Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

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Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Tabata, Osamu [Department of Micro Engineering, Kyoto University, Kyoto 606-8501 (Japan); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

2011-01-14

Research highlights: {yields} Single B-lymphoma living cells were imaged by AFM with the assistance of microfabricated pillars. {yields} The apoptosis of B-lymphoma cells triggered by rituximab without cross-linking was observed by AO/EB double fluorescent staining. {yields} The B-lymphoma cells became dramatically softer after adding rituximab. -- Abstract: The topography and mechanical properties of single B-lymphoma cells have been investigated by atomic force microscopy (AFM). With the assistance of microfabricated patterned pillars, the surface topography and ultrastructure of single living B-lymphoma cell were visualized by AFM. The apoptosis of B-lymphoma cells induced by rituximab alone was observed by acridine orange/ethidium bromide (AO/EB) double fluorescent staining. The rituximab-induced changes of mechanical properties in B-lymphoma cells were measured dynamically and the results showed that B-lymphoma cells became dramatically softer after incubation with rituximab. These results can improve our understanding of rituximab'effect and will facilitate the further investigation of the underlying mechanisms.

Usual interstitial pneumonia and nonspecific interstitial pneumonia: Correlation between CT findings at the site of biopsy with pathological diagnoses

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Sumikawa, Hiromitsu, E-mail: h-sumikawa@radiol.med.osaka-u.ac.jp [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Johkoh, Takeshi [Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Health Teachers, 3-1 Kurumazuka, Itami, Hyougo 664-8533 (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011 (Japan); Ichikado, Kazuya [Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Tikami, Kumamoto, 861-4193 (Japan); Colby, Thomas V. [Department of Pathology, Mayo Clinic, Scottsdale, AZ (United States); Fukuoka, Junya [Laboratory of Pathology, Toyama University Hospital, Toyama (Japan); Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Kataoka, Kensuke [Department of Respiratory Medicine, Tosei General Hospital, 160 Nishioiwake-cho, Seto City, Aichi (Japan); Yanagawa, Masahiro; Koyama, Mitsuhiro; Honda, Osamu; Tomiyama, Noriyuki [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan)

2012-10-15

Objectives: The aim of this study was to correlate high-resolution CT (HRCT) findings at the site of biopsy with the whole lung CT and pathologic diagnoses in usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Methods: The study included 35 patients (25 UIP and 10 NSIP) diagnosed both pathologically and clinically. 81 surgical biopsy specimens (54 UIP, and 27 NSIP) and extracted areas corresponding to biopsy sites on HRCT were analyzed. CT interpretations were compared with pathological diagnoses in both extracted images and the whole lung. Concordant and discordant cases in multiple extracted images were divided and analyzed. Then the whole cases were categorized by including or not at least one UIP diagnosis of extracted images and evaluated. Results: The diagnoses in extracted sites significantly correlated with pathological diagnoses (p = 0.047). There were significant differences in the concordances of extracted images compared with the diagnosis of whole lung and pathology (p = 0.008, 0.003, respectively). All 7 cases that were not concordant were diagnosed as radiological UIP with whole lung CT. The cases with at least one UIP diagnosis of extracted CT images were diagnosed as UIP in pathology more frequently (18 in 25) (p = 0.007). Conclusions: Radiological UIP in whole CT had more frequently discordant diagnoses from multiple extracted images than NSIP. And there were more cases in pathological UIP that included at least one UIP diagnosis of extracted images compared with pathological NSIP.

Drug-induced interstitial lung diseases. Often forgotten; Medikamenteninduzierte interstitielle Lungenerkrankungen. Haeufig vergessen

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Poschenrieder, F.; Stroszczynski, C. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Hamer, O.W. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Lungenfachklinik Donaustauf, Donaustauf (Germany)

2014-12-15

Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs. Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases. Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. (orig.) [German] Medikamenteninduzierte interstitielle Lungenerkrankungen (engl. ''drug-induced interstitial lung diseases'', DILD) sind wahrscheinlich haeufiger, als sie diagnostiziert werden. Aufgrund ihrer potenziellen Reversibilitaet ist eine erhoehte Vigilanz gegenueber DILD auch seitens der Radiologie angebracht, da diese regelmaessig ein radiomorphologisches Korrelat in der hochaufloesenden Computertomographie (''high-resolution CT'', HRCT) der Lunge aufweisen. Typische, nach eigener Erfahrung relativ haeufige Manifestationsformen von DILD sind der diffuse Alveolarschaden (engl. ''diffuse alveolar damage'', DAD), die eosinophile Pneumonie (EP), die Hypersensitivitaetspneumonitis (HP), die organisierende

The interstitial pneumonitis induced by cytostatics

International Nuclear Information System (INIS)

Dubrava, M.; Markova, I.; Mistina, L.

1998-01-01

The author presents a cause of 9-year old boy with ALL-F2B in the stage of the prevention treatment where in the its course the induced interstitial pneumonitis by cytostatics was developed. The bacterial, virus, mycological and parasitic causes of the interstitial pneumonitis on the basis of the bronchoscopy, BAL, CT, scintigraphy, laboratory and by cultivation were excluded. (authors)

Rituximab as a first-line agent for the treatment of dermatomyositis.

LENUS (Irish Health Repository)

2012-02-01

B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation

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Kim, Tae Sung; Chung, Myung Jin [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Seoul (Korea); Chung, Man Pyo [Sungkyunkwan University School of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Seoul (Korea); Choi, Yong Soo [Sungkyunkwan University School of Medicine, Division of Thoracic Surgery, Seoul (Korea)

2005-08-01

The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series. (orig.)

Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation

International Nuclear Information System (INIS)

Kim, Tae Sung; Chung, Myung Jin; Han, Joungho; Chung, Man Pyo; Choi, Yong Soo

2005-01-01

The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series. (orig.)

Rituximab selectively suppresses specific islet antibodies.

Science.gov (United States)

Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

2011-10-01

The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

Science.gov (United States)

Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

2017-06-15

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24�

A case of non-specific interstitial pneumonia with recurrent gastric carcinoma and anti-Jo-1 antibody positive myositis.

Science.gov (United States)

Ebisutani, Chikara; Ito, Isao; Kitaichi, Masanori; Tanabe, Naoya; Mishima, Michiaki; Kadowaki, Seizo

2016-07-01

We report the first case of non-specific interstitial pneumonia (NSIP) in a patient with cancer-associated myositis (CAM) that emerged along with the recurrence of the cancer. A 60-year-old woman, with a history of partial gastrectomy for gastric cancer 11 years ago, presented with exertional dyspnea with anti-Jo-1 antibody-positive myositis. Surgical lung biopsy showed NSIP with metastatic gastric cancer. Accordingly, her condition was diagnosed as CAM with cancer recurrence. In patients with a history of cancer, development of myositis may indicate cancer recurrence; therefore, careful observation would be necessary. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

Directory of Open Access Journals (Sweden)

R Goli

2017-01-01

Full Text Available Crystal-induced acute kidney injury (AKI is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.

Comparison of clinicoradiologic manifestation of nonspecific interstitial pneumonia and usual interstitial pneumonia/idiopathic pulmonary fibrosis: A report from NRITLD

Directory of Open Access Journals (Sweden)

Tafti Saeid

2008-01-01

Full Text Available Background: Ever since Katzenstein and Fiorelli introduced the term nonspecific interstitial pneumonia (NSIP to denote those cases of interstitial pneumonia that cannot be categorized as any of the other types of idiopathic interstitial pneumonias (IIP, there has been continuing debate on whether it is a real clinical entity or not. The American Thoracic Society/European Respiratory Symposium task group tried to identify idiopathic NSIP as a separate disease and exclude it from the category of IIP. However, it appears that the clinical presentation of NSIP and usual interstitial pneumonia (UIP are the same. Objective : To show that the radiologic features of NSIP and UIP should be relied upon, instead of clinical presentation and pathologic findings, to differentiate between the two. Materials and Methods: Consecutive patients who had received a diagnosis of either NSIP or UIP on the basis of open lung biopsy between January 2001 and December 2007 were identified for inclusion in this retrospective review. The study included 61 subjects: 32 men and 29 women with a mean age of 59.39 ± 14.5 years. Chest computed tomography images of all the cases were collected for a review. High resolution computed tomography (HRCT and all pathologic specimens were also evaluated. A weighted kappa coefficient was used to evaluate whether radiology can be used instead of biopsy for the diagnosis of NSIP and UIP. Comparison of the mean ages and the time intervals (i.e., interval between symptom onset and the time of diagnosis in the UIP and NSIP groups was done using the Mann-Whitney U test. Association between gender and biopsy result was evaluated by the Fisher exact test. Data were evaluated using SPSS, v.13. Results : Sixty-one patients were included in this study, 32 were male and 29 were female. On the basis of biopsy findings, 50 (82% patients had UIP and 11 (18% had NSIP. Thirty (60% of the 50 patients who had UIP were male and 20 (40% were female; 2 (18

Rituximab-Based Treatment, HCV Replication, and Hepatic Flares

Directory of Open Access Journals (Sweden)

Evangelista Sagnelli

2012-01-01

Full Text Available Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Rituximab-based treatment, HCV replication, and hepatic flares.

Science.gov (United States)

Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

2012-01-01

Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

DEFF Research Database (Denmark)

Kohno, M; Perch, M; Andersen, E

2011-01-01

A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

Mortality in patients with interstitial lung disease treated with rituximab or TNFi as a first biologic.

Science.gov (United States)

Druce, Katie L; Iqbal, Kundan; Watson, Kath D; Symmons, Deborah P M; Hyrich, Kimme L; Kelly, Clive

2017-01-01

Guidelines cautioned prescribing of tumour necrosis factor inhibitors (TNFi) to patients with rheumatoid arthritis and interstitial lung disease (RA-ILD) after reports of new or worsening of ILD. Less is known about outcomes among patients with RA-ILD who receive rituximab (RTX). This study compares mortality in patients with RA-ILD who received RTX or TNFi as their first biologic. Participants with RA-ILD recruited to the British Society for Rheumatology Biologics Register for RA were included. Death rates were calculated and risk comparisons were made using Cox regression. Causes of death, including the frequency in which ILD was recorded on death certificates were examined. 43 patients on RTX and 309 on TNFi were included. RTX recipients had shorter disease duration and less disability. Death rates were 94.8 (95%CI: 74.4 to 118.7) and 53.0 (22.9 to 104.6) per 1000 person years, respectively. The adjusted mortality risk was halved in the RTX cohort, but the difference was not statistically significant (HR 0.53, 95% CI: 0.26 to 1.10). ILD was the underlying cause of death in 1 of 7 RTX deaths (14%) and 12 of 76 TNFi deaths (16%). Patients with RA-ILD who received RTX had lower mortality rates compared to TNFi. The absence of information on ILD severity or subtype prevents conclusions of which drug represents the best choice in patients with RA-ILD and active arthritis.

Usual interstitial pneumonia and non-specific interstitial pneumonia: serial thin-section CT findings correlated with pulmonary function

Energy Technology Data Exchange (ETDEWEB)

Jeong, Yeon Joo; Lee, Kyung Soo; Chung, Man Pyo; Chung Myung Jin; Han, Joung Ho [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Mueller, Nestor L. [University of British Columbia, Vancouver (Canada); Colby, Thomas V. [Mayo Clinic Scottsdale, Scottsdale (United States); Kim, Seon Woo [Samsung Medical Center, Seoul (Korea, Republic of)

2005-09-15

We wanted to demonstrate and compare the serial high-resolution CTs (HRCT) and the pulmonary function test (PFT) findings of the usual interstitial pneumonia (UIP) and the non-specific interstitial pneumonia (NSIP). The serial HRCT scans and the PFT results were retrospectively analysed and compared for 35 patients having UIP without significant honeycombing (UIP-w/o hc, < 5% of honeycombing at CT), 35 patients having UIP with honeycombing (UIP-w/i hc, {>=} 5% of honeycombing), and 25 patients with NSIP. The mortality rates were also compared. Follow-up CT scans were available in 75 patients (29 UIP-w/o hc patients, 22 UIP-w/i hc patients and 24 NSIP patients) and the follow-up periods ranged from 150 to 2,370 days. The initial and follow-up PFT data were available for 71 patients. On the initial CT, significant differences were present between the UIP-w/i hc patients and both the UIP-w/o hc patients and the NSIP patients in the overall extent, ground-glass opacity (GGO) away from the reticulation, reticulation and honeycombing (all {rho} < 0.05). Improvement was noticed in five (17%) of 29 UIP-w/o hc patients, none of 22 UIP-w/i hc patients, and 9 (37%) of 24 NSIP patients; deterioration was noted in six (21%) UIP-w/o hc patients, two (9%) UIP-w/i hc patients and three (13%) NSIP patients ({rho} 0.044 between UIP-w/o and UIP-w/i hc; {rho} = 0.637 between UIP-w/o hc and NSIP; {rho} = 0.007 between UIP-w/i hc and NSIP). The serial changes of the pulmonary function in the NSIP patients were different from those noted for the UIP-w/i hc and UIP-w/o hc patients ({rho} = 0.440 between UIP-w/o and UIP-w/i hc; {rho} = 0.022 between UIP-w/o hc and NSIP; {rho} =0.003 between UIP-w/i hc and NSIP). Five (14%) of the 35 patients with UIP-w/o hc, 16 (46%) of the 35 patients with UIP-w/i hc and three (12%) of the 25 patients with NSIP died ({rho} = 0.002, comparison for the three groups). On CT, NSIP and UIP-w/o hc patients have similar patterns of parenchymal abnormalities and

CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

International Nuclear Information System (INIS)

Lee, Chang Hyun; Lee, Hyun Ju; Son, Kyu Ri; Chun, Eun Ju; Lim, Kun Young; Goo, Jin Mo; Im, Jung Gi; Heo, Jeong Nam; Song, Jae Woo

2006-01-01

We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. We selected patients who suffered with UIP (n 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. The amount of anterior mediastinal fat was not different among the three groups (p 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-∞, p < 0.001) and UIP (OR = 24.42, CI 4.06-∞, p < 0.001). For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

Science.gov (United States)

Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

2014-01-01

Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

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Lee, Chang Hyun; Lee, Hyun Ju; Son, Kyu Ri; Chun, Eun Ju; Lim, Kun Young; Goo, Jin Mo; Im, Jung Gi [Seoul National University College of Medicine, Seoul (Korea, Republic of); Heo, Jeong Nam; Song, Jae Woo [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2006-09-15

We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. We selected patients who suffered with UIP (n 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. The amount of anterior mediastinal fat was not different among the three groups (p 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-{infinity}, p < 0.001) and UIP (OR = 24.42, CI 4.06-{infinity}, p < 0.001). For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat.

Hypersensitivity pneumonia-nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management.

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Jacobs, Robert L; Andrews, Charles P

2003-02-01

Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic

Recurrent nitrofurantoin-induced giant cell interstitial pneumonia: Case report and literature review

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Boeun Lee

2015-01-01

Full Text Available Giant cell interstitial pneumonia (GIP is a rare form of chronic interstitial pneumonia typically associated with hard metal exposure. Only two cases of GIP induced by nitrofurantoin have been reported in the medical literature. We are reporting a case of recurrent nitrofurantoin-induced GIP. Although extremely rare, GIP needs to be included in the differential diagnosis in patients with chronic nitrofurantoin use who present with respiratory illness.

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

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Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

2015-09-01

Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

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Anza B Memon

Full Text Available B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND, such as neuromyelitis optica (NMO, multiple sclerosis (MS, and myasthenia gravis (MG. Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE, serious adverse events (SAE, and malignancies were observed.There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months and 1 SAE was observed after 11 cycles (60 months of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

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Abdullateef Abdulkareem

2017-01-01

Full Text Available Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature.

Science.gov (United States)

Abdulkareem, Abdullateef; D'Souza, Ryan S; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

Nature of interstitially induced lattice strains

International Nuclear Information System (INIS)

Emin, D.

1978-01-01

The addition of interstitial atoms to a metal lattice has been likened to the addition of extra billiard balls to an array of tangentially touching billiard balls. In such a picture the increased clustering of interstitials can lead to the buildup of larger and larger strain fields which ultimately are associated with the production of broken bonds. Simple models of the strain fields associated with the addition of particles to a lattice in which the force exerted between the added atoms and host atoms is finite have been studied. From these studies one can define situations in which the billiard-ball approach has qualitative validity and those in which it is inappropriate. Basically, those situations in which the displacements of the host atoms can be represented as involving acoustic phonons yield long-range strain fields analogous to those of the billiard-ball model with the radius of the extra billiard ball being determined by the stiffness of the host lattice and the forces between the added atom and the surrounding host atoms. If the displacements produced by the added atoms are represented as involving primarily optical phonons the displacement pattern is short-ranged and not described by the usual elasticity theory. For example, Vegard's law does not apply in these instances. Such concerns arise in considering the strains induced by interstitial helium in tritides

High-resolution computed tomography to differentiate chronic diffuse interstitial lung diseases with predominant ground-glass pattern using logical analysis of data

International Nuclear Information System (INIS)

Martin, Sophie Grivaud; Brauner, Michel W.; Rety, Frederique; Kronek, Louis-Philippe; Brauner, Nadia; Valeyre, Dominique; Nunes, Hilario; Brillet, Pierre-Yves

2010-01-01

We evaluated the performance of high-resolution computed tomography (HRCT) to differentiate chronic diffuse interstitial lung diseases (CDILD) with predominant ground-glass pattern by using logical analysis of data (LAD). A total of 162 patients were classified into seven categories: sarcoidosis (n = 38), connective tissue disease (n = 32), hypersensitivity pneumonitis (n = 18), drug-induced lung disease (n = 15), alveolar proteinosis (n = 12), idiopathic non-specific interstitial pneumonia (n = 10) and miscellaneous (n = 37). First, 40 CT attributes were investigated by the LAD to build up patterns characterising a category. From the association of patterns, LAD determined models specific to each CDILD. Second, data were recomputed by adding eight clinical attributes to the analysis. The 20 x 5 cross-folding method was used for validation. Models could be individualised for sarcoidosis, hypersensitivity pneumonitis, connective tissue disease and alveolar proteinosis. An additional model was individualised for drug-induced lung disease by adding clinical data. No model was demonstrated for idiopathic non-specific interstitial pneumonia and the miscellaneous category. The results showed that HRCT had a good sensitivity (≥64%) and specificity (≥78%) and a high negative predictive value (≥93%) for diseases with a model. Higher sensitivity (≥78%) and specificity (≥89%) were achieved by adding clinical data. The diagnostic performance of HRCT is high and can be increased by adding clinical data. (orig.)

Drift forces on vacancies and interstitials in alloys with radiation-induced segregation

International Nuclear Information System (INIS)

Wolfer, W.G.

1983-01-01

Radiation-induced segregation in alloys leads to compositional gradients around point defect sinks such as voids and dislocations. These compositional gradients in turn affect the drift forces on both interstitials and vacancies and thereby modify the bias. Linear irreversible thermodynamics is employed to derive the total drift force on interstitials and vacancies in substitutional binary alloys. The obtained results are evaluated for binary Fe-Ni alloys. It is shown that radiation-induced segregation produces new drift forces which can be of the same order of magnitude as the stress-induced drift force produced by edge dislocations in an alloy with uniform composition. Hence, segregation results in a significant modification of the bias for void nucleation and swelling. The additional drift forces on interstitials and vacancies are due to the compositional dependence of the formation and migration energies; due to the dependence of the point defect's strain energy on the local elastic properties; due to a coherency strain field caused by lattice parameter variations; and finally due to the Kirkendall force produced by the difference in tracer mobilities. Estimates of these forces given for Fe-Ni alloys indicate that the Kirkendall force is small compared to the other segregation-induced forces on interstitials. In contrast, the Kirkendall force seems to be the dominant one for vacancies. (orig.)

Rituximab treatment for fibrillary glomerulonephritis.

Science.gov (United States)

Hogan, Jonathan; Restivo, Michaela; Canetta, Pietro A; Herlitz, Leal C; Radhakrishnan, Jai; Appel, Gerald B; Bomback, Andrew S

2014-10-01

Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Nonspecific interstitial pneumonia: Histologic correlation with high-resolution CT in 29 patients

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Sumikawa, Hiromitsu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan)], E-mail: h-sumikawa@radiol.med.osaka-u.ac.jp; Johkoh, Takeshi [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Department of Medical Physics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Ichikado, Kazuya [Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Tikami, Kumamoto 861-4193 (Japan); Taniguchi, Hiroyuki; Kondoh, Yasuhiro [Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto City, Aichi (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Yanagawa, Masahiro; Inoue, Atsuo; Mihara, Naoki; Honda, Osamu; Tomiyama, Noriyuki; Nakamura, Hironobu [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0825 (Japan); Colby, Thomas V. [Department of Pathology, Mayo Clinic, Scottsdale, AZ (United States)

2009-04-15

Purpose: To determine the pathological correlation with various high-resolution CT (HRCT) findings in cases with nonspecific interstitial pneumonia (NSIP), paying special attention to pathological subgroups. Material and methods: The study involved 29 patients diagnosed with NSIP by surgical lung biopsy. A total of 54 specimens were obtained and grouped according to Katzenstein's classification (groups 1-3) for NSIP. Two observers then evaluated the HRCT findings for every biopsy site and classified the findings according to the main pattern evident into the following four radiologic pattern groups: A, ground-glass attenuation and fine reticulation; B, ground-glass and coarse reticulation; C, consolidation and D, ground-glass attenuation and consolidation. Results: The pathological pattern was NSIP group 1 in 6 patients, group 2 in 22 and group 3 in 25, while 1 specimen was normal. The main HRCT pattern was pattern A in 15 specimens, B in 8, C in 9 and D in 21. Although there were no significant correlation between HRCT patterns and histological subgroups (Chi-square test, p = 0.07), pattern C was more frequently seen in group 2 (7 of 9) and pattern A was more common in group 3 (11 of 15). HRCT pattern A corresponded pathologically to areas of thickened alveolar septa with temporal uniformity. Pattern B correlated with areas with airspace enlargement/emphysema or dilation of small airways superimposed on thickened alveolar septa. Pattern C was pathologically associated with areas of severe thickened alveolar septa, mucin stasis in the small airways and intraluminal organization. Conclusion: The pathological backgrounds of the same CT findings in patients with NSIP varied among all pathological subgroups. Areas of ground-glass attenuation and air-space consolidation did not always correspond to reversible pathological findings.

Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

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De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

2018-03-01

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

Serial high resolution CT in non-specific interstitial pneumonia: prognostic value of the initial pattern

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Screaton, N.J. [Department of Radiology, Addenbrooke' s Hospital, Cambridge (United Kingdom)]. E-mail: nicholas.screaton@papworth.nhs.uk; Hiorns, M.P. [Department of Radiology, Great Ormond Street Hospital, London (United Kingdom); Lee, K.S. [Samsung Medical Centre, Seoul (Korea); Franquet, T. [Hospital de Saint Pau, Universidad Autonoma de Barcelona, Barcelona (Spain); Johkoh, T. [Department of Medical Physics and Radiology, Osaka University Graduate School of Medicine, Osaka (Japan); Fujimoto, K. [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Ichikado, K. [First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto (Japan); Colby, T.V. [Department of Laboratory Medicine/Pathology, Mayo Clinic Scottsdale, AZ (United States); Mueller, N.L. [Department of Radiology, Vancouver General Hospital, Vancouver (Canada)

2005-01-01

AIM: To assess the relationship between initial CT pattern and serial changes in CT findings and pulmonary function tests (PFTs) in patients with non-specific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Serial high resolution (HR) CTs and PFTs were retrospectively analyzed in 38 cases of histologically proven NSIP, including 4 with cellular NSIP, 13 with mixed cellular and fibrotic NSIP, and 21 with fibrotic NSIP. The presence and extent of various CT findings were assessed. A fibrosis index (defined as the ratio of the extent of a reticular/honeycomb pattern to the overall extent of abnormal parenchyma) was derived. RESULTS: The predominant CT pattern was reticular/honeycomb in 27 (84%) cases and ground-glass/consolidation in 6 (16%) cases. Between scans, mean disease extent reduced by 5.2%. Disease extent reduced by >10% in 13 (34%) and increased by >10% in 6 (16%) patients. Histopathological subtype of NSIP did not correlate with individual CT pattern, predominant pattern, fibrosis index or serial change in disease extent on CT or PFTs. Response on follow-up CT was associated with fibrosis index, predominant pattern and extent of consolidation on initial CT. CONCLUSION: In NSIP disease, progression on CT correlates with the predominant CT pattern, fibrosis index, and extent of consolidation but not with histopathological subtype. An inflammatory (ground-glass/consolidation) predominant pattern is associated with better outcome in terms of disease extent on HRCT.

Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity.

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Hamilton, Jennifer R; Sachs, David; Lim, Jean K; Langlois, Ryan A; Palese, Peter; Heaton, Nicholas S

2016-04-05

A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not been fully studied. Because IAV has long been characterized as a cytopathic virus (based on its ability to rapidly lyse most cell types in culture), it has been a forgone conclusion that directly infected cells could not be contributing to this effect. Using a Cre recombinase-expressing IAV, we have previously shown that club cells can survive direct viral infection. We show here not only that these cells can eliminate all traces of the virus and survive but also that they acquire a heightened antiviral response phenotype after surviving. Moreover, we experimentally demonstrate temporary nonspecific viral immunity after IAV infection and show that surviving cells are required for this phenotype. This work characterizes a virally induced modulation of the innate immune response that may represent a new mechanism to prevent viral diseases.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

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Abdulkareem, Abdullateef; D’Souza, Ryan S.; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrob...

Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

Science.gov (United States)

Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

2014-10-15

Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

Science.gov (United States)

Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Pulmonary interstitial glycogenosis in the setting of lung growth abnormality: radiographic and pathologic correlation

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Castillo, Monette; Vade, Aruna; Lim-Dunham, Jennifer Eden [Loyola University Health System, Department of Radiology, Maywood, IL (United States); Masuda, Emi [Henry Ford Hospital, Department of Radiology, Detroit, MI (United States); Massarani-Wafai, Rasan [Loyola University Health System, Department of Pathology, Maywood, IL (United States)

2010-09-15

Pulmonary interstitial glycogenosis (PIG) is a rare pediatric interstitial lung disease. We report a case of a term boy presenting with tachypnea at birth requiring supplemental oxygen. Chest radiographs followed by high-resolution CT (HRCT) demonstrated hyperinflation and diffuse interstitial markings interspersed with multiple cystic spaces. An open lung biopsy demonstrated a minor component of PIG superimposed upon poor alveolarization. PIG in the setting of lung growth abnormality might be more common than previously described. Additionally, radiographic findings associated with most pediatric interstitial lung diseases are nonspecific, and histopathologic correlation is essential for diagnosis. (orig.)

Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

Directory of Open Access Journals (Sweden)

Pradnya J Londhe

2014-01-01

Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Interstitial lung disease: Diagnostic approach

OpenAIRE

Kaushik Saha

2014-01-01

Interstitial lung disease (ILD) is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion) and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiolo...

Progress in immunotherapy Rituximab

International Nuclear Information System (INIS)

El-Habbash, Manal M.; Alwindi, Abukris M.

2007-01-01

Rituximab is an anti-CD-20 chimeric monoclonal antibody that has shown substantial activity. Since its discovery, rituximab has been used with great success in a variety of hematological malignancies. Its success in the management of aggressive lymphomas led to expansion of its use in other conditions such as stem cell transplantation, post- transplant lymphoproliferative disorder, and other non-malignant conditions where B cell activation is thought to be important, such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. The side effects have been remarkably few, particularly, infection is not more common that chemotherapy alone. This article reviews the structure, mechanism of action and uses of rituximab as monotherapy or in combination with chemotherapy. (author)

Comparison of Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia: Quantification of Disease Severity and Discrimination between Two Diseases on HRCT Using a Texture-Based Automated System

Energy Technology Data Exchange (ETDEWEB)

Park, Sang Ok; Kim, Dong Soon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Young Kyung [East-West Neo Medical Center of Kyung Hee University, Seoul (Korea, Republic of); Lee, Jeong Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

2011-06-15

To evaluate the usefulness of an automated system for quantification and discrimination of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). An automated system to quantify six regional high-resolution CT (HRCT) patterns: normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EMPH; and consolidation, CONS, was developed using texture and shape features. Fifty-four patients with pathologically proven UIP (n = 26) and pathologically proven NSIP (n 28) were included as part of this study. Inter-observer agreement in measuring the extent of each HRCT pattern between the system and two thoracic radiologists were assessed in 26 randomly selected subsets using an interclass correlation coefficient (ICC). A linear regression analysis was used to assess the contribution of each disease pattern to the pulmonary function test parameters. The discriminating capacity of the system between UIP and NSIP was evaluated using a binomial logistic regression. The overall ICC showed acceptable agreement among the system and the two radiologists (r = 0.895 for the abnormal lung volume fraction, 0.706 for the fibrosis fraction, 0.895 for NL, 0.625 for GGO, 0.626 for RO, 0.893 for HC, 0.800 for EMPH, and 0.430 for CONS). The volumes of NL, GGO, RO, and EMPH contribute to forced expiratory volume during one second (FEV1) (r = 0.72, {beta} values, 0.84, 0.34, 0.34 and 0.24, respectively) and forced vital capacity (FVC) (r 0.76, {beta} values, 0.82, 0.28, 0.21 and 0.34, respectively). For diffusing capacity (DLco), the volumes of NL and HC were independent contributors in opposite directions (r = 0.65, {beta} values, 0.64, -0.21, respectively). The automated system can help discriminate between UIP and NSIP with an accuracy of 82%. The automated quantification system of regional HRCT patterns can be useful in the assessment of disease severity and may provide reliable agreement with the radiologists' results. In

Comparison of usual interstitial pneumonia and nonspecific interstitial pneumonia: quantification of disease severity and discrimination between two diseases on HRCT using a texture-based automated system.

Science.gov (United States)

Park, Sang Ok; Seo, Joon Beom; Kim, Namkug; Lee, Young Kyung; Lee, Jeongjin; Kim, Dong Soon

2011-01-01

To evaluate the usefulness of an automated system for quantification and discrimination of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). An automated system to quantify six regional high-resolution CT (HRCT) patterns: normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EMPH; and consolidation, CONS, was developed using texture and shape features. Fifty-four patients with pathologically proven UIP (n = 26) and pathologically proven NSIP (n = 28) were included as part of this study. Inter-observer agreement in measuring the extent of each HRCT pattern between the system and two thoracic radiologists were assessed in 26 randomly selected subsets using an interclass correlation coefficient (ICC). A linear regression analysis was used to assess the contribution of each disease pattern to the pulmonary function test parameters. The discriminating capacity of the system between UIP and NSIP was evaluated using a binomial logistic regression. The overall ICC showed acceptable agreement among the system and the two radiologists (r = 0.895 for the abnormal lung volume fraction, 0.706 for the fibrosis fraction, 0.895 for NL, 0.625 for GGO, 0.626 for RO, 0.893 for HC, 0.800 for EMPH, and 0.430 for CONS). The volumes of NL, GGO, RO, and EMPH contribute to forced expiratory volume during one second (FEV₁) (r = 0.72, β values, 0.84, 0.34, 0.34 and 0.24, respectively) and forced vital capacity (FVC) (r = 0.76, β values, 0.82, 0.28, 0.21 and 0.34, respectively). For diffusing capacity (DL(co)), the volumes of NL and HC were independent contributors in opposite directions (r = 0.65, β values, 0.64, -0.21, respectively). The automated system can help discriminate between UIP and NSIP with an accuracy of 82%. The automated quantification system of regional HRCT patterns can be useful in the assessment of disease severity and may provide reliable agreement with the radiologists' results. In addition, this

Discovery – Development of Rituximab

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NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

Non-specific immunization against babesiosis

International Nuclear Information System (INIS)

Cox, F.E.G.

