developed gross tumor. The tumor volume was significantly greater than nerve volumes obtained from rats in the control group. All rats with tumors developed a head tilt, while control rats had no signs of vestibular dysfunction. Tumors demonstrated histological features of schwannoma and express S100. Using this microsurgical technique, this xenograft rat model of VS develops tumors involving the cochleovestibular nerve, shifts in hearing thresholds, and vestibular dysfunction. This animal model can be used to investigate tumor-mediated hearing loss and perform preclinical drug studies for NF2.

  15. Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

    Science.gov (United States)

    Friedman, Gregory K; Moore, Blake P; Nan, Li; Kelly, Virginia M; Etminan, Tina; Langford, Catherine P; Xu, Hui; Han, Xiaosi; Markert, James M; Beierle, Elizabeth A; Gillespie, G Yancey

    2016-02-01

    Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Interleukin-4 ameliorates the functional recovery of intracerebral hemorrhage through the alternative activation of microglia/macrophage

    Directory of Open Access Journals (Sweden)

    Jianjing eYang

    2016-03-01

    Full Text Available Neuro-inflammation plays an important role in the recovery of brain injury after stroke. Microglia/macrophage is the major executor in the neuro-inflammation, which can be polarized into two distinct phenotypes: injurious/toxic classical activation (M1 phenotype and protective alternative activation (M2 phenotype. Here, we investigated whether intracerebral administration of interleukin-4 (IL-4 at an early stage could affect the activation of microglia/macrophage and the corresponding outcome after intracerebral hemorrhage (ICH. The neuro-behavior was recorded between different groups in the rat ICH model. The M1 and M2 markers were then determined by qRT-PCR, western blotting, ELISA and immunofluorescence, respectively. We observed aberrant activation of microglia/macrophage after ICH. After intracerebral injection of IL-4, M1 activation was greatly inhibited while M2 activation was enhanced, along with improving neurobehavioral recovery from deficits after ICH. Our study showed that early intracerebral injection of IL-4 potentially promotes neuro-functional recovery, probably through enhancing the alternative activation of microglia/macrophage.

  17. Pheochromocytoma complicated by intracerebral hemorrhage - a case report; Feocromocitoma complicado com acidente vascular encefalico hemorragico - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Aline Silva; Marchiori, Edson; Almeida, Fabiola Assuncao de; Martins, Renata Romano; Sales, Anderson Ribeiro; Santos, Tereza Cristina C.R.S. dos; Reis, Simone Teixeira [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Silveira, Sonia Marcelino T. da

    1999-06-01

    The authors report a case of pheochromocytoma that was complicated by intracerebral hemorrhage in a 17-year-old female patient. Computed tomography showed a solid mass, heterogeneous, on the right adrenal. The patient underwent a right adrenalectomy. She is being observed by our out-patients clinic, presenting normal blood pressure levels and a left hemiparesis. (author)

  18. The Role of Anterior Nuclei of the Thalamus: A Subcortical Gate in Memory Processing: An Intracerebral Recording Study

    Czech Academy of Sciences Publication Activity Database

    Štillová, K.; Jurák, Pavel; Chládek, Jan; Chrastina, J.; Halámek, Josef; Bočková, M.; Goldemundová, S.; Říha, I.; Rektor, I.

    2015-01-01

    Roč. 10, č. 11 (2015), e140778:1-13 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : anterior nuclei * thalamus * hippocampus * visual * verbal memory * DBS * P300 * ERP * intracerebral EEG Subject RIV: BH - Optics, Masers, Lasers Impact factor: 3.057, year: 2015

  19. Curative effect of minimally invasive puncture and drainage assisted with alteplase on treatment of acute intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Jun-Lin Hu

    2017-01-01

    >Conclusions: As for the effect on evacuation of hematoma and also the ameliorative effect on nerve injury, inflammatory reaction and oxidative stress response in treatment of acute intracerebral hemorrhage, minimally invasive puncture and drainage assisted with alteplase was superior to adjuvant therapy with urokinase.

  20. Identical event-related potentials to target and frequent stimuli of visual oddball task recorded by intracerebral electrodes

    Czech Academy of Sciences Publication Activity Database

    Kukleta, M.; Brázdil, M.; Roman, R.; Jurák, Pavel

    2003-01-01

    Roč. 114, č. 7 (2003), s. 1292 - 1297 ISSN 1388-2457 Institutional research plan: CEZ:AV0Z2065902 Keywords : event-related potential * intra-cerebral EEG recording in humans * oddball task Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.485, year: 2003

  1. Intracerebral P3-like waveforms and the length of the stimulus-response interval in a visual oddball paradigm

    Czech Academy of Sciences Publication Activity Database

    Roman, R.; Brázdil, M.; Jurák, Pavel; Rektor, I.; Kukleta, M.

    2005-01-01

    Roč. 116, č. 1 (2005), s. 160-171 ISSN 1388-2457 R&D Projects: GA ČR(CZ) GA102/05/0402 Keywords : P3 waveform * ERP s * intracerebral Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.640, year: 2005

  2. The Increase of The Mean Platelet Volume in Patients With Intracerebral Haemorrhage

    Directory of Open Access Journals (Sweden)

    Adalet Arıkanoğlu

    2012-06-01

    Full Text Available OBJECTIVE: The mean platelet volume (MPV is a biomarker of platelet function and activity. The influence of platelet function disorders on the aetiology of intracerebral haemorrhages (ICH and mortality is not clear yet. The purpose of this study is to investigate the change in the MPV values in patients with ICH and to observe its influence on mortality in a retrospective manner. METHODS: Sixty-six patients with intracerebral haemorrhage (32 males, 34 females; mean age: 61.9± 16.9 were enrolled in the study. Patients with ICH were divided into two groups as those who died within the first 10 days and those who survived. The MPV values and the haematoma volumes were compared between the groups. Also, the MPV values and platelet counts of the patients with ICH were compared with the values of healthy volunteers from similar age and sex groups (27 males, 17 females; mean age: 59.9 ±3.2. RESULTS: The MPV values of the patients with ICH measured within 24 hours following the intracerebral haemorrhage (8.33 ± 1.27 fl/mL were statistically significantly higher than the MPV values of the control group (7.76 ± 1.14 fl/mL (p=0.018. The platelet counts of the patients with ICH also measured within the first 24 hours (235.8±94.9 x103/mL were statistically significantly lower than the platelet counts of the control group (279.1 ± 94.9 x103/mL (p=0.022. No statistically significant difference in terms of the MPV values and platelet counts was observed between the patients with ICH who died within the first 10 days and those who survived (p>0.05. However, the difference observed in the haematoma volume between the patients with ICH who died within the first 10 days (31.1 ±33.7 ml and those who survived (8.7± 13.4 ml was statistically significant (p<0.001. No correlation was found between the haematoma volume and the MPV value in the patients with ICH. CONCLUSION: The increase observed in the mean platelet volume in patients with ICH may point to a

  3. Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.

    Science.gov (United States)

    Shuhendler, Adam J; Prasad, Preethy; Cai, Ping; Hui, Kelvin K W; Henderson, Jeffrey T; Rauth, Andrew M; Wu, Xiao Yu

    2013-08-01

    Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel. Tumor perfusion, morphology and nanoparticle retention were evaluated. As compared to Mat- tumors, Mat+tumors exhibited enhanced vascular perfusion and lymphatic flow, greater blood vessel and lymphatic growth within the tumor core, and more deformation and collapse of lymphatics in tumor-associated lymph nodes. These changes were accompanied by reduced nanoparticle retention in Mat+tumors. The results suggest that Matrigel is not a passive medium for tumor growth, but rather significantly alters long-term tumor architecture. These findings have significant implications for the evaluation of therapeutic nanomedicine in xenograft mouse models. Matrigel is utilized in facilitating human tumor xenograft growth in rodents. The authors demonstrate that Matrigel is not a passive medium for tumor growth; instead it significantly alters long-term tumor architecture, with major implications in the evaluation of therapeutic nanomedicine in xenograft mouse models. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

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    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  5. Outcome assessment of hemiparesis due to intracerebral hemorrhage using diffusion tensor fractional anisotropy.

    Science.gov (United States)

    Koyama, Tetsuo; Marumoto, Kohei; Uchiyama, Yuki; Miyake, Hiroji; Domen, Kazuhisa

    2015-04-01

    This study aimed to evaluate the prognostic efficacy of magnetic resonance diffusion tensor fractional anisotropy (FA) for patients with hemiparesis due to intracerebral hemorrhage. Diffusion tensor FA brain images were acquired 14-21 days after putaminal and/or thalamic hemorrhage. The ratio of FA values within the cerebral peduncles of the affected and unaffected hemispheres (rFA) was calculated for each patient (n = 40) and assessed for correlation with Brunnstrom stage (BRS, 1-6), motor component of the functional independence measure (FIM-motor, 13-91), and the total length of stay (LOS) until discharge from rehabilitation (P hemiparesis due to putaminal and/or thalamic hemorrhage, particularly hand function recovery. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Management of Acute Hypertensive Response in Intracerebral Hemorrhage Patients After ATACH-2 Trial.

    Science.gov (United States)

    Majidi, Shahram; Suarez, Jose I; Qureshi, Adnan I

    2017-10-01

    Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

  7. Gastrointestinal bleeding after intracerebral hemorrhage: a retrospective review of 808 cases.

    Science.gov (United States)

    Yang, Tie-Cheng; Li, Jian-Guo; Shi, Hong-Mei; Yu, Dong-Ming; Shan, Kai; Li, Li-Xia; Dong, Xiao-Yan; Ren, Tian-Hua

    2013-10-01

    This study examined the incidence and risk factors for gastrointestinal (GI) bleeding after spontaneous intracerebral hemorrhage (ICH). The available medical records of patients with ICH admitted from June 2008 to December 2009 for any episode of GI bleeding, possible precipitating factors and administration of ulcer prophylaxis were reviewed. The prevalence of GI bleeding was 26.7%, including 3 cases of severe GI bleeding (0.35%). Patients with GI bleeding had significantly longer hospital stay and higher in-hospital mortality compared with patients without GI bleeding. Multivariate logistic regression analyses showed that age, Glasgow Coma Scale scores, sepsis and ICH volume were independent predictors of GI bleeding. About 63.4% of patients with ICH received stress ulcer prophylaxis. GI bleeding occurred frequently after ICH, but severe events were rare. Age, Glasgow Coma Scale score, sepsis and ICH volume were independent predictors of GI bleeding occurring after ICH.

  8. Resveratrol Attenuates Neurodegeneration and Improves Neurological Outcomes after Intracerebral Hemorrhage in Mice

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    Frederick Bonsack

    2017-08-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke with a substantial public health impact. Currently, there is no effective treatment for ICH. The purpose of the study was to evaluate whether the post-injury administration of Resveratrol confers neuroprotection in a pre-clinical model of ICH. To this end, ICH was induced in adult male CD1 mice by collagenase injection method. Resveratrol (10 mg/kg or vehicle was administered at 30 min post-induction of ICH and the neurobehavioral outcome, neurodegeneration, cerebral edema, hematoma resolution and neuroinflammation were assessed. The Resveratrol treatment significantly attenuated acute neurological deficits, neurodegeneration and cerebral edema after ICH in comparison to vehicle treated controls. Further, Resveratrol treated mice exhibited improved hematoma resolution with a concomitant reduction in the expression of proinflammatory cytokine, IL-1β after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.

  9. Clinical evaluation of CT-guided stereotaxic evacuation of hypertensive intracerebral hematomas

    International Nuclear Information System (INIS)

    Kimura, Masato; Yoshinaga, Shiya; Nakayama, Yoshiya; Hirakawa, Toshihiko; Tanaka, Akira; Tomonaga, Masamichi

    1989-01-01

    The clinical results of CT-guided stereotaxic evacuation of hypertensive intracerebral hematomas which had been done in our department during the last 16 months were evaluated. They included 18 cases; 8 of thalamic, 9 of putaminal and one of cerebellar hematoma. The patients were 11 males and 7 females, with an average age of 57. The time interval from oneset to surgery was 1-21 days, 9.5 days on average. The hematoma volume estimated on a CT scan was 6-35 ml and the average rate of hematoma removal by surgery was 75%. Intraoperative monitoring with ultrasonography and postoperative infusion of Urokinase increased the removal rate. In 14 cases, the mental ability and motor function improved within days after surgery and rehabilitation was started within a short period. However, the recovery in aged people was generally poor. Rebleeding occurred postoperatively in one case, necessitating a subsequent craniotomy. (author)

  10. Experience with contrast-enhanced CT in delayed traumatic intracerebral hematoma

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    Kobayashi, Shiro; Nakazawa, Shozo; Yokota, Hiroyuki; Isayama, Kazuo; Yajima, Kouzo; Otsuka, Toshibumi [Nippon Medical School, Tokyo

    1984-02-01

    During the four-and-a-half-year period from April, 1976, to September, 1980, out of 257 patients with severe head injuries graded 8 or less by the Glasgow Coma Scale in the Department of Neurosurgery and Critical Care Medicine of the Nippon Medical School, Tokyo, Japan, 33 cases showed the development of delayed traumatic intracerebral hematoma (DTICH) upon the serial computerized tomography (CT). Contrast-enhanced CT was performed in 20 cases of the 33 patients demonstrating DTICH. Among these, 8 cases (40%) indicated the development of DTICH in the lesions of cerebral contusion (a salt-and-pepper appearance in the initial plain CT) which showed a remarkable enhancement, sustaining the extravasation of the contrast medium into the contused brain tissue. The authors discuss the pathogenesis of DTICH and suggest that vasoparalysis in the cerebral contusion might be a factor in the development of DTICH in patients with servere head injuries.

  11. Depression following intracerebral hemorrhage and the evaluation of cerebral blood flow by single photon emission tomography

    International Nuclear Information System (INIS)

    Masada, Tetsuya; Makabe, Tetsuo; Kunishio, Katsuzo; Matsumoto, Akira

    2007-01-01

    The authors studied patients who presented depression and apathy following intracerebral hemorrhage (ICH). Twelve patients who were admitted in our hospital were divided into two groups according to the presence of post-stroke depression (PSD). Five patients with PSD are in group A, and another seven patients without PSD are in group B. Zung-self depression scale (SDS) and apathy scale were used for screening of depression and apathy. PSD was recognized in 5 (42%) of patients following ICH. Single photon emission tomography (SPECT) suggested the reduction of cerebral blood flow (CBF) in the frontal lobe in all patients of the group A (100%), whereas only 29% of patients of the group B. The reduction of CBF in the frontal lobe might be involved in the mechanism of depression following ICH in subacute stage. (author)

  12. Neuroprotective intervention after hypoxia-ischemia may change intracerebral metabolic measures in a newborn piglet model

    DEFF Research Database (Denmark)

    Andelius, Ted Carl; Bøgh, Nikolaj; Pedersen, Mette Vestergaard

    Introduction Hypoxic-Ischemic Neonatal Encephalopathy (HIE) is a major contributor to neurological impairment and death in children. Due to the similarity with the human brain, newborn piglets are often used in studies of new treatments for HIE. Cell death after hypoxia ischemia (HI) occurs...... measured intracranial pressure (ICP), flow, temperature, and oxygen tension. By microdialysis we measured lactate, glucose, glycerol, and pyruvate. A NIRS-probe was placed on the right side of the head and aEEG electrodes were placed on each side. After 24 hours of stabilisation, HI was induced for 45....... Lactate/pyruvate ratio and ICP showed a parabolic pattern in the HI piglet. Conclusion We present a novel take on an already well-established animal model for HIE. We expect to provide basic knowledge of how interventions may affect intracerebral metabolic measures, pressure and gas...

  13. Percutaneous transfermoral embolization of intracerebral arteriovenous malformation by using conventional catheter

    International Nuclear Information System (INIS)

    Choo, In Wook; Park, Soo Sung; Yoon, Jung Sup; Lim, Hyo Keun; Lee, Kyu Ho; Eoh, Whan

    1988-01-01

    Non-surgical transfermoral embolization of centrally located huge intracerebral arteriovenous malformation (AVM) was successfully performed by using conventional 6.5F DAVIS II Catheter in the department of Radiology, Kangdong Sacred Heart Hospital, May 17, 1988. The large A.V.M. was located in left basal ganglia and thalamus on brain C.T. and was supplied by multiple dilated lateral lenticulostriate arteries from left middle cerebral artery and posterior thalamoperforating artery, posterior choroidal artery from left posterior cerebral artery angiographically. The AVM was partially obliterated after embolization of lateral lenticulostriate arteries and thalamoperforating artery with P.V.A. (Polyvinyl Alcohol, ivalon) using conventional 6.5F DAVIS II angiographic catheter. There was no complication which was related to those embolization procedures except transient drowsy consciousness after embolization but it is completely recovered to the level of preembolization state after 10 hours.

  14. Experience with contrast-enhanced CT in delayed traumatic intracerebral hematoma

    International Nuclear Information System (INIS)

    Kobayashi, Shiro; Nakazawa, Shozo; Yokota, Hiroyuki; Isayama, Kazuo; Yajima, Kouzo; Otsuka, Toshibumi

    1984-01-01

    During the four-and-a-half-year period from April, 1976, to September, 1980, out of 257 patients with severe head injuries graded 8 or less by the Glasgow Coma Scale in the Department of Neurosurgery and Critical Care Medicine of the Nippon Medical School, Tokyo, Japan, 33 cases showed the development of delayed traumatic intracerebral hematoma (DTICH) upon the serial computerized tomography (CT). Contrast-enhanced CT was performed in 20 cases of the 33 patients demonstrating DTICH. Among these, 8 cases (40%) indicated the development of DTICH in the lesions of cerebral contusion (a salt-and-pepper appearance in the initial plain CT) which showed a remarkable enhancement, sustaining the extravasation of the contrast medium into the contused brain tissue. The authors discuss the pathogenesis of DTICH and suggest that vasoparalysis in the cerebral contusion might be a factor in the development of DTICH in patients with servere head injuries. (author)

  15. Outcome after emergency surgery without angiography in patients with intracerebral haemorrhage after aneurysm rupture

    DEFF Research Database (Denmark)

    Bergdal, Ove; Springborg, Jacob; Hauerberg, John

    2009-01-01

    BACKGROUND: Patients with large intracerebral haematomas (ICH) from aneurysm rupture often present in a poor clinical condition and have a poor prognosis. Time delay for preoperative angiography might in some cases be unappealing. We evaluated the outcome after immediate haematoma removal...... and aneurysm occlusion without preoperative angiography. METHODS: We retrospectively identified 13 consecutive patients. We recorded clinical data and evaluated mortality and morbidity with the Glasgow Outcome Score (GOS) and Telephone Interview of Cognitive Status (TICS). FINDINGS: At follow up seven...... of thirteen patients had favourable outcome assessed by GOS. Three patients had severe disability and three patients died. None of the survived patients interviewed had impaired cognition. CONCLUSIONS: In patients presented in a critical state with aneurysmal ICH, emergency haematoma removal and aneurysm...

  16. Intracerebral hemorrhage with intraventricular extension and no hydrocephalus may not increase mortality or severe disability.

    Science.gov (United States)

    Mahta, Ali; Katz, Paul M; Kamel, Hooman; Azizi, S Ausim

    2016-08-01

    This paper aimed to test the hypothesis that intraventricular extension of spontaneous intracerebral hemorrhage (ICH) in the absence of hydrocephalus is not associated with increased mortality or severe disability. We performed a retrospective consecutive cohort study of patients with primary spontaneous ICH who were admitted to a single institution. Multivariate logistic regression analysis was used to assess the association of each variable with functional outcome as measured by the modified Rankin Scale (mRS). A total of 164 patients met our inclusion criteria and were included in the study. Only hydrocephalus (p=0.002) and hematoma volume (p=0.006) were significantly associated with mortality or poor functional outcome (mRS of 3 to 6). In contrast, the presence of intraventricular hematoma was not independently associated with poor functional outcome. The presence of intraventricular extension of ICH in the absence of hydrocephalus may not increase mortality or disability. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Prediction and observation of post-admission hematoma expansion in patients with intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Ovesen, Christian; Havsteen, Inger; Rosenbaum, Sverre

    2014-01-01

    within the hematoma along with the hematoma-size is reported to be predictive of hematoma expansion and outcome. Because patients tend to arrive earlier to the hospital, a larger fraction of acute ICH-patients must be expected to undergo hematoma expansion. This renders observation and radiological......Post-admission hematoma expansion in patients with intracerebral hemorrhage (ICH) comprises a simultaneous major clinical problem and a possible target for medical intervention. In any case, the ability to predict and observe hematoma expansion is of great clinical importance. We review...... radiological concepts in predicting and observing post-admission hematoma expansion. Hematoma expansion can be observed within the first 24 h after symptom onset, but predominantly occurs in the early hours. Thus capturing markers of on-going bleeding on imaging techniques could predict hematoma expansion...

  18. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Steiner, Thorsten; Al-Shahi Salman, Rustam; Beer, Ronnie

    2014-01-01

    graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to ...BACKGROUND: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has...... Assessment, Development and Evaluation (GRADE) approach. RESULTS: We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding...

  19. Ethnic Disparities in Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage Incidence in The Netherlands

    DEFF Research Database (Denmark)

    Agyemang, Charles; van Oeffelen, Aloysia A M; Nørredam, Marie Louise

    2014-01-01

    BACKGROUND AND PURPOSE: Data on the incidence of stroke subtypes among ethnic minority groups are limited. We assessed ethnic differences in the incidence of stroke subtypes in the Netherlands. METHODS: A Dutch nationwide register-based cohort study (n=7 423 174) was conducted between 1998 and 2010....... We studied the following stroke subtypes: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Cox proportional hazard models were used to estimate incidence differences between first-generation ethnic minorities and the Dutch majority population (ethnic Dutch). RESULTS: Compared.......16-0.72), and subarachnoid hemorrhage (0.42; 0.20-0.88 and 0.34; 0.17-0.68) compared with ethnic Dutch counterparts. The results varied by stroke subtype and sex for the other minority groups. For example, Turkish women had a reduced incidence of subarachnoid hemorrhage, whereas Turkish men had an increased incidence...

  20. NEUROGATE: a new MR-compatible device for realizing minimally invasive treatment of intracerebral tumors.

    Science.gov (United States)

    Vitzthum, Hans Ekkehart; Winkler, Dirk; Strauss, Gero; Lindner, Dirk; Krupp, Wolfgang; Schneider, Jens Peter; Schober, Ralf; Meixensberger, Jürgen

    2004-01-01

    The authors report on the handling and the practicability of a newly developed MR-compatible device, the NEUROGATE (Daum GmbH, Germany), which allows precise planning, simulation and control of stereotactic biopsy in patients with suspect intracranial lesions, and which allows minimally invasive maneuvers to be performed in a comfortable way. Twenty-eight patients were examined stereotactically in the Signa SP interventional 0.5 Tesla MRI (General Electric Medical Systems, USA), including 15 patients with malignant intracerebral tumors and poor general medical conditions (8 gliomas, 7 metastases) who were treated by laser-induced interstitial thermotherapy (LITT) after definite intraoperative neuropathological diagnosis. As a special stereotactic holding device, the NEUROGATE was favored as a reliable tool for stereotaxy and minimally invasive procedures.

  1. The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria

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    Jie Qu

    2016-01-01

    Full Text Available Intracerebral hemorrhage is an emerging major health problem often resulting in death or disability. Reactive oxygen species (ROS have been identified as one of the major damaging factors in ischemic stroke. However, there is less discussion about ROS in hemorrhage stroke. Metabolic products of hemoglobin, excitatory amino acids, and inflammatory cells are all sources of ROS, and ROS harm the central nervous system through cell death and structural damage, especially disruption of the blood-brain barrier. We have considered the antioxidant system of the CNS itself and the drugs aiming to decrease ROS after ICH, and we find that mitochondria are key players in all of these aspects. Moreover, when the mitochondrial permeability transition pore opens, ROS-induced ROS release, which leads to extensive liberation of ROS and mitochondrial failure, occurs. Therefore, the mitochondrion may be a significant target for elucidating the problem of ROS in ICH; however, additional experimental support is required.

