Improved radioimmunotherapy of hematologic malignancies. Final technical report

International Nuclear Information System (INIS)

Press, O.W.

1996-01-01

Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated

Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma; Interet d'un traitement combine par radioimmunotherapie et Avastin1 dans un modele murin de carcinome medullaire de la thyroide

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Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F. [Unite Inserm U892, Brest, (France)

2009-05-15

The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma

International Nuclear Information System (INIS)

Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F.

2009-01-01

The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

Phase II study of induction chemotherapy with TPF followed by radioimmunotherapy with Cetuximab and intensity-modulated radiotherapy (IMRT in combination with a carbon ion boost for locally advanced tumours of the oro-, hypopharynx and larynx - TPF-C-HIT

Directory of Open Access Journals (Sweden)

Mavtratzas Athanasios

2011-05-01

Full Text Available Abstract Background Long-term locoregional control in locally advanced squamous cell carcinoma of the head and neck (SCCHN remains challenging. While recent years have seen various approaches to improve outcome by intensification of treatment schedules through introduction of novel induction and combination chemotherapy regimen and altered fractionation regimen, patient tolerance to higher treatment intensities is limited by accompanying side-effects. Combined radioimmunotherapy with cetuximab as well as modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT and carbon ion therapy (C12 are able to limit toxicity while maintaining treatment effects. In order to achieve maximum efficacy with yet acceptable toxicity, this sequential phase II trial combines induction chemotherapy with docetaxel, cisplatin, and 5-FU (TPF followed by radioimmunotherapy with cetuximab as IMRT plus carbon ion boost. We expect this approach to result in increased cure rates with yet manageable accompanying toxicity. Methods/design The TPF-C-HIT trial is a prospective, mono-centric, open-label, non-randomized phase II trial evaluating efficacy and toxicity of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 50 patients with histologically proven locally advanced SCCHN following TPF induction chemotherapy. Patients receive 24 GyE carbon ions (8 fractions and 50 Gy IMRT (2.0 Gy/fraction in combination with weekly cetuximab throughout radiotherapy. Primary endpoint is locoregional control at 12 months, secondary endpoints are disease-free survival, progression-free survival, overall survival, acute and late radiation effects as well as any adverse events of the treatment as well as quality of life (QoL analyses. Discussion The primary objective of TPF-C-HIT is to evaluate efficacy and toxicity of cetuximab in combination with combined IMRT/carbon ion therapy following TPF induction in locally advanced SCCHN. Trial Registration

Radioimmunotherapy of non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Batista Cuellar, Juan F.

2016-01-01

Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

International Nuclear Information System (INIS)

Chen Zhinan; Mi Li; Xu Jing

2006-01-01

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

The feasibility of 225Ac as a source of α-particles in radioimmunotherapy

International Nuclear Information System (INIS)

Geerlings, M.W.; Hout, R. van der; Kaspersen, F.M.; Apostolides, C.

1993-01-01

This paper proposes the utilization of 225 Ac for the α-radioimmunotherapy of cancer. The isotope decays with a radioactive half-life of 10 days into a cascade of short-lived α-and β-emitting isotopes. In addition, when indicated by the pharmacokinetic requirements of particular clinical applications, 213 Bi, with a radioactive half-life of 47 min, can be chosen as an alternative source of α-particles in radioimmunotherapy. This isotope is the last α emitter in the 225 Ac decay-cascade and can be extracted from a 225 Ac source at the bedside of the patient. 225 Ac can quasi ad infinitum be obtained from one of its precursors, 229 Th, which can be made available by various means. The indications for the use of α-particles as an alternative to more traditional classes of radiation are derived from the particle-kinetic characteristics and the radioactive half-life of their source isotope, as well as from the properties of the target-selective carrier moiety for the source isotope. It may be expected that useful applications, complementary to and/or in conjunction with other means of therapy will be identified. (author)

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

International Nuclear Information System (INIS)

Buchmann, I.; Helisch, A.; Bartenstein, P.; Meyer, R.G.; Herr, W.