1980-01-01

The rodent babesias, Babesia rodhaini and the less virulent B. microti, are useful models with which to study immunity to and immunization against babesiosis. In contrast with the difficulty in inducing specific immunity to these parasites it is comparatively easy to induce non-specific immunity by prior exposure to related and unrelated intra-erythrocytic protozoa, micro-organisms such as Mycobacterium bovis (BCG) and Corynebacterium parvum, microbial extracts and muramyl dipeptide. This non-specific immunity is long lasting and extremely effective. It is characterized by the facts that (a) it occurs early in the infection at the height of the first peak of parasitaemia, and (b) it involves the intra-erythrocytic death of the parasites. After the primary parasitaemia has resolved, some parasites continue to persist at a low level and when introduced into clean mice produce only low-level 'attenuated' infections in these. Non-specific immunity is not equally effective in all strains of mice. It is suggested that immunity to babesiosis, and infections caused by other intra-erythrocytic protozoa, involves two mechanisms, the first non-specific and the second specific. The actual balance between these two mechanisms varies from parasite to parasite and from host to host. An effective vaccine would have to be based on an understanding of the roles of non-specific immunity in the actual disease under consideration, and would ideally combine an adjuvant that would also stimulate non-specific immunity and an attenuated strain of parasite that would induce a specific response. (author)

FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot Study

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Jacquelin, V. [AP-HP, Hosp. Avicenne, Department of Nuclear Medicine, Bobigny (France); Mekinian, A. [AP-HP, Hosp. Saint-Antoine, Department of Internal Medicine and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris (France); Brillet, P.Y. [AP-HP, Hosp. Avicenne, Department of Radiology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Nunes, H. [AP-HP, Hosp. Avicenne, Department of Pneumology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Fain, O. [AP-HP, Hosp. Saint-Antoine, Department of Internal Medicine and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris (France); Valeyre, D. [AP-HP, Hosp. Avicenne, Department of Pneumology, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France); Soussan, M., E-mail: michael.soussan@aphp.fr [AP-HP, Hosp. Avicenne, Department of Nuclear Medicine, Bobigny (France); Univ. Paris 13, Sorbonne Paris Cité, Bobigny (France)

2016-12-15

Purpose: Our study aimed to analyse the characteristics of nonspecific interstitial pneumonia (NSIP) using FDG-PET/CT (PET) and to evaluate its ability to predict the therapeutic response. Procedures: Eighteen NSIP patients were included. Maximum standardized uptake value (SUV{sub max}), FDG uptake extent (in percentage of lung volume), high resolution CT scan (HRCT) elementary lesions, and HRCT fibrosis score were recorded. The predictive value of the parameters for lung function improvement was evaluated using logistic regression and Receiver Operating Characteristic (ROC) curve analysis (n = 13/18). Results: All patients had an increased pulmonary FDG uptake (median SUV{sub max} = 3.1 [2–7.6]), with a median extent of 19% [6–67]. Consolidations, ground-glass opacities, honeycombing and reticulations showed uptake in 90%, 89%, 85% and 76%, respectively. FDG uptake extent was associated with improvement of pulmonary function under treatment (increase in forced vital capacity > 10%, p = 0.03), whereas SUV{sub max} and HRCT fibrosis score were not (p > 0.5). For FDG uptake extent, ROC analysis showed an area under the curve at 0.85 ± 0.11 and sensitivity/specificity was 88%/80% for a threshold fixed at 21%. Conclusions: Increased FDG uptake was observed in all NSIP patients, both in inflammatory and fibrotic HRCT lesions. The quantification of FDG uptake extent might be useful to predict functional improvement under treatment.

FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A Pilot Study

International Nuclear Information System (INIS)

Jacquelin, V.; Mekinian, A.; Brillet, P.Y.; Nunes, H.; Fain, O.; Valeyre, D.; Soussan, M.

2016-01-01

Purpose: Our study aimed to analyse the characteristics of nonspecific interstitial pneumonia (NSIP) using FDG-PET/CT (PET) and to evaluate its ability to predict the therapeutic response. Procedures: Eighteen NSIP patients were included. Maximum standardized uptake value (SUV max ), FDG uptake extent (in percentage of lung volume), high resolution CT scan (HRCT) elementary lesions, and HRCT fibrosis score were recorded. The predictive value of the parameters for lung function improvement was evaluated using logistic regression and Receiver Operating Characteristic (ROC) curve analysis (n = 13/18). Results: All patients had an increased pulmonary FDG uptake (median SUV max = 3.1 [2–7.6]), with a median extent of 19% [6–67]. Consolidations, ground-glass opacities, honeycombing and reticulations showed uptake in 90%, 89%, 85% and 76%, respectively. FDG uptake extent was associated with improvement of pulmonary function under treatment (increase in forced vital capacity > 10%, p = 0.03), whereas SUV max and HRCT fibrosis score were not (p > 0.5). For FDG uptake extent, ROC analysis showed an area under the curve at 0.85 ± 0.11 and sensitivity/specificity was 88%/80% for a threshold fixed at 21%. Conclusions: Increased FDG uptake was observed in all NSIP patients, both in inflammatory and fibrotic HRCT lesions. The quantification of FDG uptake extent might be useful to predict functional improvement under treatment.

Non-specific immunization against parasites

International Nuclear Information System (INIS)

Cox, F.E.G.

1981-01-01

Non-specific resistance to tumours can be induced by pretreating animals with micro-organisms, microbial extracts or various synthetic substances. Mycobacterium bovis, Corynebacterium parvum and a number of other micro-organisms also protect mice against rodent piroplasms and there is evidence that they are also protective against other parasites including Schistosoma mansoni. The actual mechanisms of non-specific immunity are still unclear but it is influenced by both the genetic make-up of the host and the nature of the parasite. Non-specific immunization may be a possible alternative to specific immunization and may avoid many of the potential immunopathological changes induced during parasite infections. Irradiated vaccines (Dictyocaulus viviparus, schistomiasis) are mentioned marginally only

Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

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Elham Vali Khojeini

2014-01-01

Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

Science.gov (United States)

Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

2015-01-01

Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

Internalisation of uncross-linked rituximab is not essential for the induction of caspase-independent killing in Burkitt lymphoma cell lines.

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Turzanski, Julie; Daniels, Ian; Haynes, Andrew P

2008-08-01

Characterising the mechanisms underpinning caspase-independent programmed cell death (CI-PCD) induction by uncross-linked rituximab in B-cells may positively impact upon the treatment of disease states in which the classical apoptotic pathway is disabled. The necessity of rituximab internalisation for CI-PCD induction was investigated by flow cytometry and confocal microscopy in human BL cell lines with (e.g. Mutu I) and without (Mutu III) susceptibility to rituximab-induced killing. Flow cytometry demonstrated small, significant and similar amounts of rituximab internalisation by Mutu I cells after 1, 2, 4 and 24 h (p internalisation (p = 0.02, n = 5 and p = 0.0002, n = 6, respectively) in Mutu I cells, but confocal microscopy showed no correlation between internalised rituximab and phosphatidylserine exposure. We conclude that rituximab internalisation is not essential for CI-PCD induction in BL cell lines.

Rituximab (MabThera) til behandling af aktiv reumatoid artritis

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

2006-01-01

Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

Study on the Preparation and Quality Control of 131I-Rituximab and 90Y-Rituximab for Non-Hodgkin-Lymphoma Therapy

International Nuclear Information System (INIS)

NguyenThi Thu; Duong Van Dong; Vo Thi Cam Hoa; Chu Van Khoa; Bui Van Cuong; Pham Ngoc Dien; Mai Phuoc Tho; Nguyen Thanh Binh; Dang Ho Hong Quang; Phan Quoc Thong; Mai Trong Khoa

2009-01-01

In recent years, radioimmunotherapy (RIT) has become a highly promising oncologic therapeutic modality with established clinically efficacy, particularly in the therapy of haematological malignancies. Rituximab, a chimeric monoclonal antibody targeted against the cluster designation (CD20) antigen was labelled with 131 I used in the treatment of B cell non Hodgkin's Lymphoma (NHL), B cell leukemia. In this study, the monoclonal antibody Rituximab was labelled with 131 I using chloramin T method (ChT). The optimized ChT concentration for the oxidation of 185 MBq of Na 131 I solution and 750□g of Rituximab was 20□g/20□l. The reaction time was 3 minutes at room temperature. The labeling reaction has stopped using sodiummetabisulphite (SMB). Labelling efficacy was controlled by ITLC. The reaction mixture was purified through the Sephadex G-25 PD10 Pharmacia column. The collected 131 I-Rituximab was filtered through a 0.20'm milipore sterile filter. The radiochemical labeling yield was more than 95%. Radiochemical purity of the radiopharmaceutical after purification was more than 99%. The product has been passed the test for sterility, bacterial endotoxins, to be sufficiency invivo and invitro stable and stability after labeling. 131 I-Rituximab was used for radioimmunoscintigraphy biodistribution in clinical. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 min. Rituximab solution in 0.05M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5mg/ml and 10mg/ml) was coupled with the cyclic DTPA anhydride, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation DTPA-Rituximab mixture was labelled with Y- 90 and purified and determinate of coupling efficiency. Coupling efficiency of cDTPA - to - Rituximab molar

Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

International Nuclear Information System (INIS)

Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

2010-01-01

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

Preparation & in vitro evaluation of 90Y-DOTA-rituximab

Science.gov (United States)

Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

Rituximab-related viral infections in lymphoma patients.

Science.gov (United States)

Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

2007-07-01

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Levetiracetam-induced interstitial nephritis in a patient with glioma.

Science.gov (United States)

Mahta, Ali; Kim, Ryan Y; Kesari, Santosh

2012-01-01

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enfermedad pulmonar intersticial asociada a rituximab

Directory of Open Access Journals (Sweden)

Marcelo Fernández Casares

2013-08-01

Full Text Available La introducción en la práctica clínica del anticuerpo anti-CD20 rituximab ha mejorado sustancialmente el pronóstico de diversas enfermedades autoinmunes y hematológicas. Con el incremento de su uso ha aumentado el registro de efectos adversos, entre ellos la toxicidad pulmonar. Una de sus complicaciones más serias es la enfermedad pulmonar intersticial, entidad potencialmente fatal que debe ser considerada en pacientes que han recibido rituximab y presentan disnea, fiebre y tos sin clara evidencia de infección. Presentamos un caso de enfermedad pulmonar intersticial asociada a rituximab.

Rituximab for nephrotic syndrome in children.

Science.gov (United States)

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai

2017-04-01

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

Desensitization to rituximab in a multidisciplinary setting.

Science.gov (United States)

Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

2015-10-01

The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

Lupus nephritis, pregnancy and rituximab

Directory of Open Access Journals (Sweden)

Enrique Dorado

2017-04-01

Full Text Available La nefritis lúpica (NL proliferativa es una de las complicaciones más graves del LES. La respuesta terapéutica con los esquemas clásicos no existe en el 20 al 70% de los casos, siendo la amplitud de dicho rango explicada por variaciones étnicas, falta de consenso en la definición de remisión, diferencias en los tiempos de tratamiento, seguimiento y en la clase de NL. En presencia de NL recidivante o refractaria los tratamientos y el nivel de evidencia sobre su eficacia son más limitados. Rituximab es un anticuerpo monoclonal quimérico (ratón-humano dirigido contra el antígeno CD 20 localizado en la superficie celular de los linfocitos B. Estos participan en la patogénesis del LES a partir de su maduración en células plasmáticas, producción de anticuerpos, secreción de citoquinas proinflamatorias, presentación de autoantígenos a las células T y en la activación de células T. La administración de rituximab genera un rápido y sostenido descenso de los linfocitos B CD 20+ circulantes y una reducción de los títulos de auto-anticuerpos. Se reportó una disminución significativa en los niveles de antiDNA a partir de la semana 14 y de los niveles de IgM, sin compromiso de IgG ni de IgA. Se detectó droga activa en sangre periférica luego de la semana 24 de la última infusión. La depleción de linfocitos B se puede mantener por 6 meses, su reconstitución es heterogénea y puede tardar más de un año. Esta linfopenia selectiva tendría un valor predictivo de respuesta terapéutica, la remisión clínica prolongada tendría asociación con repoblación incompleta de células B de memoria varios años luego del tratamiento. En estudios observacionales realizados en pacientes con NL refractaria se reportó respuesta terapéutica con rituximab entre 67-77 % luego de 6 a 12 meses de seguimiento. Sin embargo los resultados del estudio Lupus Nephritis Assesment with Rituximab (LUNAR, randomizado controlado, a doble ciego

Clinical evaluation of rituximab treatment for neuromyelitis optica.

Science.gov (United States)

Fernández-Megía, M J; Casanova-Estruch, B; Pérez-Miralles, F; Ruiz-Ramos, J; Alcalá-Vicente, C; Poveda-Andrés, J L

2015-10-01

Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Detection and quantification of rituximab in the human urine.

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Jacobs, Roland; Langer-Jacobus, Thais; Duong, Michelle; Stahl, Klaus; Haller, Hermann; Schmidt, Reinhold E; Schiffer, Mario

2017-12-01

B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707μg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab.

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Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the

Interstitial lung diseases with fibrosis - the pattern at high resolution

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Jarzemska, A.; Lasek, W.; Nawrocka, E.; Meder, G.; Zapala, M.

2003-01-01

Surgical lung biopsy, either open thoracotomy or video-assisted thoracoscopy is recommended in the diagnosis of interstitial lung diseases (ILD). In some cases, however, the repetitive pattern of radiological features in high-resolution computed tomography is often sufficient to confirm the diagnosis in a non-invasive manner. The purpose of the study was to determine whether patients with ILD can be selected on the basis of the HRCT pattern. Thin-section CT scans were performed in 40 patients with histologically proven idiopathic interstitial pneumonia (26 patients with usual interstitial pneumonia UIP, 2 patients with desquamative interstitial pneumonia DIP, 2 patients with bronchiolitis obliterans organizing pneumonia BOOP, 2 patients with non-specific interstitial pneumonia NSIP, 11 patients with hypersensitivity pneumonitis, and 3 patients with pulmonary histiocytosis X). The location and the intensity of lesions were taken into consideration. Clinical and histopathological findings were compared. HRCT features of interstitial lung diseases such as nodules and cystic spaces in hypersensitivity pneumonitis and pulmonary histiocytosis, and ground-glass opacities in idiopathic interstitial pneumonias (IIP) were statistically significant for differential diagnosis in ILD cases. Combination of honeycombing and ground-glass opacities found in UIP and nodules found in DIP were also statistically significant features in IIP subtypes diagnosis. In some cases, HRCT patterns of hypersensitivity pneumonitis, pulmonary histiocytosis X and IPF combined with clinical findings allowed for the accurate diagnosis without resorting to lung biopsy. Within a group of idiopathic interstitial pneumonia only in usual interstitial pneumonia characteristic pattern in thin-section CT can be defined. In other subgroups some typical features can imply a diagnosis. (author)

Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

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De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

2016-01-01

Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

Rituximab: An emerging therapeutic agent for kidney transplantation

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Joseph Kahwaji

2009-10-01

Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In

Immunotherapy with rituximab in follicular lymphomas.

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Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

2011-04-01

Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

Rituximab in treatment of idiopathic glomerulopathy

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Kamel El-Reshaid

2012-01-01

Full Text Available The aim of our study was to assess the role of rituximab (Mabthera in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS. A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD group, 31 of the 32 patients had complete remission (CR and were off any immunosuppressive therapy and one of the previous non-responders (NR did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months. Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS, while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG, 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab

B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

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S. Marinaki

2013-12-01

Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.

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Yves Allenbach

Full Text Available Anti-synthetase syndrome (anti-SS is frequently associated with myositis and interstitial lung disease (ILD. We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants. They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles at M12. Secondary endpoints were normalization of creatine kinase (CK level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point. Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718 to 74.5 IU/L (range, 40-47,857. Corticosteroid doses decreased from 52.5 mg/d (range, 10-70 to 9 mg/d (range, 7-65 and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.Clinicaltrials.gov NCT00774462.

Fluctuations of electrical and mechanical properties of diamond induced by interstitial hydrogen

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Zhuang, Chun-Qiang; Liu, Lei

2015-01-01

While experimental evidence demonstrates that the presence of hydrogen (H) impurities in diamond films plays a significant role in determining their physical properties, the small radius of the H atom makes detecting such impurities quite a challenging task. In the present work, first-principles calculations were employed to provide an insight into the effects of the interstitial hydrogen on the electrical and mechanical properties of diamond crystals at the atomic level. The migrated pathways of the interstitial hydrogen are dictated by energetic considerations. Some new electronic states are formed near the Fermi level. The interstitial hydrogen markedly narrows the bandgap of the diamond and weakens the diamond crystal. The obvious decrement of the critical strain clearly implies the presence of an H-induced embrittlement effect. Project supported by the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality, China (Grant No. IDHT20140504), the National Natural Science Foundation of China (Grant No. 51402009), and the Foundation for Young Scholars of Beijing University of Technology, China.

A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

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Solal-Céligny, Philippe; Leconte, Pierre; Bardet, Aurélie; Hernandez, Juana; Troussard, Xavier

2018-01-01

Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if management and for the design of clinical trials in these patients. © 2017 John Wiley & Sons Ltd.

Rituximab and chemotherapy in diffuse large B-cell lymphoma.

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Sonet, Anne; Bosly, André

2009-06-01

Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

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E. I. Alexeeva

2013-01-01

Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

MR imaging and histopathologic correlations of thermal injuries induced by interstitial laser applications

International Nuclear Information System (INIS)

Anzai, Y.; Lufkin, R.B.; Castro, D.J.; Farahani, K.; Chen, H.W.; Hirchowiz, S.

1991-01-01

Interstitial laser phototherapy for deep-seated tumors may become an attractive therapeutic modality when a noninvasive, accurate monitoring system is developed. In this paper, to devaluate the ability of MR imaging to differentiate reversible and irreversible thermal injuries induced by laser therapy, the precise correlation of MR and histopathologic findings are investigated in the in vivo model. Nd:YAG lasers were applied to normal musculature of rabbits, and MR examinations were performed immediately after laser exposure and followed up for up to 10 weeks. The sequential MR images were correlated with histopathologic findings. T2-weighted MR imaging clearly showed laser-induced thermal injuries on any postoperative day. MR imaging of acute thermal injuries showed a central cavity, low-signal zone of coagulative necrosis and a peripheral high-signal layer of interstitial edema. The infiltration of neutrophils followed by fibrovascular response was identified on the marginal edema layer after 6 postoperative days

Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

International Nuclear Information System (INIS)

Kim, Tae Gyu; Shin, Eun A; Kim, Joung Sook

2010-01-01

The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

Mixed Herbal Medicine Induced Diffuse Infiltrative Lung Disease: The HRCT and Histopathologic Findings

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Kim, Tae Gyu; Shin, Eun A [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Joung Sook [Mokdong Hospital, Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

2010-12-15

The purpose of this study was to evaluate the high-resolution CT (HRCT) and pathologic findings of mixed herbal medicine-induced diffuse interstitial lung disease. Eight patients (6 women and 2 men, age range: 31 to 81 years, mean age: 51.4 years) who presented with cough or dyspnea after taking mixed herbal medicine were included in this study. All the patients underwent plain chest radiography and HRCT. We obtained pathologic specimens from 7 patients via fluoroscopy guided large bore cutting needle biopsy and transbronchial lung biopsy. All the patients were treated with steroid therapy. The most common HRCT finding was bilateral diffuse ground glass opacity (n=7), followed by peribronchial consolidation (n=5) and inter- or intralobular septal thickening (n=2). For the disease distribution, the lower lung zone was dominantly involved. The pathologic results of 7 patients were nonspecific interstitial pneumonia (n=3), bronchiolitis obliterans organizing pneumonia (n=2), hypersensitivity pneumonitis (n=1) and eosinophilic pneumonia (n=1). Irrespective of the pathologic results, all 8 patients improved clinically and radiologically after steroid treatment. The HRCT findings of mixed herbal medicine-induced diffuse infiltrative lung disease were mainly bilateral diffuse ground glass opacity, peribronchial consolidation and dominant involvement of the lower lung zone. Those pathologic findings were nonspecific and the differential diagnosis could include interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis and eosinophilic pneumonia

Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

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Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

2011-03-01

The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

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Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

2018-03-05

This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.

Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.

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Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik

2017-06-01

Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.

Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation.

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Kyung Min Kim

Full Text Available Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif, a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

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Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-05-01

Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

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Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

2014-09-01

Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

A Case of Yellow Nail Syndrome Accompanying Idiopathic Interstitial Pneumonia; Successful Treatment with Clarithromycin, Methylprednisolone, and Alpha-Tocopherol

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Bilge Yılmaz Kara

2017-12-01

Full Text Available A 51-year-old woman presented with complaints of dyspnea, fatigue, and non-productive cough. Chest X-ray showed bilateral lung infiltrates. Nonspecific air-space consolidation on anterior segment of the right lower lobe, bilateral bronchiectasis and infiltrates, patchy ground-glass opacities, and interstitial thickening were reported on thorax computed tomography which was non-responsive to antibiotics. After tru-cut biopsy which only revealed a single granuloma in a particular area, alveolar septal thickening and fibrosis, slight chronic inflammation with findings of congestion, lung involvement was considered to be associated with nonspecific interstitial pneumonia. The nails on all fingers displayed yellow discoloration with mild edema in the face and the legs. The final diagnosis was yellow nail syndrome. Short-term clarithromycin and long-term oral methylprednisolone with vitamin E treatment were successful. After 4 months, all components of the syndrome almost completely regressed.

Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

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Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-01-01

Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

Myxoviruses do not induce non-specific alterations in membrane permeability early on in infection

International Nuclear Information System (INIS)

Foster, K.A.; Micklem, K.J.; Bogomolova, N.N.; Boriskin, Y.S.; Pasternak, C.A.

1983-01-01

The permeability characteristics of cells infected with myxoviruses have been studied by measuring the concentrative uptake of nutrients, the concentration of intracellular K + , and the maintenance of the Na + gradient across the plasma membrane. Cells either show no change at all (Sendai virus-infected BHK cells and measles virus-infected Vero cells) or they show a decreased ability to concentrate nutrients, while intracellular K + and the Na + gradient remain unchanged (Sendai and influenza virus-infected L-1210 cells, measles virus-infected lymphocytes and mumps virus-infected L-41 cells). In no case, therefore, was a change observed that resembles the non-specific increase in membrane permeability induced by haemolytic paramyxoviruses (35, 42) or the non-specific membrane leakiness postulated to take place in infected cells (8, 9). A preliminary account of some of these findings has been presented (39)

Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

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Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

2018-04-01

We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

Rituximab in anti-GBM disease: A retrospective study of 8 patients.

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Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

2015-06-01

Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interstitial lung involvement in rheumatoid arthritis

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David Vladimirovich Bestaev

2014-01-01

Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and extraarticular manifestations. Pulmonary involvement is one of the common extraarticular manifestations of RA and may show itself as bronchial tree lesions, rheumatoid nodules, Caplan's syndrome, and lesions in the pleura or pulmonary interstitium (interstitial lung involvement (ILI. High-resolution computed tomography allows the diagnosis of ILI in RA in nearly 70% of cases although the incidence of ILI may be lower (4 to 30% depending on diagnostic methods and patient selection criteria. There are several histopathological types of ILI, the differential diagnosis of which can be troublesome. Usual interstitial pneumonia (UIP and nonspecific interstitial pneumonia are major types of RA-associated ILI. UIP-pattern ILI has a more severe course than ILI with other histological patterns. The clinical presentation of ILI may be complicated by the likely toxic effect of a number of disease-modifying antirheumatic drugs (DMARDs used to treat RA, such as methotrexate and leflunomide, and biological agents (BAs, tumor necrosis factor-α (TNF-α inhibitors. The pathogenesis of pulmonary involvement in RA and the role of synthetic DMARDs and BAs in the development of ILI call for further investigations.An extraarticular manifestation, such as ILI, affects the choice of treatment policy in patients with RA.The relevance of a study of ILI is beyond question. The paper discusses the state-of-the-art of investigations in this area.

Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

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Klepfish, A; Rachmilevitch, E; Schattner, A

2006-11-01

A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

Directory of Open Access Journals (Sweden)

Mohit Dogra

2018-01-01

Full Text Available We report a case of progressive outer retinal necrosis (PORN in a patient of microscopic polyangitis (MPA, being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys.

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Li, Zhiming; Tasan, Cemal Cem; Springer, Hauke; Gault, Baptiste; Raabe, Dierk

2017-01-12

High-entropy alloys (HEAs) consisting of multiple principle elements provide an avenue for realizing exceptional mechanical, physical and chemical properties. We report a novel strategy for designing a new class of HEAs incorporating the additional interstitial element carbon. This results in joint activation of twinning- and transformation-induced plasticity (TWIP and TRIP) by tuning the matrix phase's instability in a metastable TRIP-assisted dual-phase HEA. Besides TWIP and TRIP, such alloys benefit from massive substitutional and interstitial solid solution strengthening as well as from the composite effect associated with its dual-phase structure. Nanosize particle formation and grain size reduction are also utilized. The new interstitial TWIP-TRIP-HEA thus unifies all metallic strengthening mechanisms in one material, leading to twice the tensile strength compared to a single-phase HEA with similar composition, yet, at identical ductility.

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

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Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

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Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

Computer simulation of strain-induced ordering in interstitial solutions based on the b.c.c. Ta lattice

International Nuclear Information System (INIS)

Blanter, M.S.; Khachaturyan, A.G.

1980-01-01

A computer simulation is made of strain-induced ordering of interstitial atoms within octahedral interstices in the Ta host lattice. The calculation technique allows to take into account infinite-range strain-induced interaction. Computer simulation of ordering process enables to model the sequence of structure changes which occur during the ordering process and to find the equilibrium structure of the stable interstitial superstructures. The structures of high-temperature ordering phases obtained by the method of static concentration waves coincide with those obtained by means of computer simulation. However computer simulation enables to predict the structures of low-temperature ordered phases which cannot be obtained by the method of concentration waves. Comparison of computer simulation results and structures of observed ordered phases demonstrates good agreement. (author)

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

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Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

2017-01-01

Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.

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Stolz, Claudia; Schuler, Martin

2009-06-01

The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.

Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

Science.gov (United States)

Zara, Gabriella; Zambello, Renato; Ermani, M

2011-12-01

Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Eficiency of different doses of rituximab in rheumatoid arthritis.

Science.gov (United States)

Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

2016-01-01

Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

Directory of Open Access Journals (Sweden)

Klaus Stahl

2017-01-01

Full Text Available Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma

Directory of Open Access Journals (Sweden)

Aguiar-Bujanda D

2015-10-01

Full Text Available David Aguiar-Bujanda, María Jesús Blanco-Sánchez, María Hernández-Sosa, Saray Galván-Ruíz, Samuel Hernández-Sarmiento Department of Medical Oncology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain Abstract: Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL, both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life. Keywords: follicular lymphoma, long-term efficacy, maintenance, rituximab, toxicity

Interstitial lung disease induced by fluoxetine: Systematic review of literature and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance database.

Science.gov (United States)

Deidda, Arianna; Pisanu, Claudia; Micheletto, Laura; Bocchetta, Alberto; Del Zompo, Maria; Stochino, Maria Erminia

2017-06-01

We investigated a pulmonary adverse drug reaction possibly induced by fluoxetine, the Interstitial Lung Disease, by performing a systematic review of published case reports on this subject, a review of the World Health Organization VigiAccess database, of the European EudraVigilance database and of a national Pharmacovigilance database (Italian Pharmacovigilance Network). The research found a total of seven cases linking fluoxetine to Interstitial Lung Disease in the literature. 36 cases of interstitial lung disease related to fluoxetine were retrieved from the VigiAccess database (updated to July 2016), and 36 reports were found in EudraVigilance database (updated to June 2016). In the Italian Pharmacovigilance database (updated to August 2016), we found only one case of Interstitial Lung Disease, codified as "pulmonary disease". Our investigation shows that fluoxetine might be considered as a possible cause of Interstitial Lung Disease. In particular, although here we do not discuss the assessment of benefits and harms of fluoxetine, since this antidepressant is widely used, our review suggests that fluoxetine-induced Interstitial Lung Disease should be considered in patients with dyspnea, associated or not with dry cough, who are treated with this drug. An early withdrawn of fluoxetine could be useful to obtain a complete remission of this adverse drug reaction and special attention should be particularly devoted to long-term therapy, and to female and elderly patients. Although the spontaneous reporting system is affected by important limitations, drug post- marketing surveillance represents an important tool to evaluate the real world effectiveness and safety of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interstitial irradiation for craniopharyngioma

International Nuclear Information System (INIS)

Barlas, O.; Bayindir, C.; Can, M.

2000-01-01

The results of interstitial irradiation treatment for craniopharyngioma in two patients with six year follow-ups are presented. Stereotactic interstitial irradiation with iodine-125 sources as sole therapy was employed in two adult patients who refused surgical resection. The diagnoses were confirmed by stereotactic biopsy. The first tumour which underwent interstitial irradiation was solid and 4 cm in diameter, and the second, 2.7 cm in diameter, had both cystic and solid components. The implanted iodine-125 seeds delivered 67 Gy and 60 Gy to tumour periphery at the rate of 12 and 14 cGy/h, respectively, were removed at the end of designated radiation periods. Tumour shrinkage and central hypo density, first observed 3 months after irradiation, continued until one tumour shrank to less than 1 cm at 12 months, and the other disappeared completely at 24 months. In both cases functional integrity was restored, and neither radiation induced toxicity nor recurrence has occurred six years after treatment. The results in these two cases suggest that solid craniopharyngiomas are sensitive to interstitial irradiation. (author)

Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

Science.gov (United States)

Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

2015-01-01

IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

Ab initio molecular dynamics simulation of interstitial diffusion in Ni–Cr alloys and implications for radiation induced segregation

Energy Technology Data Exchange (ETDEWEB)

Barnard, L., E-mail: lmbarnard@wisc.edu; Morgan, D., E-mail: ddmorgan@wisc.edu

2014-06-01

In this study, ab initio molecular dynamics, implemented via density functional theory, is used to simulate self-interstitial diffusion in pure Ni and in the Ni-18 at.% Cr model alloy. Interstitial tracer diffusivities are measured from simulation results for pure Ni and for both Ni and Cr in the Ni–18Cr alloy. An Arrhenius function fit to these tracer diffusivities is then used in a rate theory model for radiation induced segregation, along with the experimentally measured vacancy diffusivities. It is predicted that interstitial diffusion has a tendency to cause Cr enrichment near grain boundaries, partially counterbalancing the tendency for vacancy diffusion to cause Cr depletion. This results in more mild Cr depletion than would result if only the vacancy diffusion were accounted for, in better agreement with experiment. This physical description of RIS in Ni–Cr alloys, which invokes the effects of both vacancy and interstitial diffusion, is distinct from the conventional description which accounts only for the effect of vacancy diffusion.

Ab initio molecular dynamics simulation of interstitial diffusion in Ni–Cr alloys and implications for radiation induced segregation

International Nuclear Information System (INIS)

Barnard, L.; Morgan, D.