  2. Intracerebral stimulation of left and right ventral temporal cortex during object naming.

    Science.gov (United States)

    Bédos Ulvin, Line; Jonas, Jacques; Brissart, Hélène; Colnat-Coulbois, Sophie; Thiriaux, Anne; Vignal, Jean-Pierre; Maillard, Louis

    2017-12-01

    While object naming is traditionally considered asa left hemisphere function, neuroimaging studies have reported activations related to naming in the ventral temporal cortex (VTC) bilaterally. Our aim was to use intracerebral electrical stimulation to specifically compare left and right VTC in naming. In twenty-three epileptic patients tested for visual object naming during stimulation, the proportion of naming impairments was significantly higher in the left than in the right VTC (31.3% vs 13.6%). The highest proportions of positive naming sites were found in the left fusiform gyrus and occipito-temporal sulcus (47.5% and 31.8%). For 17 positive left naming sites, an additional semantic picture matching was carried out, always successfully performed. Our results showed the enhanced role of the left compared to the right VTC in naming and suggest that it may be involved in lexical retrieval rather than in semantic processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effect of intracerebral administration of catecholamines and subsequent x-irradiation on brain metabolism

    International Nuclear Information System (INIS)

    Pikulev, A.T.; Khripchenko, I.P.; Kukulyanskaya, M.F.; Chernoguzov, V.M.; Lavrova, V.M.

    1987-01-01

    The effect of X-radiation in a relatively small dose on the content of glutamic acid and enzyme activity related to its exchange, as well as on certain links of carbohydrate - energy exchange in rat brain, was studied. It is shown that changes in the activity of hexokinase at the background of intercerebral administration of adrenaline prior to irradiation are related to the switching on of nonspecific regulation mechanisms. The detected single direction of changes in hexokinase activity, level of aminoacids and enzymes of reamination in subcellar fractions of brain in intact and irradiated rats both in case of intracerebral and intraperitoneal administration of catecholamines permits to consider that the realization of nonspecific component of ionizing radiation proceeds via changes in hormonal status of organism and changes in the functions of mediator systems

  4. Showing no spot sign is a strong predictor of independent living after intracerebral haemorrhage

    DEFF Research Database (Denmark)

    Havsteen, Inger; Ovesen, Christian; Christensen, Anders F

    2014-01-01

    BACKGROUND: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus...... on the ability to identify patients with a spontaneous, acceptable outcome. METHODS: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013....... The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days...

  5. Neurobrucellosis with transient ischemic attack, vasculopathic changes, intracerebral granulomas and basal ganglia infarction: a case report

    Directory of Open Access Journals (Sweden)

    Ozyurek Seyfi C

    2010-10-01

    Full Text Available Abstract Introduction Central nervous system involvement is a rare but serious manifestation of brucellosis. We present an unusual case of neurobrucellosis with transient ischemic attack, intracerebral vasculopathy granulomas, seizures, and paralysis of sixth and seventh cranial nerves. Case presentation A 17-year-old Caucasian man presented with nausea and vomiting, headache, double vision and he gave a history of weakness in the left arm, speech disturbance and imbalance. Physical examination revealed fever, doubtful neck stiffness and left abducens nerve paralysis. An analysis of his cerebrospinal fluid showed a pleocytosis (lymphocytes, 90%, high protein and low glucose levels. He developed generalized tonic-clonic seizures, facial paralysis and left hemiparesis. Cranial magnetic resonance imaging demonstrated intracerebral vasculitis, basal ganglia infarction and granulomas, mimicking the central nervous system involvement of tuberculosis. On the 31st day of his admission, neurobrucellosis was diagnosed with immunoglobulin M and immunoglobulin G positivity by standard tube agglutination test and enzyme-linked immunosorbent assay in both serum and cerebrospinal fluid samples (the tests had been negative until that day. He was treated successfully with trimethoprim and sulfamethoxazole, doxycyline and rifampicin for six months. Conclusions Our patient illustrates the importance of suspecting brucellosis as a cause of meningoencephalitis, even if cultures and serological tests are negative at the beginning of the disease. As a result, in patients who have a history of residence or travel to endemic areas, neurobrucellosis should be considered in the differential diagnosis of any neurologic symptoms. If initial tests fail, repetition of these tests at appropriate intervals along with complementary investigations are indicated.

  6. Combining Spot Sign and Intracerebral Hemorrhage Score to Estimate Functional Outcome: Analysis From the PREDICT Cohort.

    Science.gov (United States)

    Schneider, Hauke; Huynh, Thien J; Demchuk, Andrew M; Dowlatshahi, Dar; Rodriguez-Luna, David; Silva, Yolanda; Aviv, Richard; Dzialowski, Imanuel

    2018-06-01

    The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0-3 versus 4-6). Performance of (1) the ICH score and (2) the spot sign ICH score-a scoring scale combining ICH score and spot sign number-was tested. Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2-4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1-7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2-17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P =0.14). In the PREDICT cohort, a prognostic score adding the computed tomographic angiography-based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score. © 2018 American Heart Association, Inc.

  7. Stereotactic aspiration versus craniotomy for primary intracerebral hemorrhage: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Jia-Wei Wang

    Full Text Available BACKGROUND: A wealth of evidence based on the randomized controlled trials (RCTs has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH. METHODS: According to the study strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries, relevant journals and the lists of references were also searched. After literature searching, two investigators independently performed literature screening, assessment of quality of the included trials and data extraction. The outcome measures included death or dependence, total risk of complication, and the risk of rebleeding, gastrointestinal hemorrhage and systematic infection. RESULTS: Four RCTs with 2996 participants were included. The quality of the included trials was acceptable. Stereotactic aspiration significantly decreased the odds of death or dependence at the final follow-up (odds ratio (OR: 0.80, 95% confidence interval (CI: 0.69-0.93; P = 0.004 and the risk of intracerebral rebleeding (OR: 0.44, 95% CI: 0.26-0.74; P = 0.002 compared to craniotomy with no significant heterogeneity among the study results. CONCLUSIONS: The present meta-analysis provides evidence that the stereotactic aspiration may be associated with a reduction in the odds of being dead or dependent in primary ICH, which should be interpreted with caution. Further trials are needed to identify those patients most likely to benefit from the stereotactic aspiration.

  8. Cognitive functioning over 2 years after intracerebral hemorrhage in school-aged children.

    Science.gov (United States)

    Murphy, Lexa K; Compas, Bruce E; Gindville, Melissa C; Reeslund, Kristen L; Jordan, Lori C

    2017-11-01

    Previous research investigating outcomes after pediatric intracerebral hemorrhage (ICH) has generally been limited to global and sensorimotor outcomes. This study examined cognitive outcomes after spontaneous ICH in school-aged children with serial assessments over 2 years after stroke. Seven children (age range 6-16y, median 13; six males, one female; 57% white, 43% black) presenting with spontaneous ICH (six arteriovenous malformations) were assessed at 3 months, 12 months, and 24 months after stroke. The Pediatric Stroke Outcome Measure (PSOM) quantified neurological outcome and Wechsler Intelligence Scales measured cognitive outcomes: verbal comprehension, perceptual reasoning, working memory, and processing speed. PSOM scales showed improved neurological function over the first 12 months, with mild to no sensorimotor deficits and moderate overall deficits at 1- and 2-year follow-ups (median 2-year sensorimotor PSOM=0.5, total PSOM=1.5). Changes in cognitive function indicated a different trajectory; verbal comprehension and perceptual reasoning improved over 24 months; low performance was sustained in processing speed and working memory. Age-normed centile scores decreased between 1- and 2-year follow-ups for working memory, suggesting emerging deficits compared with peers. Early and serial cognitive testing in children with ICH is needed to assess cognitive functioning and support children in school as they age and cognitive deficits become more apparent and important for function. In children with intracerebral hemorrhage (ICH), motor function improved between 3 months and 24 months. Improvements in cognitive function were variable between 3 months and 24 months. Working memory centiles declined, suggesting emerging deficits compared with peers. Processing speed improved but remained significantly below the 50th centile. Cognitive impact of ICH may increase with age in children. © 2017 Mac Keith Press.

  9. Community-based study on intracerebral hemorrhage in northern Hokkaido. Northern Hokkaido Stroke Study (NOHSS)

    International Nuclear Information System (INIS)

    Sako, Kazuhiro; Shirai, Wakako; Tokumitu, Naoki; Aizawa, Shizuka

    2008-01-01

    A survey on stroke was conducted to evaluate the incidence of intracerebral hemorrhage and the prevalence of risk factors. The subjects, comprising those patients who suffesed a stroke, were registered on the Northern Hokkaido Stroke Study between July 2002 and June 2006. The severity of their illness was rated by the National Institutes of Health Stroke Scale (NIHSS) at hospital admission, while their outcome was determined by the mortality within 3 months and the mRS (modified Rankin Scale score). Of the 1,046 registered stroke patients, 271 (25.9%) were found to suffer from cerebral hemorrhage. Their mean age was 70.3±11.7 years; male-to-female ratio, 154/117; mean NIHSS at admission, 11.8±8.1; mortality within 3 months, 19.2%; and percentage who regained independence within 3 months (mRS: ≤2), 32.5%. A history of hypertension was found in 72.6%, and 13.7% had no treatment. MRI (T2*) revealed micro-hemorrhage outside the lesions in 67.5%. Forty-seven patients (17.3%) were taking anti-platelet agents at the onset of intracerebral hemorrhage. There was no significant difference between the mortalities of the anti-platelet-agent-users and non-users but the percentage of those regaining independence within 3 months was 19.1% for the users against 37.3% for the non-users (p=0.0177), with a significantly poor outcome in the user group. In northern Hokkaido, the incidence of cerebral hemorrhage remains high, and the percentage of those with poorly controlled or uncontrolled hypertension was 30%. These findings suggest a need to educate not only the inhabitants themselves but also the physicians engaged in their care. (author)

  10. Hyperintense vessels on FLAIR: A useful non-invasive method for assessing intracerebral collaterals

    International Nuclear Information System (INIS)

    Liu Wenhua; Xu Gelin; Yue Xuanye; Wang Xiaoliang; Ma Minmin; Zhang Renliang; Wang Handong; Zhou Changsheng; Liu Xinfeng

    2011-01-01

    Objective: This study was aimed to evaluate relationship between hyperintense vessels (HV) on fluid-attenuated inversion recovery (FLAIR) and artery steno-occlusion related intracerebral collaterals. Materials and methods: A total of 233 patients with 260 atherosclerotic lesions in the M1 segment of the middle cerebral artery (MCA) were examined with FLAIR and digital subtraction angiography (DSA). HV were graded as 0, 1, 2 and 3 by its distributions in the MCA territory. Grade 0 indicated no HV; Grade 1 indicated the HV limited in Sylvian fissure; Grade 2 indicated the HV limited in Sylvian fissure and the temporal-occipital junction; Grade 3 indicated the HV extended to frontal-parietal lobes. Collateral blood flows were classified by DSA results. The relationship between HV grades and patterns of collateral flows was analyzed. Results: HV were observed in 76 out of 260 hemispheres. For patients with Grade 1 HV, most of their collateral flows (80.8%) were antegrade; for patients with Grade 2, the retrograde leptomeningeal flows were commonly manifested as anterior cerebral artery to MCA (75%); for patients with Grade 3 HV, most of the retrograde leptomeningeal flows were manifested as posterior cerebral artery to MCA (81.8%). As the grade HV increased, the frequency of retrograde leptomeningeal collateral from ACA to MCA decreased (100% to 75% and to 18.2%), and increased (0% to 25% and to 81.8%) for the retrograde leptomeningeal collateral via PCA to MCA (P < 0.001). Conclusions: The HV could assess non-invasively intracerebral collaterals in patients with steno-occlusive lesions of M1 segment of MCA.

  11. Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

    Science.gov (United States)

    Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

    2014-04-01

    Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. pO2 Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

    International Nuclear Information System (INIS)

    Ellingsen, Christine; Øvrebø, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

    2012-01-01

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO 2 ) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO 2 fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO 2 was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO 2 fluctuations, the pO 2 fluctuation frequency in these regions, and the relative amplitude of the pO 2 fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO 2 in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO 2 and, thus, protect tumor tissue from cycling hypoxia.

  13. Clinical significance of cerebral microbleeds on MRI : A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (vI)

    NARCIS (Netherlands)

    A. Charidimou (Andreas); S. Shams (Sara); J.R. Romero (Jose Rafael); J. Ding (Jie); R. Veltkamp (Roland); S. Horstmann (Solveig); G. Eiriksdottir (Gudny); M.A. van Buchem (Mark); V. Gudnason (Vilmundur); J.J. Himali (Jayandra); M.E. Gurol (Edip); A. Viswanathan (Anand); T. Imaizumi (Toshio); M.W. Vernooij (Meike); S. Seshadri (Sudha); S.M. Greenberg (Steven); O.R. Benavente (Oscar); L.J. Launer (Lenore); A. Shoamanesh (Ashkan)

    2018-01-01

    markdownabstract__Background:__ Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a

  14. Long-term results of vaginal repairs with and without xenograft reinforcement

    DEFF Research Database (Denmark)

    Mouritsen, Lone; Kronschnabl, M.; Lose, G.

    2010-01-01

    The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated by a validated questionnaire and anatomy...... in 3% of cases and 12% controls. None of the recurrence rates was significantly different for cases versus controls. No vaginal erosions were seen. Previous surgery was a significant risk factor with odds ratio 7.3 for another recurrence. Recurrence rates defined by POPQ plus symptoms were low compared...

  15. Long-term results of vaginal repairs with and without xenograft reinforcement

    DEFF Research Database (Denmark)

    Mouritsen, Lone; Kronschnabl, M.; Lose, G.

    2010-01-01

    INTRODUCTION AND HYPOTHESIS: The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. METHODS: Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated...... as POPQ > -1 plus symptoms revealed recurrence in 3% of cases and 12% controls. None of the recurrence rates was significantly different for cases versus controls. No vaginal erosions were seen. Previous surgery was a significant risk factor with odds ratio 7.3 for another recurrence. CONCLUSIONS...

  16. The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model.

    Science.gov (United States)

    Xu, Yunze; Zhu, Qi; Chen, Dongning; Shen, Zhoujun; Wang, Weiqing; Ning, Guang; Zhu, Yu

    2015-07-01

    This study aims to investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the malignant pheochromocytoma using a xenograft mouse model. Treatment with 17-AAG induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Furthermore, 17-AAG also significantly inhibited the expression of HSP90 and its client proteins. Our results validated HSP90 as an important target in pheochromocytoma and provided rationale for the testing of HSP90 inhibitors as a promising therapeutic agent in the antitumor therapy of pheochromocytoma.

  17. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

    Directory of Open Access Journals (Sweden)

    Zhu Y

    2014-12-01

    Full Text Available Yin Zhu,1,* Ming Cheng,2,* Zhen Yang,3 Chun-Yan Zeng,3 Jiang Chen,3 Yong Xie,3 Shi-Wen Luo,3 Kun-He Zhang,3 Shu-Feng Zhou,4 Nong-Hua Lu1,31Department of Gastroenterology, 2Department of Orthopedics, 3Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of China; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workAbstract: Mesenchymal stem cells (MSCs have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP. Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor

  18. Chronic moderate ethanol intake differentially regulates vitamin D hydroxylases gene expression in kidneys and xenografted breast cancer cells in female mice.

    Science.gov (United States)

    García-Quiroz, Janice; García-Becerra, Rocío; Lara-Sotelo, Galia; Avila, Euclides; López, Sofía; Santos-Martínez, Nancy; Halhali, Ali; Ordaz-Rosado, David; Barrera, David; Olmos-Ortiz, Andrea; Ibarra-Sánchez, María J; Esparza-López, José; Larrea, Fernando; Díaz, Lorenza

    2017-10-01

    Factors affecting vitamin D metabolism may preclude anti-carcinogenic effects of its active metabolite calcitriol. Chronic ethanol consumption is an etiological factor for breast cancer that affects vitamin D metabolism; however, the mechanisms underlying this causal association have not been fully clarified. Using a murine model, we examined the effects of chronic moderate ethanol intake on tumoral and renal CYP27B1 and CYP24A1 gene expression, the enzymes involved in calcitriol synthesis and inactivation, respectively. Ethanol (5% w/v) was administered to 25-hydroxyvitamin D 3 -treated or control mice during one month. Afterwards, human breast cancer cells were xenografted and treatments continued another month. Ethanol intake decreased renal Cyp27b1 while increased tumoral CYP24A1 gene expression.Treatment with 25-hydroxyvitamin D 3 significantly stimulated CYP27B1 in tumors of non-alcohol-drinking mice, while increased both renal and tumoral CYP24A1. Coadministration of ethanol and 25-hydroxyvitamin D 3 reduced in 60% renal 25-hydroxyvitamin D 3 -dependent Cyp24a1 upregulation (Pintake decreases renal and tumoral 25-hydroxyvitamin D 3 bioconversion into calcitriol, while favors degradation of both vitamin D metabolites in breast cancer cells. The latter may partially explain why alcohol consumption is associated with vitamin D deficiency and increased breast cancer risk and progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    International Nuclear Information System (INIS)

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  20. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  1. EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

    Science.gov (United States)

    Sampson, John H; Choi, Bryan D; Sanchez-Perez, Luis; Suryadevara, Carter M; Snyder, David J; Flores, Catherine T; Schmittling, Robert J; Nair, Smita K; Reap, Elizabeth A; Norberg, Pamela K; Herndon, James E; Kuan, Chien-Tsun; Morgan, Richard A; Rosenberg, Steven A; Johnson, Laura A

    2014-02-15

    Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues. We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma. At elevated doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIII(NEG) tumors, suggesting generation of host immunity against additional tumor antigens. All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies. ©2013 AACR

  2. Reemergence of Murine Typhus in the US

    Centers for Disease Control (CDC) Podcasts

    2015-04-21

    Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

  3. Intracerebral hemorrhage associated with Sneddon's syndrome: is ischemia-related angiogenesis the cause? Case report and review of the literature

    International Nuclear Information System (INIS)

    Aquino Gondim, F. de A.; Leacock, R.O.; Subrammanian, T.A.; Cruz-Flores, S.

    2003-01-01

    Sneddon's syndrome is characterized by livedo reticularis and multiple ischemic infarcts often associated with antiphospholipid antibodies. Intracerebral hemorrhage (ICH) is unusual in Sneddon's syndrome and has not been reported as the presenting complaint. We report a 38-year-old woman with a history of two miscarriages, Raynaud's phenomenon and livedo reticularis who presented acutely with ICH. Angiography showed prominent leptomeningeal and transdural anastomoses (pseudoangiomatosis). Anticardiolipin antibodies were positive. A right frontal brain biopsy failed to reveal vasculitis and a skin biopsy was nonspecific. MRI showed residual intracerebral hemorrhage (ICH), diffuse atrophy, multiple small white matter infarcts and leptomeningeal enhancement. This is the first report of Sneddon's syndrome presenting with an ICH. It shares features with the Divry-van Bogaert syndrome. We discuss the cause of the pseudoangiomatosis pattern and its role in the genesis of the hemorrhage and suggest that cerebral angiography should be done in every patient with Sneddon's syndrome, as it could impact therapy. (orig.)

  4. MRI of intracerebral haematoma at low field (0.15T) using T2 dependent partial saturation sequences

    International Nuclear Information System (INIS)

    Bydder, G.M.; Pennock, J.M.; Porteous, R.; Dubowitz, L.M.S.; Gadian, D.G.; Young, I.R.

    1988-01-01

    Results of MRI at 0.15T in twelve successive patients with intracerebral haematoma are reviewed. Using T 2 weighted spin echo (SE) and partial saturation (PS without a refocussing 180 0 pulse) sequences, low intensity areas were seen in eleven of the twelve cases. These included central regions (three cases), a peripheral rim (seven cases) and more diffuse patterns involving the brainstem and cerebral hemispheres (two cases). One case initially displayed a peripheral rim and later a central low intensity region. Central low intensity regions were seen in acute, subacute, and chronic cases. Follow up in five cases displayed an increase in signal within the haematoma in three cases and a decrease in signal intensity in two cases. Low signal intensity areas can be seen within and around intracerebral haematomas imaged with T 2 weighted sequences at low field strength. (orig.)

  5. Randomized controlled trial of early rehabilitation after intracerebral hemorrhage stroke: difference in outcomes within 6 months of stroke.

    Science.gov (United States)

    Liu, Ning; Cadilhac, Dominique A; Andrew, Nadine E; Zeng, Lingxia; Li, Zongfang; Li, Jin; Li, Yan; Yu, Xuewen; Mi, Baibing; Li, Zhe; Xu, Honghai; Chen, Yangjing; Wang, Juan; Yao, Wanxia; Li, Kuo; Yan, Feng; Wang, Jue

    2014-12-01

    Mechanisms, acute management, and outcomes for patients who experience intracerebral hemorrhage may differ from patients with ischemic stroke. Studies of very early rehabilitation have been mainly undertaken in patients with ischemic stroke, and it is unknown if benefits apply to those with intracerebral hemorrhage. We hypothesized that early rehabilitation, within 48 hours of stroke, would improve survival and functional outcomes in patients with intracerebral hemorrhage. This was a multicenter, randomized controlled study, with blinded assessment of outcome at 3 and 6 months. Eligible patients were randomized to receive standard care or standard care plus early rehabilitation. Primary outcome includes survival. Secondary outcomes includes health-related quality of life using the 36-item Short Form Questionnaire, function measured with the modified Barthel Index, and anxiety measured with the Zung Self-Rated Anxiety Scale. Two hundred forty-three of 326 patients were randomized (mean age, 59 years; 56% men). At 6 months, patients receiving standard care were more likely to have died (adjusted hazard ratio, 4.44; 95% confidence interval [CI], 1.24-15.87); for morbidity outcomes, a 6-point difference in the Physical Component Summary score of the 36-item Short Form Questionnaire (95% CI, 4.2-8.7), a 7-point difference for the Mental Component Summary score (95% CI, 4.5-9.5), a 13-point difference in Modified Barthel Index scores (95% CI, 6.8-18.3), and a 6-point difference in Self-Rating Anxiety Scale scores (95% CI, 4.4-8.3) was reported in favor of the intervention groups. For the first time, we have shown that commencing rehabilitation within 48 hours of intracerebral hemorrhage improves survival and functional outcomes at 6 months after stroke in hospitalized patients in China. http://www.chictr.org/en. Unique identifier: ChiCTR-TRC-13004039. © 2014 American Heart Association, Inc.

  6. Investigating the Relationship between Cerebrospinal Fluid and Magnetic Induction Phase Shift in Rabbit Intracerebral hematoma expansion Monitoring by MRI

    OpenAIRE

    Chen, Mingsheng; Yan, Qingguang; Sun, Jian; Jin, Gui; Qin, Mingxin

    2017-01-01

    In a prior study of intracerebral hemorrhage monitoring using magnetic induction phase shift (MIPS), we found that MIPS signal changes occurred prior to those seen with intracranial pressure. However, the characteristic MIPS alert is not yet fully explained. Combining the brain physiology and MIPS theory, we propose that cerebrospinal fluid (CSF) may be the primary factor that leads to hematoma expansion being alerted by MIPS earlier than with intracranial pressure monitoring. This paper inve...

  7. Association between cerebral microbleeds and the first onset of intracerebral hemorrhage - a 3.0 T MR study

    International Nuclear Information System (INIS)

    Sun, Shengjun; Gao, Peiyi; Sui, Binbin; Xue, Jing; Wang, Hui; Wang, Qiong; Jing, Lina; Zhai, Renyou

    2012-01-01

    Background. Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a potential risk factor for further bleeding, while the association between CMBs and the first onset of intracerebral hemorrhage has not been well investigated. Purpose. To analyze the association between CMBs and the first onset of primary intracerebral hemorrhage (pICH). Material and Methods. Two hundred and two consecutive inpatients with ICH and 234 consecutive outpatients without ICH as control group were enrolled in this study. MR imaging including T2*-GRE, T 1 W, T 2 W and fluid attenuated inversion recovery (FLAIR) sequences were performed to detect CMBs and other abnormalities. Prevalence, distribution, and grades of CMBs, as well as the location and size of the intracerebral hematoma were analyzed, respectively. Comparison was made between pICH and control group. Logistic analysis was performed to evaluate the association between CMBs and ICH. The correlation between hematoma size and CMBs grade/numbers was analyzed. Results. CMBs were detected in 140 patients in pICH (69.3%) group and 62 patients in control group (26.5%). The incidence of CMBs in pICH group was significantly higher than that in control group (P < 0.0001). As the logistic regression analysis results, CMBs was the risk factor associated with ICH, with modulation OR value of 8.363 (95% CI 5.210-13.421). The volume of ICH with CMBs was 12.57 ± 17.23 mL, and the volume of ICH without CMBs was 17.77 ± 26.97 mL. Negative correlation was demonstrated between CMBs number and ICH volume (rs = -0.1769, P = 0.0118), as well as between CMBs grade and hematoma volume (rs = -0.1185, P = 0.1557). Conclusion CMBs may be an independent risk factor for the first onset of intracerebral hemorrhage

  8. PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

    NARCIS (Netherlands)

    Meehan, Terrence F.; Conte, Nathalie; Goldstein, Theodore; Inghirami, Giorgio; Murakami, Mark A.; Brabetz, Sebastian; Gu, Zhiping; Wiser, Jeffrey A.; Dunn, Patrick; Begley, Dale A.; Krupke, Debra M.; Bertotti, Andrea; Bruna, Alejandra; Brush, Matthew H.; Byrne, Annette T.; Caldas, Carlos; Christie, Amanda L.; Clark, Dominic A.; Dowst, Heidi; Dry, Jonathan R.; Doroshow, James H.; Duchamp, Olivier; Evrard, Yvonne A.; Ferretti, Stephane; Frese, Kristopher K.; Goodwin, Neal C.; Greenawalt, Danielle; Haendel, Melissa A.; Hermans, Els; Houghton, Peter J.; Jonkers, Jos; Kemper, Kristel; Khor, Tin O.; Lewis, Michael T.; Lloyd, K. C. Kent; Mason, Jeremy; Medico, Enzo; Neuhauser, Steven B.; Olson, James M.; Peeper, Daniel S.; Rueda, Oscar M.; Seong, Je Kyung; Trusolino, Livio; Vinolo, Emilie; Wechsler-Reya, Robert J.; Weinstock, David M.; Welm, Alana; Weroha, S. John; Amant, Frédéric; Pfister, Stefan M.; Kool, Marcel; Parkinson, Helen; Butte, Atul J.; Bult, Carol J.