2005-01-01

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

Calculation of dose point kernels for five radionuclides used in radio-immunotherapy

International Nuclear Information System (INIS)

Okigaki, S.; Ito, A.; Uchida, I.; Tomaru, T.

1994-01-01

With the recent interest in radioimmunotherapy, attention has been given to calculation of dose distribution from beta rays and monoenergetic electrons in tissue. Dose distribution around a point source of a beta ray emitting radioisotope is referred to as a beta dose point kernel. Beta dose point kernels for five radionuclides such as 131 I, 186 Re, 32 P, 188 Re, and 90 Y appropriate for radioimmunotherapy are calculated by Monte Carlo method using the EGS4 code system. Present results were compared with the published data of experiments and other calculations. Accuracy and precisions of beta dose point kernels are discussed. (author)

Trial Watch: Radioimmunotherapy for oncological indications.

Science.gov (United States)

Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2014-10-01

During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients.

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.)

Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

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Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

2014-08-15

Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

Human-Mouse Dosimetry in Clinical Radioimmunotherapy - Special Emphasis on Pediatric Applications

International Nuclear Information System (INIS)

Kairemo, K.J.A.; Pyyry, J.; Heiskanen, T.; Flux, G.; Fisher, D.R.

2009-01-01

Monoclonal antibody ('MAB') has been developed for targeting secretory alpha-fetoprotein in hepatic tissue. We have used these MABs for radioimmunotherapy and dose planning of recurrent hepatoblastoma, a rare childhood malignancy This MAB has been labelled with In- 111 and Y-90 for clinical purposes, and can be applied for diagnosis and therapy of liver neoplasms. Physiology based pharmacokinetic (PBPK) modeling and simulation is a useful method for prediction of biodistribution of macromolecules, it can enhance our understanding of the underlying mechanisms and hence may help in rational design of diagnostic and therapeutic agents. Here we also discuss PBPK modeling and simulation of this MAB in mice without tumor and in a pediatric patient. In the clinical study, radiopharmacokinetic parameters for this MAB ( 111 In-DOTA-hAFP31 IgG) were calculated after serial quantitative whole body scans in a child with hepatoblastoma. A 3-D dose planning computer program was used to calculate tumor doses for In-111 and Y-90, the active tumor was delineated on PET/CT images and tumor dose calculation was done based on the In-111-MAB SPECT data using dose point kernel approach both for In-111 and Y-90. The results were compared with MIRD doses obtained for organs in SPECT imaging field, i.e. bone marrow, heart, kidneys, liver, spleen, lungs. The simulated results were fitted to experimental time series data by varying parameters which were not fixed a priori. From quantitative serial imaging based on 8 whole body images at 0-168 hrs using In-111- MAB, the half-lives of spleen, lungs, kidneys and whole body were 502 hrs, 230 hrs, 193 hrs and 490 hrs, respectively. The measured blood half-life was 132 hrs, after a total MAB dose of 50 mg and In-111 activity of 105 MBq. The presumed Y-90 dose based on this kinetic behavior was 43 MBq which should had given 0.3Gy bone marrow dose with assumption of bone marrow: blood ratio 0.4 for IgG. The calculated MIRD Y-90 doses were for

Secondary antibodies as tools to improve tumor to non tumor ratio at radioimmunolocalisation and radioimmunotherapy

International Nuclear Information System (INIS)

Ullen, A.; Riklund Aalstroem, K.; Hietala, S.O.; Nilsson, B.; Aerlestig, L.; Stigbrand, T.

1996-01-01

One way of selectively improving the efficiency of radioimmunolocalization and radioimmunotherapy is to eliminate redundant, circulating, non-targeting radiolabeled antibodies after saturation of the target sites. Secondary antibodies of different types have been proposed as clearing agents for such purposes. The conceptually different approaches of the 'secondary antibody' strategy including its advantages and limitations are discussed. This mini-review also presents a model describing the kinetics of the components (the antigen, the primary and secondary antibodies) and approaches required to improve the efficacy of both radioimmunolocalization and radioimmunotherapy. (orig.)