2014-01-01

In this study, ab initio molecular dynamics, implemented via density functional theory, is used to simulate self-interstitial diffusion in pure Ni and in the Ni-18 at.% Cr model alloy. Interstitial tracer diffusivities are measured from simulation results for pure Ni and for both Ni and Cr in the Ni–18Cr alloy. An Arrhenius function fit to these tracer diffusivities is then used in a rate theory model for radiation induced segregation, along with the experimentally measured vacancy diffusivities. It is predicted that interstitial diffusion has a tendency to cause Cr enrichment near grain boundaries, partially counterbalancing the tendency for vacancy diffusion to cause Cr depletion. This results in more mild Cr depletion than would result if only the vacancy diffusion were accounted for, in better agreement with experiment. This physical description of RIS in Ni–Cr alloys, which invokes the effects of both vacancy and interstitial diffusion, is distinct from the conventional description which accounts only for the effect of vacancy diffusion

Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

Science.gov (United States)

Kern, D G; Crausman, R S; Durand, K T; Nayer, A; Kuhn, C

1998-08-15

Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously. To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak. Case-finding survey and retrospective cohort study. Academic occupational medicine program. All workers employed at the Rhode Island plant on or after 15 June 1990. Symptomatic employees had chest radiography, pulmonary function tests, high-resolution computed tomography, and serologic testing. Those with unexplained radiographic or pulmonary function abnormalities underwent bronchoalveolar lavage, lung biopsy, or both. The case definition of "flock worker's lung" required histologic evidence of interstitial lung disease (or lavage evidence of lung inflammation) not explained by another condition. Eight cases of flock worker's lung were identified at the Rhode Island plant. Three cases were characterized by a high proportion of eosinophils (25% to 40%) in lavage fluid. Six of the seven patients who had biopsy had histologic findings of nonspecific interstitial pneumonia, and the seventh had bronchiolitis obliterans organizing pneumonia. All seven of these patients had peribronchovascular interstitial lymphoid nodules, usually with germinal centers, and most had lymphocytic bronchiolitis and interstitial fibrosis. All improved after leaving work. Review of the Canadian tissue specimens showed many similar histologic findings. Among the 165-member study cohort, a 48-fold or greater increase was seen in the sex-adjusted incidence rate of all interstitial lung disease. Work in the nylon flocking industry poses substantial risk for a previously unrecognized occupational interstitial lung disease. Nylon fiber is the suspected cause of this condition.

Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

Science.gov (United States)

Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

2013-10-01

We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

Science.gov (United States)

Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

2016-06-01

To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Acute interstitial nephritis induced by intermittent use of Rifampicin in patient with Brucellosis

International Nuclear Information System (INIS)

Salih, S. Bin; Kharal, M.; Qahtani, M.; Dahneem, L.; Nohair, S.

2008-01-01

Acute oliguric renal failure (ARF) developed in a patient 2 days after she was started on intermittent anti-Brucella therapy including rifampicin. The clinical picture was compatible with acute allergic interstitial nephritis. Renal histology revealed mainly acute tubular necrosis with mild tubulo-intertitial mononuclear cellular infiltrate. Intermittent therapy, as in our patient, has been the major factor in the development of rifampicin induced ARF in cases reviewed in literature. (author)

Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial

DEFF Research Database (Denmark)

Salles, Gilles; Seymour, John Francis; Offner, Fritz

2011-01-01

Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab...... plus chemotherapy regimen....

Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence

Directory of Open Access Journals (Sweden)

Masoud Etemadifar

2017-01-01

Full Text Available Neuromyelitis optica (NMO is an autoimmune inflammatory disease of the central nervous system with preferential involvement in the optic nerve and spinal cord with a widespread spectrum of clinical features; multiple therapeutic agents have been used with different results. Recent evidence points to B-cell-mediated humoral immunity in the pathogenesis of NMO. Rituximab targets the CD20 antigen on B-cells. Treatment leads to profound B-cell depletion, principally over an antibody-dependent cell cytotoxicity mechanism. The aim of our study was to review clinical trials to elucidate the impact of rituximab on the relapse rate, Expanded Disability Status Scale (EDSS, and progression of disability in NMO. We performed a comprehensive review of all studies that evaluated clinical and paraclinical effects of rituximab on NMO. MEDLINE-PubMed, Web of Sciences, EMBASE, and Cochrane databases up to June 2016 included in our searches. In addition, reference lists from articles identified by search as well as a key review article to identify additional articles included in the study. Rituximab targets the CD20 antigen on B-cells and decreases attack frequency and severity in patients with NMO; however, it does not remove attacks, even when modifying treatment to achieve B-cell depletion. Most of the investigations revealed that EDSS significantly in all patients with rituximab treatment will be decreased after treatment with rituximab. No new or enlarged lesions or pathological gadolinium enhancement was observed in serial brain and spinal cord magnetic resonance imaging, except for those observed concomitantly with clinical relapses and the median length of spinal cord lesions was significantly reduced after therapy. Rituximab targets the CD20 antigen and decreases attack frequency and severity in patients with NMO.

EXPERIENCE OF TREATMENT WITH RITUXIMAB IN PATIENT WITH JUVENILE POLYARTERITIS

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E.I. Alexeeva

2011-01-01

Full Text Available The article presents a case report of severe course of nodular polyarteritis. The disease was highly active, aggressive, and refractory to treatment with corticosteroids and cyclophosphamide combined with plasmapheresis and drugs for microcirculation improvement. The treatment with chimerical anti-CD20 monoclonal antibodies — rituximab — was successful. Symptoms of intoxication and tromboangiatic syndrome decreased in 4 weeks. Disease was stopped up to 16th week. The case report demonstrates high efficacy of rituximab: patient with severe nodular polyarteritis remains clinical and laboratory remission during 52 weeks.Key words: children, nodular polyarteritis, rituximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 193–200

[Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

Science.gov (United States)

Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

2014-09-15

Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Rituximab para la oftalmopatía asociada a la tiroides

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Neda Minakaran

2013-09-01

Conclusiones de los autores: Actualmente no hay pruebas suficientes para apoyar la administración de rituximab en los pacientes con OAT. Se necesitan ECA grandes que investiguen rituximab versus placebo o corticosteroides en pacientes con OAT activo para hacer valoraciones adecuadas sobre la eficacia y la seguridad de este tratamiento nuevo para esta enfermedad.

The behavior of interstitials in irradiated graphite

International Nuclear Information System (INIS)

Pedraza, D.F.

1991-01-01

A computer model is developed to simulate the behavior of self-interstitials with particular attention to clustering. Owing to the layer structure of graphite, atomistic simulations can be performed using a large parallelepipedic supercell containing a few layers. In particular, interstitial clustering is studied here using a supercell that contains two basal planes only. Frenkel pairs are randomly produced. Interstitials are placed at sites between the crystal planes while vacancies are distributed in the two crystal planes. The size of the computational cell is 20000 atoms and periodic boundary conditions are used in two dimensions. Vacancies are assumed immobile whereas interstitials are given a certain mobility. Two point defect sinks are considered, direct recombination of Frenkel pairs and interstitial clusters. The clusters are assumed to be mobile up to a certain size where they are presumed to become loop nuclei. Clusters can shrink by emission of singly bonded interstitials or by recombination of a peripheral interstitial with a neighboring vacancy. The conditions under which interstitial clustering occurs are reported. It is shown that when clustering occurs the cluster size population gradually shifts towards the largest size cluster. The implications of the present results for irradiation growth and irradiation-induced amorphization are discussed

Lipoprotein(a Induces Human Aortic Valve Interstitial Cell Calcification

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Bin Yu, PhD

2017-08-01

Full Text Available Lipoprotein(a, or Lp(a, significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001. Inhibition of MAPK38 and GSK3β significantly reduced Lp(a-induced calcification of human aortic valve interstitial cells (p < 0.001. There was abundant presence of Lp(a and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a in aortic valve calcification and suggests that interfering with the Lp(apathway could provide a novel therapeutic approach in the management of this debilitating disease.

Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

DEFF Research Database (Denmark)

Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

2012-01-01

is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.......OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...

Vaccination with lipid core peptides fails to induce epitope-specific T cell responses but confers non-specific protective immunity in a malaria model.

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Simon H Apte

Full Text Available Vaccines against many pathogens for which conventional approaches have failed remain an unmet public health priority. Synthetic peptide-based vaccines offer an attractive alternative to whole protein and whole organism vaccines, particularly for complex pathogens that cause chronic infection. Previously, we have reported a promising lipid core peptide (LCP vaccine delivery system that incorporates the antigen, carrier, and adjuvant in a single molecular entity. LCP vaccines have been used to deliver several peptide subunit-based vaccine candidates and induced high titre functional antibodies and protected against Group A streptococcus in mice. Herein, we have evaluated whether LCP constructs incorporating defined CD4(+ and/or CD8(+ T cell epitopes could induce epitope-specific T cell responses and protect against pathogen challenge in a rodent malaria model. We show that LCP vaccines failed to induce an expansion of antigen-specific CD8(+ T cells following primary immunization or by boosting. We further demonstrated that the LCP vaccines induced a non-specific type 2 polarized cytokine response, rather than an epitope-specific canonical CD8(+ T cell type 1 response. Cytotoxic responses of unknown specificity were also induced. These non-specific responses were able to protect against parasite challenge. These data demonstrate that vaccination with lipid core peptides fails to induce canonical epitope-specific T cell responses, at least in our rodent model, but can nonetheless confer non-specific protective immunity against Plasmodium parasite challenge.

The Role of Rituximab in Lymphomas O papel do Rituximab nos linfomas

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Bertrand Coiffier

2002-01-01

Full Text Available Over the last years the treatment of non-Hodgkin's lymphoma underwent a great advance in relation to the diagnosis, classification, high-dose chemotherapy, and hematopoietic stem cell transplantation. Simultaneously with this, there was the development of new drugs and support therapy which enabled an improvement in the evolution and survival of the patients. The use of monoclonal antibodies against cancer cells is an old idea and in this report the results of the role of the anti-CD20-Rituximab in lymphomas is discussed.Nos últimos anos o tratamento do linfomas não Hodgkin apresentou um grande avanço no diagnóstico, classificação, quimioterapia com altas doses e o transplante de células percursoras hematopoiéticas. Simultaneamente houve o desenvolvimento de novas drogas e no tratamento de suporte o que possibilita um avanço na evolução e sobrevida dos pacientes. A idéia do emprego de anticorpos monoclonais no tratamento do câncer é antiga e neste relato são apresentados os resultados e o papel do anti-CD20-Rituximab nos linfomas.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

Science.gov (United States)

Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-09-01

This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

HRCT of diffuse interstitial pneumonia during treatment

International Nuclear Information System (INIS)

Takahashi, Masashi; Sano, Akira; Imanaka, Kazufumi

1989-01-01

HRCT was carried out in twenty patients with diffuse interstitial pneumonia: 13 cases of IIP, 3 of BOOP, 2 of drug-induced pneumonia, 1 of rheumatoid lung and acute interstitial pneumonia of unknown origin. With special attention to inflammatory activity, the patients underwent HRCT periodically during the treatment. Correlative investigation between HRCT image and grade of accumulation in 67 Ga scintigraphy was also performed. Response to steroid therapy was clearly reflected on HRCT image, that was shown as decreasing pulmonary density or thinning of honeycomb wall. HRCT is considered to be useful in assessing the activity of diffuse interstitial pneumonia. (author)

Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

NARCIS (Netherlands)

Boumans, Maria; Teng, Onno; Thurlings, Rogier; Bijlsma, Johannes; Gerlag, Danielle; Huizinga, Tom; Vos, Koen; Stapel, Steven; Wolbink, Gertjan; Tekstra, Janneke; van Laar, Jaap; Tak, Paul P.

2013-01-01

The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Science.gov (United States)

Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

2017-09-01

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

OpenAIRE

Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

2017-01-01

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

Study On The Preparation Of 90Y-DTPA-Rituximab For Non-Hodgkin Lymphoma Treatment

International Nuclear Information System (INIS)

Nguyen Thi Thu; Duong Van Dong; Bui Van Cuong; Vo Thi Cam Hoa; Chu Van Khoa; Phan Quoc Thong

2011-01-01

Yttrium is one of the most useful radionuclides for radioimmunotherapeutic applications, especially labelling with monoclonal antibodies. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 minutes. Rituximab solution in 0.05 M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5 mg/ml and 10 mg/ml) was coupled with the cDTPAa, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation of DTPA-Rituximab mixture was labelled with Y-90, then using Sephadex G25 in order to determine coupling efficiency. Coupling efficiency at a 3:1 mole ratio was 70%. After purification, the conjugation DTPA-Rituximab was labeled with Y-90 in 0.5 M acetate buffer, pH 5, at room temperature. The labeling yield was about 99%. The radiochemical purity of 90 Y-DTPA-Rituximab was more than 98 % which determined by ITLC in 0.1 M acetate at pH 6 as mobile phase. The radiopharmaceuticals have been test for sterility, apyrogenicity and biodistribution. This is a potential radiopharmaceutical for clinical application in therapeutic Non Hodgkin Lymphoma treatments. (author)

[New toxicity of fotemustine: diffuse interstitial lung disease].

Science.gov (United States)

Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L

2012-04-01

Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin lymphoma patients in Chinese public hospitals.

Science.gov (United States)

Yu-Wen, Huang; Mei-Bian, Zhang; Xiang, Xu; Xiao-Hua, Xu; Quan, Zhou; Le, Jian

2014-03-01

Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin lymphoma (NHL). Little is known in China, a country with unequal distribution of wealth and medical insurance systems, about the impact of socioeconomic status (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2 equal groups: with rituximab therapy and with no rituximab therapy group. Selection and frequency of rituximab therapy increased with duration of education and in urban citizens (P inequality in provision of rituximab therapy among Chinese NHL patients, and this was associated with differences in SES status. Effective measures are suggested to ameliorate the inequality issue.

[Rituximab: a new therapeutic alternative in Grave's disease].

Science.gov (United States)

Tello-Winniczuk, Nina; Díaz-Jouanen, Efraín

2011-01-01

Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly young aged women, with an etiology of autoimmune basis. One of its manifestations, Graves' ophthalmopathy whose pathophysiology is unknown, represents one of the greatest therapeutic challenges in these patients, because they require aggressive treatment with steroids and multiple subsequent reconstructive surgeries in certain cases. It also represents a high burden to the health system. Drugs targeting B cells have been very effective for many autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against CD20 + cells currently being studied in various autoimmune diseases including Graves' disease. The objective of this paper is to expose possible mechanisms by which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves' disease, as well as the experience with its use acquired so far. The employment of rituximab in recently diagnosed patients or with mild ophthalmopathy is questionable with the evidence available today however, we think that it may have a role in refractory cases or those who have a contraindication for steroid use.

Molecular dynamics study of interstitial-solute interactions in irradiated alloys

International Nuclear Information System (INIS)

Lam, N.Q.; Doan, N.V.; Adda, Y.

1980-01-01

The molecular dynamics technique has been used, in conjunction with the interionic potentials of Dagens et al, to study the stability, configuration, binding, and induced migration of mixed dumbbells in an irradiated Al-Zn alloy. For the purpose of comparisons, self-interstitials in pure Al were also investigated. The Al-Al and Al-Zn interactions were described by pair potentials which extended to ninth-neighbour distances. Both the self-interstitial dumbbell and the mixed dumbbell were found to be stable in the configuration. The formation energy of the self-interstitial is 2.89 eV and the mixed-dumbbell binding energy is 0.38 eV. As a result of this strong binding, the threshold energy required to induce the migration of the mixed dumbbell is about 1.2 eV, which is significantly larger than the minimum energy of about 0.15 eV transferred to a self-interstitial to induce its jumps in pure Al. Caging motions of the mixed dumbbell were observed. The present computer-simulation results are compared with experimental measurements. (author)

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

Science.gov (United States)

Kang, E H; Lee, E B; Shin, K C; Im, C H; Chung, D H; Han, S K; Song, Y W

2005-10-01

To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC poor survival in ILD.

Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab.

Science.gov (United States)

Hamaki, T; Kami, M; Kusumi, E; Ueyama, J; Miyakoshi, S; Morinaga, S; Mutou, Y

2001-12-01

A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV. Copyright 2001 Wiley-Liss, Inc.

Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

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Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

2016-09-01

To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

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Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

Science.gov (United States)

Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-01-01

Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab {sup registered}) for patients with non-Hodgkin's lymphoma. Results of a prospective phase I/II study

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Haidenberger, Alfred; Popper, Bela-Andre; Skvortsova, Ira; Lukas, Peter [Medical Univ. Innsbruck (Austria). Dept. of Radiotherapy/Radiooncology; Fromm-Haidenberger, Sabine [Hospital Gmunden (Austria). Inst. of Radiology; Vries, Alexander de [Hospital Feldkirch (Austria). Dept. of Radiotherapy/Radiooncology; Steurer, Michael; Kantner, Johanna; Gunsilius, Eberhard [Medical Univ. Innsbruck (Austria). Dept. of Hematology

2011-05-15

Purpose: Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. Patients and Methods: A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m{sup 2}). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. Results: No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Conclusion: Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability. (orig.)

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

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Chen, Na; Chen, Meimei; Liu, Shupeng; Guo, Qiang; Chen, Zhenyi; Wang, Tingyun

2014-01-01

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

Interstitial Lung Disease

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... propranolol (Inderal, Innopran), may harm lung tissue. Some antibiotics. Nitrofurantoin (Macrobid, Macrodantin, others) and ethambutol (Myambutol) can cause lung damage. Anti-inflammatory drugs. Certain anti-inflammatory drugs, such as rituximab ( ...

Propagating self-sustained annealing of radiation-induced interstitial complexes

International Nuclear Information System (INIS)

Bokov, P M; Selyshchev, P A

2016-01-01

A propagating self-sustained annealing of radiation induced defects as a result of thermal-concentration instability is studied. The defects that are considered in the model are complexes. Each of them consists of one atom of impunity and of one interstitial atom. Crystal with defects has extra energy which is transformed into heat during defect annealing. Simulation of the auto-wave of annealing has been performed. The front and the speed of the auto-wave have been obtained. It is shown that annealing occurs in a narrow region of time and space. There are two kinds of such annealing behaviour. In the first case the speed of the auto-wave oscillates near its constant mean value and the front of temperature oscillates in a complex way. In the second case the speed of propagation is constant and fronts of temperature and concentration look like sigmoid functions. (paper)

Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia.

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Churg, Andrew; Wright, Joanne L; Bilawich, AnaMaria

2018-04-01

Organising pneumonia (OP) is composed of loose granulation tissue plugs in distal airspaces; these disappear with steroid treatment. Recently a variant labelled 'cicatricial' OP has been described in which the granulation tissue organised to much denser fibrous tissue but still retained the usual pattern of OP. Here we report 10 patients thought to have an interstitial lung disease, and who on biopsy had a variant of cicatricial OP characterised by linear bands or small nodular masses of dense fibrous tissue that does not resemble ordinary OP. The bands/nodules were usually distributed randomly but occasionally resembled fibrotic non-specific interstitial pneumonia in local areas. Small foci of loose granulation tissue at the edge of the fibrotic bands sometimes mimicked fibroblast foci. Recognisable conventional OP was always present, but often in very small amounts. Four cases, including one patient with Ehlers-Danlos syndrome, showed formation of bone in the fibrotic bands and nodules. On computerised tomography (CT) scan of the chest some cases looked like typical OP, but some demonstrated only irregularly distributed linear opacities, sometimes with associated calcification. Follow-up imaging on six cases showed that the process either markedly improved or remained stable over time; no case had progressive disease. Cicatricial OP with this pathological pattern represents an uncommon form of OP that appears to be a generally benign process which may have persisting linear opacities on CT scan but that does not progress; however, it can be confused on biopsy and CT with a fibrosing interstitial pneumonia. © 2017 John Wiley & Sons Ltd.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

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Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

2016-06-01

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

International Nuclear Information System (INIS)

Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

D E Karateev

2008-01-01

Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

Interstitial nephritis.

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Papper, S

1980-01-01

There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

Linfoma hepático primario: Evolución favorable con quimioterapia combinada con rituximab Primary hepatic lymphoma: favorable outcome with chemotherapy plus rituximab

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I. Serrano-Navarro

2008-11-01

Full Text Available Comunicamos el caso de una paciente con un linfoma hepático primario tratado con éxito con quimioterapia combinada con rituximab. Utilizando los "encabezamientos estándar para búsquedas bibliográficas informatizadas" (Medical Subject Heading revisamos los casos publicados hasta la fecha de esta infrecuente entidad.This article describes the case of a patient with a non-Hodgkin primary hepatic lymphoma who was successfully treated with chemotherapy combined with rituximab. Using the Medical Subject Headings the published reports of this rare entity were reviewed.

Rituximab treatment in primary angiitis of the central nervous system.

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Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

2018-06-01

Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

Internalization of rituximab and the efficiency of B Cell depletion in rheumatoid arthritis and systemic lupus erythematosus.

Science.gov (United States)

Reddy, Venkat; Cambridge, Geraldine; Isenberg, David A; Glennie, Martin J; Cragg, Mark S; Leandro, Maria

2015-05-01

Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell-depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence-quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell-depletion assays. The lowest levels of internalization were seen in IgD- B cells, including postswitched (IgD-CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell-depleting agents for the treatment of RA and SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Fulminante, rituximab-resistente, mucocutane pemphigus vulgaris

NARCIS (Netherlands)

Gostyński, A.; Ammatuna, E.; Huls, G.; Wouthuyzen-Bakker, M.; Jonkman, M. F.; Horváth, B.

2017-01-01

Pemphigus vulgaris is an autoimmune disease mediated by auto-antibodies against desmoglein 1 and 3. First line treatment for pemphigus consists of systemic corticosteroids and anti-CD20 therapy (rituximab) to eliminate B-cells. Since 2005, more than 100 patients with pemphigus have been treated with

Four Cases of Interstitial Lung Disease Induced by Erlotinib 
and A Review of the Literatures

Directory of Open Access Journals (Sweden)

Xiaoling WU

2012-08-01

Full Text Available Erlotinib is an agent of oral epidermal growth factor receptor (EGFR tyrosine kinase inhibitors which are used for non-small cell lung cancer. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD. ILD induced by gefitinib been often described, but the ILD induced by erlotinib is relatively less well known. We here describle four cases of ILD related to erlotinib and review recent literatures to help physicians earlier alert erlotinib-induced ILD. It is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib. Early diagnosis and timely intervention is critical in the treatment of drug-induced ILD.

Interstitial lung disease associated with human papillomavirus vaccination

Directory of Open Access Journals (Sweden)

Yasushi Yamamoto

2015-01-01

Full Text Available Vaccinations against the human papillomavirus (HPV have been recommended for the prevention of cervical cancer. HPV-16/18 AS04-adjuvanted vaccines (Cervarix are said to have favourable safety profiles. Interstitial lung diseases (ILDs can occur following exposure to a drug or a biological agent. We report a case of ILD associated with a Cervarix vaccination. A woman in her 40's, with a history of conisation, received three inoculations of Cervarix. Three months later, she presented with a cough and shortness of breath. Findings from a computed tomography of the chest and a transbronchial lung biopsy were consistent with non-specific interstitial pneumonia. Workup eliminated all other causes of the ILD, except for the vaccination. Over the 11 months of the follow-up period, her symptoms resolved without steroid therapy. The onset and spontaneous resolution of the ILD showed a chronological association with the HPV vaccination. The semi-quantitative algorithm revealed that the likelihood of an adverse drug reaction to Cervarix was “Probable”. The outcome was relatively good, but more attention should be paid to a potential risk for HPV vaccinations to cause ILDs. Wherever possible, chest radiographic examinations should be performed in order not to overlook any ILDs.

Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

Science.gov (United States)

Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

2014-04-01

Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Intralesional rituximab in primary conjunctival follicular lymphoma relapsed.

Science.gov (United States)

Rodríguez Villa, S; Ruiz Rodríguez, M J; Vargas Pabón, M

2017-07-01

A 49-year-old woman experienced a local relapse of a primary follicular lymphoma (FL) of the conjunctiva. She received 4 weekly intra-lesional injections followed by 6 monthly injections of rituximab (6mg/ml). A clinical response was achieved after first injection. No adverse ocular event or signs of lymphoma relapse were seen after 10 months of follow-up. Intralesional administration of rituximab for treating primary FL of the conjunctiva was an effective and safe therapeutic option; therefore it could be an alternative to other conventional treatments, such as radiotherapy or chemotherapy. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

T2 mapping of CT remodelling patterns in interstitial lung disease

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Buzan, Maria T.A. [Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pneumology, Cluj-Napoca (Romania); Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Eichinger, Monika; Heussel, Claus Peter [Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Kreuter, Michael; Herth, Felix J. [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Thoraxklinik at Heidelberg University Hospital, Department of Pneumology, Center for Rare and Interstitial Lung Diseases, Heidelberg (Germany); Kauczor, Hans-Ulrich [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Warth, Arne [Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); University Hospital Heidelberg, Institute for Pathology, Heidelberg (Germany); Pop, Carmen Monica [Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pneumology, Cluj-Napoca (Romania); Dinkel, Julien [Thoraxklinik at Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg (Germany); Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich (Germany); Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany)

2015-11-15

To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. (orig.)

T2 mapping of CT remodelling patterns in interstitial lung disease

International Nuclear Information System (INIS)

Buzan, Maria T.A.; Eichinger, Monika; Heussel, Claus Peter; Kreuter, Michael; Herth, Felix J.; Kauczor, Hans-Ulrich; Warth, Arne; Pop, Carmen Monica; Dinkel, Julien

2015-01-01

To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. (orig.)

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

NARCIS (Netherlands)

Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

2015-01-01

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

Institute of Scientific and Technical Information of China (English)

Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

2009-01-01

Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

Science.gov (United States)

Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

2018-04-01

CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

Science.gov (United States)

Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

Individualized rituximab treatment for relapsing neuromyelitis optica: a pediatric case report.

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He, Dian; Yu, YunLi; Yan, WeiBo; Dai, QingQing; Xu, Zhu; Chu, Lan

2014-08-01

Neuromyelitis optica is an autoimmune inflammatory disorder of the central nervous system. Current therapeutic approaches are based on small uncontrolled trials, case series, or case reports. There are only a few case reports describing rituximab for pediatric neuromyelitis optica. A 7-year-old girl with neuromyelitis optica had high disease activity with recurrent myelitis and steroid dependence. A remarkable increase of CD19(+) B-cell count in the peripheral blood mononuclear cells and seropositivity for anti-aquaporin 4 antibody were detected at each attack. After induction therapy with rituximab, the CD19(+) B-cell number was significantly reduced and sustained at low levels. The level of serum anti-aquaporin 4 antibody normalized. She was relapse-free over 1-year follow-up period. An individualized maintenance therapy scheme is underway. Treatment with rituximab for relapsing neuromyelitis optica requires an individualized regimen to optimize the frequency and dosage of administration to maximize efficacy yet minimize overtreatment and cost. Personal levels of CD19(+) B cells in peripheral blood mononuclear cells at previous attacks and responsiveness to rituximab in induction therapy may be two useful indicators in establishing individualized maintenance therapy schemes for relapsing neuromyelitis optica. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of single interstitial impurity in iron-based superconductors with sign-changed s-wave pairing symmetry

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Yu, Xiang-Long, E-mail: xlyu@theory.issp.ac.cn [Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, P. O. Box 1129, Hefei 230031 (China); Liu, Da-Yong; Quan, Ya-Min; Zheng, Xiao-Jun [Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, P. O. Box 1129, Hefei 230031 (China); Zou, Liang-Jian, E-mail: zou@theory.issp.ac.cn [Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, P. O. Box 1129, Hefei 230031 (China); Department of Physics, University of Science and Technology of China, Hefei 230026 (China)

2015-12-15

Highlights: • Effects of single interstitial impurity are studied in iron-based superconductors. • Bound states within the superconducting gap can be induced. • The interstitial impurity can induce a π phase shift of pairing order parameter. • For strong magnetic scattering the bound-state peak can appear at the Fermi level. - Abstract: We employ the self-consistent Bogoliubov-de Gennes (BdG) formulation to investigate the effect of single interstitial nonmagnetic/magnetic impurity in iron-based superconductors with s ± -wave pairing symmetry. We find that both the nonmagnetic and magnetic impurities can induce bound states within the superconducting (SC) gap and a π phase shift of SC order parameter at the impurity site. However, different from the interstitial-nonmagnetic-impurity case characterized by two symmetric peaks with respect to zero energy, the interstitial magnetic one only induces single bound-state peak. In the strong scattering regime this peak can appear at the Fermi level, which has been observed in the recent scanning tunneling microscope (STM) experiment of Fe(Te,Se) superconductor with interstitial Fe impurities (Yin et al. 2015 [44]). This novel single in-gap peak feature also distinguishes the interstitial case from the substitutional one with two peaks. These results provide important information for comparing the different impurity effects in the iron-based superconductors.

A pioneer experience in Malaysia on In-house Radio-labelling of "1"3"1I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose "1"3"1I-rituximab-BEAM conditioning autologous transplant

International Nuclear Information System (INIS)

Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

2016-01-01

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies – "9"0Y-ibritumomab tiuxetan is expensive and "1"3"1I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling "1"3"1I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling "1"3"1I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose "1"3"1I-rituximab (6000 MBq/163 mCi) combined with BEAM conditioning for autologous HSCT. - Highlights: • Usual dose: Day 0 (dosimetry) – 5 mCi, Day 7 (therapeutic) 0.75 Gy to whole body. • High dose: 6000 MBq (163 mCi) on Day − 18, BEAM conditioning starts on Day − 8. • Self-labelled "1"3"1I-rituximab is a viable treatment in resource limited environment. • "1"3"1I-rituximab may substitute autologous transplant. • High dose "1"3"1I-rituximab-BEAM is a feasible conditioning regime.

Favourable response to rituximab by an ocular adnexal primary lymphoma.

Science.gov (United States)

Luque Valentin-Fernandez, M L; Alvarez Rodríguez, F; Rodríguez Jiménez, I

2016-11-01

A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Drug-induced acute interstitial nephritis: A clinicopathological study and comparative trial of steroid regimens

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R Ramachandran

2015-01-01

Full Text Available Steroids are used in the management of drug-induced acute interstitial nephritis (AIN. The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m 2 , partial remission (PR (improvement but eGFR <60 ml/min/1.73 m 2 or resistance (no CR/PR. A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 ΁ 1.1 and 5.1 ΁ 1.2, respectively. At 3 months in Group I, eight patients each (50% achieved CR and PR. In Group II, 8 (61% achieved CR and 5 (39% PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56% was higher in CR as compared to (42% those with PR. ( P = 0.14. Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration ( P = 0.01. Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.

Detection of the free migration of the self-interstitials in magnesium

Energy Technology Data Exchange (ETDEWEB)

Lauzier, J; Hillairet, J; Duclos, D; Vieux Champagne, A

1986-05-01

This paper describes the first experimental determination of the migration temperature of freely diffusing self-interstitials in magnesium. This observation was made possible by analysis of the elastic modulus and damping variations induced by the pinning of the dislocations by self-interstitials. A marked pinning stage is found between 9 K and 14 K, which is definite evidence for the long-range diffusion of the self-interstitial at these temperatures. Prior data are discussed and reinterpreted in the light of this finding.

Impact of rituximab on patient-reported outcomes in patients with rheumatoid arthritis from the US Corrona Registry.

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Harrold, Leslie R; John, Ani; Best, Jennie; Zlotnick, Steve; Karki, Chitra; Li, YouFu; Greenberg, Jeffrey D; Kremer, Joel M

2017-09-01

To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to ≥1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially impacted by their RA disease and quality of life; 54% of patients had high disease activity. One year after rituximab initiation, 49.0, 47.1, 49.8, and 23.2% of patients reported clinically meaningful improvements in patient global, pain, fatigue, and mHAQ, respectively. Morning stiffness and EuroQol EQ-5D domains improved in 48 and 19-32% of patients, respectively. These real-world registry data demonstrated that patients with long-standing, refractory RA experienced improvements in PROs 1 year after initiating rituximab.

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

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Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

2017-04-01

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

Science.gov (United States)

Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

2014-01-01

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

Science.gov (United States)

Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

2015-01-01

Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

Mobile interstitial model and mobile electron model of mechano-induced luminescence in coloured alkali halide crystals

International Nuclear Information System (INIS)

Chandra, B.P.; Singh, Seema; Ojha, Bharti; Shrivastava, R.G.