    2017-01-01

    Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models

  9. Interrogating open issues in cancer precision medicine with patient-derived xenografts

    NARCIS (Netherlands)

    Byrne, Annette T; Alférez, Denis G; Amant, Frédéric; Annibali, Daniela; Arribas, Joaquín; Biankin, Andrew V; Bruna, Alejandra; Budinská, Eva; Caldas, Carlos; Chang, David K; Clarke, Robert B; Clevers, Hans; Coukos, George; Dangles-Marie, Virginie; Eckhardt, S Gail; Gonzalez-Suarez, Eva; Hermans, Els; Hidalgo, Manuel; Jarzabek, Monika A; de Jong, Steven; Jonkers, Jos; Kemper, Kristel; Lanfrancone, Luisa; Mælandsmo, Gunhild Mari; Marangoni, Elisabetta; Marine, Jean-Christophe; Medico, Enzo; Norum, Jens Henrik; Palmer, Héctor G; Peeper, Daniel S; Pelicci, Pier Giuseppe; Piris-Gimenez, Alejandro; Roman-Roman, Sergio; Rueda, Oscar M; Seoane, Joan; Serra, Violeta; Soucek, Laura; Vanhecke, Dominique; Villanueva, Alberto; Vinolo, Emilie; Bertotti, Andrea; Trusolino, Livio

    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer

  10. Interrogating open issues in cancer precision medicine with patient-derived xenografts

    NARCIS (Netherlands)

    Byrne, Annette T.; Alférez, Denis G.; Amant, Frédéric; Annibali, Daniela; Arribas, Joaquín; Biankin, Andrew V.; Bruna, Alejandra; Budinská, Eva; Caldas, Carlos; Chang, David K.; Clarke, Robert B.; Clevers, Hans; Coukos, George; Dangles-Marie, Virginie; Eckhardt, S. Gail; Gonzalez-Suarez, Eva; Hermans, Els; Hidalgo, Manuel; Jarzabek, Monika A.; de Jong, Steven; Jonkers, Jos; Kemper, Kristel; Lanfrancone, Luisa; Mælandsmo, Gunhild Mari; Marangoni, Elisabetta; Marine, Jean-Christophe; Medico, Enzo; Norum, Jens Henrik; Palmer, Héctor G.; Peeper, Daniel S.; Pelicci, Pier Giuseppe; Piris-Gimenez, Alejandro; Roman-Roman, Sergio; Rueda, Oscar M.; Seoane, Joan; Serra, Violeta; Soucek, Laura; Vanhecke, Dominique; Villanueva, Alberto; Vinolo, Emilie; Bertotti, Andrea; Trusolino, Livio

    2017-01-01

    Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer

  11. Patient-Derived Xenograft Models : An Emerging Platform for Translational Cancer Research

    NARCIS (Netherlands)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinska, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Maelandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These

  12. The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

    NARCIS (Netherlands)

    E.C. Townsend (Elizabeth); M.A. Murakami (Mark); A. Christodoulou (Alexandra); A.L. Christie (Amanda); J. Köster (Johannes); T.A. DeSouza (Tiffany); E.A. Morgan (Elizabeth); S.P. Kallgren (Scott); H. Liu (Huiyun); S.-C. Wu (Shuo-Chieh); O. Plana (Olivia); J. Montero (Joan); K.E. Stevenson (Kristen); P. Rao (Prakash); R. Vadhi (Raga); M. Andreeff (Michael); P. Armand (Philippe); K.K. Ballen (Karen); P. Barzaghi-Rinaudo (Patrizia); S. Cahill (Sarah); R.A. Clark (Rachael); V.G. Cooke (Vesselina); M.S. Davids (Matthew); D.J. DeAngelo (Daniel); D.M. Dorfman; H. Eaton (Hilary); B.L. Ebert (Benjamin); J. Etchin (Julia); B. Firestone (Brant); D.C. Fisher (David); A.S. Freedman (Arnold); I.A. Galinsky, () (Ilene); H. Gao (Hui); J.S. Garcia, () (Jacqueline); F. Gamache-Ottou (Francine); T.A. Graubert (Timothy); A. Gutierrez (Alejandro); E. Halilovic (Ensar); M.H. Harris (Marian); Z.T. Herbert (Zachary); S.M. Horwitz (Steven); G. Inghirami (Giorgio); A.M. Intlekofer (Andrew); M. Ito (Moriko); S. Izraeli (Shai); E.D. Jacobsen (Eric); C.A. Jacobson (Caron); S. Jeay (Sébastien); I. Jeremias (Irmela); M.A. Kelliher (Michelle); R. Koch (Raphael); M. Konopleva (Marina); N. Kopp (Nadja); S.M. Kornblau (Steven); A.L. Kung (Andrew); T.S. Kupper (Thomas); N.R. LeBoeuf (Nicole); A.S. LaCasce (Ann); E. Lees (Emma); L.S. Li (Loretta); A.T. Look (Thomas); M. Murakami (Masato); M. Muschen (Markus); D. Neuberg (Donna); S.Y. Ng (Samuel); O.O. Odejde (Oreofe); S.H. Orkin (Stuart); R.R. Paquette (Rachel); A.A. Place (Andrew); J.E. Roderick (Justine); J.A. Ryan (Jeremy); S.E. Sallan (Stephen); B. Shoji (Brent); L.B. Silverman (Lewis); R.J. Soiffer (Robert); D.P. Steensma (David); K. Stegmaier (Kimberley); R.M. Stone (Richard); J. Tamburini (Jerome); A.R. Thorner (Aaron); P. van Hummelen (Paul); M. Wadleigh (Martha); M. Wiesmann (Marion); A.P. Weng (Andrew); J.U. Wuerthner (Jens); D.A. Williams (David); B.M. Wollison (Bruce); A.A. Lane (Andrew); A. Letai (Anthony); M.M. Bertagnolli (Monica); J. Ritz (Jerome); M. Brown (Myles); H. Long (Henry); J.C. Aster (Jon); M.A. Shipp (Margaret); J.D. Griffin (James); D.M. Weinstock (David)

    2016-01-01

    textabstractMore than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address

  13. Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

    International Nuclear Information System (INIS)

    Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

    2008-01-01

    Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

  14. Noninvasive detection of temozolomide in brain tumor xenografts by magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kato, Y.; Holm, David Alberg; Okollie, B.

    2010-01-01

    demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [C-13] TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm(3) within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [C-13]TMZ...

  15. Investigating the Relationship between Cerebrospinal Fluid and Magnetic Induction Phase Shift in Rabbit Intracerebral hematoma expansion Monitoring by MRI.

    Science.gov (United States)

    Chen, Mingsheng; Yan, Qingguang; Sun, Jian; Jin, Gui; Qin, Mingxin

    2017-09-11

    In a prior study of intracerebral hemorrhage monitoring using magnetic induction phase shift (MIPS), we found that MIPS signal changes occurred prior to those seen with intracranial pressure. However, the characteristic MIPS alert is not yet fully explained. Combining the brain physiology and MIPS theory, we propose that cerebrospinal fluid (CSF) may be the primary factor that leads to hematoma expansion being alerted by MIPS earlier than with intracranial pressure monitoring. This paper investigates the relationship between CSF and MIPS in monitoring of rabbit intracerebral hemorrhage models, which is based on the MIPS measurements data, the quantified data on CSF from medical images and the amount of injected blood in the rabbit intracerebral hemorrhage model. In the investigated results, a R value of 0.792 with a significance of 0.019 is observed between the MIPS and CSF, which is closer than MIPS and injected blood. Before the reversal point of MIPS, CSF is the leading factor in MIPS signal changing in an early hematoma expansion stage. Under CSF compensation, CSF reduction compensates for hematoma expansion in the brain to keep intracranial pressure stable. MIPS decrease results from the reducing CSF volume. This enables MIPS to detect hematoma expansion earlier than intracranial pressure.

  16. MR imaging of intracerebral hemorrhage lesions: Comparison of 2.0 T and 0.5 T images

    International Nuclear Information System (INIS)

    Han, Moon Hee; Chang, Kee Hyun

    1990-01-01

    Seventeen patients with intracerebral hemorrhage lesions were examined with magnetic resonance imaging at both 2.0 T and 0.5 T, in order to evaluate the capability of detecting and characterizing the hemorrhagic lesions at each field strength and to compare the signal intensities of the hemorrhages between both field strengths. The intervals between two imagings were within 2 hours in all patients except for 4 patients with subacute hematoma and occult cerebrovascular malformations in whom the intervals were 1 to 4 days. At each field strength, both T1 and T2-weighted spin echo(SE) images were obtained in all patients. All the hemorrhagic lesions were readily detected and characterized as hemorrhagic lesions at 2.0 T, whereas one lesion of chronic hemorrhage was not detected, and three lesions(one acute hemorrhage, one chronic hemorrhage and one occult cerebrovascular malformation) could not be characterized as hemorrhagic lesions at 0.5 T. There were statistically significant differences in signal intensity of the hematomas between 2.0 T and 0.5 T on proton density-weighted and T2-weighted images in cases of acute intracerebral hematomas: the hematomas seen as low intensity at 2.0 T appeared iso-or slightly high at 0.5 T. In conclusion, the intracerebral hematomas may be difficult to detect and to characterize with SE technique at 0.5 T, and then the gradient echo technique may be useful at 0.5 T

  17. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  18. MRI characteristics of spontaneous intracerebral hemorrhage; Das kernspintomographische Erscheinungsbild der spontanen intrazerebralen Blutung

    Energy Technology Data Exchange (ETDEWEB)

    Felber, S.; Schocke, M. [Innsbruck Univ. (Austria). Klinik fuer Radiologie; Innsbruck Univ. (Austria). Inst. fuer Magnetresonanztomographie und Spektroskopie; Auer, A.; Golaszewski, S.; Amort, B. [Innsbruck Univ. (Austria). Inst. fuer Magnetresonanztomographie und Spektroskopie; Nedden, D. zur [Innsbruck Univ. (Austria). Klinik fuer Radiologie

    1999-10-01

    We review the signal characteristics of intracerebral hematomas (ICH) on magnetic resonance imaging (MRI), with special emphasis on the diagnosis of intracerebral hemorrhage within the first hours after stroke. The detection of peracute ICH was evaluated in 42 patients of a prospective, MR randomized stroke trial. These patients underwent a protocol of T1 and T2 weighted sequences, diffusion weighted sequences and MR - angiography within 6 hours after onset of acute hemiparesis. The signal behaviour of ICH in any stage after bleeding was additionally reviewed in a retrospective series of 63 patients, who were submitted for MRI over a 12 months period because of known ICH. MRI correctly identified 4 hyperacute ICH in the prospective group and 4 hyperacute ICH in the retrospective group. These ICHs had high signal on T2 weighted images, were isointense in T1 weighted images and had signal voids on the diffusion weighted sequences. The signal intensities of acute, subacute and chronic ICHs correlated to previous experiences as reported in the literature. In conclusion, MRI reliably identified all hematomas even in the hyperacute stage. Diffusion weighted images were most sensitive to the presence of deoxyhemoglobine and helpful for the differentiation and characterization of acute ischemia. Therefore, MRI at 1.5 T can be employed as an alternative to CT for the emergency diagnosis of acute stroke. (orig.) [German] In dieser Uebersicht wird das kernspintomographische (KST) Erscheinungsbild der intrazerebralen Blutung (IZB) anhand eigener Erfahrungen und der Literatur diskutiert. Besonderes Gewicht wurde auf den KST Nachweis der hyperakuten IZB innerhalb der ersten Stunden gelegt. Es wurden einerseits die Befunde von 42 Patienten einer prospektiven, KST randomisierten Schlaganfallstudie ausgewertet, bei denen die KST als Erstuntersuchung innerhalb von 6 Stunden durchgefuehrt worden war. Andererseits werteten wir retrospektiv jene KST Untersuchungen aus, die im Jahr 1998

  19. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  20. Minimal invasive puncture and drainage versus endoscopic surgery for spontaneous intracerebral hemorrhage in basal ganglia

    Directory of Open Access Journals (Sweden)

    Li Z

    2017-01-01

    Full Text Available Zhihong Li,1,* Yuqian Li,1,* Feifei Xu,2,* Xi Zhang,3 Qiang Tian,4 Lihong Li1 1Department of Neurosurgery, Tangdu Hospital, 2Department of Foreign Languages, 3Department of Biomedical Engineering, 4Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China *These authors contributed equally to this work Abstract: Two prevalent therapies for the treatment of spontaneous intracerebral hemorrhage (ICH in basal ganglia are, minimally invasive puncture and drainage (MIPD, and endoscopic surgery (ES. Because both surgical techniques are of a minimally invasive nature, they have attracted greater attention in recent years. However, evidence comparing the curative effect of MIPD and ES has been uncertain. The indication for MIPD or ES has been uncertain till now. In the present study, 112 patients with spontaneous ICH in basal ganglia who received MIPD or ES were reviewed retrospectively. Baseline parameters prior to the operation, evacuation rate (ER, perihematoma edema, postoperative complications, and rebleeding incidences were collected. Moreover, 1-year postictus, the long-term functional outcomes of patients with regard to hematoma volume (HV or Glasgow Coma Scale (GCS score were judged, respectively, by the case fatality, Glasgow Outcome Scale (GOS, Barthel Index (BI, and modified Rankin Scale (mRS. The ES group had a higher ER than the MIPD group on postoperative day 1. The MIPD group had fewer adverse outcomes, which included less perihematoma edema, anesthetic time, and blood loss, than the ES group. The functional outcomes represented by GOS, BI, and mRS were better in the MIPD group than in the ES group for patients with HV 30–60 mL or GCS score 9–14. These results indicate that ES is more effective in evacuating hematoma in basal ganglia, while MIPD is less invasive than ES. Patients with HV 30–60 mL or GCS score 9–14 may benefit more from the MIPD

  1. Serum levels of fibroblast growth factor in patients with intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Cüneyt Ölmez

    2011-09-01

    Full Text Available Objectives: Intracerebral hemorrhage (ICH is one of the most mortal subtypes of stroke. Due to the angiogenic, neurotropic, and vessel-dilating properties of basic fibroblast growth factor (bFGF in the brain, role of bFGF has been investigated in a number of neurological disorders. So far, there is only study about serum bFGF levels in patients with ICH. The first aim of the present research is to investigate whether increased serum bFGF in patients with ICH. Also, second aim was to study the association between serum levels of bFGF and clinical status in patients with ICH.Materials and methods: We measured the serum levels of bFGF in 30 patients with ICH during acute period. Age and sex matched healthy subjects (n=30 were included in controls. Serum bFGF levels were measured using an enzyme-linked immunosorbent assay method.Results: The patients with intracerebral hemorrhage had higher serum levels of bFGF when compared with the healthy controls (12.89±3.23 ng/ml, 5.28±1.75 ng/ml; p=0.001. No statistically significant difference was determined between bFGF levels of the patients who died as compared to the patients who lived (13.49±4.13 ng/ml; 12.43±3.43 ng/ml, p>0.05. No statistically significant difference was found between bFGF levels of the patients with intraventricular hemorrhage as compared to the patients without intraventricular hemorrhage (13.54±3.92 ng/ml; 12.24±2.29 ng/ml, p>0.05. There was no correlation between serum bFGF, hematoma volume, Gloskow coma scale, and National Institutes of Health stroke scale (p>0.05.Conclusion: The increased bFGF level may be one of the mechanisms that lead to angiogenesis and neuroprotection after ICH in human. . J Clin Exp Invest 2011; 2 (3: 282-286.

  2. MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors.

    Science.gov (United States)

    Yoo, Dong Hyun; Song, Sang Woo; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Park, Chul-Kee; Kim, Il Han; Choi, Seung Hong

    2015-01-01

    The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population.

  3. The Association Between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage versus Ischemic Lacunar Infarction

    Directory of Open Access Journals (Sweden)

    Emma H Kaplan

    2014-09-01

    Full Text Available Background: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH. Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (eg., cocaine, tobacco is associated with subcortical ICH over ischemia in hypertensive individuals.Methods: Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women, >2 drinks per day (men. Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia.Results: Of the 580 patients included in analysis, 217 (37% presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years. Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25% versus 15%, p=0.02, with the largest effect seen in users ≥65 years old (not statistically significant. Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p=0.29.Conclusions: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH; while use of illicit/controlled substances appears to be predictive of hemorrhage.

  4. Differentiating epileptic from non-epileptic high frequency intracerebral EEG signals with measures of wavelet entropy.

    Science.gov (United States)

    Mooij, Anne H; Frauscher, Birgit; Amiri, Mina; Otte, Willem M; Gotman, Jean

    2016-12-01

    To assess whether there is a difference in the background activity in the ripple band (80-200Hz) between epileptic and non-epileptic channels, and to assess whether this difference is sufficient for their reliable separation. We calculated mean and standard deviation of wavelet entropy in 303 non-epileptic and 334 epileptic channels from 50 patients with intracerebral depth electrodes and used these measures as predictors in a multivariable logistic regression model. We assessed sensitivity, positive predictive value (PPV) and negative predictive value (NPV) based on a probability threshold corresponding to 90% specificity. The probability of a channel being epileptic increased with higher mean (p=0.004) and particularly with higher standard deviation (pentropy is likely to be epileptic; with a threshold corresponding to 90% specificity our model can reliably select a subset of epileptic channels. Most studies have concentrated on brief ripple events. We showed that background activity in the ripple band also has some ability to discriminate epileptic channels. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Correlative study between a serial changes of rCBF and aphasia in hypertensive intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Shi Yizhen; He Guangren

    1998-01-01

    Purpose: To explore the dynamic changes of rCBF of aphasic patients and its correlation with clinical findings. Methods: 32 dominant lateral hypertensive intracerebral hemorrhagic patients underwent the language function evaluation, rCBF tomographic imaging and CT scans. Semiquantitative analysis was used. Results: 1) 19 of 32 cases were aphasia while 13 were not. 2) There was a close correlation between aphasia and the size and location of hematoma. 3) There was only hemonrrhagic foci demonstrated with CT while multiple and extensive cortical hypo-perfused area were found in SPECT, especially in aphasic cases. Frontal and temporal lobes of each aphasia were involved 100%. 4) The rCBF ratio in both Broca's and Wernicke's areas of aphasias were lower than those of non-aphasias (t = 4.31, 5.52, P < 0.001). The degree of rCBF decrement in Wernicke's area varied with different aphasic types, among which the rCBF of sensory aphasia was the lowest (t 2.53, P<0.05). 5) 10 aphasias were followed with SPECT, CT and clinic evaluation 1 week, 1 month and 3 months after hemorrhage respectively. The rCBF ratios in cerebral cortex of 5 recovery cases increased gradually, but not in 5 not recovered cases. Conclusions: SPECT was superior to CT, it can provide useful information for diagnosing and staging aphasias, especially in early stage, and can also assess the prognosis of the disease

  6. Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation (Mi SPACE for Intracerebral Hemorrhage

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    Benjamin Ritsma

    2014-01-01

    Full Text Available Background. Spontaneous intracerebral hemorrhage (ICH is common and causes significant mortality and morbidity. To date, optimal medical and surgical intervention remains uncertain. A lack of definitive benefit for operative management may be attributable to adverse surgical effect, collateral tissue injury. This is particularly relevant for ICH in dominant, eloquent cortex. Minimally invasive surgery (MIS offers the potential advantage of reduced collateral damage. MIS utilizing a parafascicular approach has demonstrated such benefit for intracranial tumor resection. Methods. We present a case of dominant hemisphere spontaneous ICH evacuated via the minimally invasive subcortical parafascicular transsulcal access clot evacuation (Mi SPACE model. We use this report to introduce Mi SPACE and to examine the application of this novel MIS paradigm. Case Presentation. The featured patient presented with a left temporal ICH and severe global aphasia. The hematoma was evacuated via the Mi SPACE approach. Postoperative reassessments showed significant improvement. At two months, bedside language testing was normal. MRI tractography confirmed limited collateral injury. Conclusions. This case illustrates successful application of the Mi SPACE model to ICH in dominant, eloquent cortex and subcortical regions. MRI tractography illustrates collateral tissue preservation. Safety and feasibility studies are required to further assess this promising new therapeutic paradigm.

  7. Association of subdural hematoma with increased mortality in lobar intracerebral hemorrhage.

    Science.gov (United States)

    Patel, Pratik V; FitzMaurice, Emilie; Nandigam, R N Kaveer; Auluck, Pavan; Viswanathan, Anand; Goldstein, Joshua N; Rosand, Jonathan; Greenberg, Steven M; Smith, Eric E

    2009-01-01

    To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary nontraumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Retrospective analysis of data collected in a prospective cohort study. Hospital. Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Presence of SDH and mortality. Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86-30.99; P = .005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42-68.23; P = .003 for those with ICH volume subdural space, may be the pathogenic mechanism.

  8. Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.

    Science.gov (United States)

    Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

    2014-05-01

    Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

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    Yu, Yao; Zhao, Wei; Zhu, Chunpeng; Kong, Zhiping; Xu, Yan; Liu, Guangzhi; Gao, Xuguang

    2015-01-01

    It has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH. From February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared. Forty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group's relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P edema after ICH, although further investigation is required to form definitive conclusions. Chinese Clinical Trial Registry ChiCTR-TRC-14004979.

  10. High Morphologic Plasticity of Microglia/Macrophages Following Experimental Intracerebral Hemorrhage in Rats

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    Shu-Sheng Yang

    2016-07-01

    Full Text Available As current efforts have limited effects on the clinical outcome of intracerebral hemorrhage (ICH, the mechanisms including microglia/macrophages that involved inflammation need further investigation. Here, 0.4 units of collagenase VII were injected into the left caudate putamen (CPu to duplicate ICH rat models. In the brains of ICH rats, microglia/macrophages, the nearest cells to the hemorrhagic center, were observed as ameboid and Prussian-blue positive. Furthermore, the ameboid microglia/macrophages were differentiation (CD 68 and interleukin-1β (IL-1β positive, and neither CD206 nor chitinase3-like 3 (Ym1 positive, suggesting their strong abilities of phagocytosis and secretion of IL-1β. According to the distance to the hemorrhagic center, we selected four areas—I, II, III, and IV—to analyze the morphology of microglia/macrophages. The processes decreased successively from region I to region IV. Microglia/macrophages in region IV had no processes. The processes in region I were radially distributed, however, they showed obvious directivity towards the hemorrhagic center in regions II and III. Region III had the largest density of compactly arrayed microglia/macrophages. All these in vivo results present the high morphologic plasticity of microglia/macrophages and their functions in the pathogenesis of ICHs.

  11. Intracerebral Hemorrhage with Intraventricular Extension—Getting the Prognosis Right Early

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    Christoph Stretz

    2017-08-01

    Full Text Available BackgroundEarly accurate outcome prognostication for patients with intracerebral hemorrhage (ICH and accompanying intraventricular hemorrhage (IVH is often challenging (1. Acute hydrocephalus often contributes to a poor clinical exam (2 and can portend significant morbidity and mortality (3. Accordingly, the inpatient neurologist may feel inclined to recommend limitations of care for an ICH patient admitted with a large IVH burden and poor exam.Case presentationWe present a patient with significant IVH and minimal ICH who deteriorated rapidly to coma after presentation. Despite this exam, an initially non-functioning diversion of cerebrospinal fluid (CSF and temporary halt of further attempts of CSF diversion in the setting of an early “do not resuscitate order,” our patient gradually improved and, with supportive ICU care and rehabilitation, was able to communicate and ambulate with assistance at 12 weeks.ConclusionPatients with ICH with IVH do have the capacity to improve dramatically even with relatively conservative management. Unless previous limitations of care exist, we recommend that early judgments of prognosis for patients with ICH and/or IVH should be delayed for at least 72 h until the patient’s clinical trajectory over time is better understood.