The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

International Nuclear Information System (INIS)

Chatal, J. F.

2000-01-01

The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

Choice of radionuclides for radioimmunotherapy

International Nuclear Information System (INIS)

DeNardo, S.J.; Jungerman, J.A.; DeNardo, G.L.; Lagunas-Solar, M.C.; Cole, W.C.; Meares, C.F.

1985-01-01

Innumerable questions need to be answered and obstacles overcome before radioimmunotherapy can be generally successful in cancer patients. Major developments have greatly enhanced the likelihood of success. The important development of appropriate radionuclides and radiochemistry for this therapy must be intimately linked with the biological and biochemical realities. All aspects must be considered, such as the specific nature of the antigenic target, the pharmacokinetics of the antibody fragment carrier, the capability of in vivo quantitation of tumor uptake and turnover time, as well as total body kinetics. With this knowledge, then, practical radiochemistry methods can be integrated with the suitable radionuclide choices, and production methods can be developed which will deliver effective and dependable products for patient therapy

Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

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Abe, Michio [Minamata City Hospital and Medical Center, Minamata City, Kumamoto 867 (Japan); Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina, E-mail: jbaranow@unmc.edu [Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198 (United States)

2011-05-25

Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy.

Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

International Nuclear Information System (INIS)

Abe, Michio; Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina

2011-01-01

Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy

Radioimmunotherapy for malignant diseases. Current contributions and future options

International Nuclear Information System (INIS)

Mahe, M.A.; Chatal, J.F.

1995-01-01

Radioimmunotherapy is based on the use of radioactive agents (iodine 131, yttrium 90), murine-derived monoclonal antibodies and specific tumour-related membrane antigens. This new treatment modality was applied in 800 patients with different types of malignant tumours which had not responded to traditional therapy. Among the haematologic tumours, the most promising results were obtained in B phenotype non-Hodgkin lymphoma. More modest results were obtained for solid tumours although good results were observed after intraperitoneal administration in patients with cancer of the ovary. The main side effects are acute reversible anaphylactic shock, haematologic toxicity and development of anti-murine human antibodies. Several methods are currently under study to increase irradiation dose delivered at the tumoural site since less than 1% of the injected radioactive dose is absorbed by tumoural cells. Several clinical studies are to be conducted in France, particularly for malignant non-Hodgkin lymphoma and cancer of the ovary. (authors). 31 refs

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

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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.)

Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

Science.gov (United States)

Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

2010-01-01

Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

Activities of AREVA Med. Extraction and purification of the 212Pb isotope from Thorium for radio-immunotherapy

International Nuclear Information System (INIS)

Miquel, Pierre

2012-01-01

After having recalled the definition of radio-immunotherapy (RIT) and the benefits of alpha RIT for the treatment of some cancers, this document explains the choice of the 212-Pb isotope instead of the 212-Bi isotope (the first one has a longer half-life than the second). The Pb isotope in fact progressively transforms itself into the Bi isotope. The production process is evoked with its important steps. A second part reports the first clinic tests performed in the Alabama Centre for the treatment of different cancer (breast, colon, ovarian, pancreas, stomach). Processes and doses are discussed

Cure of human ovarian carcinoma solid xenografts by fractionated [211At] alpha-radioimmunotherapy

DEFF Research Database (Denmark)

Bäck, Tom A; Chouin, Nicolas; Lindegren, Sture

2017-01-01

The goal of this study was to investigate if targeted alpha therapy (TAT) could be used to successfully treat also macro tumors, in addition to its established role for treating micrometastatic and minimal disease. We used an intravenous (i.v.) fractionated regimen of alpha-radioimmunotherapy (α-...

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

Science.gov (United States)

Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Radioimmunotherapy: Development of an effective approach

Energy Technology Data Exchange (ETDEWEB)

1987-01-01

Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

Radioimmunotherapy: Development of an effective approach

International Nuclear Information System (INIS)

1987-01-01

Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma

Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma

International Nuclear Information System (INIS)

Klapdor, R.; Greten, H.; Saccavini, J.C.; Dietel, M.