1996-01-01

A theoretical study is made on the mobile interstitial and mobile electron models of mechano-induced luminescence in coloured alkali halide crystals. Equations derived indicate that the mechanoluminescence intensity should depend on several factors like strain rate, applied stress, temperature, density of F-centres and volume of crystal. The equations also involve the efficiency and decay time of mechanoluminescence. Results of mobile interstitial and mobile electron models are compared with the experimental observations, which indicated that the latter is more suitable as compared to the former. From the temperature dependence of ML, the energy gaps between the dislocation band and ground state of F-centre is calculated which are 0.08, 0.072 and 0.09 eV for KCl, KBr and NaCl crystals, respectively. The theory predicts that the decay of ML intensity is related to the process of stress relaxation in crystals. (author). 33 refs., 5 figs., 1 tab

Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

Science.gov (United States)

Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

2017-06-01

In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.

Science.gov (United States)

Wongseelashote, Sarah; Tayal, Vipin; Bourke, Peter Francis

2018-02-01

Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is increasingly prescribed off-label for a range of autoimmune diseases. There has not previously been an audit of off-label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. To evaluate retrospectively off-label rituximab use in autoimmune diseases in the Top End of the Northern Territory. We performed a retrospective audit of 8 years of off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Rituximab was prescribed off-label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Rituximab has been used off-label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. © 2017 Royal Australasian College of Physicians.

Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

Science.gov (United States)

Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

2014-06-01

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Experiencia con rituximab en miopatía inflamatoria idiopática refractaria

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Elmer R. García-Salazar

2013-10-01

Full Text Available Se describe las características clínicas y de laboratorio de dos pacientes que recibieron rituximab por miopatía inflamatoria idiopática (MII. Ellas eran refractarias a tratamiento convencional con DARMES, por lo que recibieron rituximab 1 gramo cada 14 días, en dos infusiones en ciclo semestral. En las historias clínicas se obtuvo los datos clínicos de fuerza muscular proximal, lesiones cutáneas patognomónicas, elevación de CPK, TGO, DHL y VSG, resultados de electromiografía, biopsia muscular y de piel. Ninguno de los dos casos presentó reacción medicamentosa ni infecciones durante y posterior a las infusiones. Rituximab mostró efectividad en la respuesta clínica y enzimática en estas pacientes con dermatomiositis refractarias a corticoides y DARMES tradicionales.

Pneumocystis jiroveci Pneumonia in Patients with Non-Hodgkin's Lymphoma Receiving Chemotherapy Containing Rituximab

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Hung Chang

2008-11-01

Full Text Available Rituximab enhances treatment efficacy of B-lineage lymphoma by targeting CD20+ B-cells. Such target therapies may compromise the immune system and render patients susceptible to opportunistic infections. We report 2 cases of lymphoma complicated with Pneumocystis jiroveci (previously known as P. carinii pneumonia (PCP while being treated with rituximab-containing chemotherapy regimens. In both cases, PCP developed during the neutropenic period. With timely diagnosis and proper management, both were treated successfully. We searched the literature and found that such opportunistic infection occurred only infrequently in lymphoma patients, and it has not been reported in the large-scale clinical trials of rituximab. Such cases demonstrate the importance of taking PCP into diagnostic consideration in lymphoma patients receiving similar therapies.

The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias

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G. Raghu

2008-12-01

Full Text Available The idiopathic interstitial pneumonias (IIPs are a heterogeneous group of rare interstitial lung diseases (ILDs or diffuse parenchymal lung diseases, which, as their name implies, are of unknown aetiology. The past 10 yrs have seen important advances in the classification of the IIPs into idiopathic pulmonary fibrosis (IPF and its corresponding histopathological pattern of usual interstitial pneumonia (UIP, plus six non-IPF IIP subtypes. The present article will look at the current classification of IIPs, arising from the Consensus Statement of the American Thoracic Society and European Respiratory Society, and discusses the importance of differential diagnosis of IPF from the non-IPF IIP subtypes, especially nonspecific interstitial pneumonia. Diagnosis of IIPs is a dynamic process involving close collaboration between pulmonologists, radiologists and pathologists. Increasingly accurate diagnosis of IPF has been made possible by the use of high-resolution computed tomography (HRCT and refinements in surgical lung biopsy. In IPF, a lung HRCT will typically reveal irregular reticular opacities, traction bronchiestasis and, most importantly, peripheral honeycombing. In contrast, histological examination shows evidence of UIP manifesting as typically subpleural and paraseptal established fibrosis, often with honeycomb changes, associated with mild chronic inflammation and varying numbers of fibroblastic foci in continuity with the edges of areas of established fibrosis. Despite these advances, obtaining a consistent and uniform diagnosis of idiopathic interstitial pneumonias is difficult, with studies showing significant disagreement in the diagnosis of interstitial lung diseases between academic centres of expertise and community-based clinicians. Greater interaction between academic and community clinicians, together with improved education, is needed to bridge this gap.

Successful pregnancy after rituximab in a women with recurrent in vitro fertilisation failures and anti-phospholipid antibody positive.

LENUS (Irish Health Repository)

Ng, C T

2012-02-01

We report a case of successful pregnancy after rituximab in a patient with a history of in vitro fertilisation (IVF) failures and positive anti-cardiolipin antibody (ACA). Following a course of rituximab, her ACA became negative and she successfully conceived with IVF treatment. This is the first case in literature describing the use of rituximab therapy in this clinical scenario.

Interstitial Fluid Flow: The Mechanical Environment of Cells and Foundation of Meridians

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Wei Yao

2012-01-01

Full Text Available Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells caused by interstitial fluid flow. The numerical simulation results show the following: (i the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

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Gunjan Shah

2013-01-01

Full Text Available Microangiopathic hemolytic anemia (MAHA, thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery.

Análise de 39 casos de pneumonia intersticial crônica idiopática Analysis of 39 cases of idiopathic chronic interstitial pneumonia

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Rogério Rufino

2006-12-01

performed between 1977 and 1999, were reviewed, and 39 cases of idiopathic interstitial lung disease were selected and re-evaluated by two pathologists in accordance with the American Thoracic Society/European Respiratory Society classification system. RESULTS: Among those 39 cases, the diagnoses were maintained in 28 (71.8%. A new pathologic entity, nonspecific interstitial pneumonia, was included in the reclassification, and overlapping patterns were observed in 6 cases. Of the 28 cases in which the diagnosis of chronic idiopathic interstitial pneumonia remained unchanged, idiopathic pulmonary fibrosis was accompanied by cryptogenic organizing pneumonia in 4, cryptogenic organizing pneumonia was accompanied by nonspecific interstitial pneumonia in 1, and desquamative interstitial pneumonia was accompanied by nonspecific interstitial pneumonia in 1. All cases of idiopathic pulmonary fibrosis were confirmed, although 3 of those were found to be accompanied by cryptogenic organizing pneumonia. Virtually all prior diagnoses were maintained in the review of the biopsy samples (p > 0,05. CONCLUSION: The American Thoracic Society/European Respiratory Society system of classifying interstitial lung disease is a useful tool for pathologists who deal with lung biopsies.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

DEFF Research Database (Denmark)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

2018-01-01

BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data...... performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56...... days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m2) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle...

A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

Science.gov (United States)

Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

2016-10-01

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rituximab as a possible cause of posterior reversible encephalopathy syndrome

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Ahmed Imran Siddiqi

2011-09-01

Full Text Available A 66-year-old woman presented with new onset generalisedtonic-clonic seizures following her first dose ofchemotherapy comprising Rituximab, Cyclophosphamide,Hydroxydaunorubicin, Oncovin and Prednisolone (R-CHOP10 days earlier for non-Hodgkin’s lymphoma. On admission,computed tomography (CT scan of the cranium showed noabnormality. The CT was repeated within 48 hours as thepatient developed status epilepticus and papilledema; therepeat scan showed characteristics of posterior reversibleencephalopathy syndrome (PRES. Association of rituximabwith this condition was suspected as there was norecurrence of PRES after receiving two more cycles of CHOPwithout rituximab. Contrary to previously published casereports, this patient had a delayed clinical presentation.

B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis

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Meng-Kun Tsai

2015-04-01

Conclusion: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

Interstitial laser thermotherapy in neurosurgery: a review

NARCIS (Netherlands)

Menovsky, T.; Beek, J. F.; van Gemert, M. J.; Roux, F. X.; Bown, S. G.

1996-01-01

One of the most recent laser treatment modalities in neurosurgery is interstitial laser thermotherapy (ILTT). In this review, experimental and clinical studies concerning intracranial ILTT are discussed. Two methods for intra-operative control of the laser induced lesions are described; i.e.,

Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was Refractory to Corticosteroid and Omalizumab Treatments

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Aslı Bilgiç Temel

2017-02-01

Full Text Available Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP. Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP. Here we present a young BP patient who responded well to rituximab therapy and was refractory to conventional and omalizumab therapies although he had elevated IgE levels and eosinophilia. Our case supports the knowledge about the effectiveness and safety of rituximab not only in pemphigus but also in BP. On the other hand, although it did not work in our case, omalizumab may be a potentially effective agent in some carefully selected patients with certain subtypes of BP.

{sup 99m}Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

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Gmeiner Stopar, T.; Fettich, J.; Hojker, S. [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Mlinaric-Rascan, I. [University of Ljubljana, Faculty of Pharmacy, Ljubljana (Slovenia); Mather, S.J. [St Bartholomew' s Hospital, Cancer Research UK, Department Nuclear Medicine, London (United Kingdom)

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with {sup 99m}Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with {sup 99m}Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of {sup 99m}Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of {sup 99m}Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound {sup 99m}Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that {sup 99m}Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. {sup 99m}Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

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Alba, Marco A; Flores-Suárez, Luis Felipe

2016-01-01

ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

International Nuclear Information System (INIS)

Dahle, Jostein; Krogh, Cecilie; Melhus, Katrine B.; Borrebaek, Jorgen; Larsen, Roy H.; Kvinnsland, Yngve

2009-01-01

Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227 Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227 Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227 Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227 Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227 Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227 Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10 5 to 10 7 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227 Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227 Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

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López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

2015-01-01

The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

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Knight T

2017-05-01

Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD

Novel use of rituximab in a case of Riedel's thyroiditis refractory to glucocorticoids and tamoxifen.

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Soh, Shui-Boon; Pham, Alan; O'Hehir, Robyn E; Cherk, Martin; Topliss, Duncan J

2013-09-01

A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.

Remission Time after Rituximab Treatment for Autoimmune Bullous Disease: A Proposed Update Definition.

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Iranzo, Pilar; Pigem, Ramon; Giavedoni, Priscila; Alsina-Gibert, Mercè

2015-01-01

A therapeutic endpoint is a very important tool to evaluate response in clinical trials. In 2005, a consensus statement identified two late endpoints of disease activity in pemphigus: complete remission off therapy and complete remission on therapy, both definitions applying to patients without lesions for at least 2 months. The same period of time was considered for partial remission off/on therapy. These definitions were later applied to bullous pemphigoid and are considered in most studies on autoimmune bullous disease. These endpoints were established for different adjuvant agents, but at that moment, rituximab was not considered. Rituximab is known for the long duration of its effect, and in most studies relapses have been reported later than 6 months after treatment. In our opinion, time to remission after rituximab treatment should be redefined. © 2015 S. Karger AG, Basel.

Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

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Ada H V Repetto-Llamazares

Full Text Available 177Lu-DOTA-HH1 (177Lu-HH1 is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1 and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

Impact of the injected interstitial on the correlation of charged-particle and neutron-induced radiation damage

International Nuclear Information System (INIS)

Garner, F.A.

1983-01-01

The successful conclusion of an intercorrelation program developed in the U.S. Breeder program has provided significant insight on the factors governing the swelling that develops in ion-bombardment studies and its relationship to the swelling that occurs during neutron irradiation. It appears that the injected interstitial or a related phenomenon exerts a pronounced influence on ion-induced swelling. This conclusion has ramifications with respect to the conduct and interpretation of ion irradiation experiments employed to study the effect of helium or composition on swelling

High-dose-rate interstitial brachytherapy for the treatment of penile carcinoma

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Petera, J.; Odrazka, K.; Zouhar, M.; Bedrosova, J.; Dolezel, M. [Dept. of Oncology and Radiotherapy, Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic)

2004-02-01

Background: interstitial low-dose-rate (LDR) brachytherapy allows conservative treatment of T1-T2 penile carcinoma. High-dose-rate (HDR) is often considered to be dangerous for interstitial implants because of a higher risk of complications, but numerous reports suggest that results may be comparable to LDR. Nevertheless, there are no data in the literature available regarding HDR interstitial brachytherapy for carcinoma of the penis. Case report: a 64-year-old man with T1 NO MO epidermoid carcinoma of the glans is reported. Interstitial HDR brachytherapy was performed using the stainless hollow needle technique and a breast template for fixation and good geometry. The dose delivered was 18 x 3 Gy twice daily. Results: after 232 days from brachytherapy, the patient was without any evidence of the tumor, experienced no serious radiation-induced complications, and had a fully functional organ. Conclusion: HDR interstitial brachytherapy is feasible in selected case of penis carcinoma, when careful planning and small single fractions are used. (orig.)

Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

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Man-Hsin Hung

2013-04-01

Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

Nanoparticles modify dendritic cell homeostasis and induce non-specific effects on immunity to malaria.

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Xiang, Sue D; Kong, Ying Y; Hanley, Jennifer; Fuchsberger, Martina; Crimeen-Irwin, Blessing; Plebanski, Magdalena

2015-01-01

Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (DC) homeostasis, thereby promoting a persistent enhanced state of immune readiness to a subsequent infectious challenge. Particles (approximately 40 nm and 500 nm carboxylated polystyrene nanoparticles; PSNPs) alone or conjugated to a model antigen were injected in mice, and DCs in draining lymph nodes (dLNs) and bone-marrow (BM) quantified by flow cytometry. BM cells were tested for capacity to generate DCs upon culture with granulocyte and macrophage colony stimulating factor. Mice were challenged with Plasmodium yoelli. Blood parasitaemias were monitored by GIEMSA. Sera was analyzed for antibodies by ELISA. Intradermal administration of 40 nm PSNPs induced anti-inflammatory cytokines, chemokines and growth factors, increased numbers and proportions of DCs in the dLN, and increased the capacity of BM to generate DCs. Consistent with these unexpected changes, 40 nm PSNPs pre-injected mice had enhanced ability to generate immunity to a subsequent malarial infection. Intradermal administration of 40 nm PSNPs modifies DC homeostasis, which may at least in part explain the observed beneficial heterologous effects of current particulate vaccines. Further nanotechnological developments may exploit such strategies to promote beneficial non-specific effects. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

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Maximilian Richter

2016-01-01

Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

NARCIS (Netherlands)

Isaacs, John D.; Cohen, Stanley B.; Emery, Paul; Tak, Paul P.; Wang, Jianmei; Lei, Guiyuan; Williams, Sarah; Lal, Preeti; Read, Simon J.

2013-01-01

Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. To carry out a meta-analysis of trials from the rituximab

Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

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Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

2017-11-05

Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

Interstitial microwave hyperthermia treatment investigations

International Nuclear Information System (INIS)

Siauve, N; Lormel, C

2012-01-01

Microwave ablation also called interstitial hyperthermia is a medical procedure used in the treatment of many cancers, cardiac arrhythmias and other medical conditions. With this medical therapy, an electromagnetic source (antenna) is directly positioned in the target tissue and a sufficient power is injected to necrosis the tissue. The aim of this study is to propose a design procedure and develop the associated tools, for determining the optimal shape, dimensions, type and operating frequency of antenna according to the target volume. In this context, a 3D numerical predictive model of temperature elevation induced by the electric fields and two benches for thermal and electrical tissues properties characterization have been developed. To validate the procedure and the different tools, an experimental bench test which includes interstitial antenna, external microwave generator, phantom that represents the target tissue and measurement system of temperature and electric field has been elaborated.

The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

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Mishima, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Terui, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Takeuchi, K [Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo (Japan); Matsumoto-Mishima, Y; Matsusaka, S [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Utsubo-Kuniyoshi, R [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Hatake, K [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan)

2011-04-01

C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy.

Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.

Science.gov (United States)

Massicano, Adriana V F; Pujatti, Priscilla B; Alcarde, Lais F; Suzuki, Miriam F; Spencer, Patrick J; Araújo, Elaine B

2016-01-01

The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

Restraint stress intensifies interstitial K+ accumulation during severe hypoxia

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Christian eSchnell

2012-03-01

Full Text Available Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for three weeks (6 h/day. In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current (DC potential shift was shortened after stress. Moreover, K+ fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K+ levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for GFAP (glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K+ channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance and K+-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K+ accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K+ buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain.

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

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Mark T Winkler

Full Text Available Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH. We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide

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Kamel El-Reshaid

2013-04-01

Full Text Available We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to 0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome

Science.gov (United States)

Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-01-01

Abstract Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab. A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established. He received Rituximab 375 mg/m2 (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm3. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39). Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID:27684863

Rituximab does not reset defective early B cell tolerance checkpoints

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Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

2015-01-01

Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

A case of "refractory" lupus erythematosus profundus responsive to rituximab [case report].

LENUS (Irish Health Repository)

McArdle, Adrian

2012-02-01

Lupus erythematosus profundus is a rare complication of systemic lupus erythematosus characterized by the presence of deep, tender subcutaneous nodules. A 22-year-old African-American female with extensive lupus profundus resistant to conventional therapies was treated with two infusions of the anti-CD20 monoclonal antibody, rituximab, at a dosage of 1,000 mg each. The patient demonstrated a remarkable clinical response as indicated by the disappearance of the nodules. B-cell depletion therapy with rituximab used alone or in combination with other therapies may be a viable option in patients with lupus profundus refractory to current therapies.

Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study.

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Curtis, Jeffrey R; Sarsour, Khaled; Napalkov, Pavel; Costa, Laurie A; Schulman, Kathy L

2015-11-11

Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors). RA patients at least 18 years old were selected from the MarketScan databases (2010-2012) if they had at least one prescription/administration of abatacept, rituximab, tocilizumab, or anti-TNF after having discontinued a different biologic agent and meeting enrollment criteria. Cox models estimated the risk of incident ILD and ILD-related hospitalization. Sensitivity analyses used an alternate ILD case definition. We identified 13,795 episodes of biologic exposure in 11,219 patients. Mean (standard deviation) follow-up was 0.7 (0.5) years. Patients receiving alternate MOA agents were more likely to have had recent exposure to steroids, prior exposure to a greater number of biologics, and history of ILD, anemia, chronic obstructive pulmonary disease, and other pulmonary conditions. When the sensitive definition was used, unadjusted ILD incidence rates (95% confidence interval, or CI) ranged from 4.0 (1.6-8.2, abatacept) to 12.2 (5.6-23.2, infliximab) per 1000 person-years. Being older (hazard ratio (HR) 3.5; 95% CI 2.1-6.0), being male (HR 3.1; 95% CI 1.2-8.4), and having another pulmonary condition (HR 4.8; 95% CI 1.7-13.7) were associated with increased ILD incidence in either sensitive and/or specific models. There were no significant differences by biologic class. Hospitalization rates (95% CI) when the sensitive definition was used ranged from 55.6 (6.7-200.7, tocilizumab) to 262.5 (71.5-672.2, infliximab). In Cox models, recent methotrexate exposure was associated with reduced ILD hospitalization (HR 0.16; 95% CI 0.06-0.46), whereas being male (HR 2.5; 95% CI 1.3-4.8) and having had a hospitalization for asthma (HR 3

Energetics of formation and migration of self-interstitials and self-interstitial clusters in α-iron

International Nuclear Information System (INIS)

Wirth, B.D.; Odette, G.R.; California Univ., Santa Barbara, CA; Maroudas, D.; Lucas, G.E.; California Univ., Santa Barbara, CA

1997-01-01

Energetic primary recoil atoms from fast neutron irradiation generate both isolated point defects and clusters of vacancies and interstitials. Self-interstitial mobility as well as defect cluster stability and mobility play key roles in the subsequent fate of defects and, hence, in the overall microstructural evolution under irradiation. Self-interstitials and two, three and four-member self-interstitial clusters are highly mobile at low temperatures as observed in molecular-dynamics simulations and high mobility probably also extends to larger clusters. In this study, the morphology, energetics and mobility of self-interstitials and small self-interstitial clusters in α-iron are studied by molecular-statics and molecular-dynamics simulations using a Finnis-Sinclair many-body interatomic potential. Self-interstitial migration is found to be a two-step process consisting of a rotation out of the split-dumbbell configuration into the split-dumbbell configuration and translational jumps through the crowdion configuration before returning to the dumbbell configuration. Self-interstitial clusters of type split-interstitials assembled on adjacent {110} planes migrate along directions in an amoeba-like fashion by sequential local dissociation and re-association processes. (orig.)

Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept).

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Gashi, Afrim A; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

2014-01-01

To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more

Interstitial Fe in MgO

CERN Document Server

Mølholt, T E; Gunnlaugsson, H P; Svane, A; Masenda, H; Naidoo, D; Bharuth-Ram, K; Fanciulli, M; Gislason, H P; Johnston, K; Langouche, G; Ólafsson, S; Sielemann, R; Weyer, G

2014-01-01

Isolated Fe-57 atoms were studied in MgO single-crystals by emission Mossbauer spectroscopy following implantation of Mn-57 decaying to Fe-57. Four Mossbauer spectral components were found corresponding to different Fe lattice positions and/or charge states. Two components represent Fe atoms substituting Mg as Fe2+ and Fe3+, respectively; a third component is due to Fe in a strongly implantation-induced disturbed region. The fourth component, which is the focus of this paper, can be assigned to Fe at an interstitial site. Comparison of its measured isomer shift with ab initio calculations suggests that the interstitial Fe is located on, or close to, the face of the rock-salt MgO structure. To harmonize such an assignment with the measured near-zero quadrupole interaction a local motion process (cage motion) of the Fe has to be stipulated. The relation of such a local motion as a starting point for long range diffusion is discussed.

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

International Nuclear Information System (INIS)

Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

2007-01-01

Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

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Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

Directory of Open Access Journals (Sweden)

Mariana P. Miranda-Hernández

2015-01-01

Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

Science.gov (United States)

Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

2015-01-01

Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

The diffuse interstitial lung disease - with emphasis in the idiopathic interstitial pneumonias

International Nuclear Information System (INIS)

Bustillo P, Jose G; Pacheco, Pedro M; Matiz, Carlos; Ojeda, Paulina; Carrillo B, Jorge A.

2003-01-01

The term diffuse interstitial lung disease, it refers to those diseases that commit the interstice basically, the space between the membrane basal epithelial and endothelial, although the damage can also commit the outlying air spaces and the vessels; the supplement is centered in the diffuse interstitial lung illness of unknown cause; well-known as idiopathic interstitial pneumonias, making emphasis in the more frequents, the pulmonary fibrosis idiopathic or cryptogenic fibrosant alveolitis

Diffuse neutron scattering study of metallic interstitial solid solutions

International Nuclear Information System (INIS)

Barberis, P.

1991-10-01

We studied two interstitial solid solutions (Ni-C(1at%) and Nb-O(2at%) and two stabilized zirconia (ZrO2-CaO(13.6mol%) and ZrO2-Y2O3(9.6mol%) by elastic diffuse neutron scattering. We used polarized neutron scattering in the case of the ferromagnetic Ni-based sample, in order to determine the magnetic perturbation induced by the C atoms. Measurements were made on single crystals in the Laboratoire Leon Brillouin (CEA-CNRS, Saclay, France). An original algorithm to deconvolve time-of-flight spectra improved the separation between elastically and inelastically scattered intensities. In the case of metallic solutions, we used a simple non-linear model, assuming that interstitials are isolated and located in octahedral sites. Results are: - in both compounds, nearest neighbours are widely displaced away from the interstitial, while next nearest neighbours come slightly closer. - the large magnetic perturbation induced by carbon in Nickel decreases with increasing distance on the three first neighbour shells and is in good agreement with the total magnetization variation. - no chemical order between solute atoms could be evidenced. Stabilized zirconia exhibit a strong correlation between chemical order and the large displacements around vacancies and dopants. (Author). 132 refs., 38 figs., 13 tabs

Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

Science.gov (United States)

Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

2017-09-01

Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients.

Science.gov (United States)

Radaelli, M; Moiola, L; Sangalli, F; Esposito, F; Barcella, V; Ferrè, L; Rodegher, M; Colombo, B; Fazio, R; Martinelli, V; Comi, G

2016-04-01

To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.

La interstitial defect-induced insulator-metal transition in the oxide heterostructures LaAl O3 /SrTi O3

Science.gov (United States)

Zhou, Jun; Yang, Ming; Feng, Yuan Ping; Rusydi, Andrivo

2017-11-01

Perovskite oxide interfaces have attracted tremendous research interest for their fundamental physics and promising all-oxide electronic applications. Here, based on first-principles calculations, we propose a surface La interstitial promoted interface insulator-metal transition in LaAl O3 /SrTi O3 (110). Compared with surface oxygen vacancies, which play a determining role on the insulator-metal transition of LaAl O3 /SrTi O3 (001) interfaces, we find that surface La interstitials can be more experimentally realistic and accessible for manipulation and more stable in an ambient atmospheric environment. Interestingly, these surface La interstitials also induce significant spin-splitting states with a Ti dy z/dx z character at a conducting LaAl O3 /SrTi O3 (110) interface. On the other hand, for insulating LaAl O3 /SrTi O3 (110) (<4 unit cells LaAl O3 thickness), a distortion between La (Al) and O atoms is found at the LaAl O3 side, partially compensating the polarization divergence. Our results reveal the origin of the metal-insulator transition in LaAl O3 /SrTi O3 (110) heterostructures, and also shed light on the manipulation of the superior properties of LaAl O3 /SrTi O3 (110) for different possibilities in electronic and magnetic applications.

Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion

NARCIS (Netherlands)

Mihajloviç, Jovan; Bax, Pieter; van Breugel, Erwin; Blommestein, Hedwig M.; Hoogendoorn, Mels; Hospes, Wobbe; Postma, Maarten J.

Purpose: The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands.  Methods: Using a prospective, observational, bottom-up microcosting study, we collected primary data on the

Nonspecific microvascular vasodilation during iontophoresis is attenuated by application of hyperosmolar saline.

Science.gov (United States)

Asberg, A; Holm, T; Vassbotn, T; Andreassen, A K; Hartmann, A

1999-07-01

Iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) combined with laser Doppler skin blood perfusion measurements are used for determination of endothelial-dependent and -independent vasodilation. However, the method is biased by nonspecific vasodilation. The primary aim of this study was to investigate if iontophoresis-induced nonspecific vasodilation may be attenuated by addition of high molar concentrations of NaCl to the iontophoresis solutions. Secondary we investigated the applicability of 5 mol/liter NaCl solution as vehicle for ACh and SNP in this method. Skin perfusion changes were determined for iontophoresis of pure vehicles, deionized water and 5 mol/liter NaCl solution, in 12 healthy volunteers. Responses in skin perfusion to iontophoresis of ACh and SNP dissolved in both vehicles were also investigated. Addition of 5 mol/liter NaCl to deionized water significantly attenuated the nonspecific vasodilation and lowered the potential applied over the skin. The inter- and intraindividual coefficients of variation to ACh and SNP responses became, however, higher using hyperosmolar vehicle. During iontophoresis of SNP (in deionized water) we were unable to distinguish between SNP and vehicle effects. This study shows that the nonspecific vasodilation induced by iontophoresis can be attenuated by addition of 5 mol/liter NaCl, possibly due to lower electrical potential over the skin. However, the variability of the method was not improved. When deionized water was used as vehicle the effect of SNP could not be differentiated from that of the vehicle. This was not the case for ACh. Copyright 1999 Academic Press.

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis

Directory of Open Access Journals (Sweden)

Olivia Meira Dias

2014-01-01

Full Text Available The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs. There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

Directory of Open Access Journals (Sweden)

G.C. dos Santos

2013-11-01

Full Text Available Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

Ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study

Science.gov (United States)

Burger, Jan A.; Keating, Michael J.; Wierda, William G.; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y.; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M.; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O’Brien, Susan

2014-01-01

Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), is an effective therapy for patients with relapsed chronic lymphocytic leukemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab (iR) in patients with high-risk CLL. Methods In this single-arm, phase 2 studywe enrolled 40 patients with high-risk CLL at MD Anderson Cancer Center, Houston, Texas, USA. Patients with symptomatic CLL requiring therapy received 28 day cycles of once-daily ibrutinib 420 mg , together with rituximab (weekly during cycle 1, then once per cycle until cycle 6), followed by continuous single-agent ibrutinib. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01520519 and is no longer accruing patients. Findings Between February 28, 2012 and September 11, 2012, we enrolled 40 CLL patients with high-risk disease features. 20 patients had del17p or TP53 mutations (16 previously treated, 4 untreated), 13 had relapsed CLL with del11q, and 7 patients a PFS infections occurred in 4 patients (10%), no grade 4 or 5 infections occurred. At 18 months, the Kaplan Meier estimate of progression-free survival was 78% (95% CI 60.6–88.5) (del[17p] or TP53 mutation: 72%, 95% CI: 45.6–87.6) Interpretation Ibrutinib in combination with rituximab is a well-tolerated regimen for patients with high-risk CLL. It induces high rates of remissions and has positive impact on QOL in this difficult-to-treat patient population. These encouraging data merit further investigation of the added benefit of rituximab as combination partner for ibrutinib in an ongoing randomized trial, in which single-agent ibrutinib is compared to iR combination therapy (NCT02007044). Funding Pharmacyclics, Inc., Cancer Prevention and Research Institute of Texas (CPRIT), Leukemia & Lymphoma Society, NCI Grant P30 CA

Heparan sulfate proteoglycans mediate interstitial flow mechanotransduction regulating MMP-13 expression and cell motility via FAK-ERK in 3D collagen.

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Zhong-Dong Shi

2011-01-01

Full Text Available Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP expression in rat vascular smooth muscle cells (SMCs and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS chains from proteoglycan (PG core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1 suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13 expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction

Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

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Pierre de Flon

Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

Science.gov (United States)

Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

2017-02-22

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

DEFF Research Database (Denmark)

Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

2007-01-01

In this review, the authors summarise the clinical results obtained after therapy with rituximab in autoimmune diseases, including Graves' disease and Graves' ophthalmopathy. On the basis of qualitative and quantitative analyses of B- and T-cell subsets, and autoantibody levels obtained in other...... diseases before and after rituximab therapy, the authors interpret the results of the only two clinical investigations of the efficacy of rituximab in the treatment of Graves' disease and Graves' opthalmopathy reported so far. No significant effect on autoantibody levels was observed. Nonetheless, 4 out...... of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

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Takafumi Suda

2015-01-01

Full Text Available Pulmonary involvement is common in rheumatoid arthritis (RA and affects all the components of the lung. Interstitial lung disease (ILD is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

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Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

2016-07-01

Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

Basal interstitial water pressure in laboratory debris flows over a rigid bed in an open channel

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N. Hotta

2012-08-01

Full Text Available Measuring the interstitial water pressure of debris flows under various conditions gives essential information on the flow stress structure. This study measured the basal interstitial water pressure during debris flow routing experiments in a laboratory flume. Because a sensitive pressure gauge is required to measure the interstitial water pressure in shallow laboratory debris flows, a differential gas pressure gauge with an attached diaphragm was used. Although this system required calibration before and after each experiment, it showed a linear behavior and a sufficiently high temporal resolution for measuring the interstitial water pressure of debris flows. The values of the interstitial water pressure were low. However, an excess of pressure beyond the hydrostatic pressure was observed with increasing sediment particle size. The measured excess pressure corresponded to the theoretical excess interstitial water pressure, derived as a Reynolds stress in the interstitial water of boulder debris flows. Turbulence was thought to induce a strong shear in the interstitial space of sediment particles. The interstitial water pressure in boulder debris flows should be affected by the fine sediment concentration and the phase transition from laminar to turbulent debris flow; this should be the subject of future studies.