  12. Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study

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    Heeley Emma L

    2011-01-01

    Full Text Available Abstract Background We aimed to examine current practice of the management and secondary prevention of intracerebral haemorrhage (ICH in China where the disease is more common than in Western populations. Methods Data on baseline characteristics, management in-hospital and post-stroke, and outcome of ICH patients are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment study, a multi-centre, prospective, 62 hospital registry in China during 2006-07. Results Nearly all ICH patients (n = 1572 received an intravenous haemodiluting agent such as mannitol (96% or a neuroprotectant (72%, and there was high use of intravenous traditional Chinese medicine (TCM (42%. Neurosurgery was undertaken in 137 (9% patients; being overweight, having a low Glasgow Coma Scale (GCS score on admission, and Total Anterior Circulation Syndrome (TACS clinical pattern on admission, were the only baseline factors associated with this intervention in multivariate analyses. Neurosurgery was associated with nearly three times higher risk of death/disability at 3 months post-stroke (odd ratio [OR] 2.60, p Conclusions The management of ICH in China is characterised by high rates of use of intravenous haemodiluting agents, neuroprotectants, and TCM, and of antihypertensives for secondary prevention. The controversial efficacy of these therapies, coupled with the current lack of treatments of proven benefit, is a call for action for more outcomes based research in ICH.

  13. Steps to consider in the approach and management of critically ill patient with spontaneous intracerebral hemorrhage

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    Godoy, Daniel Agustin; Piñero, Gustavo Rene; Koller, Patricia; Masotti, Luca; Di Napoli, Mario

    2015-01-01

    Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurological-neurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it’s important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery. PMID:26261773

  14. CT perfusion mapping of hemodynamic disturbances associated to acute spontaneous intracerebral hemorrhage

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    Fainardi, Enrico; Borrelli, Massimo; Saletti, Andrea; Ceruti, Stefano; Tamarozzi, Riccardo; Schivalocchi, Roberta; Cavallo, Michele; Azzini, Cristiano; Chieregato, Arturo

    2008-01-01

    We sought to quantify perfusion changes associated to acute spontaneous intracerebral hemorrhage (SICH) by means of computed tomography perfusion (CTP) imaging. We studied 89 patients with supratentorial SICH at admission CT by using CTP scanning obtained within 24 h after symptom onset. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV) and mean transit time (rMTT) levels were measured in four different regions of interest manually outlined on CT scan: (1) hemorrhagic core; (2) perihematomal low-density area; (3) 1 cm rim of normal-appearing brain tissue surrounding the perilesional area; and (4) a mirrored area, including the clot and the perihematomal region, located in the non-lesioned contralateral hemisphere. rCBF, rCBV, and rMTT mean levels showed a centrifugal distribution with a gradual increase from the core to the periphery (p 20 ml) hematomas (p<0.01 and p <0.02, respectively). Multi-parametric CTP mapping of acute SICH indicates that perfusion values show a progressive improvement from the core to the periphery. In the first 24 h, perihemorrhagic region was hypoperfused with CTP values which were not suggestive of ischemic penumbra destined to survive but more likely indicative of edema formation. These findings also argue for a potential influence of early amounts of bleeding on perihematomal hemodynamic abnormalities. (orig.)

  15. Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

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    Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

    2015-06-15

    Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

  16. Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats.

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    Wasserman, Jason K; Yang, Helen; Schlichter, Lyanne C

    2008-10-01

    Intracerebral hemorrhage (ICH) usually affects older humans but almost no experimental studies have assessed aged animals. We address how aging alters inflammation, neuron death and lesion resolution after a hemorrhage in the rat striatum. In the normal aged brain, microglia displayed a 'dystrophic' phenotype, with shorter cellular processes and large gaps between adjacent cells, and there was more astrocyte reactivity. The ICH injury was monitored as hematoma volume and number of dying neurons at 1 and 3 days, and the volume of the residual lesion, ventricles and lost tissue at 28 days. Inflammation at 1 and 3 days was assessed from densities of microglia with resting vs. activated morphologies, or expressing the lysosomal marker ED1. Despite an initial delay in neuron death in aged animals, by 28 days, there was no difference in neuron density or volume of tissue lost. However, lesion resolution was impaired in aged animals and there was less compensatory ventricular expansion. At 1 day after ICH, there were fewer activated microglia/macrophages in the aged brain, but by 3 days there were more of these cells at the edge of the hematoma and in the surrounding parenchyma. In both age groups a glial limitans had developed by 3 days, but astrocyte reactivity and the spread of activated microglia/macrophages into the surrounding parenchyma was greater in the aged. These findings have important implications for efforts to reduce secondary injury after ICH and to develop anti-inflammatory therapies to treat ICH in aged humans.

  17. Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice.

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    Li, Qian; Wan, Jieru; Lan, Xi; Han, Xiaoning; Wang, Zhongyu; Wang, Jian

    2017-09-01

    Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model. We found that the effects of VK-28 were similar to those of deferoxamine (DFX), a well-studied iron chelator. Both decreased cell death and ROS production in OHSCs and in vivo, decreased iron-deposition and microglial activation around hematoma in vivo, and improved neurologic function. Moreover, compared with DFX, VK-28 polarized microglia to an M2-like phenotype, reduced brain water content, deceased white matter injury, improved neurobehavioral performance, and reduced overall death rate after ICH. The protection of VK-28 was confirmed in a blood-injection ICH model and in aged-male and young female mice. Our findings indicate that VK-28 is protective against iron toxicity after ICH and that, at the dosage tested, it has better efficacy and less toxicity than DFX does.

  18. Scale invariance properties of intracerebral EEG improve seizure prediction in mesial temporal lobe epilepsy.

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    Kais Gadhoumi

    Full Text Available Although treatment for epilepsy is available and effective for nearly 70 percent of patients, many remain in need of new therapeutic approaches. Predicting the impending seizures in these patients could significantly enhance their quality of life if the prediction performance is clinically practical. In this study, we investigate the improvement of the performance of a seizure prediction algorithm in 17 patients with mesial temporal lobe epilepsy by means of a novel measure. Scale-free dynamics of the intracerebral EEG are quantified through robust estimates of the scaling exponents--the first cumulants--derived from a wavelet leader and bootstrap based multifractal analysis. The cumulants are investigated for the discriminability between preictal and interictal epochs. The performance of our recently published patient-specific seizure prediction algorithm is then out-of-sample tested on long-lasting data using combinations of cumulants and state similarity measures previously introduced. By using the first cumulant in combination with state similarity measures, up to 13 of 17 patients had seizures predicted above chance with clinically practical levels of sensitivity (80.5% and specificity (25.1% of total time under warning for prediction horizons above 25 min. These results indicate that the scale-free dynamics of the preictal state are different from those of the interictal state. Quantifiers of these dynamics may carry a predictive power that can be used to improve seizure prediction performance.

  19. Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved

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    Lewis Buss

    2016-05-01

    Full Text Available Down syndrome (DS, which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer’s disease (AD dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein (APP gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH, the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies of the APP region on chromosome 21, here called ‘dup-APP’, which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight.

  20. Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study.

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    Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

    2016-02-05

    Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2) = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke.

  1. History and Mechanism for Treatment of Intracerebral Hemorrhage with Scalp Acupuncture

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    Zhe Liu

    2012-01-01

    Full Text Available Intracerebral hemorrhage (ICH is an important public health problem with high rates of mortality, morbidity, and disability, but no clinically proven treatment strategy is available to date. Scalp acupuncture (SA refers to a therapy for treating diseases by needling and stimulating the specific areas of the scalp. The evidence from clinical studies suggested that SA therapy may produce significant benefits for patients with acute ICH. However, the therapeutic mechanisms are yet not well addressed. Therefore, in this paper, we provide a comprehensive overview on the history and mechanisms of SA therapy on acute ICH. Although SA has been practiced for thousands of years in China and could date back to 5 BC, SA therapy for acute ICH develops only in the recent 30 years. The possible mechanisms associated with the therapeutic effects of SA on ICH include the influence on hematoma, brain edema, and blood brain barrier, the products released from haematoma, the immune and inflammatory reaction, focal perihemorrhagic hypoperfusion and hemorheology, neuroelectrophysiology, and so on. At last, the existence of instant effect of SA on acute ICH and its possible mechanisms are presented.

  2. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage.

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    Jauch, Edward C; Lindsell, Christopher J; Adeoye, Opeolu; Khoury, Jane; Barsan, William; Broderick, Joseph; Pancioli, Arthur; Brott, Thomas

    2006-08-01

    Early hematoma expansion in spontaneous intracerebral hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that hemodynamic parameters are associated with the increase in hematoma volume owing to their relationship to blood vessel wall stresses. We performed a post hoc analysis of clinical and computed tomography (CT) data from patients enrolled in a prospective observational study of ICH patients presenting within 3 hours from symptom onset. Hematoma volumes were measured at hospital arrival and at 1 and 20 hours from presentation. Blood pressure and heart rate, recorded at 19 time points between presentation and 20 hours, were used to derive hemodynamic variables. Multivariable logistic-regression models were constructed to assess the relation between hemodynamic parameters and hematoma growth, adjusted for clinical covariates. From the original study, 98 patients underwent baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial hematoma growth was observed in 28% within the first hour. Of the 65 patients not undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours. Neither baseline or peak hemodynamic parameters nor changes in hemodynamic parameters were significantly associated with hematoma growth at either 1 or 20 hours. We found no blood pressure or heart rate parameters, individually or in combination, that were associated with hematoma growth. Our data suggest the influence of hemodynamic parameters on vessel wall stress to be an unlikely target for intervention in reducing the risk of early hematoma growth in ICH.

  3. Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain

    International Nuclear Information System (INIS)

    Bouchet, Audrey; Lemasson, Benjamin; Christen, Thomas; Potez, Marine; Rome, Claire; Coquery, Nicolas; Le Clec’h, Céline; Moisan, Anaick; Bräuer-Krisch, Elke; Leduc, Géraldine; Rémy, Chantal; Laissue, Jean A.; Barbier, Emmanuel L.; Brun, Emmanuel; Serduc, Raphaël

    2013-01-01

    Purpose: Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. Methods: Tissue responses to MRT (two orthogonal arrays (2 × 400 Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR S O 2 ) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. Results: In tumors, MR S O 2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR S O 2 , although vessel inter-distances increased slightly. Conclusion: We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia

  4. Comparison of TMS and DTT for predicting motor outcome in intracerebral hemorrhage.

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    Jang, Sung Ho; Ahn, Sang Ho; Sakong, Joon; Byun, Woo Mok; Choi, Byung Yun; Chang, Chul Hoon; Bai, Daiseg; Son, Su Min

    2010-03-15

    TMS (transcranial magnetic stimulation) and DTT (diffusion tensor tractography) have different advantages in evaluating stroke patients. TMS has good clinical accessibility and economical benefit. On the contrary, DTT has a unique advantage to visualize neural tracts three-dimensionally although it requires an expensive and large MRI machine. Many studies have demonstrated that TMS and DTT have predictive values for motor outcome in stroke patients. However, there has been no study on the comparison of these two evaluation tools. In the current study, we compared the abilities of TMS and DTT to predict upper motor outcome in patients with ICH (intracerebral hemorrhage). Fifty-three consecutive patients with severe motor weakness were evaluated by TMS and DTT at the early stage (7-28 days) of ICH. Modified Brunnstrom classification (MBC) and the motricity index of upper extremity (UMI) were evaluated at onset and 6 months after onset. Patients with the presence of a motor evoked potential (MEP) in TMS or a preserved corticospinal tract (CST) in DTT showed better motor outcomes than those without (p=0.000). TMS showed higher positive predictive value than DTT. In contrast, DTT showed higher negative predictive value than TMS. TMS and DTT had different advantages in predicting motor outcome, and this result could be a reference to predict final neurological deficit at the early stage of ICH.

  5. Pathomorphological changes of lungs and functional biochemical parameters of respiratory function in patients with intracerebral hemorrhages

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    S. I. Tertyishniy

    2013-08-01

    Full Text Available Pulmonary complications and closely related with them systemic functional-biochemical abnormalities are the most common complications of cerebral stroke. The purpose of the work was to research functional-biochemical parameters of respiratory function and to find it’s association with morphological changes in the lungs because of intracerebral hemorrhage. 37 sectional observations in patients who die of intracerebral hemorrhage were analized. It was conducted analysis of morphological transformations and retrospective analysis of functional-biochemical findings of respiratory functions, in order to detect changes of systemic hemodynamics, oxygen balance and ion-osmotic one and acid-alkaline status. The results of the study. The changes of blood gas composition and acid-alkaline status are registered in the lungs in the background of microcirculation disturbance from the first hours of development of intracerebral hemorrhage. During the first days of the onset of disease the partial oxygen pressure in arterial blood (РаО2 decreased 50,88% in comparison with the calculated normative findings. Partial pressure of carbon dioxide (РаСО2 in the arterial blood rosed by 52,17%. Without conducting artificial lung ventilation PO2 in venous blood decreased by 45,9%, and PCO2 increased by 40%. I has been marked a decrease in the oxygen capacity of the blood, due to the reduction of hemoglobin content in the blood to 103,7 minus 2 g/l and the concomitant decline in hematocrit up to 0,24-0,3. Deficit of the foundations has averaged from -6 to -10 mmol/l. These changes have led to a impression of the respiratory and metabolic acidosis, with a significant increase in the concentration of hydrogen ions. In the first day after the development of the disease with a rapid growing marks of swelling of the brain with concomitant dislocation of the brain stem, blood pH was 7,28 minus 0,02. It has been histologically determined interstitial edema, that

  6. Ambient temperature and volume of perihematomal edema in acute intracerebral haemorrhage: the INTERACT1 study.

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    Zheng, Danni; Arima, Hisatomi; Heeley, Emma; Karpin, Anne; Yang, Jie; Chalmers, John; Anderson, Craig S

    2015-01-01

    As no human data exist, we aimed to determine the relation between ambient temperature and volume of perihematomal 'cerebral' edema in acute spontaneous intracerebral haemorrhage (ICH) among Chinese participants of the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). INTERACT1 was a multicenter, open, blind outcome assessed, randomized controlled trial of intensive (systolic target ambient temperature (mean, minimum, maximum, and range) on the day of each participant's ICH obtained from China Meteorological Data Sharing Service System were linked to other data including edema volumes. Multivariable regression analyses were performed to evaluate association between ambient temperature and edema volumes. A generalized linear regression model with a generalized estimating equations approach (GEE) was used to assess any association of ambient temperature and change in edema volume over 72 h. A total of 250 of all 384 Chinese participants had complete data that showed positive associations between ambient temperature (mean and minimum temperatures) and edema volumes at each time point over 72 h after hospital admission (all P ambient temperature and perihematomal edema volume in acute spontaneous ICH. © 2014 World Stroke Organization.

  7. Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in Aged Mice.

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    Chen, Cheng; Yao, Li; Cui, Jing; Liu, Bao

    2018-01-01

    Fisetin is commonly used as an anti-inflammatory and neuroprotective drug. In this study, we aimed to investigate the efficacy of fisetin in alleviating intracerebral hemorrhage (ICH)-induced brain injury. Mouse ICH models were constructed using the collagenase-induction method. ICH mice received fisetin treatment at the dose of 10-90 mg/kg, followed by the evaluation of neurological deficit through neurologic severity scores (mNSS), brain water content and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis of cell apoptosis. Cytokine levels were also assessed with enzyme-linked immunosorbent assay. The activation of astrocytes and microglia was evaluated through S100 staining and Western blot analysis of ionized calcium-binding adaptor molecule 1 respectively. Nuclear factor kappa-B (NF-κB) signaling was also evaluated by Western blot. ICH mice demonstrated dramatic increase in mNSS, brain edema and cell apoptosis, indicating severe brain deficit. Fisetin treatment lowered these parameters, suggesting the alleviation of brain injury. Levels of proinflammatory cytokines were reduced, accompanied by a prominent decrease in activated astrocytes and microglia. NF-κB signaling was also attenuated by fisetin treatment. Fisetin effectively alleviates ICH by downregulating proinflammatory cytokines and attenuating NF-κB signaling. These data suggest fisetin as a valuable natural flavonol for clinical management of ICH-induced brain injury. © 2018 S. Karger AG, Basel.

  8. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

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    Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

    2013-01-01

    Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

  9. Prediction and Observation of Post-Admission Hematoma Expansion in Patients with Intracerebral Hemorrhage

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    Ovesen, Christian; Havsteen, Inger; Rosenbaum, Sverre; Christensen, Hanne

    2014-01-01

    Post-admission hematoma expansion in patients with intracerebral hemorrhage (ICH) comprises a simultaneous major clinical problem and a possible target for medical intervention. In any case, the ability to predict and observe hematoma expansion is of great clinical importance. We review radiological concepts in predicting and observing post-admission hematoma expansion. Hematoma expansion can be observed within the first 24 h after symptom onset, but predominantly occurs in the early hours. Thus capturing markers of on-going bleeding on imaging techniques could predict hematoma expansion. The spot sign observed on computed tomography angiography is believed to represent on-going bleeding and is to date the most well investigated and reliable radiological predictor of hematoma expansion as well as functional outcome and mortality. On non-contrast CT, the presence of foci of hypoattenuation within the hematoma along with the hematoma-size is reported to be predictive of hematoma expansion and outcome. Because patients tend to arrive earlier to the hospital, a larger fraction of acute ICH-patients must be expected to undergo hematoma expansion. This renders observation and radiological follow-up investigations increasingly relevant. Transcranial duplex sonography has in recent years proven to be able to estimate hematoma volume with good precision and could be a valuable tool in bedside serial observation of acute ICH-patients. Future studies will elucidate, if better prediction and observation of post-admission hematoma expansion can help select patients, who will benefit from hemostatic treatment. PMID:25324825

  10. Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

    Science.gov (United States)

    Chang, J J; Kim-Tenser, M; Emanuel, B A; Jones, G M; Chapple, K; Alikhani, A; Sanossian, N; Mack, W J; Tsivgoulis, G; Alexandrov, A V; Pourmotabbed, T

    2017-11-01

    Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. Patients with acute onset (minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required. © 2017 EAN.

  11. Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy.

    Science.gov (United States)

    Wu, Zehan; Zou, Xiang; Zhu, Wei; Mao, Ying; Chen, Liang; Zhao, Fan

    2016-12-15

    Intracerebral hemorrhage is the least treatable type of stroke and affects millions of people worldwide. Treatment for ICH varies from medicine to surgery, but the rate of mortality and mobility still remains high. Minocycline is a tetracycline antibiotic increasingly recognized for its neuroprotective potential. In earlier studies, we demonstrated that many secondary injuries caused by ICH could be significantly reduced by injection of minocycline in rat models. The following research investigates the role of minocycline in reducing brain injury. Twenty-four rats were administered 100μl autologous arterial blood injections into the right basal ganglia, treated with minocycline or vehicle and euthanized on the 1st, 3rd, and 7th day. Immunohistochemistry, TUNEL, and western blot analysis were performed to analyze the effects of minocycline on apoptosis and autophagy. After the injection of minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7; Beclin-1, LC3BII/I, caspase-3/8 were all suppressed after treatment. The relationship between Cathepsin D and minocycline remained unknown. Our studies suggest the potential medicinal value of minocycline, through both anti-autophagy and anti-apoptosis pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Outcomes from intracerebral hemorrhage among patients pre-treated with statins

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    Flávio Ramalho Romero

    2011-06-01

    Full Text Available OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH. We investigated whether the statin use before ICH, was associated with functional independence, 90 days after treatment. METHOD: We analyzed 124 consecutive ICH patients with 90-day outcome data who were enrolled in a prospective cohort study between 2006 and 2009. Eighty-three patients were included in this study. Among ICH survivors, univariate Cox regression models and Kaplan-Meier plots were used to determine subject characteristics that were associated with an increased risk of recurrence. Statin usage was determined through interviewing the patient at the time of ICH and confirmed by reviewing their medical records. Independent status was defined as Glasgow Outcome Scale grades 4 or 5. RESULTS: Statins were used by 20 out of 83 patients (24% before ICH onset. There was no effect from pre-ICH statin use on functional independence rates (28% versus 29%, P=0.84 or mortality (46% versus 45%, P=0.93. CONCLUSION: Pre-ICH statin use is not associated with changes to ICH functional outcome or mortality.

  13. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats.

    Science.gov (United States)

    Li, Hui-Qin; Li, Yan; Chen, Zi-Xian; Zhang, Xiao-Guang; Zheng, Xia-Wei; Yang, Wen-Ting; Chen, Shuang; Zheng, Guo-Qing

    2016-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa's scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH ( P electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

  14. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

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    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  15. Patient-tailored multimodal neuroimaging, visualization and quantification of human intra-cerebral hemorrhage

    Science.gov (United States)

    Goh, Sheng-Yang M.; Irimia, Andrei; Vespa, Paul M.; Van Horn, John D.

    2016-03-01

    In traumatic brain injury (TBI) and intracerebral hemorrhage (ICH), the heterogeneity of lesion sizes and types necessitates a variety of imaging modalities to acquire a comprehensive perspective on injury extent. Although it is advantageous to combine imaging modalities and to leverage their complementary benefits, there are difficulties in integrating information across imaging types. Thus, it is important that efforts be dedicated to the creation and sustained refinement of resources for multimodal data integration. Here, we propose a novel approach to the integration of neuroimaging data acquired from human patients with TBI/ICH using various modalities; we also demonstrate the integrated use of multimodal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data for TBI analysis based on both visual observations and quantitative metrics. 3D models of healthy-appearing tissues and TBIrelated pathology are generated, both of which are derived from multimodal imaging data. MRI volumes acquired using FLAIR, SWI, and T2 GRE are used to segment pathology. Healthy tissues are segmented using user-supervised tools, and results are visualized using a novel graphical approach called a `connectogram', where brain connectivity information is depicted within a circle of radially aligned elements. Inter-region connectivity and its strength are represented by links of variable opacities drawn between regions, where opacity reflects the percentage longitudinal change in brain connectivity density. Our method for integrating, analyzing and visualizing structural brain changes due to TBI and ICH can promote knowledge extraction and enhance the understanding of mechanisms underlying recovery.

  16. Gender Differences in Patients with Intracerebral Hemorrhage: A Hospital-Based Multicenter Prospective Study

    Directory of Open Access Journals (Sweden)

    Monique Bueno Alves

    2012-10-01

    Full Text Available Gender differences are well described for patients with ischemic stroke. Conversely, sex disparities in stroke presentation, risk factors, treatment, and outcomes for intracerebral hemorrhage (ICH were not previously studied. Our objective was to compare the frequency of risk factors, management patterns, symptoms at presentation, complication rates, and outcomes between genders in patients with ICH in Fortaleza, Brazil. Methods: Data were prospectively collected from patients admitted to 19 hospitals in Fortaleza with a diagnosis of ICH by trained research coordinators from June 2009 to October 2010. Daily visits to the selected hospitals were performed, and all patients admitted with a diagnosis of ICH were prospectively evaluated. Results: We evaluated 364 patients, 47.5% of whom were women. Men were younger (59.3 ± 14.58 years vs. 66.3 ± 14.6 years, p Conclusion: Overall risk factors for ICH in men and women were similar in our series. Men had a higher frequency of alcohol abuse and smoking. Women were older, had an increased time length from symptoms onset to hospital admission and had a worse prognosis at discharge. A better understanding of the gender disparities in patients with ICH will hopefully lead to better outcomes in both sexes in the future.