1985-01-01

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. 131 I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131 I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden. (orig./MG) [de

Bivalent fragment of the ior-CEA1 antibody. A challenge to the positive CEA tumors radioimmunotherapy

International Nuclear Information System (INIS)

Ravelo, Rolando; Sanchez, Iradia; Pimentel, Gilmara; Oliva, Juan; Perez, Lincidio; Ayala, Marta; Bell, Hansell; Gavilondo, Jorge

2006-01-01

The directed radiotherapy of the solid tumors with fragments recombinants of radiolabelled antibodies is a topic of current investigation, so much at preclinical level as clinical. This work describes the preclinical characterization of a new fragment type diabody of the AcMo ior CEA1 that has been labelled with 131 I for their use in the diagnosis and the therapy of CEA positive tumors. The radiolabelling methodology used allows the incorporation of more than 90% of the radio iodine to the molecule without committing the capacity of recognition of its antigen significantly. The combination of the favourable properties pharmacy kinetic and high selective accumulation in the tumor, they make of the diabody anti CEA an appropriate candidate for the radioimmunodiagnosis and the radioimmunotherapy of tumors that expresses CEA (Author)

Radioimmunotherapy of human lymphoma in athymic, nude mice as monitored by 31P nuclear magnetic resonance

International Nuclear Information System (INIS)

Adams, D.A.; DeNardo, G.L.; DeNardo, S.J.; Matson, G.B.; Epstein, A.L.; Bradbury, E.M.

1985-01-01

Human B cell lymphoma (Raji) growing in athymic, nude mice has been successfully treated with a single pulse dose of 131 I-labeled monoclonal antibody (Lym-1) specific for this tumor. Sequential in vivo measurements of phosphate metabolites in the tumors by 31 P surface coil nuclear magnetic resonance showed a significant initial decrease of phosphocreatine following radioimmunotherapy. Diminution of relative ATP to Pi peak area ratio suggesting tissue damage occurred within 3-4 days. The sequence of alterations of nuclear magnetic resonance spectra from tumors of treated mice were strikingly different from sequential nuclear magnetic resonance spectra obtained from tumors of control mice. These observations lead us to conclude that 31 P surface coil nuclear magnetic resonance is a promising non-invasive method for assessing and predicting the efficacy of radioimmunotherapy. Further spatial discrimination of the region of tissue observed by the surface coil nuclear magnetic resonance experiment is under exploration in an effort to increase the utility of these methods

Development of dosimetric approaches to treatment planning for radioimmunotherapy. DOE annual report

International Nuclear Information System (INIS)

1998-01-01

The objective of quantitative imaging is to Provide pharmacokinetic information for patients that is analogous to that provided by biodistribution studies in mice. Radio nuclide images depict the distribution of labeled antibodies in-vivo; thus the amount of radio nuclide in a specific organ or site can be estimated by relating the counts detected in a defined region of interest to the total radio nuclide content. This pharmacokinetic information can be used to obtain definitive and relevant answers to basic questions of importance for optimizing radioimmunoimaging and radioimmunotherapy and, in addition, can provide a data base from which to calculate the distribution of radiation absorbed doses. The projects supported by this program routinely employ quantitative imaging in evaluating therapies. Quantitative imaging is performed by a certified nuclear medicine technician using the Siemens gamma camera interfaced with the microVAX II. The technician processes the imaging data and obtains pharmacokinetic information from it using programs developed by us and others. During this grant period project staff have acquired and analyzed a large amount of data on the pharmacokinetics, dosimetry and toxicity of radiolabeled monoclonal therapy. Important dosimetry data on the whole body, marrow and tumor doses are available and all studies are archived so that they can be retrospectively analyzed

Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts

International Nuclear Information System (INIS)

Wessels, B.W.; Vessella, R.L.; Palme, D.F. II; Berkopec, J.M.; Smith, G.K.; Bradley, E.W.