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

Science.gov (United States)

Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

2018-04-03

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

Lipid-derived free radical production in superantigen-induced interstitial pneumonia

Science.gov (United States)

Miyakawa, Hisako; Mason, Ronald P.; Jiang, JinJie; Kadiiska, Maria B.

2009-01-01

We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. PMID:19376221

Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

Science.gov (United States)

Chanan-Khan, Asher; Cramer, Paula; Demirkan, Fatih; Fraser, Graeme; Silva, Rodrigo Santucci; Grosicki, Sebastian; Pristupa, Aleksander; Janssens, Ann; Mayer, Jiri; Bartlett, Nancy L; Dilhuydy, Marie-Sarah; Pylypenko, Halyna; Loscertales, Javier; Avigdor, Abraham; Rule, Simon; Villa, Diego; Samoilova, Olga; Panagiotidis, Panagiots; Goy, Andre; Mato, Anthony; Pavlovsky, Miguel A; Karlsson, Claes; Mahler, Michelle; Salman, Mariya; Sun, Steven; Phelps, Charles; Balasubramanian, Sriram; Howes, Angela; Hallek, Michael

2016-02-01

Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

Science.gov (United States)

Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Interstitial pregnancy: role of MRI

International Nuclear Information System (INIS)

Filhastre, M.; Lesnik, A.; Dechaud, H.; Taourel, P.

2005-01-01

We report the MRI features of two cases of interstitial pregnancy. In both cases, MRI was able to localize the ectopic pregnancy by showing a gestational structure surrounded by a thick wall in the upper part of the uterine wall separated from the endometrium by an uninterrupted junctional zone. Because US may confuse angular and interstitial pregnancies and because interstitial pregnancy has a particular evolutive course, MR imaging may play a key role in the diagnosis and management of women with interstitial pregnancy. (orig.)

A simple device to protect against osteoradionecrosis induced by interstitial irradiation

International Nuclear Information System (INIS)

Levendag, P.C.; Visch, L.L.; Driver, N.

1990-01-01

The incidence of osteoradionecrosis has declined since the introduction of preventive oral hygiene programs and meticulous dental evaluations before and after irradiation. Nevertheless, radiation dose per se still remains an important factor in osteoradionecrosis. Interstitial radiation has received much attention in the past decade since the use of flexible afterloading systems. It has become common practice in large oncology centers to implant radiation carriers in bulky tumor in the oral cavity and/or oropharynx. For interstitial radiation, with or without external radiation, minimal tumor doses are often cited to be more than 70 Gy. Unfortunately, if the mandible receives more than 70 Gy, it is at risk for the development of osteoradionecrosis. Therefore a simple protective lead device has been designed for routine use in brachytherapy in oral cavity tumors to reduce the dose to the mandible. This device will diminish the potential risk of osteoradionecrosis development

Clinical importance of non-specific lipid transfer proteins as food allergens

NARCIS (Netherlands)

van Ree, R.

2002-01-01

Non-specific lipid transfer proteins (nsLTPs) have recently been identified as plant food allergens. They are good examples of true food allergens, in the sense that they are capable of sensitizing, i.e. inducing specific IgE, as well as of eliciting severe symptoms. This is in contrast with most

EFFICACY OF RECURRENT RITUXIMAB TREATMENT IN PATIENT WITH SEVERE REFRACTORY SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

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E.I. Alexeeva

2011-01-01

Full Text Available The article contains clinical case description of a severe systemic juvenile rheumatoid arthritis, that was refractory to classic immunosuppressant therapy. The disease was characterized by such extraarticular manifestations as fever, lymphadenopathy,  hepatosplenomegaly, polyserositis, generalized joint involvement and high activity in lab tests. As a result of severe clinical course of the disease, patients develop bilateral aseptic bone necrosis in coxofemoral joints and coxarthrosis. Against the background of glucocorticosteroid treatment the patient has developed hormone-dependency and hormone resistance. Inclusion into the treatment of anti-CD20 monoclonal antibodies (rituximab has stopped systemic manifestations of the disease, inflammation in the joints, normalized lab activity rates. The positive therapeutic effect allowed to perform surgery due to bilateral coxarthrosis. These results show that rituximab is highly effective in children with systemic juvenile rheumatoid arthritis, that is resistant to classic immunosupressants and glucocorticoides. Key words: children, systemic juvenile rheumatoid arthritis, rituximab, recurrent treatment, prosthetics, hip joint. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 157–163.

Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

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Zhao Jiangning

2012-08-01

Full Text Available Abstract Indolent lymphoma (IL, the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone and R-FM (fludarabine, mitoxantrone. The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

Formation and annealing of metastable (interstitial oxygen)-(interstitial carbon) complexes in n- and p-type silicon

CERN Document Server

Makarenko, L F; Lastovskii, S B; Murin, L I; Moll, M; Pintilie, I

2014-01-01

It is shown experimentally that, in contrast to the stable configuration of (interstitial carbon)-(interstitial oxygen) complexes (CiOi), the corresponding metastable configuration (CiOi{*}) cannot be found in n-Si based structures by the method of capacitance spectroscopy. The rates of transformation CiOi{*} -> CiOi are practically the same for both n- and p-Si with a concentration of charge carriers of no higher than 10(13) cm(-3). It is established that the probabilities of the simultaneous formation of stable and metastable configurations of the complex under study in the case of the addition of an atom of interstitial carbon to an atom of interstitial oxygen is close to 50\\%. This is caused by the orientation dependence of the interaction potential of an atom of interstitial oxygen with an interstitial carbon atom, which diffuses to this oxygen atom.

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

Science.gov (United States)

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

LENUS (Irish Health Repository)

Maung, Su W

2013-10-01

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg\\/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24\\/34) with 26·5% (9\\/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21\\/24) and 3 months in 12·5% (3\\/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12\\/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg\\/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.

B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

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Annelieke A.A. van der Linde

2011-12-01

Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

Science.gov (United States)

Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M; Ascherman, Dana P; Levesque, Marc C

2016-06-01

To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. Following rituximab, anti-Jo-1 levels decreased over time (P myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

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Maria Sancho

2017-01-01

Full Text Available Cyclophosphamide- (CYP- induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO production. We investigated the changes in the number and distribution of interstitial cells (ICs and in the expression of endothelial NO synthase (eNOS in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer. IC immunolabeling with CD34, PDGFRα, and vimentin was enhanced, as reflected by higher colocalization indexes of the distinct pairs of markers. Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented eNOS expression and ICs proliferation, as well as the increased voiding frequency and urinary tract weight provoked by CYP. As similar results were obtained in the urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.

Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

Science.gov (United States)

2015-01-01

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

Directory of Open Access Journals (Sweden)

Aditi Pandit

2013-01-01

Full Text Available Association of Grave′s ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave′s ophthalmopathy successfully treated with rituximab.

Gigantic uphill drift of vacancies and self-interstitials in silicon

International Nuclear Information System (INIS)

Voronkov, V.V.; Falster, R.

2009-01-01

Point defect transport in a growing crystal includes a drift along the temperature gradient, G, at a velocity αG. It was not clear if the drift is negligible or strong in silicon crystal growth. It is now found that reported microdefect patterns in crystals grown with a temporarily halt provide a clear evidence in favour of a strong (even gigantic) drift of both kinds of intrinsic point defects. The drift coefficients α V (for vacancies) and α I (for self-interstitials) are deduced by fitting the simulating defect profiles to the observed location of halt-induced interstitial region immersed into a vacancy-type crystal.

Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

DEFF Research Database (Denmark)

Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

2016-01-01

For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

Science.gov (United States)

Kahl, Brad S.; Hong, Fangxin; Williams, Michael E.; Gascoyne, Randy D.; Wagner, Lynne I.; Krauss, John C.; Habermann, Thomas M.; Swinnen, Lode J.; Schuster, Stephen J.; Peterson, Christopher G.; Sborov, Mark D.; Martin, S. Eric; Weiss, Matthias; Ehmann, W. Christopher; Horning, Sandra J.

2014-01-01

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. PMID:25154829

Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab.

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Hayes, Jerrard M; Frostell, Asa; Karlsson, Robert; Müller, Steffen; Martín, Silvia Míllan; Pauers, Martin; Reuss, Franziska; Cosgrave, Eoin F; Anneren, Cecilia; Davey, Gavin P; Rudd, Pauline M

2017-10-01

Fc gamma receptors (FcγR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcγRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcγR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcγ receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcγR were characterized and we discuss the CHO-FcγRIIIa Phe158/Val158 and CHO-FcγRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcγR glycosylation. The glycan profiles of CHO expressed FcγRI and FcγRIIIa Phe158/Val158 were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

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Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

2014-08-12

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

DEFF Research Database (Denmark)

Larsen, Janni Lisander; Jacobsen, Soren

2013-01-01

To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

Smoking-related interstitial lung diseases

International Nuclear Information System (INIS)

Marten, K.

2007-01-01

The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

In-gap bound states induced by interstitial Fe impurities in iron-based superconductors

Energy Technology Data Exchange (ETDEWEB)

Zhang, Degang, E-mail: degangzhang@yahoo.com

2015-12-15

Highlights: • We provide an explanation for the interesting STM observation of the robust zero energy bound state on the interstitial Fe impurities in iron-based superconductors. - Abstract: Based on a two-orbit four-band tight binding model, we investigate the low-lying electronic states around the interstitial excess Fe ions in the iron-based superconductors by using T-matrix approach. It is shown that the local density of states at the interstitial Fe impurity (IFI) possesses a strong resonance inside the gap, which seems to be insensitive to the doping and the pairing symmetry in the Fe–Fe plane, while a single or two resonances appear at the nearest neighboring (NN) Fe sites. The location and height of the resonance peaks only depend on the hopping t and the pairing parameter Δ{sub I} between the IFI and the NN Fe sites. These in-gap resonances are originated in the Andreev’s bound states due to the quasiparticle tunneling through the IFI, leading to the change of the magnitude of the superconducting order parameter. When both t and Δ{sub I} are small, this robust zero-energy bound state near the IFI is consistent with recent scanning tunneling microscopy observations.

Effects of applied strain on nanoscale self-interstitial cluster formation in BCC iron

Energy Technology Data Exchange (ETDEWEB)

Gao, Ning; Setyawan, Wahyu; Kurtz, Richard J.; Wang, Zhiguang

2017-09-01

The effect of applied strains on the configurational evolution of self-interstitial clusters in BCC iron (Fe) is explored with atomistic simulations. A novel cluster configuration is discovered at low temperatures (<600 K), which consists of <110> dumbbells and <111> crowdions in a specific configuration, resulting in an immobile defect. The stability and diffusion of this cluster at higher temperatures is explored. In addition, an anisotropy distribution factor of a particular [hkl] interstitial loop within the family of loops is calculated as a function of strain. The results show that loop anisotropy is governed by the angle between the stress direction and the orientation of the <111> crowdions in the loop, and directly linked to the stress induced preferred nucleation of self-interstitial atoms.

Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

Science.gov (United States)

Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

2013-03-27

Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

Bone tissue engineering: the role of interstitial fluid flow

Science.gov (United States)

Hillsley, M. V.; Frangos, J. A.

1994-01-01

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents.

Science.gov (United States)

Xue, Kai; Gu, Juan J; Zhang, Qunling; Mavis, Cory; Hernandez-Ilizaliturri, Francisco J; Czuczman, Myron S; Guo, Ye

2016-02-01

Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were

The value of rituximab treatment in primary Sjögren's syndrome

NARCIS (Netherlands)

Verstappen, Gwenny M.; van Nimwegen, Jolien F.; Vissink, Arjan; Kroese, Frans G. M.; Bootsma, Hendrika

The rationale for B cell depletion therapy with rituximab in primary Sjogren's syndrome relies upon the well-established role of B cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B cell activity are significantly affected by treatment, both in the target

Temperature control in interstitial laser cancer immunotherapy

Science.gov (United States)

Bandyopadhyay, Pradip K.; Holmes, Kyland; Burnett, Corinthius; Zharov, Vladimir P.

2003-07-01

Positive results of Laser-Assisted Cancer Immunotherapy (LACI) have been reported previously in the irradiation of superficial tumors. This paper reports the effect of LACI using laser interstitial therapy approach. We hypothesize that the maximum immuno response depends on laser induced tumor temperature. The measurement of tumor temperature is crucial to ensure necrosis by thermal damage and immuno response. Wister Furth female rats in this study were inoculated with 13762 MAT B III rat mammary adinocarcinoma. LACI started seven to ten days following inoculation. Contrary to surface irradation, we applied laser interstitial irradiation of tumor volume to maximize the energy deposition. A diode laser with a wavelength of 805 nm was used for tumor irradiation. The laser energy was delivered inside the tumor through a quartz fiber. Tumor temperature was measured with a micro thermocouple (interstitial), while the tumor surface temperature was controlled with an IR detector. The temperature feedback demonstrates that it is possible to maintain the average tumor temperature at the same level with reasonable accuracy in the desired range from 65°C-85°C. In some experiments we used microwave thermometry to control average temperature in deep tissue for considerable period of time, to cause maximum thermal damage to the tumor. The experimental set-up and the different temperature measurement techniques are reported in detail, including the advantages and disadvantages for each method.

Intracranial interstitial radiation

International Nuclear Information System (INIS)

Willis, D.; Rittenmeyer, H.; Hitchon, P.

1986-01-01

Primary malignant brain tumors are fatal, with 90% of patients having these tumors dying within two years following diagnosis. Cranial interstitial radiation therapy, a technique under investigation to control these tumors, involves implantation of radioactive iodine 125 seeds into the tumor bed by stereotaxic technique. The interstitial radiation technique, monitoring of radiation, and nursing care of patients are discussed. Case histories are presented, along with discussion of results attained using this therapy, and its future

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

Directory of Open Access Journals (Sweden)

Øystein Fluge

Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

International Nuclear Information System (INIS)

Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

2005-01-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 131 I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with 131 I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of 131 I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

Directory of Open Access Journals (Sweden)

Hrvoje Holik

2015-09-01

Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

Effects of applied strain on nanoscale self-interstitial cluster formation in BCC iron

Science.gov (United States)

Gao, Ning; Setyawan, Wahyu; Kurtz, Richard J.; Wang, Zhiguang

2017-09-01

The effect of applied strains on the configurational evolution of self-interstitial clusters in BCC iron (Fe) is explored with atomistic simulations. A novel cluster configuration is discovered at low temperatures (family of 〈 hkl 〉 loops is calculated as a function of strain. The results show that loop anisotropy is governed by the angle between the stress direction and the orientation of the 〈 111 〉 crowdions in the loop, and directly linked to the stress induced preferred nucleation of self-interstitial atoms.

Do We Need Exercise Tests to Detect Gas Exchange Impairment in Fibrotic Idiopathic Interstitial Pneumonias?

Directory of Open Access Journals (Sweden)

Benoit Wallaert

2012-01-01

Full Text Available In patients with fibrotic idiopathic interstitial pneumonia (f-IIP, the diffusing capacity for carbon monoxide (DLCO has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. The aim of this study was to compare DLCO, resting PaO2, P(A-aO2 at cardiopulmonary exercise testing peak, and oxygen desaturation during a 6-min walk test (6MWT. Results were obtained in 121 patients with idiopathic pulmonary fibrosis (IPF, n=88 and fibrotic nonspecific interstitial pneumonias (NSIP, n=33. All but 3 patients (97.5% had low DLCO values (35 mmHg and 100 (83% demonstrated significant oxygen desaturation during 6MWT (>4%. Interestingly 27 patients had low DLCO and normal P(A-aO2, peak and/or no desaturation during the 6MWT. The 3 patients with normal DLCO also had normal PaO2, normal P(A-aO2, peak, and normal oxygen saturation during 6MWT. Our results demonstrate that in fibrotic IIP, DLCO better defines impairment of pulmonary gas exchange than resting PaO2, exercise P(A-aO2, peak, or 6MWT SpO2.

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats.

Directory of Open Access Journals (Sweden)

Yuki Otani

Full Text Available Therapeutic monoclonal antibodies (mAbs have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F and GnGn (G0 were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

Migration of di- and tri-interstitials in silicon

International Nuclear Information System (INIS)

Posselt, M.; Gao, F.; Zwicker, D.

2005-01-01

A comprehensive study on the migration of di- and tri-interstitials in silicon is performed using classical molecular dynamics simulations with the Stillinger-Weber potential. The initial di- and tri-interstitial configurations with the lowest formation energies are determined, and then, the defect migration is investigated for temperatures between 800 and 1600 K. The defect diffusivity and the self-diffusion coefficient per defect are calculated. Compared to the mono-interstitial, the di-interstitial migrates faster, whereas the tri-interstitial diffuses slower. The migration mechanism of the di-interstitial shows a pronounced dependence on the temperature. Like in the case of the mono-interstitial, the mobility of the di-interstitial is higher than the mobility of the lattice atoms during the defect diffusion. On the other hand, the tri-interstitial mobility is lower than the corresponding atomic mobility. The implications of the present results for the analysis of experimental data on defect evolution and migration are discussed

Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

International Nuclear Information System (INIS)

Camats, Nuria; Ruiz-Herrera, Aurora; Parrilla, Juan Jose; Acien, Maribel; Paya, Pilar; Giulotto, Elena; Egozcue, Josep; Garcia, Francisca; Garcia, Montserrat

2006-01-01

The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs

Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

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Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Ruiz-Herrera, Aurora [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Acien, Maribel [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Paya, Pilar [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Giulotto, Elena [Dipartimento di Genetica e Microbiologia Adriano Buzzati Traverso, Universita degli Studi di Pavia, 27100 Pavia (Italy); Egozcue, Josep [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Montserrat [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain) and Departament de Biologia Cellular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)]. E-mail: Montserrat.Garcia.Caldes@uab.es

2006-03-20

The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs.

First-principles studies of di-arsenic interstitial and its implications for arsenic-interstitial diffusion in crystalline silicon

International Nuclear Information System (INIS)

Kim, Yonghyun; Kirichenko, Taras A.; Kong, Ning; Larson, Larry; Banerjee, Sanjay K.

2007-01-01

We propose new structural configurations and novel diffusion mechanisms for neutral di-arsenic interstitial (As 2 I 2 ) in silicon with a first-principle density functional theory simulation within the generalized gradient approximation. With an assumption of excess silicon interstitials and high arsenic concentrations, neutral As 2 I 2 is expected to be favorable and mobile with low-migration barrier. Moreover, because the diffusion barrier of arsenic interstitial pairs (AsI) is very low ( 2 I 2 can be easily formed and likely intermediate stage of larger arsenic interstitial clusters

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

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Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

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Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide; Ogata, Fusa; Okuyama, Shuhei; Choyke, Peter L; Kobayashi, Hisataka

2018-02-21

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

Molecular evidence for the induction of large interstitial deletions on mouse chromosome 8 by ionizing radiation

International Nuclear Information System (INIS)

Turker, Mitchell S.; Pieretti, Maura; Kumar, Sudha

1997-01-01

The P19H22 mouse embryonal carcinoma cell line is characterized by a hemizygous deficiency for the chromosome 8 encoded aprt (adenine phosphoribosyltransferase) gene and heterozygosity for many chromosome 8 loci. We have previously demonstrated that this cell line is suitable for mutational studies because it is permissive of events ranging in size from base-pair substitutions at the aprt locus to apparent loss of chromosome 8. Large mutational events, defined by loss of the remaining aprt allele, were found to predominate in spontaneous mutants and those induced by ionizing radiation. In this study we have used a PCR based assay to screen for loss of heterozygosity at microsatellite loci both proximal and distal to aprt in 137 Cs-induced and spontaneous aprt mutants. This approach allowed us to distinguish apparent interstitial deletional events from apparent recombinational events. Significantly, 32.5% (26 of 80) of the mutational events induced by 137 Cs appeared to be interstitial deletions as compared with 7.7% (6 of 78) in the spontaneous group. This difference was statistically significant (p 137 Cs caused a significant number of deletion mutations. Most 137 Cs-induced interstitial deletions were larger than 6 cM, whereas none of the spontaneous deletions were larger than 6 cM. These results provide further support for the notion that ionizing radiation induces deletion mutations and validate the use of the P19H22 cell line for the study of events induced by ionizing radiation

Interstitial Cells of Blood Vessels

Directory of Open Access Journals (Sweden)

Vladimír Pucovský

2010-01-01

Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.

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Fichel, Fanny; Baudot, Nathalie; Gaitz, Jean-Pierre; Trad, Salim; Barbe, Coralie; Francès, Camille; Senet, Patricia

2014-01-01

In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy (NVC) pattern is observed in 90% of cases and seems to be associated with severity and progression of the disease. To describe the characteristics of SSc patients with normal or nonspecific (normal/nonspecific) NVC. In a retrospective cohort study, clinical features and visceral involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc controls with the SSc-specific NVC pattern. Normal/nonspecific NVC versus SSc-specific NVC pattern was significantly associated with absence of skin sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). Normal/nonspecific NVC in SSc patients appears to be associated with less severe skin involvement and less frequent severe pulmonary involvement. © 2014 S. Karger AG, Basel.

Superconducting electron tunneling as detection method for low frequency resonant vibration modes of interstitials in fcc lead

International Nuclear Information System (INIS)

Adrian, H.

1981-01-01

The influence of crystal defects on the phonon spectra was studied for fcc lead using superconducting tunneling spectroscopy. The theory predicts low frequency modes for the vibrational states of interstitials in (100) dumbbell configuration. Low temperature irradiation of superconducting point contacts with fast ions (point contact thickness small compared to the average ion range) showed radiation-induced structures in the low-energy part of the Eliashberg function for lead. These resonant modes are reduced by annealing at 18.5 K; they are attributed to small interstitial clusters. The radiation-induced structures are completely removed by room temperature annealing. (orig.)

Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

Science.gov (United States)

Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

2014-11-01

Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed. Copyright © 2014. Published by Elsevier B.V.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

Science.gov (United States)

Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

2016-01-01

A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

Chylothorax in dermatomyositis complicated with interstitial pneumonia.

Science.gov (United States)

Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi

2017-04-01

Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

Efficacy and Safety of Rituximab in the Treatment of Vasculitic Leg Ulcers Associated with Hepatitis C Virus Infection

Directory of Open Access Journals (Sweden)

Fabio Bonilla-Abadía

2012-01-01

Full Text Available Vasculitic leg ulcers are a cutaneous manifestation of hepatitis C virus (HCV infection often associated with cryoglobulinemia. Their treatment is difficult and is based on steroids and immunosuppressive drugs with an erratic response and a high probability of adverse reaction. We report three patients with vasculitic leg ulcers associated with hepatitis C virus infection who were treated successfully with rituximab. The pain control and healing were achieved quickly. No adverse effects with rituximab in these patients were presented.

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review.

Science.gov (United States)

Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-09-01

Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion.

[Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review].

Science.gov (United States)

Pons, Isaac; Espinosa, Gerard; Cervera, Ricard

2015-02-02

Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement. Copyright © 2013 Elsevier España, S.L.U. All rights

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

DEFF Research Database (Denmark)

Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

2016-01-01

BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less....... The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included...

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

In-vitro analysis of early calcification in aortic valvular interstitial cells using Laser-Induced Breakdown Spectroscopy (LIBS).

Science.gov (United States)

Davari, Seyyed Ali; Masjedi, Shirin; Ferdous, Zannatul; Mukherjee, Dibyendu

2018-01-01

Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in-vitro VIC cultures. Laser-induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in-vitro detection of calcium depositions in VICs at various osteogenic differentiation stages. VICs isolated from porcine aortic valves were cultured in osteogenic media over various days. Colorimetric calcium assays based on arsenazo dye and Von Kossa staining measured the calcium depositions within VICs. Simultaneously, LIBS signatures for Ca I (422.67 nm) atomic emission lines were collected for estimating calcium depositions in lyophilized VIC samples. Our results indicate excellent linear correlation between the calcium assay and our LIBS measurements. Furthermore, unlike the assay results, the LIBS results could resolve calcium signals from cell samples with as early as 2 days of osteogenic culture. Quantitatively, the LIBS measurements establish the limit of detection for calcium content in VICs to be ∼0.17±0.04 μg which indicates a 5-fold improvement over calcium assay. Picture: Quantitative LIBS enables in-vitro analysis for early stage detection of calcium deposition within aortic valvular interstitial cells (VICs). © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental depletion of different renal interstitial cell populations

International Nuclear Information System (INIS)

Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

1988-01-01

To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

Science.gov (United States)

Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

2018-04-10

The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane 3 , was originally published electronically on the publisher's internet portal (currently SpringerLink).

Early detection of interstitial pneumonia by 67Ga-citrate scintigraphy

International Nuclear Information System (INIS)

Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada

1985-01-01

In this paper we report our recent experience indicating usefulness of 67 Ga-citrate scintigraphy in 4 cases with inflammatory pulmonary diseases. These cases showed abnormal pulmonary 67 Ga uptake with normal chest radiographs. The first case with malignant lymphoma and the second one with lung cancer suffered from pulmonary infection following secondary immuno-insufficiency due to radiotherapy and chemotherapy. Pneumocystis carinii was suspected as causative agent in the first case, and gram negative bacilli in the second case. The third case with lung cancer developed radiation pneumonia after radiotherapy. The fourth case with acute bronchitis developed drug induced interstitial pneumonia presumably due to minocycline administration. It is concluded that 67 Ga-citrate scintigraphy is more sensitive for early detection of interstitial pneumonia than routine chest radiography. (author)

Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

International Nuclear Information System (INIS)

Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

2013-01-01

Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of 177 LuCl 3 , reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Trotman, Judith; Tedeschi, Alessandra; Matous, Jeffrey V; Macdonald, David; Tam, Constantine; Tournilhac, Olivier; Ma, Shuo; Oriol, Albert; Heffner, Leonard T; Shustik, Chaim; García-Sanz, Ramón; Cornell, Robert F; de Larrea, Carlos Fernández; Castillo, Jorge J; Granell, Miquel; Kyrtsonis, Marie-Christine; Leblond, Veronique; Symeonidis, Argiris; Kastritis, Efstathios; Singh, Priyanka; Li, Jianling; Graef, Thorsten; Bilotti, Elizabeth; Treon, Steven; Buske, Christian

2017-02-01

In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58-74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenstr

Response to rituximab in a refractory case of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus

Directory of Open Access Journals (Sweden)

Niaz Faraz

2010-01-01

Full Text Available Thrombotic thrombocytopenic purpura (TTP is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secon-dary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythe-matosus (SLE and may be refractory to treatment with plasma exchange, requiring immuno-suppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued re-mission after eight months of follow-up. Rituximab appears to be an effective treatment in re-fractory cases of TTP associated with SLE.

Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

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Mella Olav

2009-07-01

Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion. Methods In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab. Results All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1 or double rituximab infusion (patients 2 and 3. Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen. Conclusion These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

Balance point characterization of interstitial fluid volume regulation.

Science.gov (United States)

Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

2009-07-01

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P(i)) and protein concentrations (C(i)) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P(i) and C(i) as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P(i) and C(i) arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P(i) and C(i) result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P(i) is unaffected by interstitial compliance. These simple algebraic solutions predict P(i) and C(i) that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.

Interstitial cystitis

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... symptoms get better. Reduce or stop consuming caffeine, chocolate, carbonated beverages, citrus drinks, and foods with a ... rarely done anymore Support Groups Some people may benefit from taking part in interstitial cystitis support groups . ...

Interstitial Cystitis

Science.gov (United States)

... relieve symptoms. Diet. Alcohol, tomatoes, spices, carbonated drinks, chocolate, caffeine, citrus fruits and drinks, pickled foods, artificial ... at scheduled times and using relaxation techniques. Physical therapy. People who have interstitial cystitis may have painful ...

Changes of bronchoalveolar cell pattern and lecithin content in experimental interstitial pneumonia

International Nuclear Information System (INIS)

Manabe, Hideki; Yasuoka, Susumu; Tsubura, Eiro

1978-01-01

The pathogenesis of diffuse interstitial fibrosing pneumonitis (DIFP) was studied by histological observations and analysis of the cells and lecithin content of bronchoalveolar lavage of rats with cyclophosphamide (CY)-induced pneumonitis or irradiation pneumonitis. The rats developed diffuse interstitial pneumonitis one week after the last of 5 intraperitoneal injections of 50 mg/kg of CY and gradually recovered in the next 14 weeks. The number of alveolar macrophages and the lecithin content in the bronchoalveolar lavage from these rats corresponded to the degree of inflammatory change of the lung tissue. The results of cell counts and analysis of the bronchoalveolar lavage from rats with irradiated pneumonitis were similar to those on rats with CY-induced pneumonitis, except that in irradiated rats the lecithin content of the lavage decreased with increase in severity of pulmonary fibrosis. These results indicate that the cell number and lecithin content of bronchoalveolar lavage are good parameters for use in diagnosis of DIFP. (auth.)

Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

Science.gov (United States)

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

2014-10-04

Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

Interstitial cystitis: painful bladder syndrome

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R F Sholan

2018-02-01

Full Text Available Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 000 women are diagnosed with interstitial cystitis. Diagnosis of the disease is difficult and is substantially based on clinical symptoms. Pelvic pain, urinary urgency, frequency and nocturia are the basic complaints in this pathology. The diagnosis requires exclusion of diseases with similar manifestations. So interstitial cystitis is frequently misdiagnosed as urinary tract infection, overactive bladder, urethral obstruction or diverticulosis, chronic prostatitis, bladder cancer, vulvodynia, endometriosis, and chronic pelvic pain. Etiopathogenesis of the disease is uncertain, which makes etiologic treatment impossible. Currently scientific discussions on the causes of disease continue as well as different treatment regimens are offered, but are often ineffective, palliative and temporary. The treatment for intersticial cystitis should focus on restoring normal bladder function, prevention of relapse of symptoms and improvement of patients’ quality of life. The literature review presents current view on the terminology, epidemiology, diagnosis and treatment of interstitial cystitis.

Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

DEFF Research Database (Denmark)

El Fassi, Daniel; Banga, J Paul; Gilbert, Jacqueline A

2008-01-01

involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66+/-22%, upon treatment with rituximab and methimazole for 21 days (p

Interstitial shadow on chest CT is associated with the onset of interstitial lung disease caused by chemotherapeutic drugs

International Nuclear Information System (INIS)

Niho, Seiji; Goto, Koichi; Yoh, Kiyotaka; Kim, Y.H.; Ohmatsu, Hironobu; Kubota, Kaoru; Saijo, Nagahiro; Nishiwaki, Yutaka

2006-01-01

Pretreatment computerized tomography (CT) films of the chest was studied to clarify the influence of interstitial shadow on developing interstitial lung disease (ILD). Eligible patients were those lung cancer patients who started to receive first-line chemotherapy between October 2001 and March 2004. Patients who received thoracic radiotherapy to the primary lesion, mediastinum, spinal or rib metastases were excluded. We reviewed pretreatment conventional CT and plain X-ray films of the chest. Ground-glass opacity, consolidation or reticular shadow without segmental distribution was defined as interstitial shadow, with this event being graded as mild, moderate or severe. If interstitial shadow was detected on CT films of the chest, but not via plain chest X-ray, it was graded as mild. Patients developing ILD were identified from medial records. A total of 502 patients were eligible. Mild, moderate and severe interstitial shadow was identified in 7, 8 and 5% of patients, respectively. A total of 188 patients (37%) received tyrosine kinase inhibitor (TKI) treatment, namely gefitinib or erlotinib. Twenty-six patients (5.2%) developed ILD either during or after chemotherapy. Multivariate analyses revealed that interstitial shadow on CT films of the chest and treatment history with TKI were associated with the onset of ILD. It is recommended that patients with interstitial shadow on chest CT are excluded from future clinical trials until this issue is further clarified, as it is anticipated that use of chemotherapeutic agents frequently mediate onset of ILD in this context. (author)

Rituximab: a novel treatment for refractory Riedel’s thyroiditis

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Leanne Hunt

2018-02-01

Full Text Available This case report reviews the rare condition of Riedel’s thyroiditis via a patient case. The report highlights the difficulties that one may encounter when managing such a case in regards to patient symptoms, side effects of medications and the relapsing nature of the condition. The case report also highlights novel treatment in the treatment of Riedel’s thyroiditis, rituximab, how this works and the resolution of symptoms that we have achieved with our patient on this treatment.