  17. Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Rosado-de-Castro

    2016-01-01

    Full Text Available Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

  18. Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

    Science.gov (United States)

    Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

    2018-06-01

    Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Pulsed terahertz imaging of breast cancer in freshly excised murine tumors

    Science.gov (United States)

    Bowman, Tyler; Chavez, Tanny; Khan, Kamrul; Wu, Jingxian; Chakraborty, Avishek; Rajaram, Narasimhan; Bailey, Keith; El-Shenawee, Magda

    2018-02-01

    This paper investigates terahertz (THz) imaging and classification of freshly excised murine xenograft breast cancer tumors. These tumors are grown via injection of E0771 breast adenocarcinoma cells into the flank of mice maintained on high-fat diet. Within 1 h of excision, the tumor and adjacent tissues are imaged using a pulsed THz system in the reflection mode. The THz images are classified using a statistical Bayesian mixture model with unsupervised and supervised approaches. Correlation with digitized pathology images is conducted using classification images assigned by a modal class decision rule. The corresponding receiver operating characteristic curves are obtained based on the classification results. A total of 13 tumor samples obtained from 9 tumors are investigated. The results show good correlation of THz images with pathology results in all samples of cancer and fat tissues. For tumor samples of cancer, fat, and muscle tissues, THz images show reasonable correlation with pathology where the primary challenge lies in the overlapping dielectric properties of cancer and muscle tissues. The use of a supervised regression approach shows improvement in the classification images although not consistently in all tissue regions. Advancing THz imaging of breast tumors from mice and the development of accurate statistical models will ultimately progress the technique for the assessment of human breast tumor margins.

  20. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

    Science.gov (United States)

    Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

    2016-07-01

    Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in reducing UL tumor growth by interfering with the main cellular processes regulating cell proliferation and apoptosis are in agreement with previous studies on the effects of HF on other fibrotic diseases. HF can be considered as a candidate for reducing the size of leiomyomas, particularly prior to surgery. This project was funded by NIH PO1HD057877 and R01 HD064402. Authors report no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights

  1. Localization of indium-111 in human malignant tumor xenografts and control by chelators

    International Nuclear Information System (INIS)

    Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

    1999-01-01

    The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

  2. An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Mosakhani Neda

    2012-03-01

    Full Text Available Abstract Background Xenografts have been shown to provide a suitable source of tumor tissue for molecular analysis in the absence of primary tumor material. We utilized ES xenograft series for integrated microarray analyses to identify novel biomarkers. Method Microarray technology (array comparative genomic hybridization (aCGH and micro RNA arrays was used to screen and identify copy number changes and differentially expressed miRNAs of 34 and 14 passages, respectively. Incubated cells used for xenografting (Passage 0 were considered to represent the primary tumor. Four important differentially expressed miRNAs (miR-31, miR-31*, miR-145, miR-106 were selected for further validation by real time polymerase chain reaction (RT-PCR. Integrated analysis of aCGH and miRNA data was performed on 14 xenograft passages by bioinformatic methods. Results The most frequent losses and gains of DNA copy number were detected at 9p21.3, 16q and at 8, 15, 17q21.32-qter, 1q21.1-qter, respectively. The presence of these alterations was consistent in all tumor passages. aCGH profiles of xenograft passages of each series resembled their corresponding primary tumors (passage 0. MiR-21, miR-31, miR-31*, miR-106b, miR-145, miR-150*, miR-371-5p, miR-557 and miR-598 showed recurrently altered expression. These miRNAS were predicted to regulate many ES-associated genes, such as genes of the IGF1 pathway, EWSR1, FLI1 and their fusion gene (EWS-FLI1. Twenty differentially expressed miRNAs were pinpointed in regions carrying altered copy numbers. Conclusion In the present study, ES xenografts were successfully applied for integrated microarray analyses. Our findings showed expression changes of miRNAs that were predicted to regulate many ES associated genes, such as IGF1 pathway genes, FLI1, EWSR1, and the EWS-FLI1 fusion genes.

  3. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

  4. Volumetrical and morphological responses of human laryngeal squamous cell carcinoma xenografts treated with fractionated irradiation

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Gasteren, H. van; Jerusalem, C.R.; Kal, H.B.

    1988-01-01

    Xenografts of both primary human laryngeal squamous cell carcinoma and its metastases were irradiated with five daily fractions of 5.0 Gy. Tumor volume changes, morphology, mitotic index and mitotic figures were studied. Primary xenografts disappeared within 17±3 days. Grafts of metastases showed complete regression within 26±5 days, or regrowth after a delay period. Mitotic activity was higher in the grafts of metastases. The number of mitotic figures decreased and ceased within 14 days in the primary tumor, while some were still occasionally noted in the grafts of metastases. Telophase stages were practically absent after the first fraction. This study suggests that the response of metastases to radiation therapy is lower than the response of the primary tumor. (orig.) [de

  5. Tumor Repression of VCaP Xenografts by a Pyrrole-Imidazole Polyamide.

    Directory of Open Access Journals (Sweden)

    Amanda E Hargrove

    Full Text Available Pyrrole-imidazole (Py-Im polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress.

  6. Clonal dominance between subpopulations of mixed small cell lung cancer xenografts implanted ectopically in nude mice

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Spang-Thomsen, M

    1995-01-01

    Clonal evolution of neoplastic cells during solid tumour growth leads to the emergence of new tumour cell subpopulations with diverging phenotypic characteristics which may alter the behaviour of a malignant disease. Cellular interaction was studied in mixed xenografts in nude mice and during...... clone 54B was found to dominate the parent 54A clone when grown as mixed subcutaneous xenografts in nude mice, whereas no dominance was exerted during in vitro growth. The in vivo dominance could not be explained by differences in growth kinetics between the two tumour cell lines, and the interaction...... was not dependent on 54B being in excess in mixed tumours. The dominance was dependent on close in vivo contact as no remote effect on the growth of 54A was found when the dominating 54B cells were growing in the opposite flank of tumour-bearing mice. Irradiation inactivated 54B cells were unable to exert...

  7. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E

    1992-01-01

    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  8. Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.

    Science.gov (United States)

    Fergusson, R. J.; Anderson, L. E.; Macpherson, J. S.; Robins, P.; Smyth, J. F.

    1988-01-01

    The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas. PMID:3390369

  9. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

  10. Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in three human tumor xenografts

    International Nuclear Information System (INIS)

    Floersheim, G.L.; Racine, C.

    1995-01-01

    One Ewing's sarcoma and 2 colon carcinomas were grown as xenografts in immunosuppressed mice. The mice were treated with diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body γ-radiation on the growth of the subcutaneously implanted tumors was assessed. Growth delay or regression of the tumors in mice treated with the calcium antagonists prior to irradiation was not reduced as compared to only irradiated controls. (orig.) [de

  11. Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

    OpenAIRE

    Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

    2013-01-01

    In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain ...

  12. Anterior cruciate ligament reconstruction with a novel porcine xenograft: the initial Italian experience

    Science.gov (United States)

    ZAFFAGNINI, STEFANO; GRASSI, ALBERTO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; DI SARSINA, TOMMASO ROBERTI; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

    2015-01-01

    At the current state of the art in anterior cruciate ligament (ACL) reconstruction, multiple techniques have been presented but none has given clearly defined and improved results. One of the main issues concerns the choice of graft. The concept of using xenograft tissue, defined as a graft tissue from one species and destined for implantation in an unlike species, was introduced in order to try to overcome the mechanical and biological concerns associated with synthetic materials and the safety and quality concerns and availability problems of allograft tissue. Xenograft tissue carries the risk of producing an immunological reaction. In order to try to overcome or attenuate the immune response against porcine xenograft tissue, the Z-Process® (Aperion Biologics Inc, San Antonio, Texas, USA) has been developed and used to produce the Z-Lig® family of devices for ACL reconstruction procedures. Z-Lig® is a tendon graft with or without bone blocks, sourced from animal tissue in a manner consistent with what has normally been sourced from human tissue, and processed to overcome anti-Gal-mediated rejection and to attenuate other immunological recognition in humans. All this while ensuring sterility, viral inactivation and preservation of mechanical proprieties appropriate for an ACL reconstruction device. The Z-Lig® device has been tested in skeletally mature monkeys and given interesting and promising results from the preclinical performance and safety profile point of view. On this basis, it was possible to proceed with the first clinical trial involving humans, which gave similar encouraging results. The Z-Lig® device has also been implanted in Italy at the Rizzoli Orthopaedic Institute in Bologna, as a part of international multicenter prospective randomized blinded controlled study aimed at comparing xenograft with allograft tissue. PMID:26605257

  13. Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

    OpenAIRE

    Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

    2015-01-01

    Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 pa...

  14. Biological characterization of two xenografts derived from human CUPs (carcinomas of unknown primary

    Directory of Open Access Journals (Sweden)

    Bernheim Alain

    2007-12-01

    Full Text Available Abstract Background Carcinomas of unknown primary site (CUP are epithelial malignancies revealed by metastatic lesions in the absence of any detectable primary tumor. Although they often adopt an aggressive clinical pattern, their basic biology remains poorly understood. Laboratory research on their biology have been hampered so far by the absence of cell lines representative of CUPs. Methods We attempted xenografts of CUP clinical specimens in immunodeficient mice and subsequent in vitro culture of transplanted malignant cells. Whenever possible, malignant xenografted or cultured cells were characterized by microsatellite genotyping, immunohistology, electron microscopy, multifish chromosome analysis and search of TP 53 gene mutations. Results Successful xenografts were achieved in 2 cases out of 4. One of them (Capi1 was lost after 3 passages whereas the other one (Capi3 has been adapted to in vitro culture and is currently available to the scientific community with reliable identification based on microsatellite genotyping. Both Capi1 and Capi3 have histological characteristics of adenocarcinomas and display intense expression of EMA, CEA and cytokeratin 7. Multifish chromosome analysis demonstrated a translocation involving chromosomes 4 and 21 in both specimens. Distinct rare missense mutations of the TP53 gene were detected in Capi1 (codon 312 and Capi3 (codon 181; the codon 181 mutation is consistent with a previously reported similar finding in a small series of CUP specimens. Finally, intense membrane expression of c-kit was recorded in Capi3. Conclusion Our data suggest that xenografted tumors can be obtained from a substantial fraction of CUP clinical specimens. The hypothesis of a preferential association of CUPs with TP 53 mutations of codon 181 deserves further investigations. The Capi3 cell line will be a useful tool for assessment of novel c-kit inhibitors.

  15. A comprehensive patient-derived xenograft collection representing the heterogeneity of melanoma

    OpenAIRE

    Krepler, Clemens; Sproesser, Katrin; Brafford, Patricia; Beqiri, Marilda; Garman, Bradley; Xiao, Min; Shannan, Batool; Watters, Andrea; Perego, Michela; Zhang, Gao; Vultur, Adina; Yin, Xiangfan; Liu, Qin; Anastopoulos, Ioannis N; Wubbenhorst, Bradley

    2017-01-01

    Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological he...

  16. Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study

    Science.gov (United States)

    Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.

    2017-02-01

    Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

  17. A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

    Directory of Open Access Journals (Sweden)

    Clemens Krepler

    2017-11-01

    Full Text Available Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX. Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor

  18. Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry.

    Science.gov (United States)

    Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; López, Daniel H; Guardiola-Serrano, Francisca; Escribá, Pablo V; Barceló-Coblijn, Gwendolyn; Fernández, José A

    2016-02-01

    Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na(+) adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na(+)/K(+) ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na(+) and K(+) adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results. Graphical Abstract ᅟ.

  19. Inhibitory effect of Dendrobium officinale polysaccharide on human gastric cancer cell xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Liying ZHANG

    2017-10-01

    Full Text Available Abstract This study investigated the inhibitory effect of Dendrobium officinale polysaccharide (DOPA on human gastric cancer cell SGC-7901 xenografts in nude mice. The nude mice with SGC-7901 xenografts were randomly divided into model, 5-fluorouracil (5-Fu, low-dose DOPA, middle-dose DOPA and high-dose DOPA group. The later four groups were intragastrically administrated with 100, 200 and 400 mg·kg–1·day–1 DOPA, 400 mg·kg–1·day–1 5-Fu and normal saline, respectively. After treatment for 20 days, the tumor inhibition rate of in high-dose DOPA group was basically equivalent to 5-Fu group. Compared with 5-Fu, DOPA had no obvious toxic side effect on spleen or thymus indexes, routine blood indexes or liver and kidney functions of nude mice. Compared with model group, the serum tumor necrosis factor-α and interleukin-2 levels in middle- and high-dose DOPA group were significantly increased (P < 0.05, Bax protein expression was significantly increased (P < 0.05, and Bcl-2 protein expression was significantly decreased (P < 0.05. DOPA can inhibit the growth of SGC-7901 cell xenografts in nude mice. The mechanism may be related to its increase of serum TNF-α and IL-2 levels, up-regulation of Bax protein expression and down-regulation of Bcl-2 protein expression.

  20. Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism

    Directory of Open Access Journals (Sweden)

    Aixue LIU

    Full Text Available Abstract The present study investigated the effects of curcumin (Cur on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control, 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05. The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05, and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05. Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

  1. Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1980-01-01

    The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

  2. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1981-12-01

    Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

  3. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

    2014-02-26

    The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

  4. [Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft].

    Science.gov (United States)

    Chappard, D; Zhioua, A; Grizon, F; Basle, M F; Rebel, A

    1993-12-01

    Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

  5. The utility of fecal corticosterone metabolites and animal welfare assessment protocols as predictive parameters of tumor development and animal welfare in a murine xenograft model

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Jørgensen, Pernille Schønning; Pipper, Christian Bressen

    2013-01-01

    consumption, and an animal welfare assessment (AWA) protocol revealed marked differences between control and cancer lines as the size of the tumor increased. However, only the AWA protocol was effective in predicting the tumor size and the level of fecal corticosterone metabolites (FCM). FCM levels were...

  6. The Association between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage Versus Ischemic Lacunar Infarction.

    Science.gov (United States)

    Kaplan, Emma H; Gottesman, Rebecca F; Llinas, Rafael H; Marsh, Elisabeth B

    2014-01-01

    Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.

  7. Top 100 Most-Cited Articles on Spontaneous Intracerebral Hemorrhage: A Bibliometric Analysis.

    Science.gov (United States)

    Nasir, Syed Ali Raza; Gilani, Jaleed Ahmed; Fatima, Kaneez; Faheem, Urooba; Kazmi, Omar; Siddiqi, Javed; Khosa, Faisal

    2018-02-01

    A bibliometric uses the citation count of an article to determine its impact on the clinical world. There is a paucity of literature concerning top article citations on spontaneous intracerebral hemorrhage (ICH). The main objective of this investigation was to bridge this gap and to provide understanding of the trends on the most influential articles written on this subject. The Scopus Library database was searched to determine the citations of all articles published on spontaneous ICH. Articles that focused on other forms of ICH, such as trauma-related hemorrhages, subarachnoid hemorrhages, or hemorrhages caused by anticoagulation, vascular malformations, or cavernomas, were excluded from our list. The articles were divided into 2 groups: "specific" articles, which focused specifically on spontaneous ICH, and "generalized" articles, which were about ICH in general, including spontaneous as well as other forms of ICH. We did not apply any time or study-type restriction in our search. The top 100 cited articles were selected and analyzed by 2 independent investigators. J. Broderick was the author with most publications in the list (n = 21). The largest subset of spontaneous ICH articles was published in the 5-year periods from 1996 to 2000 and 2001 to 2005 (n = 27 each). The United States had the highest number of articles (n = 49). The journal with the highest number of top 100 cited articles was Stroke, with 39, followed by Neurology with 16. Our study identifies the trends related to spontaneous ICH by analyzing the citation frequency of the most-cited articles in the field. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Aphasia caused by intracerebral hemorrhage; CT-scan findings and prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Kazuhide; Segawa, Hiromu; Shiokawa, Yoshiaki; Hasegawa, Isao; Sano, Keiji (Fuji Brain Institute and Hospital, Shizuoka (Japan))

    1992-10-01

    It is generally accepted that cases of aphasia can be divided into several groups according to verbal fluency, auditory comprehension, and repetition abilities. Although many authors have studied aphasia and its location by means of a CT scan, the primary lesion on a CT scan with regard to the subtypes of aphasia still remains controversial. In this report we present our new CT classification for the syndromes of aphasia and the prognosis. Twenty-one patients with intracerebral hematoma (ICH) were followed up for more than 3 months after onset. ICH was classified according to the mode of the horizontal extension of the hematoma on a CT scan. Four lines were decided as follows: Line (a) is between the anterior horn of the lateral ventricle and the midpoint of the third ventricle; Line (b) is the vertical line to the saggital line which originates from the midpoint of the third ventricle; Line (c) is between the trigone of the lateral ventricle and the midpoint of the third ventricle. The CT classification consisted of 4 types: in Type A, ICH was located anterior to line (a); in Type B, ICH was located between line (a) and line (b); in Type C, ICH was located between line (b) and line (c); Type B+C, was a combination of Type B and Type C. Transcortical motor aphasia belonged to the Type A group. Transcortical sensory aphasia belonged to the Type B and Type B+C groups. Wernicke's and anomic aphasia belonged to the Type C group. Conduction and global aphasia belonged to the Type B+C group. Pure Broca's aphasia could not be observed in this series. Several relationships between the syndromes of aphasia and its CT findings were evident. On the other hand, the syndromes of aphasia and the degree of recovery were not correlated, except for global aphasia. (author).

  9. Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage.

    Science.gov (United States)

    Li, Qi; Yang, Wen-Song; Chen, Sheng-Li; Lv, Fu-Rong; Lv, Fa-Jin; Hu, Xi; Zhu, Dan; Cao, Du; Wang, Xing-Chen; Li, Rui; Yuan, Liang; Qin, Xin-Yue; Xie, Peng

    2018-01-01

    In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials. © 2018 S. Karger AG, Basel.

  10. Intraoperative Active Bleeding in Endoscopic Surgery for Spontaneous Intracerebral Hemorrhage is Predicted by the Spot Sign.

    Science.gov (United States)

    Miki, Koichi; Yagi, Kenji; Nonaka, Masani; Iwaasa, Mitsutoshi; Abe, Hiroshi; Morishita, Takashi; Arima, Hisatomi; Inoue, Tooru

    2018-05-30

    Endoscopic evacuation of hematoma (EEH) has recently been applied to treat patients with spontaneous intracerebral hemorrhage (sICH). Intraoperative active bleeding (IAB), which is occasionally observed in EEH, might lead to greater blood loss, further brain damage, and more postoperative recurrent hemorrhage. However, no definite predictor of IAB has been established. Because the spot sign is associated with other hemorrhagic complications, we aimed to evaluate whether it predicts IAB. We retrospectively assessed the incidence and risk factors of IAB, including the spot sign, in 127 sICH patients who underwent EEH within 6 hours after computed tomography angiography at our institution between June 2009 and December 2017. The study included 53 women and 74 men with an average age of 66.7 ± 11.8 years. IAB occurred in 40 (31.5%) of the 127 patients, and it was more frequent in patients with the spot sign than in patients without it (14/24 [58.3%] vs. 26/103 [25.2%]; P = 0.003). Multivariable regression analyses suggested that the spot sign was an independent predictor of IAB (odds ratio [OR], 3.02; 95% confidence interval [CI], 1.10-8.30; P = 0.03). In addition, earlier surgery gradually increased the risk of IAB, and surgery within 4 hours of onset was an independent risk factor (OR, 4.34; 95% CI, 1.12-16.9; P = 0.03, referring to postonset 8 hours or more). The spot sign and early surgery were independent predictors of IAB in EEH for sICH. In patients with sICH and spot sign, complete treatment of IAB by electrocoagulation might be important for minimizing surgical complications. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Spot sign as a predictor of rebleeding after endoscopic surgery for intracerebral hemorrhage.

    Science.gov (United States)

    Miki, Koichi; Yagi, Kenji; Nonaka, Masani; Iwaasa, Mitsutoshi; Abe, Hiroshi; Morishita, Takashi; Arima, Hisatomi; Inoue, Tooru

    2018-05-25

    OBJECTIVE In patients with spontaneous intracerebral hemorrhage (sICH), postoperative recurrent hemorrhage (PRH) is one of the most severe complications after endoscopic evacuation of hematoma (EEH). However, no predictors of this complication have been identified. In the present study, the authors retrospectively investigated whether PRH can be preoperatively predicted by the presence of the spot sign on CT scans. METHODS In total, 143 patients with sICH were treated by EEH between June 2009 and March 2017, and 127 patients who underwent preoperative CT angiography were included in this study. Significant correlations of PRH with the patients' baseline, clinical, and radiographic characteristics, including the spot sign, were evaluated using multivariable logistic regression models. RESULTS The incidence of and risk factors for PRH were assessed in 127 patients with available data. PRH occurred in 9 (7.1%) patients. Five (21.7%) cases of PRH were observed among 23 patients with the spot sign, whereas only 4 (3.8%) cases of PRH occurred among 104 patients without the spot sign. The spot sign was the only independent predictor of PRH (OR 5.81, 95% CI 1.26-26.88; p = 0.02). The following factors were not independently associated with PRH: age, hypertension, poor consciousness, antihemostatic factors (thrombocytopenia, coagulopathy, and use of antithrombotic drugs), the location and size of the sICH, other radiographic findings (black hole sign and blend sign), surgical duration and procedures, and early surgery. CONCLUSIONS The spot sign is likely to be a strong predictor of PRH after EEH among patients with sICH. Complete and careful control of bleeding in the operative field should be ensured when surgically treating such patients. New surgical strategies and procedures might be needed to improve these patients' outcomes.

  12. Significance of satellite sign and spot sign in predicting hematoma expansion in spontaneous intracerebral hemorrhage.

    Science.gov (United States)

    Yu, Zhiyuan; Zheng, Jun; Ali, Hasan; Guo, Rui; Li, Mou; Wang, Xiaoze; Ma, Lu; Li, Hao; You, Chao

    2017-11-01

    Hematoma expansion is related to poor outcome in spontaneous intracerebral hemorrhage (ICH). Recently, a non-enhanced computed tomography (CT) based finding, termed the 'satellite sign', was reported to be a novel predictor for poor outcome in spontaneous ICH. However, it is still unclear whether the presence of the satellite sign is related to hematoma expansion. Initial computed tomography angiography (CTA) was conducted within 6h after ictus. Satellite sign on non-enhanced CT and spot sign on CTA were detected by two independent reviewers. The sensitivity and specificity of both satellite sign and spot sign were calculated. Receiver-operator analysis was conducted to evaluate their predictive accuracy for hematoma expansion. This study included 153 patients. Satellite sign was detected in 58 (37.91%) patients and spot sign was detected in 38 (24.84%) patients. Among 37 patients with hematoma expansion, 22 (59.46%) had satellite sign and 23 (62.16%) had spot sign. The sensitivity and specificity of satellite sign for prediction of hematoma expansion were 59.46% and 68.97%, respectively. The sensitivity and specificity of spot sign were 62.16% and 87.07%, respectively. The area under the curve (AUC) of satellite sign was 0.642 and the AUC of spot sign was 0.746. (P=0.157) CONCLUSION: Our results suggest that the satellite sign is an independent predictor for hematoma expansion in spontaneous ICH. Although spot sign has the higher predictive accuracy, satellite sign is still an acceptable predictor for hematoma expansion when CTA is unavailable. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. CT angiography spot sign in intracerebral hemorrhage predicts active bleeding during surgery.

    Science.gov (United States)

    Brouwers, H Bart; Raffeld, Miriam R; van Nieuwenhuizen, Koen M; Falcone, Guido J; Ayres, Alison M; McNamara, Kristen A; Schwab, Kristin; Romero, Javier M; Velthuis, Birgitta K; Viswanathan, Anand; Greenberg, Steven M; Ogilvy, Christopher S; van der Zwan, Albert; Rinkel, Gabriel J E; Goldstein, Joshua N; Klijn, Catharina J M; Rosand, Jonathan

    2014-09-02

    To determine whether the CT angiography (CTA) spot sign marks bleeding complications during and after surgery for spontaneous intracerebral hemorrhage (ICH). In a 2-center study of consecutive spontaneous ICH patients who underwent CTA followed by surgical hematoma evacuation, 2 experienced readers (blinded to clinical and surgical data) reviewed CTAs for spot sign presence. Blinded raters assessed active intraoperative and postoperative bleeding. The association between spot sign and active intraoperative bleeding, postoperative rebleeding, and residual ICH volumes was evaluated using univariable and multivariable logistic regression. A total of 95 patients met inclusion criteria: 44 lobar, 17 deep, 33 cerebellar, and 1 brainstem ICH; ≥1 spot sign was identified in 32 patients (34%). The spot sign was the only independent marker of active bleeding during surgery (odds ratio [OR] 3.4; 95% confidence interval [CI] 1.3-9.0). Spot sign (OR 4.1; 95% CI 1.1-17), female sex (OR 6.9; 95% CI 1.7-37), and antiplatelet use (OR 4.6; 95% CI 1.2-21) were predictive of postoperative rebleeding. Larger residual hematomas and postoperative rebleeding were associated with higher discharge case fatality (OR 3.4; 95% CI 1.1-11) and a trend toward increased case fatality at 3 months (OR 2.9; 95% CI 0.9-8.8). The CTA spot sign is associated with more intraoperative bleeding, more postoperative rebleeding, and larger residual ICH volumes in patients undergoing hematoma evacuation for spontaneous ICH. The spot sign may therefore be useful to select patients for future surgical trials. © 2014 American Academy of Neurology.