The role of interstitial changes in the progression of chronic kidney disease

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Beata Sulikowska

2015-07-01

Full Text Available Interstitium – the renal tubulointerstitial compartment – is located between the renal tubule basement membrane and microcirculation vessels. Interstitial fibroblasts produce the extracellular matrix and constitute the structure’s cellular skeleton, regulating spatial relationships between its components (microenvironment.The tubular epithelium and endothelium cooperate within an integrated microenvironment. Structural or functional impairment of the extracellular matrix, microcirculation vessels or tubular epithelium results in disturbances of tubulointerstitial compartment components.In the course of glomerular kidney diseases, the intrarenal RAA system becomes activated and inflammatory mediators are released. Interstitial inflammation and microcirculatory disorders develop, inducing adverse consequences, manifested mainly through the process of hypoxia and inflammation.Inflammation-induced increase in interleukin-1 (TNF-α expression leads to increased concentrations of VEGF, ICAM-1, angiotensin II, IL-6 and IL-8. Cytokines activate fibroblasts, myofibroblasts and endothelial cells. Fibrosis is also triggered by HIF-1alpha pathway activation, resulting in vascular growth and fibroblast proliferation. This reaction likewise occurs through activation of NF-ĸβ, EPO, GLUT-1, IGF-1 and INOS.Interstitial fibrosis is one of the factors determining the clinical course of kidney diseases. Apart from inducing fibrosis, microcirculatory disorders lead to the progression of hypoxia.Angiogenesis is a part of the repair process accompanying fibrosis. Its determinant is the normal function and structure of endothelial cells manifested by their ability to migrate and proliferate in response to, inter alia, angiopoietins, VEGF and nitric oxide synthase.Administering a three-drug RAAS-inhibiting therapy to patients with chronic glomerulopathies improves tubular function, measured by the decrease in excretion of NAG and propeptide of type III

Theeffectivenessofginger compress on non-specific low back pain ...

African Journals Online (AJOL)

Theeffectivenessofginger compress on non-specific low back pain. ... for a total of ten sessions and control group (n=7) did not received any treatment. ... in pain relief and reduces functional disability in patients with non-specific low back pain.

Resonant vibrations of self-interstitials in fcc metals with application to specific heat and neutron scattering

International Nuclear Information System (INIS)

Ram, P.N.; Dederichs, P.H.

1981-07-01

Some aspects of resonant vibrations of self-interstitials in the 100-dumbbell configuration in fcc-metals are discussed by extending previous calculations of Zeller et al. and Schober et al. Employing a simple defect model with nearest-neighbour interaction the local frequency spectrum of the defect is calculated showing several localized modes and low-frequency resonant modes. The change in the total density of states due to the defects is expressed as the derivative of a generalized phase shift which is used to calculate the change in the lattic specific heat due to single interstitials. Inelastic neutron scattering away from the one-phonon lines is proposed as a method to observe the resonant modes induced by self-interstitials. The model calculation in Cu shows that the well defined resonant modes due to dumbbell vibrations have appreciable intensity and could presumably be detected in neutron scattering measurements. The effect of di-interstitials on the phonon dispersion in Al is also discussed. (orig./GSCH)

Temperature monitoring with FBG sensor during diffuser-assisted laser-induced interstitial thermotherapy (Conference Presentation)

Science.gov (United States)

Pham, Ngot T.; Lee, Seul Lee; Lee, Yong Wook; Kang, Hyun Wook

2017-02-01

Temperature variations are often monitored by using sensors operating at the site of treatment during Laser-induced Interstitial Thermotherapy (LITT). Currently, temperature measurements during LITT have been performed with thermocouples (TCs). However, TCs could directly absorb laser light and lead to self-heating (resulting in an over-estimation). Fiber Bragg grating (FBG) sensors can instead overcome this limitation of the TCs due to its insensitivity to electromagnetic interference. The aim of the current study was to quantitatively evaluate the FBG temperature sensor with a K-type thermocouple to real-time monitor temperature increase in ex vivo tissue during diffuser-assisted LITT. A 4-W 980-nm laser was employed to deliver optical energy in continuous mode through a 600-µm core-diameter diffusing applicator. A goniometric measurement validated the uniform light distribution in polar and longitudinal directions. The FBG sensor showed a linear relationship (R2 = 0.995) between wavelength shift and temperature change in air and tissue along with a sensitivity of 0.0114 nm/˚C. Regardless of sensor type, the measured temperature increased with irradiation time and applied power but decreased with increasing distance from the diffuser surface. The temperature elevation augmented the degree of thermal coagulation in the tissue during LITT (4.0±0.3-mm at 99˚C after 120-s). The temperature elevation augmented the degree of thermal coagulation in the tissue during LITT s irradiation). The FBG-integrated diffuser was able to monitor the interstitial temperature in tubular tissue (porcine urethra) real-time during laser treatment. However, the thermal coagulation thickness of the porcine urethra was measured to be 1.5 mm that was slightly thicker ( 20%) than that of the bovine liver after 4-W 980-nm laser for 48 s. The FBG temperature sensor can be a feasible tool to real-time monitor the temporal development of the temperature during the diffuser-assisted LITT to

Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

Science.gov (United States)

Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

2012-02-01

Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

International Nuclear Information System (INIS)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

Energy Technology Data Exchange (ETDEWEB)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren's syndrome.

Science.gov (United States)

Hershberg, Uri; Meng, Wenzhao; Zhang, Bochao; Haff, Nancy; St Clair, E William; Cohen, Philip L; McNair, Patrice D; Li, Ling; Levesque, Marc C; Luning Prak, Eline T

2014-02-11

Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means

Gallium interstitial contributions to diffusion in gallium arsenide

Science.gov (United States)

Schick, Joseph T.; Morgan, Caroline G.

2011-09-01

A new diffusion path is identified for gallium interstitials, which involves lower barriers than the barriers for previously identified diffusion paths [K. Levasseur-Smith and N. Mousseau, J. Appl. Phys. 103, 113502 (2008), P. A. Schultz and O. A. von Lilienfeld, Modelling and Simulation in Materials Science and Engineering 17, 084007 (2009)] for the charge states which dominate diffusion over most of the available range of Fermi energies. This path passes through the ⟨110⟩ gallium-gallium split interstitial configuration, and has a particularly low diffusion barrier of 0.35 eV for diffusion in the neutral charge state. As a part of this work, the character of the charge states for the gallium interstitials which are most important for diffusion is investigated, and it is shown that the last electron bound to the neutral interstitial occupies a shallow hydrogenic bound state composed of conduction band states for the hexagonal interstitial and both tetrahedral interstitials. How to properly account for the contributions of such interstitials is discussed for density-functional calculations with a k-point mesh not including the conduction band edge point. Diffusion barriers for gallium interstitials are calculated in all the charge states which can be important for a Fermi level anywhere in the gap, q = 0, +1, +2, and +3, for diffusion via the ⟨110⟩ gallium-gallium split interstitial configuration and via the hexagonal interstitial configuration. The lowest activation enthalpies over most of the available range of Fermi energies are found to correspond to diffusion in the neutral or singly positive state via the ⟨110⟩ gallium-gallium split interstitial configuration. It is shown that several different charge states and diffusion paths contribute significantly for Fermi levels within 0.2 eV above the valence band edge, which may help to explain some of the difficulties [H. Bracht and S. Brotzmann, Phys. Rev. B 71, 115216 (2005)] which have been

Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

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Young J. Lee

2018-01-01

Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

Science.gov (United States)

Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

2015-01-01

Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

Launching biosimilar rituximab: an industry opinion on biosimilar uptake in Europe.

Science.gov (United States)

Trollope, Richard; Johnson, Sue; Ireland, Henry

2017-06-01

Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima ® ) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars. He now heads up the biosimilar franchise at Mundipharma International as it launches biosimilar rituximab (Truxima ® ) - the first biosimilar monoclonal antibody for the treatment of cancer, which will be distributed by Napp Pharmaceuticals in the UK. Sue Johnson, PhD, Medical Insights at Mundipharma International Limited, is a scientist by background and completed her postdoc fellowship at Harvard Medical School. On returning to the UK, she began her career in the pharmaceutical industry, working in UK Medical Affairs before transitioning to a European role with Mundipharma 2 years ago, where she leads on Medical Insights for the biosimilars franchise.

Modeling of interstitial diffusion of ion-implanted boron

International Nuclear Information System (INIS)

Velichko, O.I.; Knyazheva, N.V.

2009-01-01

A model of the interstitial diffusion of ion-implanted boron during rapid thermal annealing of silicon layers previously amorphized by implantation of germanium has been proposed. It is supposed that the boron interstitials are created continuously during annealing due to generation, dissolution, or rearrangement of the clusters of impurity atoms which are formed in the ion-implanted layers with impurity concentration above the solubility limit. The local elastic stresses arising due to the difference of boron atomic radius and atomic radius of silicon also contribute to the generation of boron interstitials. A simulation of boron redistribution during thermal annealing for 60 s at a temperature of 850 C has been carried out. The calculated profile agrees well with the experimental data. A number of the parameters of interstitial diffusion have been derived. In particular, the average migration length of nonequilibrium boron interstitials is equal to 12 nm. It was also obtained that approximately 1.94% of boron atoms were converted to the interstitial sites, participated in the fast interstitial migration, and then became immobile again transferring into a substitutional position or forming the electrically inactive complexes with crystal lattice defects. (authors)

Regulation of tumor invasion by interstitial fluid flow

International Nuclear Information System (INIS)

Shieh, Adrian C; Swartz, Melody A

2011-01-01

The importance of the tumor microenvironment in cancer progression is undisputed, yet the significance of biophysical forces in the microenvironment remains poorly understood. Interstitial fluid flow is a nearly ubiquitous and physiologically relevant biophysical force that is elevated in tumors because of tumor-associated angiogenesis and lymphangiogenesis, as well as changes in the tumor stroma. Not only does it apply physical forces to cells directly, but interstitial flow also creates gradients of soluble signals in the tumor microenvironment, thus influencing cell behavior and modulating cell–cell interactions. In this paper, we highlight our current understanding of interstitial fluid flow in the context of the tumor, focusing on the physical changes that lead to elevated interstitial flow, how cells sense flow and how they respond to changes in interstitial flow. In particular, we emphasize that interstitial flow can directly promote tumor cell invasion through a mechanism known as autologous chemotaxis, and indirectly support tumor invasion via both biophysical and biochemical cues generated by stromal cells. Thus, interstitial fluid flow demonstrates how important biophysical factors are in cancer, both by modulating cell behavior and coupling biophysical and biochemical signals

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

Science.gov (United States)

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Development of DOTA-Rituximab to be Labeled with 90Y for Radioimmunotherapy of B-cell Non-Hodgkin Lymphoma

Science.gov (United States)

Johari doha, Fariba; Rahmani, Siyavash; Rikhtechi, Pedram; Rasaneh, Samira; Sheikholislam, Zahra; Shahhosseini, Soraya

2017-01-01

NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. PMID:28979315

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

Science.gov (United States)

Cabral, Vanderlea Poeys; Andrade, Carlos Augusto Ferreira de; Passos, Sonia Regina Lambert; Martins, Maria de Fátima Moreira; Hökerberg, Yara Hahr Marques

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs. Copyright © 2016. Published by Elsevier Editora Ltda.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

Science.gov (United States)

Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

2015-01-01

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

Magnetic resonance thermometry for monitoring photothermal effects of interstitial laser irradiation

Science.gov (United States)

Goddard, Jessica; Jose, Jessnie; Figueroa, Daniel; Le, Kelvin; Liu, Hong; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

2012-03-01

Selective photothermal interaction using dye-assisted non-invasive laser irradiation has limitations when treating deeper tumors or when the overlying skin is heavily pigmented. We developed an interstitial laser irradiation method to induce the desired photothermal effects. An 805-nm near-infrared laser with a cylindrical diffuser was used to treat rat mammary tumors by placing the active tip of the fiber inside the target tumors. Three different power settings (1.0 to 1.5 watts) were applied to treat animal tumors with an irradiation duration of 10 minutes. The temperature distributions of the treated tumors were measured by a 7.1-Tesla magnetic resonance imager using proton resonance frequency (PRF) method. Three-dimensional temperature profiles were reconstructed and assessed using PRF. This is the first time a 7.1-Tesla magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. This study provides a basic understanding of the photothermal interaction needed to control the thermal damage inside tumor using interstitial laser irradiation. It also shows that PRF can be used effectively in monitoring photothermal interaction. Our long-term goal is to develop a PRF-guided laser therapy for cancer treatment.

Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

Science.gov (United States)

Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

2017-02-01

Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

Tumorous interstitial lung disease

International Nuclear Information System (INIS)

Dinkel, E.; Meyer, E.; Mundinger, A.; Helwig, A.; Blum, U.; Wuertemberger, G.

1990-01-01

The radiological findings in pulmonary lymphangitic carcinomatosis and in leukemic pulmonary infiltrates mirror the tumor-dependent monomorphic interstitial pathology of lung parenchyma. It is a proven fact that pulmonary lymphangitic carcinomatosis is caused by hematogenous tumor embolization to the lungs; pathogenesis by contiguous lymphangitic spread is the exception. High-resolution CT performed as a supplement to the radiological work-up improves the sensitivity for pulmonary infiltrates in general and thus makes the differential diagnosis decided easier. Radiological criteria cannot discriminate the different forms of leukemia. Plain chest X-ray allows the diagnosis of pulmonary involvement in leukemia due to tumorous infiltrates and of tumor- or therapy-induced complications. It is essential that the radiological findings be interpreted with reference to the stage of tumor disease and the clinical parameters to make the radiological differential diagnosis of opportunistic infections more reliable. (orig.) [de

Prolonged extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome in a child affected by rituximab-resistant autoimmune hemolytic anemia: a case report

Directory of Open Access Journals (Sweden)

Beretta Chiara

2009-04-01

Full Text Available Abstract Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our

Interstitial lung disease in anti-synthetase syndrome: Initial and follow-up CT findings

Energy Technology Data Exchange (ETDEWEB)

Debray, Marie-Pierre, E-mail: marie-pierre.debray@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Radiology, 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Borie, Raphael, E-mail: raphael.borie@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Pneumology A and Centre de Compétence Maladies Pulmonaires rares, DHU Fire 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Inserm, U1152, Paris (France); Revel, Marie-Pierre, E-mail: marie-pierre.revel@htd.aphp.fr [AP-HP, Cochin Hospital, Department of Radiology, 27, Rue du Fg Saint Jacques, 75679 Paris Cedex 14 (France); Naccache, Jean-Marc, E-mail: jean-marc.naccache@tnn.aphp.fr [AP-HP, Avicenne Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, Bobigny (France); AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Khalil, Antoine, E-mail: antoine.khalil@tnn.aphp.fr [AP-HP, Tenon Hospital, Department of Radiology, 4, rue de la Chine, 75020 Paris (France); Toper, Cécile, E-mail: cecile.toper@gmail.com [AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Israel-Biet, Dominique, E-mail: dominique.israel-biet@egp.aphp.fr [Université Paris Descartes and AP-HP, Department of Pneumology, Georges Pompidou European Hospital, 20, rue Leblanc, 75015 Paris (France); and others

2015-03-15

Purpose: To describe the initial and follow-up CT features of interstitial lung disease associated with anti-synthetase syndrome (AS-ILD). Materials and methods: Two independent thoracic radiologists retrospectively analysed thin-section CT images obtained at diagnosis of AS-ILD in 33 patients (17 positive for anti-Jo1, 13 for anti-PL12, and three for anti-PL7 antibodies). They evaluated the pattern, distribution and extent of the CT abnormalities. They also evaluated the change in findings during follow-up (median 27 months; range 13–167 months) in 26 patients. Results: At diagnosis, ground-glass opacities (100%), reticulations (87%) and traction bronchiectasis (76%) were the most common CT findings. Consolidations were present in 45% of patients. A non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) or mixed NSIP-OP CT pattern were observed in 15 out of 33 (45%), seven out of 33 (21%) and eight out of 33 (24%) patients, respectively, whereas the CT pattern was indeterminate in three patients. During follow-up, consolidations decreased or disappeared in 11 out of 12 patients (92%), among which seven within the first 6 months, but honeycombing progressed or appeared in ten out of 26 patients (38%) and overall disease extent increased in nine out of 26 patients (35%). Conclusion: CT features at diagnosis of AS-ILD mainly suggest NSIP and OP, isolated or in combination. Consolidations decrease or disappear in most cases but the disease may progress to fibrosis in more than one third of patients.

High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

Energy Technology Data Exchange (ETDEWEB)

Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

2016-03-15

Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

Persistence and selection of an expanded B-cell clone in the setting of rituximab therapy for Sjögren’s syndrome

Science.gov (United States)

2014-01-01

Introduction Subjects with primary Sjögren’s syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab. Methods To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Results Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection. Conclusions For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an

Interstitial hydraulic conductivity and interstitial fluid pressure for avascular or poorly vascularized tumors.

Science.gov (United States)

Liu, L J; Schlesinger, M

2015-09-07

A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling of long-range migration of boron interstitials

International Nuclear Information System (INIS)

Velichko, O.I.; Burunova, O.N.

2009-01-01

A model of the interstitial migration of ion-implanted dopant in silicon during low-temperature thermal treatment has been formulated. It is supposed that the boron interstitials are created during ion implantation or at the initial stage of annealing. During thermal treatment a migration of these impurity interstitials to the surface and in the bulk of a semiconductor occurs. On this basis, a simulation of boron redistribution during thermal annealing for 35 minutes at a temperature of 800 0 C has been carried out. The calculated boron profile agrees well with the experimental data. A number of the parameters describing the interstitial diffusion have been derived. In particular, the average migration length of nonequilibrium boron interstitials is equal to 0.092 μm at a temperature of 800 0 C. To carry out modeling of ion-implanted boron redistribution, the analytical solutions of nonstationary diffusion equation for impurity interstitials have been obtained. The case of Dirichlet boundary conditions and the case of reflecting boundary on the surface of a semiconductor have been considered. (authors)

Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

Energy Technology Data Exchange (ETDEWEB)

Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

Acute interstitial nephritis with acetaminophen and alcohol intoxication

Directory of Open Access Journals (Sweden)

Alexopoulou Iakovina

2011-04-01

Full Text Available Abstract Drug-induced acute interstitial nephritis (AIN represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis.

Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

International Nuclear Information System (INIS)

Griffiths, R. I.; Gleeson, M. L.; Danese, M. D.; Griffiths, R. I.; Mikhael, J.

2012-01-01

Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab.

Science.gov (United States)

Prior, Sandra; Hufton, Simon E; Fox, Bernard; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

2018-01-01

The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product.

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

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Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

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Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

2018-01-01

Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

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Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

2015-03-01

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

Science.gov (United States)

Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

2016-12-30

Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

Púrpura trombocitopênica trombótica - remissão completa em paciente com mau prognóstico após tratamento com plasmaférese terapêutica e rituximabe Successful outcome in poor-prognostic acute thrombotic thrombocytopenic purpura treated with plasma exchange and rituximab

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Cesar de Almeida Neto

2008-02-01

Full Text Available A púrpura trombocitopênica trombótica (PTT é uma doença rara e fatal que deve ser diagnosticada e tratada prontamente a fim de se obter melhor resposta terapêutica. Apresentamos um caso de PTT aguda grave tratada com plasmaférese e rituximabe. Ao diagnóstico, a paciente apresentava anemia hemolítica microangiopática, icterícia, febre, convulsões, seguidas por coma e choque hipovolêmico. Os exames laboratoriais iniciais mostravam DHL=2.860 IU/L, contagem de plaquetas de 37 x 10(9/L, hemoglobina de 5,1 g/dL e no esfregaço de sangue periférico havia a presença de esquizócitos. Iniciado tratamento para PTT com pulsoterapia com metilprednisolona e plasmaféreses terapêuticas diárias com troca de uma volemia plasmática e substituição com plasma fresco congelado. Após cinco sessões de plasmaférese, houve piora no quadro neurológico, acompanhado por aumento importante de DHL, ALT, AST e a contagem de plaquetas era de 72 x 10(9/L. Iniciamos o uso de rituximabe na dose padrão de 375mg/m²/semana/4 semanas e passamos a utilizar plasma pobre em crioprecipitado como reposição durante as plasmaféreses. Dois dias após a mudança na conduta terapêutica, houve importante melhora do quadro neurológico, estabilização da contagem de plaquetas e queda acentuada de DHL. Após 23 procedimentos de plasmaférese e quatro doses de rituximabe, a paciente apresentou remissão completa, mantida há 34 meses. A plasmaférese terapêutica com plasma pobre em crioprecipitado e o uso concomitante de rituximabe foi uma estratégia útil no tratamento deste caso de PTT aguda grave. Porém, ensaios clínicos prospectivos e randomizados são necessários para confirmar estes achados.Thrombotic thrombocytopenic purpura (TTP is a rare severe disease that must be diagnosed and treated promptly for a successful outcome. We report a case of severe acute TTP treated with plasma exchange and rituximab. The patient presented at diagnosis with severe

Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue

DEFF Research Database (Denmark)

Gravhølt, C H; Schmitz, Ole; Simonsen, L

1999-01-01

.0005). Administration of GH induced an increase in interstitial glycerol in both abdominal and femoral adipose tissue (ANOVA: abdominal, P = 0. 04; femoral, P = 0.03). There was no overall difference in the response to GH in the two regions during the study period as a whole (ANOVA: P = 0.5), but during peak...... stimulation of lipolysis abdominal adipose tissue was, in absolute but not in relative terms, stimulated more markedly than femoral adipose tissue (ANOVA: P = 0. 03 from 45 to 225 min). Peak interstitial glycerol values of 253 +/- 37 and 336 +/- 74 micromol/l were seen after 135 and 165 min in femoral...... and abdominal adipose tissue, respectively. ATBF was not statistically different in the two situations (ANOVA: P = 0.7). In conclusion, we have shown that a physiological pulse of GH increases interstitial glycerol concentrations in both femoral and abdominal adipose tissue, indicating activated lipolysis...

B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus H; Bonnema, Steen J

2007-01-01

Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might...

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine

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Mandrik O

2015-08-01

Full Text Available Olena Mandrik,1 Isaac Corro Ramos,2 Saskia Knies,1,3 Maiwenn Al,1,2 Johan L Severens1,2 1Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Institute of Medical Technology Assessment (iMTA, Erasmus University Rotterdam, Rotterdam, the Netherlands; 3National Health Care Institute, Diemen, the Netherlands Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

DEFF Research Database (Denmark)

Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J

2005-01-01

. Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results...

Stability and mobility of self-interstitials and small interstitial clusters in α-iron: ab initio and empirical potential calculations

International Nuclear Information System (INIS)

Willaime, F.; Fu, C.C.; Marinica, M.C.; Dalla Torre, J.

2005-01-01

The stability and mobility of self-interstitials and small interstitial clusters, I n , in α-Fe is investigated by means of calculations performed in the framework of the density functional theory using the SIESTA code. The mono-, di- and tri-interstitials are shown to be made of (parallel) dumbbells and to migrate by nearest-neighbor translation-rotation jumps, according to Johnson's mechanism. The orientation of the dumbbells becomes energetically more favourable for I 5 and larger clusters. The performance of a semi-empirical potential recently developed for Fe, including ab initio self-interstitial data in the fitted properties, is evaluated over the present results. The superiority over previous semi-empirical potentials is confirmed. Finally the impact of the present results on the formation mechanism of loops, observed experimentally in α-Fe is discussed

Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

Energy Technology Data Exchange (ETDEWEB)

Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

2005-10-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

Science.gov (United States)

Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

2015-02-27

Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

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Theodore-Oklota C

2016-09-01

Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

Clinical and economic aspects of the use of rituximab in non-Hodgkin's lymphoma

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Camila Bezerra Melo Figueirêdo

2014-09-01

Full Text Available Non-Hodgkin's lymphoma (NHL consists of a group of neoplasias involving mainly B cells and represents 90% of all lymphomas. The current available therapy is based on chemotherapy associated with the monoclonal antibody rituximab (Mab Thera(r, which targets the CD20 protein, present in over 80% of NHL mature B cells. Recent clinical reports show a preference for combining the benefits of immunotherapy and adjuvant chemotherapy, thus generating safe and effective alternative treatments. The current review aimed at evaluating various aspects related to the use of rituximab for NHL, highlighting the possible inhibitory mechanisms of cell proliferation, the achieved clinical results, and the expected clinical and economic outcomes of treatments. The results from clinical tests indicate the need for a better understanding of the critical mechanisms of action of this antibody, which may maximize its therapeutic efficacy. This therapy not only represents a viable option to treat most types of NHLs, especially when associated with conventional chemotherapy, but also offers cost-utility and cost-effectiveness advantages.

Hydrogen solution in tetrahedral or octahedral interstitial sites in Al

International Nuclear Information System (INIS)

Zeng, C.A.; Hu, J.P.; Ouyang, C.Y.

2011-01-01

Highlights: → The physical nature of the site preference for H solution in BCC Al is revealed. → The site preference is result of competition between Al-H bonding interaction and local lattice distortion. → The Al-H bonding interaction lowers the solution energy while the local lattice distortion increases the solution energy. - Abstract: It is reported that H atoms prefer to stay at interstitial (defect) sites with larger space in most metals. However, H atom prefers to occupy tetrahedral interstitial sites (T-site) that provide smaller space than octahedral sites (O-site) in Al. This paper studied the H-Al interactions from first principles calculations. Through analysis of the H-induced electronic states and the local atomic relaxations, we show that H-Al bonding interaction is stronger for T-site H, which is in favor of the solution energy. On the other hand, larger local atomic distortion is observed around the T-site H, which increases the total energy.

[Modern Views on Children's Interstitial Lung Disease].

Science.gov (United States)

Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

2015-01-01

Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

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Robert I. Griffiths

2012-01-01

Full Text Available Rituximab improves survival in follicular lymphoma (FL, but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C, doxorubicin, vincristine (V, and prednisone (P or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years, 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI $9,302–$28,643 and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27 over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337 per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

Macroglobulinemia de Waldenström - remissão completa após tratamento com rituximabe Successful outcome in Waldenström's macroglobulinemia treated with rituximab

Directory of Open Access Journals (Sweden)

Flavia C. F. Pimenta

2008-10-01

Full Text Available A macroglobulinemia de Waldenström (MW é uma patologia rara dos linfócitos B caracterizada pela produção monoclonal de IgM, e que pode manifestar-se clinicamente com fadiga, astenia, perda de peso, sangramento de mucosas e do trato gastrintestinal, lifonodonomegalias, hepatoesplenomegalia e alterações neurológicas. A doença é mais comum em pacientes idosos, e seus sintomas são decorrentes da hiperviscosidade sangüínea. Na MW observa-se hipergamaglobulinemia com pico monoclonal na eletroforese de proteínas séricas, níveis elevados de IgM e demais imunoglobulinas normais ou diminuídas, imunofenotipagem com linfócitos B CD19+, CD20+ e CD24+, aspirado de medula óssea hipercelular, e biópsia de medula óssea hipercelular com infiltração difusa de linfócitos, linfócitos plasmocitóides e plasmócitos. Atualmente, anticorpos monoclonais estão sendo usados na terapêutica da MW com grande sucesso. O rituximabe, anticorpo monoclonal anti -CD20, tem mostrado excelentes resultados no tratamento da MW, inclusive naqueles indivíduos que não obtiveram resposta adequada ao tratamento convencional. Nós reportamos o caso de uma mulher de 78 anos de idade com história de fadiga, astenia, anorexia, sonolência, inquietação, urticária, dificuldade para deambular e perda excessiva de peso, aproximadamente 22 kg em um período de cinco meses, cujo tratamento foi realizado com rituximabe. O objetivo deste relato é apresentar uma paciente com diagnóstico de MW e revisar aspectos clínicos e terapêutico atual da doença.Waldenström's macroglobulinemia is a rare pathology of B lymphocytes characterized by the production of monoclonal IgM, causing clinical manifestations which may include fatigue, asthenia, weight loss, bleeding of the mucosa and intestinal tract, lymphadenomegaly, hepatosplenomegaly and neurological alterations. The disease is more frequent among elderly patients and its symptoms are a result of the hyperviscosity of

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

Science.gov (United States)

Takahashi, Kota; Saito, Kazuhide; Takahara, Shiro; Fuchinoue, Shohei; Yagisawa, Takashi; Aikawa, Atsushi; Watarai, Yoshihiko; Yoshimura, Norio; Tanabe, Kazunari; Morozumi, Kunio; Shimazu, Motohide

2017-08-01

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Smoking-related interstitial lung diseases: histopathological and imaging perspectives

Energy Technology Data Exchange (ETDEWEB)

Desai, S.R.; Ryan, S.M.; Colby, T.V

2003-04-01

The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed.

Smoking-related interstitial lung diseases: histopathological and imaging perspectives

International Nuclear Information System (INIS)

Desai, S.R.; Ryan, S.M.; Colby, T.V.

2003-01-01

The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed

Microstructures and phase transformations in interstitial alloys of tantalum

International Nuclear Information System (INIS)

Dahmen, U.

1979-01-01

The analysis of microstructures, phases, and possible ordering of interstitial solute atoms is fundamental to an understanding of the properties of metal-interstitial alloys in general. As evidenced by the controversies on phase transformations in the particular system tantalum--carbon, our understanding of this class of alloys is inferior to our knowledge of substitutional metal alloys. An experimental clarification of these controversies in tantalum was made. Using advanced techniques of electron microscopy and ultrahigh vacuum techology, an understanding of the microstructures and phase transformations in dilute interstitial tantalum--carbon alloys is developed. Through a number of control experiments, the role and sources of interstitial contamination in the alloy preparation (and under operating conditions) are revealed. It is demonstrated that all previously published work on the dilute interstitially ordered phase Ta 64 C can be explained consistently in terms of ordering of the interstitial contaminants oxygen and hydrogen, leading to the formation of the phases Ta 12 O and Ta 2 H

Interstitial Granulomatous Dermatitis (IGD

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Tiberiu Tebeica

2017-07-01

Full Text Available We report the case of a 42 years old male patient suffering from skin changes , which appeared in the last 7-8 years.  Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of lymphocytes and histiocytes dispersed among collagen bundles, with variable numbers of neutrophils scattered throughout. Some histiocytes were clustered in poorly formed granuloma that included rare giant cells, with discrete Palisades and piecemeal collagen degeneration, but without mucin deposition or frank necrobiosis of collagen. The clinical and histologic findings were supportive for interstitial granulomatous dermatitis. Interstitial granulomatous dermatitis (IGD is a poorly understood entity that was regarded by many as belonging to the same spectrum of disease or even synonym with palisaded and neutrophilic granulomatous dermatitis (PNGD. Although IGD and PNGD were usually related to connective tissue disease, mostly rheumatoid arthritis, some patients with typical histologic findings of IGD never develop autoimmune disorders, but they have different underlying conditions, such as metabolic diseases, lymphoproliferative disorders or other malignant tumours. These observations indicate that IGD and PNGD are different disorders with similar manifestations.

A new non-specificity measure in evidence theory based on belief intervals

Institute of Scientific and Technical Information of China (English)

Yang Yi; Han Deqiang; Jean Dezert

2016-01-01

In the theory of belief functions, the measure of uncertainty is an important concept, which is used for representing some types of uncertainty incorporated in bodies of evidence such as the discord and the non-specificity. For the non-specificity part, some traditional measures use for reference the Hartley measure in classical set theory;other traditional measures use the simple and heuristic function for joint use of mass assignments and the cardinality of focal elements. In this paper, a new non-specificity measure is proposed using lengths of belief intervals, which represent the degree of imprecision. Therefore, it has more intuitive physical meaning. It can be proved that our new measure can be rewritten in a general form for the non-specificity. Our new measure is also proved to be a strict non-specificity measure with some desired properties. Numerical examples, simulations, the related analyses and proofs are provided to show the characteristics and good properties of the new non-specificity definition. An example of an application of the new non-specificity measure is also presented.

Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow

International Nuclear Information System (INIS)

Semino, Carlos E.; Kamm, Roger D.; Lauffenburger, Douglas A.

2006-01-01

We show here that autocrine ligand activation of epidermal growth factor (EGF) receptor in combination with interstitial flow is critically involved in the morphogenetic response of endothelial cells to VEGF stimulation. Human umbilical vein endothelial cell (HUVEC) monolayers cultured on a collagen gel and exposed to low interstitial flow in the absence of EGF and VEGF remained viable and mitotic but exhibited little evidence of vascular morphogenesis. Addition of VEGF produced a flow-dependent morphogenetic response within 48 to 72 h, characterized by branched capillary-like structures. The response was substantially abolished by inhibitors related to the autocrine EGF receptor pathway including Galardin, AG1478, PD98059, and an EGF receptor-blocking antibody, indicating that regulation of the morphogenetic process operates via autocrine EGF receptor activation. Moreover, we observed that in our system the EGF receptor was always activated independently of the interstitial flow, and, in addition, the EGF receptor inhibitors used above reduced the phosphorylation state of the receptor, correlating with inhibition of capillary morphogenesis. Finally, 5'bromo-2'-deoxyuridine (BrdU) labeling identified dividing cells at the monolayer but not in the extending capillary-like structures. EGF pathway inhibitors Galardin and AG1478 did not reduce BrdU incorporation in the monolayer, indicating that the EGF-receptor-mediated morphogenetic behavior is mainly due to cell migration rather than proliferation. Based on these results, we propose a two-step model for in vitro capillary morphogenesis in response to VEGF stimulation with interstitial fluid flow: monolayer maintenance by mitotic activity independent of EGF receptors and a migratory response mediated by autocrine EGF receptor activation wherein cells establish capillary-like structures

An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica

Science.gov (United States)

Collongues, Nicolas; de Seze, Jérôme

2016-01-01

Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future. PMID:27134673

An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica.

Science.gov (United States)

Collongues, Nicolas; de Seze, Jérôme

2016-05-01

Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking. In the present review, we describe the state of the art about rituximab treatment in NMOSD, including adults and children, plus its efficacy and tolerance and we also underline the questions that should be addressed in the near future.

Acute interstitial pneumonia

International Nuclear Information System (INIS)

Cuervo M, Francisco; Carrillo Bayona, Jorge; Ojeda, Paulina

2004-01-01

The paper refers to a 71 year-old patient, to who is diagnosed acute interstitial pneumonia; with square of 20 days of evolution of cough dry emetizant, fever, general uneasiness, migraine, progressive dyspnoea and lost of weight

An approach to interstitial lung disease in India

Directory of Open Access Journals (Sweden)

J N Pande

2014-07-01

Full Text Available Interstitial lung diseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP, also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lung diseases based on personal experience over the past three decades is reported here. Key words: Usual interstitial pneumonia – sarcoidosis – pneumoconiosis – bronchoscopy – lung biopsy 

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

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Daniel Antunes Silva Pereira

2015-04-01

Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

Science.gov (United States)

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; Ppulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

USE OF RITUXIMAB IN AUTOIMMUNE DISEASES: NEW ASPECTS

Directory of Open Access Journals (Sweden)

Dmitry Evgenyevich Karateyev

2010-01-01

Full Text Available It has been noted that off-label indication for Rituximab (RTX in rheumatological care indubitably requires its confirmation in the randomized clinical trials. A particular cautious approach should be taken in extending the indications for therapy with gene-engineering biologicals because of the intricacy and interaction of different immunoregulatory mechanisms. Nonetheless, it is stated that much clinical experience with RTX used in most severely ill therapy-resistant patients may serve as a basis for its prescription in a number of most complex inflammatory rheumatic diseases (RDs. There is new evidence for the use of RTX in various RDs differing in their clinical picture, course, and pathogenesis, such as spondyloarthritis, systemic lupus erythematosus, systemic vasculitis.

Nye behandlinger af Graves' sygdom med fokus på det B-lymfocyt-depleterende antistof rituximab

DEFF Research Database (Denmark)

Nielsen, Claus Henrik; El Fassi, Daniel; Hegedüs, Laszlo

2008-01-01

Graves' disease (GD) is caused by autoantibodies to the thyrotropin receptor (TRAb). In a controlled study using the B-lymphocyte depleting agent rituximab (RTX), an RTX-specific effect was found on long-term remission following methimazole (MMI) therapy. However, benefits were limited to patients...

Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with ⁹⁰Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

Science.gov (United States)

Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; Akhlaghi, Mehdi

2014-07-29

On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL

Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty tissue using exponential functions

Energy Technology Data Exchange (ETDEWEB)

Salas, Nelson Jr. [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Manns, Fabrice [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Milne, Peter J [Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th Ave, McKnight Bldg, Miami, FL 33136 (United States); Denham, David B [Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th Ave, McKnight Bldg, Miami, FL 33136 (United States); Minhaj, Ahmed M [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Parel, Jean-Marie [Biomedical Optics and Laser Laboratory, Department of Biomedical Engineering, University of Miami College of Engineering, PO Box 248294, Coral Gables, FL 33124 (United States); Robinson, David S [Center for Breast Care, St Luke' s Hospital of Kansas City, 4400 Broadway, Suite 509, Kansas City, MO 64111 (United States)

2004-05-07

A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T < 100 deg. C) during LITT than the traditional model using a single exponential function. Analysis of the ellipsoid coagulation volume induced in tissue indicates that the 980 nm wavelength does not penetrate deep enough in fibro-fatty tissue to produce a desired 30 mm diameter (14.1 x 10{sup 3} mm{sup 3}) coagulation volume without unwanted tissue liquefaction and carbonization.

Targeting the humoral immune system of patients with rheumatoid arthritis

NARCIS (Netherlands)

Teng, Yoe Kie Onno

2008-01-01

The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell

Inactivation of p27kip1 Promoted Nonspecific Inflammation by Enhancing Macrophage Proliferation in Islet Transplantation.

Science.gov (United States)

Li, Yang; Ding, Xiaoming; Fan, Ping; Guo, Jian; Tian, Xiaohui; Feng, Xinshun; Zheng, Jin; Tian, Puxun; Ding, Chenguang; Xue, Wujun

2016-11-01

Islet transplantation suffers from low efficiency caused by nonspecific inflammation-induced graft loss after transplantation. This study reports increased islet loss and enhanced inflammatory response in p27-deficient mice (p27-/-) and proposes a possible mechanism. Compared with wild type, p27-/- mice showed more severe functional injury of islet, with increased serum levels of inflammatory cytokines IL-1 and TNF-α, inducing macrophage proliferation. Furthermore, the increased number, proapoptotic proteins, and nuclear factor-kappa b (NF-κB) phosphorylation status of the infiltrating macrophages were accompanied by increased TNF-α mRNA level of islet graft site in p27-/- mice. Moreover, in vitro, we found that macrophages were still activated and cocultured with islet and promoted islet loss even blocking the direct effect of TNF-α on islets. Malondialdehyde (MDA, an end product of lipid peroxidation) in islet and media were increased after cocultured with macrophages. p27 deficiency also increased macrophage proliferation and islet injury. Therefore, p27 inactivation promotes injury islet graft loss via the elevation of proliferation and inflammatory cytokines secretion in infiltrating macrophages which induced nonspecific inflammation independent of TNF-α/nuclear factor-kappa b pathway. This potentially represents a promising therapeutic target in improving islet graft survival.

New insights into canted spiro carbon interstitial in graphite

Science.gov (United States)

EL-Barbary, A. A.

2017-12-01

The self-interstitial carbon is the key to radiation damage in graphite moderator nuclear reactor, so an understanding of its behavior is essential for plant safety and maximized reactor lifetime. The density functional theory is applied on four different graphite unit cells, starting from of 64 carbon atoms up to 256 carbon atoms, using AIMPRO code to obtain the energetic, athermal and mechanical properties of carbon interstitial in graphite. This study presents first principles calculations of the energy of formation that prove its high barrier to athermal diffusion (1.1 eV) and the consequent large critical shear stress (39 eV-50 eV) necessary to shear graphite planes in its presence. Also, for the first time, the gamma surface of graphite in two dimensions is calculated and found to yield the critical shear stress for perfect graphite. Finally, in contrast to the extensive literature describing the interstitial of carbon in graphite as spiro interstitial, in this work the ground state of interstitial carbon is found to be canted spiro interstitial.

Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

DEFF Research Database (Denmark)

Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

2013-01-01

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

Regulation of proliferation of embryonic heart mesenchyme: Role of transforming growth factor-beta 1 and the interstitial matrix

International Nuclear Information System (INIS)

Choy, M.; Armstrong, M.T.; Armstrong, P.B.

1990-01-01

Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

NARCIS (Netherlands)

Xu-Monette, Z.Y.; Moller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkaer, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab,

Interstitial-mediated diffusion and clustering for transmutation elements Re and Os precipitation in W

Science.gov (United States)

Zhou, Hong-Bo; Li, Yu-Hao; Lu, Guang-Hong

Under high energy (14 eV) neutrons irradiation in nuclear fusion devoices, tungsten (W) will undergo transmutation to its near-neighbors in the periodic table, such as rhenium (Re), osmium (Os), etc. The transmutation elements Re and Os will precipitate and form new Re/Os-rich phase, and further significantly degrade the mechanical properties of W. Here, we have investigated the mechanism for the irradiation-induced Re/Os clustering in W using the first-principles method and thermodynamic models. It is found that there is strong attraction between Re/Os and self-interstitial atom (SIA) in W. The SIA can be easily trapped by Re/Os once overcoming a low energy barrier, and form W-Re/Os complex dumbbell. The diffusion energy barrier of W-Re/Os is much lower than that of Re/Os diffusing via mono-vacancy or even vacancy clusters. Further, the W-Re/Os can be easily trapped by the substitutional Re/Os atoms, and form high stable Re-Re/Os-Os dumbbell structure. Most importantly, the Re-Re/Os-Os dumbbell can serve as trapping centre for subsequent interstitial-Re/Os, leading to the growth of Re/Os-rich clusters in W. Our finding suggests an interstitial-mediated mechanism for the irradiation-induced Re/Os clustering in W. This research is supported by the National Magnetic Confinement Fusion Program with Grant No. 2013GB109002, and the National Natural Science Foundation of China with Grant No. 11675011.

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

Directory of Open Access Journals (Sweden)

Simona Corso

2018-05-01

Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

Radiation induced structural changes in alpha-copper-zinc alloys

International Nuclear Information System (INIS)

Schuele, W.; Gieb, M.

1991-01-01

During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

Tumor interstitial fluid

DEFF Research Database (Denmark)

Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

2013-01-01

Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical...

High-resolution CT of lymphoid interstitial pneumonia

International Nuclear Information System (INIS)

Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

1989-01-01

Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy

NARCIS (Netherlands)

Pieters, Bradley R.; Hart, Augustinus A. M.; Russell, Nicola S.; Jansen, Edwin P. M.; Peterse, Johannes L.; Borger, Jacques; Rutgers, Emiel J. Th

2003-01-01

Background and purpose: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in

Synergistic effects of interstitial impurities and radiation defects on mechanical characteristics of ferritic steels

International Nuclear Information System (INIS)

Charit, I.; Seok, C.S.; Murty, K.L.

2007-01-01

Ferritic steels are generally used in pressure vessels and various reactor support structures in light water reactors. They are known to exhibit radiation embrittlement in terms of decreased toughness and increased ductile-brittle transition temperature as a result of exposure to neutron radiation. The superimposed effects of strain aging due to interstitial impurity atoms on radiation embrittlement were considered first by Wechsler, Hall and others. Here we summarize some of our efforts on the investigation of synergistic effects between interstitial impurity atoms (IIAs) and radiation-induced point defects, which result in interesting effects at appropriate temperature and strain rate conditions. Two materials, a mild steel and a pressure vessel steel (A516 Gr.70), are evaluated using tensile and three-point bend tests

Effects of medicinal herbs "Plantago asiatica", "Houttuynia cordata" and "Mentha haplocalyx" on non-specific immune responses of cobia (Rachycentron canadum).

Science.gov (United States)

Wu, Yu-Sheng; Chen, Yin-Yu; Ueng, Pien-Sheng; Nan, Fan-Hua

2016-11-01

This study investigated the effects of orally administered Plantago asiatica, Houttuynia cordata, and Mentha haplocalyx on the growth and nonspecific immune responses of cobia (Rachycentron canadum). The nonspecific immune parameters assessed were weight gain, feed conversion ratio, superoxide anion (O 2 - ) production, superoxide dismutase (SOD) activity, phagocytic rate, phagocytic index, lysozyme activity, serum albumin and globulin, and albumin:globulin (A/G) ratio. The growth experiment indicated that 6-week dietary treatments did not significantly affect on the growth of cobia. Nonspecific immune responses showed that O 2 - production, SOD and lysozyme activity, and phagocytosis were significantly increased after the oral administration of P. asiatica and H. cordata, and the serum albumin:globulin ratio (A/G) gradually decreased. In this study, treatment of the Mentha haplocalyx on the cobia didn't present with the inducing of the phagocytosis ability compared with the treatment of P. asiatica and H. cordata. We suggest that oral administration of the 10 g/kg or 20 g/kg of the P. asiatica and H. cordata is exactly inducing the phagocytosis, ROS production, lysozyme activity and SOD production in the cobia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolution of anisotropy in bcc Fe distorted by interstitial boron

Science.gov (United States)

Gölden, Dominik; Zhang, Hongbin; Radulov, Iliya; Dirba, Imants; Komissinskiy, Philipp; Hildebrandt, Erwin; Alff, Lambert

2018-01-01

The evolution of magnetic anisotropy in bcc Fe as a function of interstitial boron atoms was investigated in thin films grown by molecular beam epitaxy. The thermodynamic nonequilibrium conditions during film growth allowed one to stabilize an interstitial boron content of about 14 at .% accompanied by lattice tetragonalization. The c /a ratio scaled linearly with the boron content up to a maximum value of 1.05 at 300 °C substrate growth temperature, with a room-temperature magnetization of. In contrast to nitrogen interstitials, the magnetic easy axis remained in-plane with an anisotropy of approximately -5.1 ×106erg /cm3 . Density functional theory calculations using the measured lattice parameters confirm this value and show that boron local ordering indeed favors in-plane magnetization. Given the increased temperature stability of boron interstitials as compared to nitrogen interstitials, this study will help to find possible ways to manipulate boron interstitials into a more favorable local order.

Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram

Directory of Open Access Journals (Sweden)

Irfan Moinuddin

2015-01-01

Full Text Available Allergic interstitial nephritis (AIN is an underdiagnosed cause of acute kidney injury (AKI. Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.

Non-Specific Reactions during Immunomagnetic Separation of Listeria

Directory of Open Access Journals (Sweden)

Iveta Zachová

2005-01-01

Full Text Available Problems occurring during the immunomagnetic separation (IMS of Listeria using immunomagnetic particles Dynabeads® anti-Listeria (Dynal Biotech, Norway were specified. Characteristics of these particles were compared with anti-Listeria spp. magnetite particles (Quantum Magnetics, USA. Pure cultures of Listeria innocua, Arthrobacter spp., Bacillus subtilis, Citrobacter braakii, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae and Staphylococcus aureus were used to evaluate non-specific reactions during IMS. Gram-positive microorganisms, especially Staphylococcus aureus and Arthrobacter spp., were found to be responsible for non-specific reactions in most cases. The capacity of Dynabeads® anti-Listeria particles was determined to be about 10 % of the initial pure cultures of Listeria spp., after 10 min of incubation. Non-specific reactions during IMS of Listeria were examined on the artificially inoculated food samples in which Gram-positive bacteria showed the highest percentage of capture. Influence of washing in two buffers was also studied.

Interstitial integrals in the multiple-scattering model

International Nuclear Information System (INIS)

Swanson, J.R.; Dill, D.

1982-01-01

We present an efficient method for the evaluation of integrals involving multiple-scattering wave functions over the interstitial region. Transformation of the multicenter interstitial wave functions to a single center representation followed by a geometric projection reduces the integrals to products of analytic angular integrals and numerical radial integrals. The projection function, which has the value 1 in the interstitial region and 0 elsewhere, has a closed-form partial-wave expansion. The method is tested by comparing its results with exact normalization and dipole integrals; the differences are 2% at worst and typically less than 1%. By providing an efficient means of calculating Coulomb integrals, the method allows treatment of electron correlations using a multiple scattering basis set

Nonspecific suppressor elements in murine allogeneic radiation chimeras

International Nuclear Information System (INIS)

Urso, P.; Gengozian, N.

1979-01-01

Spleen cells from long-term mouse allogeneic radiation chimeras were tested for their ability to modulate the graft-versus-host (GVH) or plaque-forming cell (PFC) response of normal lymphocytes transplanted in lethally x-irradiated recipients. In vivo GVH proliferation of normal lymphocytes (syngeneic to donor cells of the chimera) against antigens of host-type in which the chimeric state had been established was reduced by chimera cells. Inhibition varied, some chimeras suppressing GVH more than others and a few not suppressing at all. The suppressive effect was abrogated if the chimera cells were treated with anti-THETA; treatment with anti-IgM did not eliminate this activity. When mixtures of normal donor lymphocytes and chimera cells were given to irradiated recipients genetically different from host or donor, reduction of donor cell GVH also occurred. Further, chimera cells reduced the GVH activity of normal host cells in irradiated recipients differing from the host at one H-2 locus and from the donor at minor histocompatibility loci. The modulating effect of spleen cells from chimeras on the PFC response by normal lymphocytes also varied. Six chimeras induced a 25 to 90% suppression, two enhanced the response, and one showed no effect. Where suppression occurred, treatment of chimera cells with anti-THETA most often, but not always, restored PFC production. Our results show that the suppressive action of splenic lymphoid cells by chimeras is highly nonspecific and variable in expression. We suggest that tolerance in chimeras may be mediated by nonspecific suppressor elements leading to unresponsiveness to a variety of antigens including SRBC

Off-label use of rituximab for systemic lupus erythematosus in Europe

DEFF Research Database (Denmark)

Ryden-Aulin, Monica; Boumpas, Dimitrios T; Bultink, Irene

2016-01-01

Objectives: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. Methods...... organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. Conclusions: RTX use for SLE...

Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology

International Nuclear Information System (INIS)

Dias, Carla Roberta; Jeger, Simone; Osso, Joao Alberto; Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

2011-01-01

Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20 + B-cell tumors. Rituximab radiolabeled with β - emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the 99m Tc- and 188 Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX wt ) as well as a reduced form (RTX red ) was labeled with 99m Tc/ 188 Re(CO) 3 . The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX red were superior to that of RTX wt ( 99m Tc: 98% after 3 h for RTX red vs. 70% after 24 h for RTX wt ). 99m Tc(CO) 3 -RTX red was used without purification for in vitro and in vivo studies whereas 188 Re(CO) 3 -RTX red was purified to eliminate free 188 Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 o C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of 99m Tc(CO) 3 -RTX red but not with pre-purified 188 Re(CO) 3 -RTX red . Both conjugates revealed high binding affinity to the CD20 antigen (K d =5-6 nM). Tumor uptake of 188 Re(CO) 3 -RTX red was 2.5 %ID/g and 0.8 %ID/g for 99m Tc(CO) 3 -RTX red 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for 99m Tc(CO) 3 -RTX red and for 188 Re

Smoking-related interstitial lung diseases; Interstitielle Lungenerkrankungen bei Rauchern

Energy Technology Data Exchange (ETDEWEB)

Marten, K. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Inst. fuer Roentgendiagnostik

2007-03-15

The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

International Nuclear Information System (INIS)

Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

2003-01-01

Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

Thermal analysis of laser interstitial thermotherapy in ex vivo fibro-fatty tissue using exponential functions

International Nuclear Information System (INIS)

Salas, Nelson Jr.; Manns, Fabrice; Milne, Peter J; Denham, David B; Minhaj, Ahmed M; Parel, Jean-Marie; Robinson, David S

2004-01-01

A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T 3 mm 3 ) coagulation volume without unwanted tissue liquefaction and carbonization

Time scales of transient enhanced diffusion: Free and clustered interstitials

Science.gov (United States)

Cowern, N. E. B.; Huizing, H. G. A.; Stolk, P. A.; Visser, C. C. G.; de Kruif, R. C. M.; Kyllesbech Larsen, K.; Privitera, V.; Nanver, L. K.; Crans, W.

1996-12-01

Transient enhanced diffusion (TED) and electrical activation after nonamorphizing Si implantations into lightly B-doped Si multilayers shows two distinct timescales, each related to a different class of interstitial defect. At 700°C, ultrafast TED occurs within the first 15 s with a B diffusivity enhancement of > 2 × 10 5. Immobile clustered B is present at low concentration levels after the ultrafast transient and persists for an extended period (˜ 10 2-10 3 s). The later phase of TED exhibits a near-constant diffusivity enhancement of ≈ 1 × 10 4, consistent with interstitial injection controlled by dissolving {113} interstitial clusters. The relative contributions of the ultrafast and regular TED regimes to the final diffusive broadening of the B profile depends on the proportion of interstitials that escape capture by {113} clusters growing within the implant damage region upon annealing. Our results explain the ultrafast TED recently observed after medium-dose B implantation. In that case there are enough B atoms to trap a large proportion of interstitials in SiB clusters, and the remaining interstitials contribute to TED without passing through an intermediate {113} defect stage. The data on the ultrafast TED pulse allows us to extract lower limits for the diffusivities of the Si interstitial ( DI > 2 × 10 -10 cm 2s -1) and the B interstitial(cy) defect ( DBi > 2 × 10 -13 cm 2s -1) at 700°C.

Analysis of Dissolved Organic Nutrients in the Interstitial Water of Natural Biofilms.

Science.gov (United States)

Tsuchiya, Yuki; Eda, Shima; Kiriyama, Chiho; Asada, Tomoya; Morisaki, Hisao

2016-07-01

In biofilms, the matrix of extracellular polymeric substances (EPSs) retains water in the interstitial region of the EPS. This interstitial water is the ambient environment for microorganisms in the biofilms. The nutrient condition in the interstitial water may affect microbial activity in the biofilms. In the present study, we measured the concentrations of dissolved organic nutrients, i.e., saccharides and proteins, contained in the interstitial water of biofilms formed on the stones. We also analyzed the molecular weight distribution, chemical species, and availability to bacteria of some saccharides in the interstitial water. Colorimetric assays showed that the concentrations of saccharides and proteins in the biofilm interstitial water were significantly higher (ca. 750 times) than those in the surrounding lake waters (p Chromatographic analyses demonstrated that the saccharides in the interstitial waters were mainly of low molecular-weight saccharides such as glucose and maltose, while proteins in the interstitial water were high molecular-weight proteins (over 7000 Da). Bacterial growth and production of EPS occurred simultaneously with the decrease in the low molecular-weight saccharide concentrations when a small portion of biofilm suspension was inoculated to the collected interstitial water, suggesting that the dissolved saccharides in the interstitial water support bacterial growth and formation of biofilms.

Di-interstitial defect in silicon revisited

International Nuclear Information System (INIS)

Londos, C. A.; Antonaras, G.; Chroneos, A.

2013-01-01

Infrared spectroscopy was used to study the defect spectrum of Cz-Si samples following fast neutron irradiation. We mainly focus on the band at 533 cm −1 , which disappears from the spectra at ∼170 °C, exhibiting similar thermal stability with the Si-P6 electron paramagnetic resonance (EPR) spectrum previously correlated with the di-interstitial defect. The suggested structural model of this defect comprises of two self-interstitial atoms located symmetrically around a lattice site Si atom. The band anneals out following a first-order kinetics with an activation energy of 0.88 ± 0.3 eV. This value does not deviate considerably from previously quoted experimental and theoretical values for the di-interstitial defect. The present results indicate that the 533 cm −1 IR band originates from the same structure as that of the Si-P6 EPR spectrum

Association of hypovitaminosis Dwith persistent non-specific musculoskeletal pains

International Nuclear Information System (INIS)

Alam, H.M.A.; Kamran, M.; Rehman, S.U.; Khan, D.A.; Hussain, K.

2017-01-01

The study was conducted in Pakistani population to find association of vitamin D deficiency with persistent non-specific musculoskeletal pains by comparing with pain free controls. Study Design: Case control study. Material and Methods: Patients aged 12 years or more presenting to Medical OPD with persistent nonspecific musculoskeletal pains for more than 3 months were selected as cases, while healthy individuals served as controls Results: A total of 60 cases (patients with persistent non-specific pains) presenting to medical outpatients department at Military Hospital Rawalpindi and 60 controls were studied. Mean age of cases was 43.9 +- 14.0 years and amongst controls were 33.2 +- 17.8 years. Mean serum vitamin D level of 32.8 nmol/L was reported in cases whereas mean serum vitamin D level amongst controls was 26.7 +- 17.8 nmol/L. Hypovitaminosis D amongst cases and controls was 86.6% and 95% respectively. The proportion of vitamin D deficiency did not differ significantly as compared to controls. There was non-significant difference in proportion of deficiency amongst cases and controls. Conclusion: Overall there was no association between persistent non-specific musculoskeletal pains and vitamin D deficiency. (author)

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

Science.gov (United States)

Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

2011-08-15

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up.

Science.gov (United States)

Evangelopoulos, M E; Andreadou, E; Koutsis, G; Koutoulidis, V; Anagnostouli, M; Katsika, P; Evangelopoulos, D S; Evdokimidis, I; Kilidireas, C

2017-01-15

Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate. All patients were found positive for NMO IgG. All patients (three with NMO and two with NMOSD, 1 patient with recurrent optic neuritis and 1 patient with recurrent myelitis) had received rituximab treatment for six years. One patient with NMOSD received cyclophosphamide prior to rituximab while two were misdiagnosed as multiple sclerosis and had received interferon treatment. All received rituximab infusion of 375mg/m 2 once per week for 4weeks and then every two months for the first two years and then every six months. B-cell counts were measured every two months and were kept in almost undetectable levels. No relapse was noted during the treatment period while EDSS score was improved in all patients. No severe adverse effects occurred during RTX treatment. Rituximab treatment on NMO and NMOSD patients showed significant improvement in disability and relapse-rate without any significant adverse effects. Copyright © 2016. Published by Elsevier B.V.

Clinical scale preparation and evaluation of {sup 131}I-Rituximab for Non-Hodgkin's lymphoma

Energy Technology Data Exchange (ETDEWEB)

Kameswaran, Mythili; Vimalnath, K. Viswanathan; Rajeswari, Ardhi; Joshi, Prahlad Vasudeo; Samuel, Grace [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, H.D. [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

2014-09-01

Radioimmunotherapy (RIT) with anti CD20 MoAb conjugated to a β{sup -} emitting radioisotope like {sup 131}I or {sup 90}Y has the added advantage of delivering radiation not only to tumor cells that bind the antibody but also due to a crossfire effect, to neighboring tumor cells inaccessible to the antibody. In order to make available an indigenous radioimmunotherapeutic agent for Non Hodgkin's Lymphoma (NHL), radioiodinated Rituximab has been prepared and evaluated at a clinical scale. Radioiodination of Rituximab was performed by the conventional Chloramine T method using 7.4 GBq Na{sup 131}I in a lead shielded plant. Six batches of radioiodination were prepared and characterized by electrophoresis and HPLC to evaluate the reproducibility of the product. The product remained stable retaining the radiochemical purity > 95% upto 5 days after radioiodination. In vitro cell binding studies and biodistribution studies in normal Swiss mice have indicated the potential of this molecule as a radioimmunotherapeutic agent for NHL. (orig.)

Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei).

Science.gov (United States)

Wu, Yu-Sheng; Liau, Shu-Yu; Huang, Cheng-Ting; Nan, Fan-Hua

2016-10-01

This study mainly evaluated the effects of orally administered beta 1,3/1,6-glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rituximab enhances radiation-triggered apoptosis in non-Hodgkin's lymphoma cells via caspase-dependent and - independent mechanisms

International Nuclear Information System (INIS)

Skvortsova, I.; Skvortsov, S.; Popper, B.A.; Haidenberger, A.; Saurer, M.; Gunkel, A.R.; Zwierzina, H.; Lukas, P.

2006-01-01

Rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, is currently employed in the treatment of malignant non-Hodgkin's lymphoma (NHL) either alone or in combination with other cytotoxic approaches. The present study examines the effects of ionizing radiation in combination with RTX on proliferation and apoptosis development in B-lymphoma RL and Raji cells. RTX was used at a concentration of 10 μg/mL 24 hours prior to irradiation at a single dose of 9 Gy. CD20 expression, cell viability, apoptosis, mitochondrial membrane potential and apoptosis-related proteins were evaluated in the treated B cells. The constitutive level of CD20 expression in RL and Raji lymphoma cells did not play an essential role in RTX-induced cell growth delay. Both lymphoma cells showed similar inhibition of cell proliferation without apoptosis development in response to RTX treatment. Exposure to ionizing radiation induced cell growth delay and apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance and activation of cell growth at 24 hours after irradiation, which was accompanied by increased radiation-triggered CD20 expression. The simultaneous exposure of lymphoma cells to ionizing radiation and RTX abrogated radioresistance of Raji cells and significantly enhanced cell growth delay and apoptosis in RL cells. X-linked inhibitor of apoptosis protein (XIAP) and the inducible form of heat shock protein 70 (Hsp70) were positively modulated by RTX in combination with ionizing radiation in order to induce apoptosis. Furthermore, it was demonstrated that mitochondrial membrane potential dissipation is not an essential component to induce apoptosis-inducing factor (AIF) maturation and apoptosis. Our results show that RTX-triggered enhancement of radiation-induced apoptosis and cell growth delay is achieved by modulation of proteins involved in programmed cell death. (author)

Surface charges promote nonspecific nanoparticle adhesion to stiffer membranes

Science.gov (United States)

Sinha, Shayandev; Jing, Haoyuan; Sachar, Harnoor Singh; Das, Siddhartha

2018-04-01

This letter establishes the manner in which the electric double layer induced by the surface charges of the plasma membrane (PM) enhances the nonspecific adhesion (NSA) of a metal nanoparticle (NP) to stiffer PMs (i.e., PMs with larger bending moduli). The NSA is characterized by the physical attachment of the NP to the membrane and occurs when the decrease in the surface energy (or any other mechanism) associated with the attachment process provides the energy for bending the membrane. Such an attachment does not involve receptor-ligand interactions that characterize the specific membrane-NP adhesion. Here, we demonstrate that a significant decrease in the electrostatic energy caused by the NP-attachment-induced destruction of the charged-membrane-electrolyte interface is responsible for providing the additional energy needed for bending the membrane during the NP adhesion to stiffer membranes. A smaller salt concentration and a larger membrane charge density augment this effect, which can help to design drug delivery to cells with stiffer membranes due to pathological conditions, fabricate NPs with biomimetic cholesterol-rich lipid bilayer encapsulation, etc.

Irradiation-induced segregation in multi-component alloys

International Nuclear Information System (INIS)

Chen, I.W.