  14. Localized hypothermia aggravates bleeding in the collagenase model of intracerebral hemorrhage.

    Science.gov (United States)

    John, Roseleen F; Williamson, Michael R; Dietrich, Kristen; Colbourne, Frederick

    2015-03-01

    Animal studies testing whether therapeutic hypothermia is neuroprotective after intracerebral hemorrhage (ICH) have been inconclusive. In rodents, ICH is often produced in the striatum by infusing collagenase, which causes prolonged hemorrhaging from multiple vessels. Our previous data shows that this bleeding (hematoma) is worsened by systemic hypothermia given soon after collagenase infusion. In this study we hypothesized that localized brain hypothermia would also aggravate bleeding in this model (0.2 U of collagenase in 1.2 μL of saline). We also evaluated cooling after intrastriatal thrombin infusion (1 U in 30 μL of saline)-a simplified model of ICH thought to cause bleeding. Focal hypothermia was achieved by flushing cold water through an implanted cooling device attached to the skull underneath the temporalis muscle of adult rats. Previous work and data at this time shows this method cools the striatum to ∼33°C, whereas the body remains normothermic. In comparison to normothermic groups, cooling significantly worsened bleeding when instituted at 6 hours (∼94 vs. 42 μL, p=0.018) and 12 hours (79 vs. 61 μL, p=0.042) post-ICH (24-hour survival), but not after a 24-hour delay (36-hour survival). Rats were cooled until euthanasia when hematoma size was determined by a hemoglobin-based spectrophotometry assay. Cooling did not influence cerebral blood volume after just saline or thrombin infusion. The latter is explained by the fact that thrombin did not cause bleeding beyond that caused by saline infusion. In summary, local hypothermia significantly aggravates bleeding many hours after collagenase infusion suggesting that bleeding may have confounded earlier studies with hypothermia. Furthermore, these findings serve as a cautionary note on using cooling even many hours after cerebral bleeding.

  15. Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

    Science.gov (United States)

    Rivera-Lara, Lucia; Murthy, Santosh B; Nekoovaght-Tak, Saman; Ali, Hasan; McBee, Nichol; Dlugash, Rachel; Ram, Malathi; Thompson, Richard; Awad, Issam A; Hanley, Daniel F; Ziai, Wendy C

    2018-03-27

    Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

  16. Intensive care management of patients with severe intracerebral haemorrhage after endovascular treatment of brain arteriovenous malformations

    International Nuclear Information System (INIS)

    Keller, E.; Yonekawa, Y.; Imhof, H.G.; Tanaka, M.; Valavanis, Anton

    2002-01-01

    We studied the impact of emergency neurosurgery and intensive care on the outcome for patients with severe intracerebral haemorrhage after endovascular treatment of brain arteriovenous malformations (AVMs). We reviewed the case notes of 18 patients with severe haemorrhage after embolisation of a brain AVM between 1986 and 2001. During this period the treatment changed: before 1993, these patients were not surgically treated, and they died, while after 1994, all patients underwent emergency surgery. We established a standardised protocol for emergency treatment and intensive care in May 1998, and emergency surgery was performed as soon as possible after the onset of symptoms of haemorrhage. Postoperative intensive care was according to a standardised regime. During these 15 years, 24 out of 605 patients undergoing 1066 interventions had a haemorrhage during or after the procedure, of which 18 were severe (3% of patients, 1.7% of interventions). All patients had a severe clinical deficit (mean Glasgow coma scale 4.2); eight had uni- or bilateral mydriasis. From 1989 to April 1998 four (31%) of 13 patients died, one (7.5%) remained in a vegetative state and eight (61.5%) made a good recovery. All five patients treated between 1998 and 2001 had a favourable outcome. The mean time from onset of the symptoms of haemorrhage to reaching the operation room was 129 min between 1989 and 1998 and 24 min between 1998 and 2001. Standardised emergency treatment and intensive care with early resuscitation, minimal radiological exploration before rapid surgery improved the outcome. A short time between the onset of the symptoms of haemorrhage and evacuation of the haematoma may be the most important factor for a favourable outcome. (orig.)

  17. Prognostic Significance of Ultraearly Hematoma Growth in Spontaneous Intracerebral Hemorrhage Patients Receiving Hematoma Evacuation.

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    Yu, Zhiyuan; Zheng, Jun; Guo, Rui; Ma, Lu; Li, Mou; Wang, Xiaoze; Lin, Sen; You, Chao; Li, Hao

    2018-01-01

    To investigate the association between ultraearly hematoma growth (uHG) and clinical outcome in patients with spontaneous intracerebral hemorrhage (sICH) receiving hematoma evacuation. Supratentorial sICH patients receiving hematoma evacuation within 24 hours after ictus were enrolled in this study. uHG was defined as baseline hematoma volume/onset-to-computed tomography (CT) time (mL/h). The outcome was assessed by the modified Rankin Scale (mRS) score at 3 months. Unfavorable outcome was defined as mRS >2. A total of 93 patients were enrolled in this study. The mean uHG was 10.3 ± 5.5 mL/h. In 69 (74.2%) of patients, the outcome was unfavorable at 3 months. The uHG in patients with unfavorable outcome were significantly higher than in those with favorable outcome (11.0 ± 6.1 mL/h vs. 8.3 ± 2.5 mL/h, P = 0.003). The optimal cutoff of uHG for predicting unfavorable outcome was 8.7 mL/h. The sensitivity, specificity, positive predictive value, and negative predictive value of uHG >8.7 mL/h for predicting unfavorable outcome were 56.5%, 75.0%, 86.7%, and 37.5%, respectively. uHG is a helpful predictor of unfavorable outcome in sICH patients treated with hematoma evacuation. The optimal cutoff of uHG to assist in predicting unfavorable outcome in sICH patients receiving hematoma evacuation is 8.7mL/h. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Neurosurgical outcomes after intracerebral hemorrhage: results of the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST).

    Science.gov (United States)

    Steiner, Thorsten; Vincent, Catherine; Morris, Stephen; Davis, Stephen; Vallejo-Torres, Laura; Christensen, Michael C

    2011-01-01

    The value of neurosurgical interventions after spontaneous intracerebral hemorrhage (SICH) is uncertain. We evaluated clinical outcomes in patients diagnosed with SICH within 3 hours of symptom onset who underwent hematoma evacuation or external ventricular drainage (EVD) of the hematoma in the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST). FAST was a randomized, multicenter, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. Neurosurgical procedures (hematoma evacuation and external ventricular drainage) performed at any point after hospital admission were prospectively recorded. Clinical outcomes evaluated were post-SICH disability, as assessed by the modified Rankin Scale; neurologic impairment, as assessed by the National Institutes of Health Stroke Scale; and mortality at 90 days after SICH onset. The impact of neurosurgical procedures on clinical outcomes was evaluated using multivariate logistic regression analysis, controlling for relevant baseline characteristics. Fifty-five of 821 patients underwent neurosurgery. Patients who underwent hematoma evacuation or EVD were on average younger, had greater baseline neurologic impairment, and lower levels of consciousness compared with patients who did not undergo neurosurgery. After adjusting for these differences and other relevant baseline characteristics, we found that neurosurgery was generally associated with unfavorable outcomes at day 90. Among the patients who underwent hematoma evacuation, those with lobar ICH had less ICH expansion than those with deep gray matter ICH, and the smaller expansion was associated with lower mortality. ICH volume was substantially decreased in patients who underwent hematoma evacuation between 24 and 72 hours after hospital admission, and this was associated with better clinical outcome. In conclusion, a small number of patients who underwent neurosurgery in FAST exhibited no overall clinical benefit

  19. Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.

    Directory of Open Access Journals (Sweden)

    Gaelle Bettus

    Full Text Available In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD signal derived from resting state functional magnetic resonance imaging (fMRI reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG and resting-state functional MRI (fMRI in 5 patients suffering from intractable temporal lobe epilepsy (TLE. Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal. This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional

  20. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    Science.gov (United States)

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  1. Evolution of traumatic intracerebral hematoma. Analysis of sequential CT scans since per-acute stage

    Energy Technology Data Exchange (ETDEWEB)

    Nagaseki, Yoshishige; Horikoshi, Satoru [Gunma Univ., Maebashi (Japan). School of Medicine; Tamura, Masaru

    1984-05-01

    To clarify the evolution of traumatic intracerebral hematoma (TICH), initial computerized tomography (CT) scans of 28 TICH cases performed within one hour after head trauma were studied along with their follow-up CT scans. They were classified into the following two groups; per-acute group included seven cases in which TICH was completed on the initial CT scans taken within one hour after head injury and acute group included 21 cases in which the initial CT scans revealed isodensity or high density spot and repeat CT scans disclosed TICH by 48 hours after injury. In the per-acute group, initial CT scans showed a homogeneous, well defined, and high density mass (1.5-6.5 cm in diameter). In sequential CT scans of the three cases, the hematoma did not increase but spontaneously disappeared. Other four cases died early after head trauma. Their initial CT scans revealed a large high density mass (3-6.5 cm in diameter) combined with other extracerebral hemorrhages. In the acute group, initial CT scans demonstrated isodensity or high density spot and sequential CT scans showed mottled appearance of salt and pepper appearance, and after a while showed fusion of small high density areas to become a massive high density area (contusional hematoma) by 48 hours after injury. In six cases of this group, the contusional hematoma was removed within 24 hours after injury and in one case at 3.5 days. In other 14 cases, the hematomas shrank or disappeared spontaneously. From these results, it was considered that evolution of TICH's were classified into the two groups; per-acute group resulting from rupture of vessels and acute group resulting from contusion.

  2. Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yuhao Sun

    Full Text Available A number of studies have reported an association of angiotensin-converting enzyme (ACE gene polymorphism with primary intracerebral hemorrhage (PICH, however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH.PubMed and Embase databases (through Dec 2012 were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs were estimated and potential sources of heterogeneity and bias were explored.A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07-2.35 for DD vs. DI+II. However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16-2.66 for DD vs. DI+II, but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36-3.88, P = 0.784 for DD vs. DI+II. The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models.These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.

  3. Intracerebral cavernous hemangioma after cranial irradiation in childhood. Incidence and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Strenger, V.; Sovinz, P.; Lackner, H.; Dornbusch, H.J.; Moser, A.; Urban, C. [Graz Medical Univ. (Austria). Div. of Pediatric Hematology and Oncology; Lingitz, H. [Graz Medical Univ. (Austria). Dept. of Therapeutic Radiology and Oncology; Eder, H.G. [Graz Medical Univ. (Austria). Dept. of Neurosurgery

    2008-05-15

    Background and Purpose: Radiotherapy is an integral part of various therapeutic regimens in pediatric and adult oncology. Endocrine dysfunction, neurologic and psychiatric deficits, secondary malignancies and radiation-induced necrosis are well-known possible late effects of cranial irradiation. However, only sporadic cases of radiation-induced cavernous hemangiomas (RICH) have been reported so far. Patients and Methods: Pediatric patients who underwent cranial radiation therapy for malignant diseases between January 1980 and December 2003 were retrospectively analyzed. After the end of therapy they entered a detailed follow-up program. Results: Of 171 patients, eight (three patients with medulloblastoma, three patients with acute lymphoblastic leukemia, and one patient each with ependymoma and craniopharyngioma) developed intracerebral cavernoma 2.9-18.4 years after irradiation representing a cumulative incidence (according to the Kaplan-Meier method) of 2.24%, 3.86%, 4.95%, and 6.74% within 5, 10, 15, and 20 years following radiation therapy, respectively. In patients treated in the first 10 years of life, RICH occurred with shorter latency and significantly more often (p = 0.044) resulting in an even higher cumulative incidence. Conclusion: These findings and previously published cases show that cavernous hemangiomas may occur after irradiation of the brain several years after the end of therapy irrespective of the radiation dose and type of malignancy. Particularly children < 10 years of age at the time of irradiation are at higher risk. Since patients with RICH frequently do not show symptoms but hemorrhage is a possible severe complication, imaging of the central nervous system should be performed routinely for longer follow- ups, particularly in patients who were treated as young children. (orig.)

  4. Volume-Dependent Overestimation of Spontaneous Intracerebral Hematoma Volume by the ABC/2 Formula

    International Nuclear Information System (INIS)

    Chih-Wei Wang; Chun-Jung Juan; Hsian-He Hsu; Hua-Shan Liu; Cheng-Yu Chen; Chun-Jen Hsueh; Hung-Wen Kao; Guo-Shu Huang; Yi-Jui Liu; Chung-Ping Lo

    2009-01-01

    Background: Although the ABC/2 formula has been widely used to estimate the volume of intracerebral hematoma (ICH), the formula tends to overestimate hematoma volume. The volume-related imprecision of the ABC/2 formula has not been documented quantitatively. Purpose: To investigate the volume-dependent overestimation of the ABC/2 formula by comparing it with computer-assisted volumetric analysis (CAVA). Material and Methods: Forty patients who had suffered spontaneous ICH and who had undergone non-enhanced brain computed tomography scans were enrolled in this study. The ICH volume was estimated based on the ABC/2 formula and also calculated by CAVA. Based on the ICH volume calculated by the CAVA method, the patients were divided into three groups: group 1 consisted of 17 patients with an ICH volume of less than 20 ml; group 2 comprised 13 patients with an ICH volume of 20 to 40 ml; and group 3 was composed of 10 patients with an ICH volume larger than 40 ml. Results: The mean estimated hematoma volume was 43.6 ml when using the ABC/2 formula, compared with 33.8 ml when using the CAVA method. The mean estimated difference was 1.3 ml, 4.4 ml, and 31.4 ml for groups 1, 2, and 3, respectively, corresponding to an estimation error of 9.9%, 16.7%, and 37.1% by the ABC/2 formula (P<0.05). Conclusion: The ABC/2 formula significantly overestimates the volume of ICH. A positive association between the estimation error and the volume of ICH is demonstrated

  5. Characterization of intraventricular and intracerebral hematomas in non-contrast CT.

    Science.gov (United States)

    Nowinski, Wieslaw L; Gomolka, Ryszard S; Qian, Guoyu; Gupta, Varsha; Ullman, Natalie L; Hanley, Daniel F

    2014-06-01

    Characterization of hematomas is essential in scan reading, manual delineation, and designing automatic segmentation algorithms. Our purpose is to characterize the distribution of intraventricular (IVH) and intracerebral hematomas (ICH) in NCCT scans, study their relationship to gray matter (GM), and to introduce a new tool for quantitative hematoma delineation. We used 289 serial retrospective scans of 51 patients. Hematomas were manually delineated in a two-stage process. Hematoma contours generated in the first stage were quantified and enhanced in the second stage. Delineation was based on new quantitative rules and hematoma profiling, and assisted by a dedicated tool superimposing quantitative information on scans with 3D hematoma display. The tool provides: density maps (40-85HU), contrast maps (8/15HU), mean horizontal/vertical contrasts for hematoma contours, and hematoma contours below a specified mean contrast (8HU). White matter (WM) and GM were segmented automatically. IVH/ICH on serial NCCT is characterized by 59.0HU mean, 60.0HU median, 11.6HU standard deviation, 23.9HU mean contrast, -0.99HU/day slope, and -0.24 skewness (changing over time from negative to positive). Its 0.1(st)-99.9(th) percentile range corresponds to 25-88HU range. WM and GM are highly correlated (R (2)=0.88; phematoma density distributions is at 55.6±5.8HU with the corresponding GM/hematoma percentiles of 88(th)/40(th). Objective characterization of IVH/ICH and stating the rules quantitatively will aid raters to delineate hematomas more robustly and facilitate designing algorithms for automatic hematoma segmentation. Our two-stage process is general and potentially applicable to delineate other pathologies on various modalities more robustly and quantitatively.

  6. MRI study for CT-guided stereotactic aspiration of intracerebral hematoma

    International Nuclear Information System (INIS)

    Takahashi, Toshie; Okada, Hitoshi; Kaneko, Uichi; Nishino, Akiko; Ueno, Shinji; Owada, Yuji.

    1994-01-01

    Twenty-five patients with acute hypertensive intracerebral hematomas, diagnosed by computed tomography (CT), underwent CT-guided stereotactic aspiration. Magnetic resonance (MR) images were obtained immediately before aspiration, using T 1 -weighted (TR=500 msec, TE=15 msec) and T 2 -weighted (TR=2500 msec, TE=120 msec) sequences and a 0.5 Tesla MR system. On the basis of the MR images the hematomas were divided into peripheral, central, and core segments. The signal intensities were divided into seven grades based on the comparison with white matter. The sequential changes in each segment on the MR images were evaluated, and the ratio of hematoma removal vs. size of residual hematoma was assessed by preoperative MR imaging and pre-and post-operative CT. The hematomas were located in the putamen in 13 cases, the thalamus in 8, combined in 2, and subcortex in 2. The hematomas, targeted in their centers, were evacuated by the aspiration procedure alone, 1 to 12 days after onset (day 0=day of onset). The results were as follows : 1) The proportion of hematomas removed was high after day 4. 2) Sequential T 1 -weighted images showed that the peripheral segments gradually increased in signal intensity, appearing as high-intensity rings that gradually filled and could be easily aspirated. 3) In those cases in which sequential T 2 -weighted images showed the central segments gradually increasing in signal intensity, the hematomas were easily aspirated if the signal was either iso-intense or hyper-intense. 4) Several hematomas had a core that appeared as a high intensity signal on T1-weighted images and as a low intensity signal on T 2 -weighted images; these hematomas could not be aspirated. (author)

  7. The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats.

    Science.gov (United States)

    Wang, Juan; Wang, Gaiqing; Yi, Jinying; Xu, Yi; Duan, Shuna; Li, Tong; Sun, Xin-Gang; Dong, Liang

    2017-09-01

    Intracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats. 164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group. The high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1-7days after ICH, decreased BBB permeability and edema formation in 1-3days following ICH. Our study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Factors affecting the occurrence of symptomatic intracerebral haemorrhage after intravenous thrombolysis depending on the haemorrhage definition.

    Science.gov (United States)

    Sledzińska-Dźwigał, M; Sobolewski, Piotr; Szczuchniak, W

    2013-01-01

    Symptomatic intracerebral haemorrhage (sICH) remains the most feared complication of systemic thrombolysis in patients with ischaemic stroke. The aim of the study was to analyze the impact of different factors on the occurrence of sICH, depending on definition used. We retrospectively evaluated the influence of several factors on the occurrence of sICH (according to definitions used in ECASS2, SITS-MOST and NINDS studies) in 200 patients treated with systemic thrombolysis from 2006 to 2011. Multivariate analysis of impact of individual variables on the occurrence of haemorrhagic transformation (HT) and parenchymal haemorrhage type 2 (PH2) were performed. Haemorrhagic transformation occurred in 35 cases (17.5%). SICH was found in 10 cases according to ECASS2, in 7 cases according to SITS and in 13 cases according to NINDS. Older age was related to higher risk of sICH, regardless which definition was used (ECASS2: p = 0.014, SITS-MOST: p = 0.048, NINDS: p = 0.008), and female sex was related to higher risk of sICH according to NINDS and ECASS2 definition (p = 0.002 and p = 0.04, respectively). Blood glucose level and high NIHSS score (> 14 pts) were found as risk factor of sICH in ECASS2 definition (p = 0.044 and p = 0.03, respectively). In multivariate logistic regression higher NIHSS scores were associated with HT independent of age, gender and glucose level (p = 0.012). Multivariate analysis showed no impact of age, gender, severity of stroke and glucose level on presence of PH2. Definition of sICH can determine variables that are related to a high risk of this complication. In our study most factors correlated with sICH using the ECASS2 definition.

  9. Affective attitudes to face images associated with intracerebral EEG source location before face viewing.

    Science.gov (United States)

    Pizzagalli, D; Koenig, T; Regard, M; Lehmann, D

    1999-01-01

    We investigated whether different, personality-related affective attitudes are associated with different brain electric field (EEG) sources before any emotional challenge (stimulus exposure). A 27-channel EEG was recorded in 15 subjects during eyes-closed resting. After recording, subjects rated 32 images of human faces for affective appeal. The subjects in the first (i.e., most negative) and fourth (i.e., most positive) quartile of general affective attitude were further analyzed. The EEG data (mean=25+/-4. 8 s/subject) were subjected to frequency-domain model dipole source analysis (FFT-Dipole-Approximation), resulting in 3-dimensional intracerebral source locations and strengths for the delta-theta, alpha, and beta EEG frequency band, and for the full range (1.5-30 Hz) band. Subjects with negative attitude (compared to those with positive attitude) showed the following source locations: more inferior for all frequency bands, more anterior for the delta-theta band, more posterior and more right for the alpha, beta and 1.5-30 Hz bands. One year later, the subjects were asked to rate the face images again. The rating scores for the same face images were highly correlated for all subjects, and original and retest affective mean attitude was highly correlated across subjects. The present results show that subjects with different affective attitudes to face images had different active, cerebral, neural populations in a task-free condition prior to viewing the images. We conclude that the brain functional state which implements affective attitude towards face images as a personality feature exists without elicitors, as a continuously present, dynamic feature of brain functioning. Copyright 1999 Elsevier Science B.V.

  10. Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

    Science.gov (United States)

    Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

    2018-06-05

    Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Time course of NMR images and T1 values associated with hypertensive intracerebral hematoma

    International Nuclear Information System (INIS)

    Inao, Suguru; Furuse, Masahiro; Saso, Katsuyoshi; Yoshida, Kazuo; Motegi, Yoshimasa; Kaneoke, Yoshiki; Kamata, Noriko; Izawa, Akira

    1986-01-01

    The present study describes time courses in tissue T 1 values, as well as in NMR imagings, associated with hypertensive intracerebral hematoma (ICH). Non-operative 21 cases of ICH were examined by FONAR QED 80-α NMR system, which possessed dual modes of image display and focal T 1 measurement (static magnetic field : 433 gauss). As the first step of examination SSFP images are displayed and then, at the regions of interest, absolute values of T 1 are measured by field focusing technique. The extent of ICH was revealed as high density zone in NMR imaging, occasionally represented much wider extent of high density area than the finding on X-ray CT. Prolonged T 1 values were obtained from such high density zone. This widespread high density area was regarded to reflect the spread of perifocal brain edema. T 1 value of the hematoma itself was rather shortened in its initial phase within 2 weeks, thereafter followed by prolongation in the time lapse. This seemed to reflect the alterations in the properties of hematoma such as clot formation in earlier phase and resolution in later phase. On the contrary, T 1 in the brain tissue surrounded to hematoma was apparently prolonged in the early phase within 2 weeks, representing the maximal values of 312 msec arround 2 to 4 weeks after the onset, and then gradually normalized in the period over 1 month. This alteration in tissue T 1 likely represents the processes of edema formation and its regression in perifocal zone. T 1 values measured in perifocal region might be available for the evaluation of edema state in association with cerebrovascular accident. (author)

  12. Perfusion magnetic resonance imaging characteristics of intracerebral tuberculomas and its role in differentiating tuberculomas from metastases

    International Nuclear Information System (INIS)

    Sankhe, Shilpa; Baheti, Akshay; Ihare, Ashish; Mathur, Shobhit; Dabhade, Poonam; Sarode, Ashish

    2013-01-01

    Background: Intracerebral tuberculomas usually manifest as ring-enhancing of nodular lesions on magnetic resonance imaging (MRI). These imaging findings are also observed in other lesions like metastases and toxoplasmosis. Purpose: To study the MRI perfusion characteristics of tuberculomas and its potential role in their definitive diagnosis. Material and Methods: Thirty-four tuberculomas were evaluated by conventional and perfusion MRI. The relative cerebral blood volume (rCBV) values of the center, peripheral wall, and perilesional neuroparenchymal tissue were calculated using rCBV maps. Ten ring-enhancing metastases were similarly evaluated and rCBV values of their peripheral walls were calculated. Results: Thirty-one of the 34 tuberculomas were ring-enhancing or conglomerate lesions and revealed hypoperfused centers with hyperperfused peripheral walls, with the mean rCBV ± SD being 0.42 ± 0.25 and 2.04 ± 0.61, respectively. Three nodular enhancing lesions showed predominantly homogenous hyperperfusion, with the mean rCBV measuring 2.96 ± 0.39 (mean ± SD). The perilesional neuroparenchyma was hypoperfused in both cases. The metastases revealed mean rCBV ratio of the peripheral wall to be 5.43 ± 2.1 (mean ± SD). Analysis of the values by ROC curve method revealed a cut-off value of ≥3.745 for differentiating ring-enhancing metastases from ring-enhancing tuberculomas. Conclusion: Perfusion MR is a useful tool for the assessment of tuberculomas and can help differentiate them from neoplasms like metastases. It also has a potential role in monitoring therapy and for early detection of drug resistance

  13. Perfusion magnetic resonance imaging characteristics of intracerebral tuberculomas and its role in differentiating tuberculomas from metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sankhe, Shilpa; Baheti, Akshay [Dept. of Radiology, Seth GS Medical Coll. and KEM Hospital, Thane (India)], e-mail: akshaybaheti@gmail.com; Ihare, Ashish; Mathur, Shobhit; Dabhade, Poonam; Sarode, Ashish [Dept. of Radiology, Seth GS Medical Coll. and KEM Hospital, Thane (India)

    2013-04-15

    Background: Intracerebral tuberculomas usually manifest as ring-enhancing of nodular lesions on magnetic resonance imaging (MRI). These imaging findings are also observed in other lesions like metastases and toxoplasmosis. Purpose: To study the MRI perfusion characteristics of tuberculomas and its potential role in their definitive diagnosis. Material and Methods: Thirty-four tuberculomas were evaluated by conventional and perfusion MRI. The relative cerebral blood volume (rCBV) values of the center, peripheral wall, and perilesional neuroparenchymal tissue were calculated using rCBV maps. Ten ring-enhancing metastases were similarly evaluated and rCBV values of their peripheral walls were calculated. Results: Thirty-one of the 34 tuberculomas were ring-enhancing or conglomerate lesions and revealed hypoperfused centers with hyperperfused peripheral walls, with the mean rCBV {+-} SD being 0.42 {+-} 0.25 and 2.04 {+-} 0.61, respectively. Three nodular enhancing lesions showed predominantly homogenous hyperperfusion, with the mean rCBV measuring 2.96 {+-} 0.39 (mean {+-} SD). The perilesional neuroparenchyma was hypoperfused in both cases. The metastases revealed mean rCBV ratio of the peripheral wall to be 5.43 {+-} 2.1 (mean {+-} SD). Analysis of the values by ROC curve method revealed a cut-off value of {>=}3.745 for differentiating ring-enhancing metastases from ring-enhancing tuberculomas. Conclusion: Perfusion MR is a useful tool for the assessment of tuberculomas and can help differentiate them from neoplasms like metastases. It also has a potential role in monitoring therapy and for early detection of drug resistance.

  14. Aphasia caused by intracerebral hemorrhage; CT-scan findings and prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Kazuhide; Segawa, Hiromu; Shiokawa, Yoshiaki; Hasegawa, Isao; Sano, Keiji [Fuji Brain Institute and Hospital, Shizuoka (Japan)

    1992-10-01

    It is generally accepted that cases of aphasia can be divided into several groups according to verbal fluency, auditory comprehension, and repetition abilities. Although many authors have studied aphasia and its location by means of a CT scan, the primary lesion on a CT scan with regard to the subtypes of aphasia still remains controversial. In this report we present our new CT classification for the syndromes of aphasia and the prognosis. Twenty-one patients with intracerebral hematoma (ICH) were followed up for more than 3 months after onset. ICH was classified according to the mode of the horizontal extension of the hematoma on a CT scan. Four lines were decided as follows: Line (a) is between the anterior horn of the lateral ventricle and the midpoint of the third ventricle; Line (b) is the vertical line to the saggital line which originates from the midpoint of the third ventricle; Line (c) is between the trigone of the lateral ventricle and the midpoint of the third ventricle. The CT classification consisted of 4 types: in Type A, ICH was located anterior to line (a); in Type B, ICH was located between line (a) and line (b); in Type C, ICH was located between line (b) and line (c); Type B+C, was a combination of Type B and Type C. Transcortical motor aphasia belonged to the Type A group. Transcortical sensory aphasia belonged to the Type B and Type B+C groups. Wernicke's and anomic aphasia belonged to the Type C group. Conduction and global aphasia belonged to the Type B+C group. Pure Broca's aphasia could not be observed in this series. Several relationships between the syndromes of aphasia and its CT findings were evident. On the other hand, the syndromes of aphasia and the degree of recovery were not correlated, except for global aphasia. (author).

  15. Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: Systematic review and meta-analysis.

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    Neshika Samarasekera

    Full Text Available We sought to summarize Computed Tomography (CT/Magnetic Resonance Imaging (MRI features of intracerebral hemorrhage (ICH associated with cerebral amyloid angiopathy (CAA in published observational radio-pathological studies.In November 2016, two authors searched OVID Medline (1946-, Embase (1974- and relevant bibliographies for studies of imaging features of lobar or cerebellar ICH with pathologically proven CAA ("CAA-associated ICH". Two authors assessed studies' diagnostic test accuracy methodology and independently extracted data.We identified 22 studies (21 cases series and one cross-sectional study with controls of CT features in 297 adults, two cross-sectional studies of MRI features in 81 adults and one study which reported both CT and MRI features in 22 adults. Methods of CAA assessment varied, and rating of imaging features was not masked to pathology. The most frequently reported CT features of CAA-associated ICH in 21 case series were: subarachnoid extension (pooled proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies and an irregular ICH border (64%, 95% CI 32-91%, I2 = 85%, five studies. CAA-associated ICH was more likely to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA-associated ICH 7/41 vs. non-CAA ICH 0/42; χ2 = 7.8, p = 0.005. Superficial siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 = 35%, 3 studies.Subarachnoid extension and an irregular ICH border are common imaging features of CAA-associated ICH, but methodologically rigorous diagnostic test accuracy studies are required to determine the sensitivity and specificity of these features.

  16. Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage

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    Mohamad Saekhu

    2016-07-01

    Full Text Available Background: The outcome of patients with spontaneous supratentorial intracerebral hemorrhage (SSICH is unsatisfactory. Inflammatory response secondary to brain injury as well as those resulted from surgical procedure were considered responsible of this outcome. This study was intended to elucidate the anti-inflammatory activity of tigecycline by measuring TNF-α level and its neuroprotective effect as represented by inhospital mortality rate.Methods: Patients with SSICH who were prepared for hematoma evacuation were randomized to receive either tigecycline (n=35 or fosfomycine (n=37 as prophylactic antibiotic. TNF-α level was measured in all subjects before surgery and postoperatively on day-1 and day-7. A repeated brain CT Scan was performed on postoperative day-7. The Glasgow outcome scale (GOS and length of stay (LOS were recorded at the time of hospital discharge. Data were analyzed using Mann-Whitney and Chi square test. Relative clinical effectiveness was measured by calculating the number needed to treat (NNT.Results: There was a significant difference regarding the proportion of subject who had  reduced TNF-α level on postoperative day-7 between the groups receiving tigecycline and fosfomycine (62% vs 29%, p=0.022. Decrease brain edema on CT control (86% vs 80%, p=0.580. Tigecycline administration showed a tendency of better clinical effectiveness in lowering inhospital mortality (17% vs 35%; p=0.083; OR=0.49; NNT=5 and worse clinical outcome / GOS ≤ 2 (20% vs 38% ; p=0.096; OR=0.41; NNT=6. LOS ≥ 15 hari ( 40% vs 27%; p=0.243; OR=1.81; NNT=8.Conclusion: Tigecycline showed anti-inflammatory and neuroprotective activities. These activities were associated with improved clinical outcome in patients with SSICH after hematoma evacuation.

  17. Differences in Neuropeptide Y Secretion Between Intracerebral Hemorrhage and Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Schebesch, Karl-M; Bründl, Elisabeth; Schödel, Petra; Hochreiter, Andreas; Scheitzach, Judith; Bele, Sylvia; Brawanski, Alexander; Störr, Eva-M; Lohmeier, Anette; Proescholdt, Martin

    2017-07-01

    Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Seventy-nine patients were prospectively included: SAH patients (n=66) (historic population) and intracerebral hemorrhage patients (n=13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P<0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.

  18. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats

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    Hui-Qin Li

    2016-01-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20 exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa’s scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P<0.05. In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

  19. Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

    Science.gov (United States)

    Zhu, Yan; Deng, Li; Tang, Huajun; Gao, Xiaoqing; Wang, Youhua; Guo, Kan; Kong, Jiming; Yang, Chaoxian

    2017-05-01

    Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

    Science.gov (United States)

    Luh, Hui-Tzung; Huang, Abel Po-Hao; Yang, Shih-Hung; Chen, Chien-Ming; Cho, Der-Yang; Chen, Chun-Chung; Kuo, Lu-Ting; Li, Chieh-Hsun; Wang, Kuo-Chuan; Tseng, Wei-Lung; Hsing, Ming-Tai; Yang, Bing-Shiang; Lai, Dar-Ming; Tsai, Jui-Chang

    2018-01-01

    Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings. Copyright © 2017. Published by Elsevier B.V.

  1. Early-Stage Estimated Value of Blend Sign on the Prognosis of Patients with Intracerebral Hemorrhage

    Science.gov (United States)

    Zhou, Ningquan; Wang, Chao

    2018-01-01

    Background and Purpose This study aimed to explore the relationship between blend sign and prognosis of patients with intracerebral hemorrhage (ICH). Methods Between January 2014 and December 2016, the results of cranial computed tomography imaging within 24 h after the onset of symptoms from 275 patients with ICH were retrospectively analyzed. The patients with or without blend sign were compared to observe and analyze the difference in coagulation function abnormality, rebleeding, mortality, and bad prognosis rates in the early stages. Results Of the 275 patients with ICH, 47 patients had Blend Sign I (17.09%) and 17 patients had Blend Sign II (6.18%). The coagulation function abnormality rate had no statistical difference among Blend Sign I, Blend Sign II, and conventional groups (P > 0.05). In the Blend Sign I group, the rebleeding rate was 4.26%, bad prognosis rate was 25.53%, and mortality rate was 6.38%, which were not statistically significantly different compared with those in the conventional group (P > 0.05). The rebleeding rate in the Blend Sign II group was 47.06%, bad prognosis rate was 82.35%, and mortality rate was 47.06%, which were statistically significantly different compared with those in the conventional and Blend Sign I groups (P Blend Sign I, the prognosis was equivalent to that in the conventional group, with no statistically significant difference. The rebleeding, bad prognosis, and mortality rates were higher in the Blend Sign II group than in the conventional group and deserved more attention.

  2. Childhood Stature and Growth in Relation to First Ischemic Stroke or Intracerebral Hemorrhage.

    Science.gov (United States)

    Gjærde, Line Klingen; Truelsen, Thomas Clement; Baker, Jennifer Lyn

    2018-03-01

    Attained height, an indicator of genetic potential and childhood growth environment, is inversely associated with stroke, but the mechanisms are poorly understood. We investigated whether childhood height and growth are associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH). In a cohort of Danish schoolchildren born 1930 to 1989, with measured height from 7 to 13 years, we investigated associations of childhood stature and growth with risks of adult IS and ICH. Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) with CIs separately for women and men. Among 311 009 individuals, 10 412 were diagnosed with IS and 2546 with ICH. Height at 7 years was inversely and significantly associated with IS in both sexes (per z score, equivalent to ≈5.2 cm in women and 5.1 cm in men; women: HR=0.89 [95% CI: 0.87-0.92]; men: HR=0.90 [95% CI: 0.88-0.92]) and with ICH in men (HR=0.89 [95% CI: 0.84-0.94]) but not in women (HR=0.97 [95% CI: 0.91-1.04]). Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from 7 to 13 years were observed for IS or ICH. Short stature at 7 to 13 years is significantly associated with increased risks of IS in both sexes and with ICH in men. Growth during this period of childhood is not significantly associated with either of these stroke subtypes, suggesting that underlying mechanisms linking height with risks of stroke may exert their influence already by early childhood. © 2018 American Heart Association, Inc.

  3. Development of a mechanics-based model of brain deformations during intracerebral hemorrhage evacuation

    Science.gov (United States)

    Narasimhan, Saramati; Weis, Jared A.; Godage, Isuru S.; Webster, Robert; Weaver, Kyle; Miga, Michael I.

    2017-03-01

    Intracerebral hemorrhages (ICHs) occur in 24 out of 100,000 people annually and have high morbidity and mortality rates. The standard treatment is conservative. We hypothesize that a patient-specific, mechanical model coupled with a robotic steerable needle, used to aspirate a hematoma, would result in a minimally invasive approach to ICH management that will improve outcomes. As a preliminary study, three realizations of a tissue aspiration framework are explored within the context of a biphasic finite element model based on Biot's consolidation theory. Short-term transient effects were neglected in favor of steady state formulation. The Galerkin Method of Weighted Residuals was used to solve coupled partial differential equations using linear basis functions, and assumptions of plane strain and homogeneous isotropic properties. All aspiration models began with the application of aspiration pressure sink(s), calculated pressures and displacements, and the use of von Mises stresses within a tissue failure criterion. With respect to aspiration strategies, one model employs an element-deletion strategy followed by aspiration redeployment on the remaining grid, while the other approaches use principles of superposition on a fixed grid. While the element-deletion approach had some intuitive appeal, without incorporating a dynamic grid strategy, it evolved into a less realistic result. The superposition strategy overcame this, but would require empirical investigations to determine the optimum distribution of aspiration sinks to match material removal. While each modeling framework demonstrated some promise, the superposition method's ease of computation, ability to incorporate the surgical plan, and better similarity to existing empirical observational data, makes it favorable.

  4. Intracerebral Hemorrhage; towards physiological imaging of hemorrhage risk in acute and chronic bleeding.

    Directory of Open Access Journals (Sweden)

    Raphael eJakubovic

    2012-05-01

    Full Text Available Despite improvements in management and prevention of intracerebral hemorrhage (ICH, there has been little improvement in mortality over the last 30 years. Hematoma expansion, primarily during the first few hours is highly predictive of neurological deterioration, poor functional outcome and mortality. For each 10% increase in ICH size, there is a 5% increase in mortality and an additional 16% chance of poorer functional outcome. As such, both the identification and prevention of hematoma expansion are attractive therapeutic targets in ICH. Previous studies suggest that contrast extravasation seen on CT Angiography (CTA, MRI, and digital subtraction angiography correlates with hematoma growth, indicating ongoing bleeding. Contrast extravasation on the arterial phase of a CTA has been coined the CTA Spot Sign. These easily identifiable foci of contrast enhancement have been identified as independent predictors of hematoma growth, mortality and clinical outcome in primary ICH. The Spot Sign score, developed to stratify risk of hematoma expansion, has shown high inter-observer agreement. Post-contrast leakage or delayed CTA Spot Sign, on post contrast CT following CTA or delayed CTA respectively are seen in an additional ~8% of patients and explain apparently false negative observations on early CTA imaging in patients subsequently undergoing hematoma expansion. CT perfusion provides an opportunity to acquire dynamic imaging and has been shown to quantify rates of contrast extravasation. Intravenous recombinant factor VIIa(rFVIIa within 4 hours of ICH onset has been shown to significantly reduce hematoma growth. However, clinical efficacy has yet to be proven. There is compelling evidence that cerebral amyloid angiopathy (CAA may precede the radiographic evidence of vascular disease and as such contribute to microbleeding. The interplay between microbleeding, CAA,CTA Spot Sign and genetic composition (ApoE genotype may be crucial in developing a

  5. Study on the effect of edaravone on changes of plasma ET-1 and CGRP levels in patients with traumatic intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Zhang Chunyin; Cai Liang; Guo Jia; Guan Ming; Gan Xilun

    2009-01-01

    Objective: To investigate the effect of edaravone treatment on plasma ET-1 and CGRP levels changes in patients with traumatic intracerebral hemorrhage. Methods: Plasma ET-1 and CGRP levels were measured with RIA in 40 patients with traumatic intracerebral hemorrhage both before and after treatment with 60mg of edaravone i. v. q. d. for 5 days, 40 patients both before and after treatment with conventional treatment only (without edaravone) and 30 controls (once only). Results: The plasma ET-1 levels were significantly increased in all the patients at admission than those in controls. After treatment, the levels in all the patients dropped significantly, but the levels were significantly lower in edaravone-treated patients than those in non-edaravone-treated patients (P<0.01). The reverse was true for plasma CGRP levels. Conclusion: Edaravone treatment could correct the abnormal plasma ET-1 and CGRP levels in patients with traumatic intracerebral hemorrhage and might be beneficial to recovery. (authors)

  6. Study on the effect of edaravone on changes of plasma ET-1 and CGRP levels in patients with traumatic intracerebral hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Chunyin, Zhang; Liang, Cai; Jia, Guo; Ming, Guan; Xilun, Gan [Department of Nuclear Medicine, The Affiliated Hospital, Luzhou Medical College, Luzhou (China)

    2009-04-15

    Objective: To investigate the effect of edaravone treatment on plasma ET-1 and CGRP levels changes in patients with traumatic intracerebral hemorrhage. Methods: Plasma ET-1 and CGRP levels were measured with RIA in 40 patients with traumatic intracerebral hemorrhage both before and after treatment with 60mg of edaravone i. v. q. d. for 5 days, 40 patients both before and after treatment with conventional treatment only (without edaravone) and 30 controls (once only). Results: The plasma ET-1 levels were significantly increased in all the patients at admission than those in controls. After treatment, the levels in all the patients dropped significantly, but the levels were significantly lower in edaravone-treated patients than those in non-edaravone-treated patients (P<0.01). The reverse was true for plasma CGRP levels. Conclusion: Edaravone treatment could correct the abnormal plasma ET-1 and CGRP levels in patients with traumatic intracerebral hemorrhage and might be beneficial to recovery. (authors)

  7. [Two cases of mesial temporal lobe epilepsy associated with old intracerebral hemorrhage in the lateral temporal lobe without "dual pathology"].

    Science.gov (United States)

    Morioka, T; Nishio, S; Hisada, K; Muraishi, M; Ishibashi, H; Mamiya, K; Ohfu, M; Fukui, M

    1998-05-01

    Two cases of intractable temporal lobe epilepsy associated with old intracerebral hemorrhage in the lateral temporal lobe were reported. Although preoperative magnetic resonance imaging (MRI) failed to reveal hippocampal atrophy with T2 hyperintensity, electrocorticographic (ECoG) recording with chronic invasive subdural electrodes indicated the mesial temporal lobe to be an ictal onset zone. After anterior temporal lobectomy involving the lesion and hippocampectomy, the patients became seizure-free. Hippocampal sclerosis, namely "dual pathology", was not noted on histological examination. Careful ECoG recording with chronic subdural electrodes is mandatory even when the preoperative MRI does not demonstrate the radiological hippocampal sclerosis.

  8. Comparison of quantitative estimation of intracerebral hemorrhage and infarct volumes after thromboembolism in an embolic stroke model

    DEFF Research Database (Denmark)

    Eriksen, Nina; Rasmussen, Rune Skovgaard; Overgaard, Karsten

    2014-01-01

    . Group 1 was treated with saline, and group 2 was treated with 20 mg/kg recombinant tissue plasminogen activator to promote intracerebral hemorrhages. Stereology, semiautomated computer estimation, and manual erythrocyte counting were used to test the precision and efficiency of determining the size...... measurements, the stereological method was the most efficient and advantageous. CONCLUSIONS: We found that stereology was the superior method for quantification of hemorrhagic volume, especially for rodent petechial bleeding, which is otherwise difficult to measure. Our results suggest the possibility...

  9. Comparison between Modified Neuroendoscopy and Craniotomy Evacuation of Spontaneous Intra-Cerebral Hemorrhages: Study of Clinical Outcome and Glasgow Outcome Score

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    Arie Ibrahim

    2016-08-01

    Full Text Available Background and Purposes: Stroke is still one of a leading health-care problem in industrial country and in the developing country. Spontaneous Intra-cerebral Hemorrhage accounts for 30–60% of all stroke admissions into a hospital. Presence of intra-cerebral hemorrhage is considered a poor prognostic factor due to the resultant obstruction to the mass effect following the presence of blood resulting in raised intracranial pressure. While the craniotomy procedure failed to show more benefits over functional outcome, a less invasive and quicker surgical decompression might improve the outcome. Neuroendoscopy is one of promising optional  on minimal invasive  treatment  for spontaneous intra-cerebral hemorrhage. Material and Methods: We evaluated Glasgow Outcome Score and clinical outcome of patients with Spontaneous Intra-cerebral Hemorrhage who underwent modified neuroendoscopic surgery and craniotomy. Randomized control trial was performed during 27 months in 43 patients. Twenty-five patients treated with neuroendoscopy surgery and 18 patients with craniotomy. The removal of intra-cerebral hemorrhage was done by a modified neuroendoscopic transparent sheath made of silastic material, derived from pieces of thoracic tube No. 21F as a conduit working channel. Results: We analyzed statistically, clinical outcome assessment and Glasgow Outcome Scale 6 months post operative follow-up period. The mortality rate was significantly higher by Pearson chi-square methods, in craniotomy group n=12 (63.2% compared with neuroendoscopy group, n=7 (36.8% (p<.005. Patients with Glasgow Outcome Scale score 3–5 was higher in neuroendoscopy group, n=18 (75% compared with craniotomy group n=6 (25%. The survival rate analyzed by Kaplan Meier methods, found that patients in the neuroendoscopy group were a significantly longer survival rate compare with the craniotomy group during 6 months post operative follow-up period. Conclusions: Treatment of spontaneous

  10. Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

    Directory of Open Access Journals (Sweden)

    Jakobsen Maria

    2011-02-01

    Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

  11. Association between p75 neurotrophin receptor gene expression and cell apoptosis in tissues surrounding hematomas in rat models of intracerebral hemorrhage.

    Science.gov (United States)

    He, Baixiang; Bao, Gang; Guo, Shiwen; Xu, Gaofeng; Li, Qi; Wang, Ning

    2012-03-15

    Animal models of intracerebral hemorrhage were established by injection of autologous blood into the caudate nucleus in rats. Cell apoptosis was measured by flow cytometry and immunohistochemical staining of the p75 neurotrophin receptor. p75 neurotrophin receptor protein was detected by immunohistochemistry. p75 neurotrophin receptor mRNA was examined by quantitative real-time polymerase chain reactions. At 24 hours after modeling, cellular apoptosis occured around hematoma with upregulation of p75 neurotrophin receptor protein and mRNA was observed, which directly correlated to apoptosis. This observation indicated that p75 neurotrophin receptor upregulation was associated with cell apoptosis around hematomas after intracerebral hemorrhage.

  12. Azithromycin prophylaxis and treatment of murine toxoplasmosis.

    Science.gov (United States)

    Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

    2005-03-01

    To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

  13. Efficacy of posaconazole in murine experimental sporotrichosis.

    Science.gov (United States)

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2012-05-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

  14. Irradiation Design for an Experimental Murine Model

    International Nuclear Information System (INIS)

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-01-01

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  15. Thrombopoietin inhibits murine mast cell differentiation

    Science.gov (United States)

    Martelli, Fabrizio; Ghinassi, Barbara; Lorenzini, Rodolfo; Vannucchi, Alessandro M; Rana, Rosa Alba; Nishikawa, Mitsuo; Partamian, Sandra; Migliaccio, Giovanni; Migliaccio, Anna Rita

    2009-01-01

    We have recently shown that Mpl, the thrombopoietin receptor, is expressed on murine mast cells and on their precursors and that targeted deletion of the Mpl gene increases mast cell differentiation in mice. Here we report that treatment of mice with thrombopoietin, or addition of this growth factor to bone marrow-derived mast cell cultures, severely hampers the generation of mature cells from their precursors by inducing apoptosis. Analysis of the expression profiling of mast cells obtained in the presence of thrombopoietin suggests that thrombopoietin induces apoptosis of mast cells by reducing expression of the transcription factor Mitf and its target anti-apoptotic gene Bcl2. PMID:18276801

  16. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    International Nuclear Information System (INIS)

    Kodama, Atsushi; Yanai, Tokuma; Sakai, Hiroki; Matsuura, Satoko; Murakami, Mami; Murai, Atsuko; Mori, Takashi; Maruo, Kouji; Kimura, Tohru; Masegi, Toshiaki

    2009-01-01

    Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

  17. Increased expression of Apo-J and Omi/HtrA2 after Intracerebral Hemorrage in rats.

    Science.gov (United States)

    Li, Feng; Yang, Jing; Guo, Xiaoyan; Zheng, Xiaomei; Lv, Zhiyu; Shi, Chang Qing; Li, Xiaogang

    2018-03-23

    To investigate the changes of Apo-J and Omi/HtrA2 protein expression in rats with intracerebral hemorrage. 150 SD adult rats were randomly divided into 3 groups: (1) Normal Control (NC) group, (2) Sham group, (3) Intracerebral Hemorrage (ICH) group. The data were collected at 6h, 12h, 1d, 2d, 3d, 5d and 7d. Apoptosis was measured by Tunel staining. The distributions of the Apo-J and Omi/HtrA2 proteins were determined by immunohistochemical staining. The levels of Apo-J mRNA and Omi/HtrA2 mRNA expressions were examined by RT-PCR. Apoptosis in ICH group was higher than Sham and NC groups (p<0.05). Both the Apo-J and Omi/HtrA2 expression levels were increased in the peripheral region of hemorrhage, with a peak at 3d. The Apo-J mRNA level positively correlated with HtrA2 mRNA level in ICH group (r=0.883, p<0.001). The expressions of Apo-J and Omi/HtrA2 paralelly increased in peripheral region of rat cerebral hemorrhage. Local high expressed Apo-J in the peripheral regions might play a neuroprotective role by inhibiting apoptosis via Omi/HtrA2 pathway after hemorrhage. Copyright © 2018. Published by Elsevier Inc.