1983-01-01

A unified analysis of irradiation-induced segregation in multi-component alloys is developed using the formulation of irreversible thermodynamics. Three distinct mechanisms for segregation, namely the inverse Kirkendall effect, the vacancy-wind effect, and the solute drag of interstitials, are identified. In particular, the inverse Kirkendall effect due to interstitials arises only if a solute-interstitial interaction or a mutual conversion among interstitials via lattice atom intermediaries operates simultaneously. In the limit of fast conversion a para-equilibrium state may be reached between interstitials and lattice atoms, and the interstitial mechanism becomes formally analogous to the vacancy mechanism. Although the past treatment of rate phenomena in this field was apparently limited to the latter case, the importance of the consideration of separate chemical potentials for interstitials of different species, in segregation and other irradiation effects, is emphasized. (orig.)

Advanced sickle cell associated interstitial lung disease presenting ...

African Journals Online (AJOL)

Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

Segregation of cascade induced interstitial loops at dislocations: possible effect on initiation of plastic deformation

Energy Technology Data Exchange (ETDEWEB)

Trinkaus, H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Festkoerperforschung; Singh, B.N. [Materials Research Department, Risoe National Laboratory, DK-4000 Roskilde (Denmark); Foreman, A.J.E. [Materials Performance Department, Harwell Laboratory, Oxfordshire OX11 0RA (United Kingdom)

1997-11-01

In metals and alloys subjected to cascade damage dislocations are frequently found to be decorated with a high density of small clusters of self-interstitial atoms (SIAs) in the form of dislocation loops. In the present paper it is shown that this effect may be attributed to the glide and trapping of SIA loops, produced directly in cascades (rather than to the enhanced agglomeration of single SIAs), in the strain field of the dislocations. The conditions for the accumulation of glissile SIA loops near dislocations as well as the dose and temperature dependencies of this phenomenon are discussed. It is suggested that the decoration of dislocations with loops may play a key role in radiation hardening subjected to cascade damage. It is shown, for example, that the increase in the upper yield stress followed by a yield drop and plastic instability in metals andalloys subjected to cascade damage cannot be rationalized in terms of conventional dispersed barrier hardening (DBH) but may be understood in terms of cascade induced source hardening (CISH) in which the dislocations are considered to be locked by the loops decorating them. Estimates for the stress necessary to pull a dislocation away from its loop `cloud` are used to discuss the dose and temperature dependence of plastic flow initiation. (orig.). 55 refs.

Segregation of cascade induced interstitial loops at dislocations: possible effect on initiation of plastic deformation

International Nuclear Information System (INIS)

Trinkaus, H.; Foreman, A.J.E.

1997-01-01

In metals and alloys subjected to cascade damage dislocations are frequently found to be decorated with a high density of small clusters of self-interstitial atoms (SIAs) in the form of dislocation loops. In the present paper it is shown that this effect may be attributed to the glide and trapping of SIA loops, produced directly in cascades (rather than to the enhanced agglomeration of single SIAs), in the strain field of the dislocations. The conditions for the accumulation of glissile SIA loops near dislocations as well as the dose and temperature dependencies of this phenomenon are discussed. It is suggested that the decoration of dislocations with loops may play a key role in radiation hardening subjected to cascade damage. It is shown, for example, that the increase in the upper yield stress followed by a yield drop and plastic instability in metals andalloys subjected to cascade damage cannot be rationalized in terms of conventional dispersed barrier hardening (DBH) but may be understood in terms of cascade induced source hardening (CISH) in which the dislocations are considered to be locked by the loops decorating them. Estimates for the stress necessary to pull a dislocation away from its loop 'cloud' are used to discuss the dose and temperature dependence of plastic flow initiation. (orig.)

Interstitial impurity interactions and dislocation microdynamics in Mo crystals

International Nuclear Information System (INIS)

Kwok, D.N.

1975-05-01

The effects of interstitial impurities on the mechanical properties of molybdenum are explored by comparing results obtained for crystals of various interstitial contents controlled by ultra-high vacuum outgassing. Results show a modulus reduction for as-grown samples and for outgassed specimens at low applied stresses. As a function of plastic microstrain, the values of modulus defect for both as-grown and outgassed specimens saturate at the same value. Interstitial impurities act as pinning agents to dislocation bowing, but when all the easy dislocation loops have broken away from local interstitial pins, the modulus defect reaches a constant saturation value. Etch pitting techniques were used to correlate microstrain observations with dislocation generation and motion. It has been found that edge dislocation generation and movement are active in the microstrain region while screw dislocations are relatively inactive until the macrostrain region is reached. Dislocation velocities range from 10 -6 to 10 -3 cm/s and the average distance between interstitial impurity pinning points is found to be approximately 8 x 10 -4 cm. (U.S.)

Effects of γ irradiation of hydra: elimination of interstitial cells from viable hydra

International Nuclear Information System (INIS)

Fradkin, M.; Kakis, H.; Campbell, R.D.

1978-01-01

Hydra attenuata and H. magnipapillata were γ-irradiated from a cesium source. All doses which had any observable effect (3000 rad and above) resulted in a reduction in the number of interstitial cells and of their differentiated product cells, or in the complete elimination of these cells. Interstitial cells were essentially completely eliminated within 5 days after irradiation doses above 5500 rad, and these hydra died. Irradiation doses of 4200 to 5500 rad resulted in a mixture of effects: some hydra recovered completely, some lost all interstitial cells and died, and some lost interstitial cells but could be propagated, as asexually reproducing clones, by hand feeding them. Hydra of some of these hand-fed clones entirely lacked interstitial cells and did not recover interstitial cells during subsequent culturing. Yet when these hydra were repopulated by interstitial cells from a normal hydra, they were restored to normal. Nerve cells became depleted more slowly than interstitial cells following irradiation, so animals can be obtained which possess nerve but no stem (interstitial) cells. The nerve cells and other derivatives of interstitial cells eventually disappear upon prolonged culture of the hydra. Thus γ irradiation can be used to eliminate interstitial cells from hydra, leaving viable polyps composed only of epithelial cells

Selective Uterine Artery Embolization for Management of Interstitial Ectopic Pregnancy

International Nuclear Information System (INIS)

Yang, Seung Boo; Lee, Sang Jin; Joe, Hwan Sung; Goo, Dong Erk; Chang, Yun Woo; Kim, Dong Hun

2007-01-01

Interstitial pregnancy is defined as any gestation that develops in the uterine portion of the fallopian tubes lateral to the round ligament. Interstitial pregnancies account for 2-4% of all ectopic pregnancies and have been reported to have an associated 2% to 2.5% maternal mortality rate. The traditional treatment for interstitial pregnancy using surgical cornual resection may cause infertility or uterine rupture in subsequent pregnancies. Recently, the early identification of intact interstitial pregnancy has been made possible in many cases with high resolution transvaginal ultrasound as well as more sensitive assays for betahuman chorionic gonadotropin (β-hCG). The treatment includes: hysteroscopic transcervical currettage, local and systemic methotrexate (MTX) therapy and prostaglandin or potassium chloride injection of the ectopic mass under sonographic guidance. We describe a case of successful treatment of interstitial pregnancy using uterine artery embolization, after failure of methotrexate treatment

Selective Uterine Artery Embolization for Management of Interstitial Ectopic Pregnancy

Energy Technology Data Exchange (ETDEWEB)

Yang, Seung Boo; Lee, Sang Jin; Joe, Hwan Sung; Goo, Dong Erk; Chang, Yun Woo [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of); Kim, Dong Hun [Chosun University Hospital, Gwangju (Korea, Republic of)

2007-04-15

Interstitial pregnancy is defined as any gestation that develops in the uterine portion of the fallopian tubes lateral to the round ligament. Interstitial pregnancies account for 2-4% of all ectopic pregnancies and have been reported to have an associated 2% to 2.5% maternal mortality rate. The traditional treatment for interstitial pregnancy using surgical cornual resection may cause infertility or uterine rupture in subsequent pregnancies. Recently, the early identification of intact interstitial pregnancy has been made possible in many cases with high resolution transvaginal ultrasound as well as more sensitive assays for betahuman chorionic gonadotropin ({beta}-hCG). The treatment includes: hysteroscopic transcervical currettage, local and systemic methotrexate (MTX) therapy and prostaglandin or potassium chloride injection of the ectopic mass under sonographic guidance. We describe a case of successful treatment of interstitial pregnancy using uterine artery embolization, after failure of methotrexate treatment.

Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

DEFF Research Database (Denmark)

Andersen, Niels S; Pedersen, Lone B; Laurell, Anna

2009-01-01

PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

Biomechanical aspects of nonspecific back pain

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Ridwan Harrianto

2010-12-01

Full Text Available Low back pain (LBP is a common problem in adult life, since despite its benign nature it is commonly associated with incapacity, productivity loss due to sick leave, and correspondingly high costs to the individual worker. Psychosocial and lifestyle factors and work-place exposures have been implicated in the onset of symptoms. Heavy physical work, static work postures, frequent bending and twisting, lifting and postural movements, repetitive work, and whole body vibrations are occupational factors associated with LBP. The usual classification of LBP is related to the duration of the complaints (acute, subacute, and chronic. However, these terms fail to take into account several clinically important aspects of the course of LBP, which is frequently recurrent and thus neither acute nor chronic. More realistically, LBP should be classified as specific and nonspecific. Approximately 90% of LBP cases have no identifiable cause and is designated nonspecific LBP. However, despite its high prevalence, the etiology and nature of nonspecific LBP are not yet well understood. Its pathophysiology remains complex and multifaceted. Multiple anatomic structures and elements of the lumbar spine (e.g. bones, ligaments, tendons, discs, and muscles are all suspected of playing a role. Many of these components of the lumbar spine have sensory innervations that can generate nociceptive signals in response to tissue-damaging stimuli. Other causes could be neuropathic (e.g. sciatica. Some cases of LBP most likely involve mixed nociceptive and neuropathic etiologies.

Lack of spontaneous and radiation-induced chromosome breakage at interstitial telomeric sites in murine scid cells.

Science.gov (United States)

Wong, H-P; Mozdarani, H; Finnegan, C; McIlrath, J; Bryant, P E; Slijepcevic, P

2004-01-01

Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient mammalian cells are sensitive to both spontaneous and radiation-induced chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are not known. To investigate factors that predispose ITSs to chromosome breakage we used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved in the repair of DNA double-strand breaks. Interestingly, our results revealed lack of both spontaneous and radiation-induced chromosome breakage at ITSs found in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs to chromosome breakage is associated with the functional DNA double-strand break repair machinery. To investigate if this is the case we used scid cells in which DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of ITSs in scid cells with functional DNA-PKcs, presumably through chromosome breakage at ITSs, but their unchanged frequency in positive and negative control cells. Therefore, our results indicate that the functional DNA double-strand break machinery is required for elevated sensitivity of ITSs to chromosome breakage. Interestingly, we observed significant differences in mitotic chromosome condensation between scid cells and their counterparts with restored DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect in chromatin organization. Increased condensation of mitotic chromosomes in the scid background was also confirmed in vivo. Therefore, our results indicate a previously unanticipated role of DNA-PKcs in chromatin organisation, which could contribute to the lack of ITS sensitivity to chromosome breakage in murine scid cells. Copyright 2003 S. Karger AG, Basel

Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

DEFF Research Database (Denmark)

Natarajan, Arutselvan; Gowrishankar, Gayatri; Nielsen, Carsten Haagen

2012-01-01

PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed....... The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n¿=¿3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n¿=¿6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20......TM, n¿=¿6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. RESULTS: PETRIT was obtained with a specific activity of 545...

Desquamative interstitial pneumonia: A case report

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Lovrenski Aleksandra

2014-01-01

Full Text Available Introduction. Desquamative interstitial pneumonia is one of the rarest idiopathic interstitial pneumonias and the rarest form of smoking-related interstitial lung diseases. It was first described by Liebow in 1965. Histologically, it is characterized by the presence of eosinophilic macrophages uniformly filling airspaces which often contain a finely granular light-brown pigment that does not stain for hemosiderin. The alveolar walls are usually mildly thickened by fibrous tissue and infiltrated by a moderate number of lymphocytes. Case Outline. Our patient was a 56-year-old male, heavy smoker, with bilateral lung infiltrations of unknown etiology and several months of discomfort in the form of dry cough and shortness of breath. Lung function tests showed a moderate restrictive ventilation disorder and a severe reduction of diffusing capacity. Since bronchoscopic specimens did not reveal lung lesion etiology, an open lung biopsy of the lower left pulmonary lobe was performed, and based on the obtained surgical material the pathohistologically diagnosis of desquamative interstitial pneumonia was established. The patient was started on corticosteroid and immunosuppressive therapy, and he ceased smoking. At the last control examination, two years after the onset of symptoms, the patient was feeling well, and high-resolution computed tomography (HRCT scan of the thorax showed regression of pathological changes. Conclusion. Although, as in our case, the majority of DIP patients improve on treatment, some patients still develop progressive irreversible fibrosis despite therapy.

Evidence of interstitial microsegregation in iron obtained by ion microscopy

International Nuclear Information System (INIS)

Price, C.W.

1984-01-01

Segregation of impurity atoms to the strain fields of dislocations and the effective locking of the dislocations by the impurity atmospheres have been suggested earlier by others. The formation of interstitial atmospheres and their effect in iron was first treated mathematically by Cottrell and Bilby (Proc. Phys. Soc.; A62: 49(1949). Hirth and Lothe (Theory of Discolations, McGraw-Hill, New York (1968) reviewed more recent evidence of interstitial effects and theoretical treatments of interstitial dislocation interactions. This paper describes additional evidence of microsegregation of several interstitial elements in iron that were detected using secondary-ion mass spectroscopy (SIMS). 10 references, 2 figures

Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model

Science.gov (United States)

Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

2016-02-01

Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

Smoking-related interstitial lung diseases: radiologic-pathologic correlation

International Nuclear Information System (INIS)

Hidalgo, Alberto; Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta; Bordes, Ramon

2006-01-01

Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

Smoking-related interstitial lung diseases: radiologic-pathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Hidalgo, Alberto [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Hospital de la Santa Creu i Sant Pau, Thoracic Radiology, Department of Radiology, Barcelona (Spain); Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Bordes, Ramon [Universidad Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

2006-11-15

Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

Determination of the population of octahedral and tetrahedral interstitials in zirconium hydrides

International Nuclear Information System (INIS)

Fedorov, V.M.; Gogava, V.V.; Shilo, S.I.; Biryukova, E.A.

1983-01-01

Results of neutron investigations of ZrHsub(1.66), ZrHsub(1.75) and ZrHsub(1.98) zirconium hydrides are presented. Investigations were conducted using plane polycrystal samples by multidetector system of scattered neutron detection. Neutron diffraction method was used to determine the number of interstitial hydrogen atoms in interstitials of the lattice cell in the case of statistic atom distribution. The numbers of interstitial atoms in octahedral interstitials for zirconium hydrides were determined experimentally; the difference of potential energies of hydrogen atoms in octa- and tetrahedral interstitials was determined as well. It is shown that experimentally determined difference of potential energies of hydrogen atoms, occupying octa- and tetrahedral positions in investigated zirconium hydrides results at room temperature in the pretailing occupation of tetrahedral interstitials by hydrogen atoms (85-90%); the occupation number grows with temperature decrease and the ordering of interstitial vacancies with formation of hydrogen superstructure takes place at low temperatures

Nonspecific Arm Pain

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Ali Moradi

2013-12-01

Full Text Available Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Nonspecific Arm Pain

Directory of Open Access Journals (Sweden)

Ali Moradi

2013-12-01

Full Text Available   Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Factors affecting radiation injury after interstitial brachytherapy for brain tumors

International Nuclear Information System (INIS)

Leibel, S.A.; Gutin, P.H.; Davis, R.L.

1991-01-01

The effects of brachytherapy on normal brain tissue are not easily delineated in the clinical setting because of the presence of concurrent radiation-induced changes in the coexistent brain tumor. Sequential morphologic studies performed after the implantation of radioactive sources into the brains of experimental animals have provided a better understanding of the character and magnitude of the structural changes produced by interstitial irradiation on normal brain tissue. Furthermore, the clinical experience accumulated thus far provides not only relevant information, but also some guidelines for future treatment policies. In this paper, the authors summarize the experimental findings and review the pathologic and clinical features of brain injury caused by interstitial brachytherapy. A number of studies in the older literature examined the effects of radioisotopes such as radium-226 (38--43), radon-22 (44--46), gold-198 (29,47--50), tantalum-182 (29,51,52) yttrium-9- (50,53,54), and cobalt-60 (29,50,55). This review is restricted to low- and high-activity encapsulated iodine-125 ( 125 I) and iridium-192 ( 192 Ir), the isotopes that are most commonly used in current clinical practice

HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab

NARCIS (Netherlands)

Raterman, Hennie G.; Levels, Han; Voskuyl, Alexandre E.; Lems, Willem F.; Dijkmans, Ben A.; Nurmohamed, Michael T.

2013-01-01

An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid

Radionuclide study for the interstitial lung disease

International Nuclear Information System (INIS)

Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo

1991-01-01

The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with 81m Kr, distribution of compliance in thoraco-pulmonary system (C) by 81m Kr gas bolus inhalation method, perfusion study (Q) with 99m Tc-MAA, 67 Ga scintigraphy and an assessment of pulmonary epithelial permeability with 99m Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO 2 was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. 67 Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of 67 Ga. 67 Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by 99m Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author)

Four cases of recalcitrant pemphigus vulgaris salvaged with rituximab

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Samyak Ganjre

2017-01-01

Full Text Available Although the long-term use of immunosuppressives – supplemented with more aggressive treatments such as immunoadsorption, intravenous immunoglobulins, or plasmapheresis in recalcitrant cases has dramatically improved the prognosis of pemphigus vulgaris, opportunistic infections secondary to immunosuppression continue to cause significant mortality. We report four cases– three old ones, who had accumulated significant morbidities over their disease duration ranging from 5 to 10 years, and the fourth, a teenage female intolerant to corticosteroids and idiosyncratic to methotrexate– who achieved complete remission on administration of rituximab by the lymphoma protocol. One of the old cases who had recalcitrant mucositis experienced its complete subsidence without any adjuvant whatsoever. All continue to remain asymptomatic for 11–20 months. None had infusion reactions or any delayed side effects.

Risk factors of non-specific spinal pain in childhood.

Science.gov (United States)

Szita, Julia; Boja, Sara; Szilagyi, Agnes; Somhegyi, Annamaria; Varga, Peter Pal; Lazary, Aron

2018-05-01

Non-specific spinal pain can occur at all ages and current evidence suggests that pediatric non-specific spinal pain is predictive for adult spinal conditions. A 5-year long, prospective cohort study was conducted to identify the lifestyle and environmental factors leading to non-specific spinal pain in childhood. Data were collected from school children aged 7-16 years, who were randomly selected from three different geographic regions in Hungary. The risk factors were measured with a newly developed patient-reported questionnaire (PRQ). The quality of the instrument was assessed by the reliability with the test-retest method. Test (N = 952) and validity (N = 897) datasets were randomly formed. Risk factors were identified with uni- and multivariate logistic regression models and the predictive performance of the final model was evaluated using the receiver operating characteristic (ROC) method. The final model was built up by seven risk factors for spinal pain for days; age > 12 years, learning or watching TV for more than 2 h/day, uncomfortable school-desk, sleeping problems, general discomfort and positive familiar medical history (χ 2  = 101.07; df = 8; p < 0.001). The probabilistic performance was confirmed with ROC analysis on the test and validation cohorts (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing possibility for non-specific spinal pain depending on the number of the identified risk factors (χ 2  = 65.0; df = 4; p < 0.001). Seven significant risk factors of non-specific spinal pain in childhood were identified using the new, easy to use and reliable PRQ which makes it possible to stratify the children according to their individual risk. These slides can be retrieved under Electronic Supplementary Material.

Nonspecific eating disorders - a subjective review.

Science.gov (United States)

Michalska, Aneta; Szejko, Natalia; Jakubczyk, Andrzej; Wojnar, Marcin

2016-01-01

The aim of this paper was to characterise nonspecific eating disorders (other than anorexia nervosa and bulimia nervosa). The Medline database was searched for articles on nonspecific eating disorders. The following disorders were described: binge eating disorder (BED), pica, rumination disorder, avoidant/restrictive food intake disorder, night eating syndrome (NES), sleep-related eating disorder (SRED), bigorexia, orthorexia, focusing on diagnosis, symptoms, assessment, comorbidities, clinical implications and treatment. All of the included disorders may have dangerous consequences, both somatic and psychological. They are often comorbid with other psychiatric disorders. Approximately a few percent of general population can be diagnosed with each disorder, from 0.5-4.7% (SRED) to about 7% (orthorexia). With the growing literature on the subject and changes in DSM-5, clinicians recognise and treat those disorders more often. More studies have to be conducted in order to differentiate disorders and treat or prevent them appropriately.

A case of cocaine-induced eosinophilic pneumonia: Case report and review of the literature

Directory of Open Access Journals (Sweden)

Felix Reyes, MD

Full Text Available Cocaine is a commonly abused recreational drug in the United States. An adult man developed non-specific pleuritic chest pain, pharyngitis and odynophagia after inhaling cocaine. Initial laboratory results revealed eosinophilia. Bronchoalveolar lavage also showed eosinophilia in the lavage fluid. These findings suggested the diagnosis of eosinophilic pneumonia. Chest imaging revealed scattered bilateral opacities and interstitial infiltrates. After initiation of systemic corticosteroids, the patient reported symptomatic resolution and radiographic clearance was achieved at 2 months follow up.

Interstitial lung disease during trimethoprim/sulfamethoxazole administration

International Nuclear Information System (INIS)

Yuzurio, Syota; Horita, Naokatsu; Shiota, Yutaro; Kanehiro, Arihiko; Tanimoto, Mitsune

2010-01-01

We studied clinical and radiographic features of interstitial lung disease (ILD) during trimethoprim/sulfamethoxazole (TMP/SMX) administration. Ten patients who had received prednisolone treatment for underlying diffuse pulmonary disease showed various ILDs after introduction of TMP/SMX. The radiographic features of the ILDs were not consistent with infectious disease or exacerbation of the underlying disease, and these diagnoses were excluded radiographically and on clinical grounds during the differential diagnosis of the ILDs. These ILDs emerged relatively early after introduction of TMP/SMX, which is consistent with the former case report of drug-induced ILD (DI-ILD) caused by TMP/SMX. Therefore DI-ILDs caused by TMP/SMX were suspected in these cases. In most of these cases, the ILDs were clinically mild and disappeared immediately although administration of TMP/SMX was continued. (author)

Peroxiredoxin 5 Protects TGF-β Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells.

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Hoon-In Choi

Full Text Available Renal fibrosis is a common final pathway of end-stage kidney disease which is induced by aberrant accumulation of myofibroblasts. This process is triggered by reactive oxygen species (ROS and proinflammatory cytokines generated by various source of injured kidney cells. Peroxiredoxin 5 (Prdx5 is a thiol-dependent peroxidase that reduces oxidative stress by catalyzing intramolecular disulfide bonds. Along with its antioxidant effects, expression level of Prdx5 also was involved in inflammatory regulation by immune stimuli. However, the physiological effects and the underlying mechanisms of Prdx5 in renal fibrosis have not been fully characterized. Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO for 1 or 7 days. For the in vitro model, NRK49F cells, a rat kidney interstitial fibroblast cell lines, were treated with transforming growth factor β (TGF-β for 0, 1, 3, or 5 days. To access the involvement of its peroxidase activity in TGF-β induced renal fibrosis, wild type Prdx5 (WT and double mutant Prdx5 (DM, converted two active site cysteines at Cys 48 and Cys 152 residue to serine, were transiently expressed in NRK49F cells. The protein expression of Prdx5 was reduced in UUO kidneys. Upregulation of fibrotic markers, such as fibronectin and alpha-smooth muscle actin (α-SMA, declined at 5 days in time point of higher Prdx5 expression in TGF-β treated NRK49F cells. The overexpression of wild type Prdx5 by transient transfection in NRK49F cells attenuated the TGF-β induced upregulation of fibronectin and α-SMA. On the other hand, the transient transfection of double mutant Prdx5 did not prevent the activation of fibrotic markers. Overexpression of Prdx5 also suppressed the TGF-β induced upregulation of Stat3 phosphorylation, while phosphorylation of Smad 2/3 was unchanged. In conclusion, Prdx5 protects TGF-β induced fibrosis in NRK49F cells by modulating Stat3 activation in a peroxidase activity dependent manner.

Microdefects and self-interstitial diffusion in crystalline silicon

Energy Technology Data Exchange (ETDEWEB)

Knowlton, W.B.

1998-05-01

In this thesis, a study is presented of D-defects and self-interstitial diffusion in silicon using Li ion (Li{sup +}) drifting in an electric field and transmission electron microscopy (TEM). Obstruction of Li{sup +} drifting has been found in wafers from certain but not all FZ p-type Si. Incomplete Li{sup +} drifting always occurs in the central region of the wafers. This work established that interstitial oxygen is not responsible for hindering Li{sup +} drifting. TEM was performed on a samples from the partially Li{sup +} drifted area and compared to regions without D-defects. Precipitates were found only in the region containing D-defects that had partially Li{sup +} drifted. This result indicates D-defects are responsible for the precipitation that halts the Li{sup +} drift process. Nitrogen (N) doping has been shown to eliminate D-defects as measured by conventional techniques. Li{sup +} drifting and D-defects provide a useful means to study Si self-interstitial diffusion. The process modeling program SUPREM-IV was used to simulate the results of Si self-interstitial diffusion obtained from Li{sup +} drifting experiments. Anomalous results from the Si self-interstitial diffusion experiments forced a re-examination of the possibility of thermal dissociation of D-defects. Thermal annealing experiments that were performed support this possibility. A review of the current literature illustrates the need for more research on the effects of thermal processing on FZ Si to understand the dissolution kinetics of D-defects.

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

International Nuclear Information System (INIS)

Beyer, G.J.; Soloviev, D.; Buchegger, F.; Miederer, M.; Vranjes-Duric, S.; Comor, J.J.; Kuenzi, G.; Hartley, O.; Senekowitsch-Schmidtke, R.

2004-01-01

This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10 6 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 μg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149 Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

Fine interstitial clusters as recombinators in decomposing solid solutions under irradiation

International Nuclear Information System (INIS)

Trushin, Yu.V.

1991-01-01

Behaviour of interstitial clusters and their roll in processes of radiation swelling of metals are described. It is shown that occurrence of coherent advanced precipitations during decomposition of solid solutions under irradiation leads to matrix supersaturation over interstitial atoms. This enhances recombination of unlike defects due to vacancy precipitation on fine interstitial clusters. Evaluation of cluster sizes was conducted

Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

Science.gov (United States)

Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David

2016-06-01

Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

Science.gov (United States)

Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

LENUS (Irish Health Repository)

Garvey, J P

2009-11-01

Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

Non-specific Effects of Vaccines and Stunting: Timing May Be Essential

Directory of Open Access Journals (Sweden)

Mike L.T. Berendsen

2016-06-01

Conclusions: We found a general time-dependent pattern of non-specific effects of vaccination, with positive associations for vaccinations given early in life and negative associations for vaccinations given later in infancy. If confirmed in further research, our findings may provide a new perspective on the non-specific effects of vaccination.

Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

2000-04-01

From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

Recurrent activity in higher order, modality non-specific brain regions

DEFF Research Database (Denmark)

Lou, Hans Olav Christensen; Joensson, Morten; Biermann-Ruben, Katja

2011-01-01

It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity...... in the visual system as a response to visual stimulation. In contrast recurrent activity has never been demonstrated before in higher order modality non-specific regions. Using magneto-encephalography and Granger causality analysis, we tested in a paralimbic network the hypothesis that stimulation may enhance...... causal recurrent interaction between higher-order, modality non-specific regions. The network includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices together with pulvinar thalami, a network known to be effective in autobiographic memory retrieval and self...

A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

DEFF Research Database (Denmark)

Birgens, Henrik Sverre; Frederiksen, Henrik; Hasselbalch, Hans C

2013-01-01

The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and ritu...

Radionuclide study for the interstitial lung disease

Energy Technology Data Exchange (ETDEWEB)

Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo (Jikei Univ., Tokyo (Japan). School of Medicine)

1991-07-01

The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with {sup 81m}Kr, distribution of compliance in thoraco-pulmonary system (C) by {sup 81m}Kr gas bolus inhalation method, perfusion study (Q) with {sup 99m}Tc-MAA, {sup 67}Ga scintigraphy and an assessment of pulmonary epithelial permeability with {sup 99m}Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO{sub 2} was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. {sup 67}Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of {sup 67}Ga. {sup 67}Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by {sup 99m}Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author).

Lumbopelvic Core Stabilization Exercise and Pain Modulation Among Individuals with Chronic Nonspecific Low Back Pain.

Science.gov (United States)

Paungmali, Aatit; Joseph, Leonard H; Sitilertpisan, Patraporn; Pirunsan, Ubon; Uthaikhup, Sureeporn

2017-11-01

Lumbopelvic stabilization training (LPST) may provide therapeutic benefits on pain modulation in chronic nonspecific low back pain conditions. This study aimed to examine the effects of LPST on pain threshold and pain intensity in comparison with the passive automated cycling intervention and control intervention among patients with chronic nonspecific low back pain. A within-subject, repeated-measures, crossover randomized controlled design was conducted among 25 participants (7 males and 18 females) with chronic nonspecific low back pain. All the participants received 3 different types of experimental interventions, which included LPST, the passive automated cycling intervention, and the control intervention randomly, with 48 hours between the sessions. The pressure pain threshold (PPT), hot-cold pain threshold, and pain intensity were estimated before and after the interventions. Repeated-measures analysis of variance showed that LPST provided therapeutic effects as it improved the PPT beyond the placebo and control interventions (P pain intensity under the LPST condition was significantly better than that under the passive automated cycling intervention and controlled intervention (P pain threshold under the LPST condition also showed a significant trend of improvement beyond the control (P pain threshold were evident. Lumbopelvic stabilization training may provide therapeutic effects by inducing pain modulation through an improvement in the pain threshold and reduction in pain intensity. LPST may be considered as part of the management programs for treatment of chronic low back pain. © 2017 World Institute of Pain.

Investigations of lymphatic drainage from the interstitial space

Science.gov (United States)

Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

2017-11-01

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

A study on applying Ra needle interstitial brachytherapy for oral cancer

International Nuclear Information System (INIS)

Yoshida, Shunichi; Komiya, Yoshiaki; Uchida, Ikuhiro; Tashiro, Kazuyoshi

1999-01-01

To investigate applicability of Ra needle interstitial brachytherapy, 93 cases of oral squamous carcinoma were examined. The patients underwent Ra needle interstitial brachytherapy as thorough therapy in our hospital. The criteria of applying Ra needle interstitial brachytherapy was diameter of within 5 cm and depth within 2 cm of tumor size. Ra needle interstitial brachytherapy was applied to 82 cases of tongue, 10 cases of oral floor and one case of lower lip carcinomas. The local control rate was 92.5%, and secondary neck metastasis was 32.3% in all cases applied Ra needle interstitial brachytherapy. The results were not bad compared with surgical treatment. However, the 5-year cumulative survival rate was 64.9%, which was not good enough at the result to obtain a good local control rate and secondary neck metastasis rate. The result was relative to low treatment result of local recurrence cases with Ra needle interstitial brachytherapy. To improve the result, it is important to distinguish local recurrence from radioinduced ulcer, and to start early secondary treatment. The cases in which cervical lymph node metastasis was found as the first examination underwent neck dessection after Ra needle interstitial brachytherapy. The 5-year cumulative survival rate was 83.3% in N1 cases and 40.6% in N2 cases, and the result of N2 cases was poorer than N1 cases with a significant difference. The results indicate that a needle having a diameter of within 5 cm, depth of within 2 cm and less than N1 can be applied during Ra needle interstitial brachytherapy for complete cure of cancer. (author)