  18. Analysis of Glial Fibrillary Acidic Protein (GFAP Serum Levels on Spontaneous Intracerebral Hemorrhage Non-Lesion Patients

    Directory of Open Access Journals (Sweden)

    Suzy Indharty

    2016-04-01

    Full Text Available Background: Stroke is one of the root causes of brain disorders at the height of the productive age and ranks second cause of death after heart disease in most countries in the world. Fairly large-scale study conducted by ASNA (ASEAN Neurological Association in 28 Hospitals in Indonesia. This study was conducted in patients with acute stroke who were treated in hospital (hospital-based study and conducted a survey of factors - risk factors, treatment duration and mortality and morbidity. Method: This is a cross sectional study, with intracerebral hemorrhage Head CT scan examination then examined serum levels of plasma GFAP her at the time of patient entry from RSUP. H. Adam Malik Medan from March 2014 -May 2014. Results: In this research, we found the frequency of male patients as many (62.5%, while as many women (37.5%. Predominant age range in patients encountered in this study were 46-51 years old and are the dominant ethnic Batak tribe (43.8%. Conclusion: There were no significant differences between groups in serum GFAP levels with bleeding volume ≥ 30 cc compared to those with bleeding volume <30 cc (p = 0.599. GFAP is a biomarker to distinguish whether stroke patients including intracerebral hemorrhage or ischemic stroke Further longitudinal study would be needed to confirm the role.

  19. Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature.

    Science.gov (United States)

    Naunheim, Matthew R; Nahed, Brian V; Walcott, Brian P; Kahle, Kristopher T; Soupir, Chad P; Cahill, Daniel P; Borges, Lawrence F

    2010-09-01

    Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH.

  20. SIC, an intracerebral radiosensitive probe for in vivo neuropharmacology investigations in small laboratory animals: theoretical considerations and practical characteristics

    Science.gov (United States)

    Pain, F.; Laniece, P.; Mastrippolito, R.; Charon, Y.; Comar, D.; Leviel, V.; Pujol, J. F.; Valentin, L.

    2000-02-01

    Although high-resolution tomographs provide a new approach that strongly simplifies the measurement of in vivo tracer biodistribution and kinetics in small animals, they suffer from an important drawback: the need for animal anesthesia or immobilization, which restricts the neurophysiological investigations. Furthermore, quantitative in vivo experiments realized on the brain sometimes only require a simple measurement of the radioactivity achieved on a few local points and do not necessarily imply the use of a tomograph, which is a detector of high cost. These constraints led the authors to develop an interacerebral /spl beta/ sensitive probe, sonde intracerebrate (SIC) (French acronym of intracerebral probe) that will allow chronic measurements of the neurophysiological activity in awake and unrestrained small animals. The volume to which the probe is sensitive and the noise contributions to the relevant signal have been evaluated through Monte Carlo simulations. Characterizations of a first prototype based on a small piece of scintillating fiber (500-/spl mu/m diameter and 1-mm length) fused to a same diameter optical fiber coupled in turn to a photomultiplier are also presented. A first configuration of the detector is finally proposed.

  1. [Virulence of Sporothrix globosa in murine models].

    Science.gov (United States)

    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Day-night variability of hematoma expansion in patients with spontaneous intracerebral hemorrhage.

    Science.gov (United States)

    Yao, Xiaoying; Wu, Bo; Xu, Ye; Siwila-Sackman, Erica; Selim, Magdy

    2015-06-01

    The levels of several coagulation factors, able to influence hemostatic balance, display circadian variations. We hypothesized that the onset and extent of hematoma expansion (HE) following intracerebral hemorrhage (ICH) also display diurnal patterns. We reviewed clinical, laboratory, and radiological data from 111 consecutive patients with spontaneous ICH who had baseline head computed tomography (CT) scans within 3 h of ICH onset and follow-up CT during the following 72 h. We defined any HE (AHE) as any increase in hematoma volume from baseline to follow-up CT and significant HE (SHE) as an absolute increase in hematoma volume >6 mL or relative increase >33%. We categorized the patients into 2 groups based on the timing of the initial CT scans--day group (from 0800 to 2000 h) and night group (from 2000 to 0800 h)--and performed logistic regression analyses. We also analyzed the differences in the rates of HE between the groups during six 4-h periods spanning 24 h, using χ(2) tests. We found that the rates of AHE and SHE were higher in the day versus night group (75% vs. 48%; p = 0.009 for AHE and 47.6% vs. 25.9%; p = 0.047 for SHE). On multivariable logistic regression, day group assignment was independently associated with AHE (adjusted odds ratio = 3.53; p = 0.008) but not with SHE. Both AHE and SHE peaked in the early afternoon (1200-1600 h) and reached a nadir during the 2000 to 2400 h time period, and they were significantly different between the time periods (0000-0400, 0400-0800, 0800-1200, 1200-1600, 1600-2000, and 2000-2400 h); p = 0.002 and 0.029, respectively. These exploratory findings support the presence of a daily pattern in the occurrence of HE, with a higher risk during the day hours. Our results could have implications for future therapeutic efforts targeting HE in ICH and for the triage of ICH patients. They require further validation. © 2015 The Author(s).

  3. Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Eckman Mark H

    2008-05-01

    Full Text Available Abstract Background Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER given the poor neurologic outcomes after ICH with conventional management. Methods We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE. We assumed no substantial cost differences in care between the two strategies except: 1 cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408; 2 cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death; and 3 differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home, and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE. Results In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER Conclusion Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.

  4. Cholinesterase inhibition and acetylcholine accumulation following intracerebral administration of paraoxon in rats

    International Nuclear Information System (INIS)

    Ray, A.; Liu, J.; Karanth, S.; Gao, Y.; Brimijoin, S.; Pope, C.

    2009-01-01

    We evaluated the inhibition of striatal cholinesterase activity following intracerebral administration of paraoxon assaying activity either in tissue homogenates ex vivo or by substrate hydrolysis in situ. Artificial cerebrospinal fluid (aCSF) or paraoxon in aCSF was infused unilaterally (0.5 μl/min for 2 h) and ipsilateral and contralateral striata were harvested for ChE assay ex vivo. High paraoxon concentrations were needed to inhibit ipsilateral striatal cholinesterase activity (no inhibition at < 0.1 mM; 27% at 0.1 mM; 79% at 1 mM paraoxon). With 3 mM paraoxon infusion, substantial ChE inhibition was also noted in contralateral striatum. ChE histochemistry generally confirmed these concentration- and side-dependent effects. Microdialysates collected for up to 4 h after paraoxon infusion inhibited ChE activity when added to striatal homogenate, suggesting prolonged efflux of paraoxon. Since paraoxon efflux could complicate acetylcholine analysis, we evaluated the effects of paraoxon (0, 0.03, 0.1, 1, 10 or 100 μM, 1.5 μl/min for 45 min) administered by reverse dialysis through a microdialysis probe. ChE activity was then monitored in situ by perfusing the colorimetric substrate acetylthiocholine through the same probe and measuring product (thiocholine) in dialysates. Concentration-dependent inhibition was noted but reached a plateau of about 70% at 1 μM and higher concentrations. Striatal acetylcholine was below the detection limit at all times with 0.1 μM paraoxon but was transiently elevated (0.5-1.5 h) with 10 μM paraoxon. In vivo paraoxon (0.4 mg/kg, sc) in adult rats elicited about 90% striatal ChE inhibition measured ex vivo, but only about 10% inhibition measured in situ. Histochemical analyses revealed intense AChE and glial fibrillary acidic protein staining near the cannula track, suggesting proliferation of inflammatory cells/glia. The findings suggest that ex vivo and in situ cholinesterase assays can provide very different views into enzyme

  5. Role of ghrelin in small intestinal motility following pediatric intracerebral hemorrhage in mice.

    Science.gov (United States)

    Zan, Jieyu; Song, Lei; Wang, Jiejie; Zou, Rong; Hong, Fei; Zhao, Jinhua; Cheng, Yijun; Xu, Ming

    2017-11-01

    Small intestinal motility (SIM) disorder is a common complication following pediatric intracerebral hemorrhage (ICH), leading to a poor prognosis in patients. Previous studies have shown that ghrelin is involved in SIM in various diseases; however, the role of ghrelin in pediatric ICH‑induced SIM disorder remains to be elucidated. The present study was designed to investigate the association between ghrelin and SIM post‑ICH, and to examine the effect of exogenous ghrelin administration on SIM in vivo. An ICH model was induced in mice by autologous blood infusion. Neurobehavioral deficits were evaluated using a Rotarod test, forelimb placing test, and corner turn test. Intestinal mucosal damage was examined using hematoxylin and eosin staining. SIM was measured using charcoal meal staining. An enzyme‑linked immunosorbent assay was used to evaluate serum levels of ghrelin and nitric oxide (NO). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were performed to determine the levels of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) at the mRNA and protein levels. Nω‑nitro‑L‑arginine methyl ester hydrochloride (L‑NAME), L‑arginine, atropine, phentolamine and propranolol were used to manipulate the putative pathways induced by ghrelin. Neurological dysfunction was observed post‑ICH. ICH caused damage to the intestinal mucosa and delayed SIM. Serum levels of ghrelin increased between 3 h and 3 days, peaking at 12 h, and showed a significant negative correlation with SIM post‑ICH. Ghrelin administration dose‑dependently attenua-ted ICH‑induced SIM disorder. Ghrelin also decreased NO levels by downregulating the mRNA and protein expression levels of iNOS, but not those of nNOS or eNOS, post‑ICH. Consistently, the effect was enhanced by L‑NAME and weakened by L‑arginine, respectively. The protective effect of ghrelin was

  6. Low-Density Lipoprotein and Intracerebral Hematoma Expansion in Daily Alcohol Users

    Directory of Open Access Journals (Sweden)

    Gayle R. Pletsch

    2014-01-01

    Full Text Available Background: Epidemiological studies suggest that the intracerebral hemorrhage (ICH rate correlates with alcohol consumption. Alcohol leads to elevated blood pressure (BP and inhibition of platelet aggregation. These factors could promote excessive bleeding. To our knowledge, in the setting of normal liver function tests, there are no studies that have systematically evaluated the relationship between daily alcohol use and hematoma expansion. The aim of this study is to compare the baseline ICH characteristics, frequency of hematoma expansion, and outcomes in patients with ICH who are daily alcohol users with those who are not daily alcohol users. Methods: A retrospective chart review was performed on consecutive patients who presented from July 2008 to July 2013 to the Tulane University Hospital in New Orleans, La., USA, with a spontaneous ICH. Ninety-nine patients who met these criteria were admitted. Patients who underwent hematoma evacuation were excluded. Hemorrhage volumes were calculated based on the ABC/2 method. Low-density lipoprotein (LDL was dichotomized into low (2 and nonparametric equivalents where appropriate. ICH growth in 24 h and LDL were evaluated using linear regression. Results: Of the 226 patients who met inclusion criteria, 20.4% had a history of daily alcohol use. The average age was 61 years (range 19-94, 55.6% of the patients were males, and 67.1% were of African American origin. Daily alcohol use was associated with male gender, lower rate of home antihypertensive, higher presenting BP, and lower platelet counts, but there was no difference in ICH characteristics, ICH growth, or clinical outcome. Daily alcohol use in patients with a low LDL level was associated with supratentorial location and trends for lower baseline Glasgow Coma Scale score, higher ICH score, and follow-up ICH volume, but no significant difference in significant hematoma expansion or clinical outcome except for a trend for higher mortality was found

  7. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  8. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  9. The effects of a picosecond pulsed electric field on angiogenesis in the cervical cancer xenograft models.

    Science.gov (United States)

    Wu, Limei; Yao, Chenguo; Xiong, Zhengai; Zhang, Ruizhe; Wang, Zhiliang; Wu, Yutong; Qin, Qin; Hua, Yuanyuan

    2016-04-01

    The application of picosecond pulsed electric field (psPEF) is a new biomedical engineering technique used in cancer therapy. However, its effects on cervical cancer angiogenesis are not clear. Therefore, the aim of the present study is to investigate the effects of psPEF on angiogenesis in cervical cancer xenograft models. Xenograft tumors were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with HeLa cells, then were placed closely between tweezer-type plate electrodes and subjected to psPEF with a gradually increased electric field intensity (0kV/cm, 50kV/cm, 60kV/cm, 70kV/cm). The direct effect on tumor tissue was observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). The changes of blood vessels and oxygen saturation (sO2) of tumors were monitored in vivo by photoacoustic tomography (PAT). The microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factors (HIF-1α and HIF-2α) were detected by immunohistochemical technique (IHC). Their protein expressions and gene transcription levels were evaluated using western blot (WB) and quantitative reverse transcription and polymerase chain reaction (RT-PCR). PsPEF induced obvious necrosis of cervical cancer tissue; with the increasing of electric field intensity, the MVD, vascular PA signal and sO2 values declined significantly. The protein expression and gene transcription levels of VEGF, HIF1α and HIF2α were significantly decreased at the same time. PsPEF exhibited dramatic anti-tumor and anti-angiogenesis effects in cervical cancer xenograft models by exerting direct effect on cancer cells and vascular endothelial cells and indirect effect on tumor angiogenesis-related factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    Science.gov (United States)

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  11. Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis.

    Science.gov (United States)

    Roubelakis, Apostolos; Karangelis, Dimos; Sadeque, Syed; Yanagawa, Bobby; Modi, Amit; Barlow, Clifford W; Livesey, Steven A; Ohri, Sunil K

    2017-07-01

    The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction abnormalities (46.7%). The mean length of hospital stay was 26 days. At pre-discharge echocardiography, the conduit mean gradient was 9.3±3.3mmHg and there was either none (n=6), trace (n=6) or mild aortic insufficiency (n=1). There was no incidence of mid-term death, prosthesis-related complications or recurrent endocarditis. Xenograft bioconduits may be safe and effective for aortic valve and root replacement for complex PVE with aortic root abscess. Although excess early mortality reflects the complexity of the patient population, there was good valve hemodynamics, with no incidence of recurrent endocarditis or prosthesis failure in the mid-term. Our data support the continued use and evaluation of this biological prosthesis in this high-risk patient cohort.

  12. Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

    International Nuclear Information System (INIS)

    Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

  13. Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research

    Science.gov (United States)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinská, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Mælandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    2014-01-01

    Recently, there has been increasing interest in the development and characterization of patient derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histological and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. This paper summarizes the current state of the art in this field including methodological issues, available collections, practical applications, challenges and shortcoming, and future directions, and introduces a European consortium of PDX models. PMID:25185190

  14. Stimulation of osteoblast activity by induction of Aloe vera and xenograft combination

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2011-12-01

    Full Text Available Background: Tooth extraction is generally followed by alveolar ridge resorption that later can cause flat ridge. Aloe vera have biogenic stimulator and hormone activities for wound healing. Purpose: This study was aimed to know osteoblast activities in alveolar bone after induction of Aloe vera and XCB combination. Methods: Fifty four of Cavia cabaya were divided into three main groups. Group I was control group. Group II was filled with xenograft concelous bovine (XCB and group III was filled with the combination of Aloe vera gel and XCB. Then, each group was divided into three sub groups according to timing, they are 14, 30, and 60 days after tooth extraction and application. Histology and morphology examination were performed on the harvested specimens. Results: There were significant differences between the control group and the other groups filled with the combination of Aloe vera and XCB. Conclusion: In conclusion, the application of Aloe vera gel and xenograft combination decrease the number of osteoclast and increase the number of osteoblast in post tooth extraction alveolar bone structure indicating the new growth of alveolar bone.Latar belakang: Pencabutan gigi pada umumnya selalu diikuti resopsi tulang alveolar, sehingga bila terjadi dalam waktu yang lama ridge akan menjadi flat. Aloe vera adalah bahan stimulasi biogenik dan mempunyai aktivitas hormon untuk proses penyembuhan luka. Tujuan: Tujuan dari penelitian ini adalah untuk mengetahui aktivitas osteoblas pada tulang alveol dengan pemberian kombinasi Aloe vera gel dan xenograft concelous bovine (XCB. Metode: Lima puluh empat ekor Cavia cabaya, dibagi menjadi 3 kelompok besar, kelompok pertama adalah kelompok kontrol yaitu hanya dilakukan pencabutan saja tanpa perlakuan, kelompok ke-2 yaitu kelompok yang setelah dicabut diberi XCB saja dan kelompok ke-3 yaitu kelompok yang setelah pencabutan diberi kombinasi Aloe vera gel dengan XCB pada luka bekas pencabutan gigi. Kemudian masing

  15. Interpretive conundrum on the exclusion criterion of "transplantation with xenografts" for tissue and cell donation.

    Science.gov (United States)

    Cox, Michael A; Brubaker, Scott A

    2012-06-01

    In the context of the EU Directives for human tissues and cells (2004/23/EC, 2006/17/EC and 2006/86/EC) further interest has arisen on the practical application of a few clauses. One such aspect, for the evaluation phase of a potential donor, is the interpretation of the exclusion criterion "transplantation with xenografts." This article outlines the consensus viewpoints regarding the earlier evaluation of the risks related to xenotransplantation and describes the current status of the terminology and recommendations/laws in several healthcare sectors. The application of uniform terminology is encouraged within the healthcare sectors at the international level.

  16. Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

    Science.gov (United States)

    Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

    2017-06-01

    Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

  17. Analyzing the mechanisms of cell killing by ionizing radiation in monolayer, spheroids and xenografted tumours

    International Nuclear Information System (INIS)

    Horas, J.A.; Olguín, O.R.; Rizzotto, M.G.

    2017-01-01

    A relationship between oxygen enhancement ratio (OER) and parameters of Linear Quadratic (LQ) model in hypoxic and aerobic conditions in several cell lines grown as monolayer, spheroids and transplanted tumors (xenograft) is tested. By considering this relationship, the two mechanisms of cell death by radiation appear. Surviving Fraction (SF) fits are compared in both oxygenation conditions by using the LQ. The data are obtained from literature. The existence of such mechanisms and their implications in the different systems studied is shown. The validity of one or other mechanism in each case is determined and the OER dependence with dose. (authors) [es

  18. Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

    NARCIS (Netherlands)

    C.J.J. Van Asch (Charlotte J.J.); B.K. Velthuis (Birgitta K.); G.J.E. Rinkel (Gabriël J.E.); A. Algra (Ale); G.A.P. de Kort (G. A P); T.D. Witkamp (Theo); J.C.M. De Ridder (Johanna C.M.); K.M. Van Nieuwenhuizen (Koen M.); F.-E. De Leeuw (Frank-Erik); W.J. Schonewille (Wouter); P.L.M. de Kort (Paul); D.W.J. Dippel (Diederik); T.W.M. Raaymakers (Theodora W.M.); J. Hofmeijer; M.J.H. Wermer (Marieke); H. Kerkhoff (Henk); K. Jellema (Korné); I.M. Bronner (Irene M.); M.J.M. Remmers (Michel ); H.P. Bienfait (Henri); R.J.G.M. Witjes (Ron J.G.M.); J.P. Greving (Jacoba); C.J.M. Klijn (Catharina J.M.); H.F. de Leeuw (Frank); H.B. Boogaarts; E.J. van Dijk (Ewoud); W.J. Schonewille; W.M.J. Pellikaan; C. Puppels-De Waard; P.L.M. De Kort; J.P. Peluso; J. van Tuijl (Jordie); J. Hofmeijer; F.B.M. Joosten (Frank); D.W.J. Dippel (Diederik); L. Khajeh (Ladbon); T.W.M. Raaijmakers; M.J. Wermer; M.A.A. van Walderveen (Marianne); H. Kerkhoff; E. Zock; K. Jellema (Korné); G.J. Lycklama à Nijeholt (Geert); I.M. Bronner; M.J.M. Remmers; R.J.G.M. Witjes; H.P. Bienfait; K.E. Droogh-Greve; R. Donders (Rogier); V.I.H. Kwa; T.H.C.M.L. Schreuder (Tobien H. C. M. L.); C.L. Franke (Cees); J.S. Straver; C. Jansen; S.L.M. Bakker (Stef); C.C. Pleiter (C.); M.C. Visser; C.J.J. Van Asch; B.K. Velthuis (Birgitta); G.J.E. Rinkel (Gabriel); K.M. Van Nieuwenhuizen; C.J.M. Klijn (Catharina J.M.)

    2015-01-01

    textabstractStudy question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This

  19. Acute post-stroke blood pressure relative to premorbid levels in intracerebral haemorrhage versus major ischaemic stroke: a population-based study

    Science.gov (United States)

    Fischer, Urs; Cooney, Marie Therese; Bull, Linda M; Silver, Louise E; Chalmers, John; Anderson, Craig S; Mehta, Ziyah; Rothwell, Peter M

    2014-01-01

    Summary Background It is often assumed that blood pressure increases acutely after major stroke, resulting in so-called post-stroke hypertension. In view of evidence that the risks and benefits of blood pressure-lowering treatment in acute stroke might differ between patients with major ischaemic stroke and those with primary intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure levels in these two disorders. Methods In a population-based study in Oxfordshire, UK, we recruited all patients presenting with stroke between April 1, 2002, and March 31, 2012. We compared all acute-phase post-event blood pressure readings with premorbid readings from 10-year primary care records in all patients with acute major ischaemic stroke (National Institutes of Health Stroke Scale >3) versus those with acute intracerebral haemorrhage. Findings Of 653 consecutive eligible patients, premorbid and acute-phase blood pressure readings were available for 636 (97%) individuals. Premorbid blood pressure (total readings 13 244) had been measured on a median of 17 separate occasions per patient (IQR 8–31). In patients with ischaemic stroke, the first acute-phase systolic blood pressure was much lower than after intracerebral haemorrhage (158·5 mm Hg [SD 30·1] vs 189·8 mm Hg [38·5], pblood pressure after intracerebral haemorrhage was substantially higher than premorbid levels (mean increase of 40·7 mm Hg, pblood pressure also increased steeply in the days and weeks before intracerebral haemorrhage (regression pblood pressure reading after primary intracerebral haemorrhage was more likely than after ischaemic stroke to be the highest ever recorded (OR 3·4, 95% CI 2·3–5·2, pblood pressure within 3 h of onset was 50 mm Hg higher, on average, than the maximum premorbid level whereas that after ischaemic stroke was 5·2 mm Hg lower (pblood pressure is substantially raised compared with usual premorbid levels after intracerebral haemorrhage, whereas acute

  20. Human/murine chimeric 81C6 F(ab')2 fragment: preclinical evaluation of a potential construct for the targeted radiotherapy of malignant glioma

    International Nuclear Information System (INIS)

    Boskovitz, Abraham; Akabani, Gamal H.; Pegram, Charles N.; Bigner, Darrell D.; Zalutsky, Michael R.

    2004-01-01

    We have obtained encouraging responses in recent Phase I studies evaluating 131 I-labeled human/murine chimeric 81C6 anti-tenascin monoclonal antibody (ch81C6) administered into surgically-created tumor resection cavities in brain tumor patients. However, because the blood clearance is slow, hematologic toxicity has been higher than seen with murine 81C6 (mu81C6). In the current study, a series of paired-label experiments were performed in athymic mice bearing subcutaneous D-245 MG human glioma xenografts to compare the biodistribution of the fragment ch81C6 F(ab') 2 labeled using Iodogen to a) intact ch81C6, b) mu81C6, and c) ch81C6 F(ab') 2 labeled using N-succinimidyl 3-[ 131 I]iodobenzoate. Tumor retention of radioiodine activity for the F(ab') 2 fragment was comparable to that for intact ch81C6 for the first 24 h and to that for mu81C6 for the first 48 h; as expected, blood and other normal tissue levels declined faster for ch81C6 F(ab') 2. Radiation dosimetry calculations suggest that 131 I-labeled ch81C6 F(ab') 2 may warrant further evaluation as a targeted radiotherapeutic for the treatment of brain tumors