1989-01-01

Growth delay was measured in TK-82 renal cell carcinoma (RCC) xenografts implanted in nude mice receiving single fraction external beam irradiation (SF-XRT), multifraction external beam irradiation (MF-XRT), or radioimmunotherapy (RIT). Thermoluminescent dosimeter(s) (TLD) and autoradiography were used to ascertain the average absorbed dose delivered and the degree of heterogeneous uptake of radiolabeled antibody for the RIT irradiations. For intravenous administered activities of 100, 200, 400, and 600 microCi of I-131 labeled A6H antibody, volume doubling times (VDT) and TLD absorbed dose measurements for each administered activity were 7 days (341 cGy), 38 days (383 cGy), 85 days (886 cGy) and no regrowth (1034 cGy), respectively. For SF-XRT irradiations of 500, 1000, and 1500 cGy, VDT times were 11, 62, and 103 days, respectively. MF-XRT of 4 X 250 cGy over a 2-week period yielded a VDT of 25 days. Marked peripheral activity deposition was noted on most autoradiographs from multiple tumor samples. These data suggest that an equivalent to superior tumor growth delay is obtained for absorbed doses delivered by exponentially decaying low dose rate radioimmunotherapy RIT compared to similar doses of acute dose rate XRT as quantitated by the TLD method

A pretargeting system for tumor PET imaging and radioimmunotherapy

Directory of Open Access Journals (Sweden)

Françoise eKraeber-Bodéré

2015-03-01

Full Text Available Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.

Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

International Nuclear Information System (INIS)

Buchmann, I.

2008-01-01

patients with multiple myeloma may markedly be improved using a combination of α- and β-anti-CD45-mAbs. This review provides a systematic and critical overview of the currently used radionuclides and antibodies for the treatment of AML, MDS and multiple myeloma and summarizes the present literature on clinical trials of myeloablative radioimmunotherapies for conditioning before both, autologous and allogeneic stem cell transplantation. (orig.)

Dosimetry and quantitative radionuclide imaging in radioimmunotherapy: Final report, July 15, 1992-July 14, 1996

International Nuclear Information System (INIS)

Leichner, P.K.

1996-09-01

Brief summaries of the principal accomplishments of this project on the development of quantitative SPECT for high energy photons (87Y, 19F) and stability testing of 87Y-labeled antibodies in the nude mouse model, development of an unified approach to photon and beta particle dosimetry, quantitative SPECT for nonuniform attenuation, and development of patient-specific dosimetry in radioimmunotherapy

Development of dosimetric approaches to treatment planning for radioimmunotherapy. Annual report 1989--1990

Energy Technology Data Exchange (ETDEWEB)

DeNardo, S.J.

1990-12-31

The objective of quantitative imaging is to provide pharmacokinetic information for patients that is analogous to that provided by biodistribution studies in mice. Radionuclide images depict the distribution of labeled antibodies in-vivo; thus the amount of radionuclide in a specific organ or site can be estimated by relating the counts detected in a defined region of interest to the total radionuclide content. This pharmacokinetic information can be used to obtain definitive and relevant answers to basic questions of importance for optimizing radioimmunoimaging and radioimmunotherapy and, in addition, can provide a data base from which to calculate the distribution of radiation absorbed doses. The research employs quantitative imaging in evaluating therapies. Quantitative imaging is performed by a certified nuclear medicine technician using the Siemens gamma camera interfaced with the microVAX II. The technician processes the imaging data and obtains pharmacokinetic information from it using programs developed by the authors and others. A large amount of data has been acquired and analyzed on the pharmacokinetics, dosimetry and toxicity of radiolabeled monoclonal therapy. Important dosimetry data on the whole body, marrow and tumor doses are available and all studies are archived so that they can be retrospectively analyzed. Although the radiation absorbed doses delivered to tumor sites were modest, significant biological responses were found.

Criteria for the selection of nuclides for radioimmunotherapy

International Nuclear Information System (INIS)

Adelstein, S.J.; Kassis, A.I.

1986-01-01

This report describes many factors that need to be considered if radioimmunotherapy is to become a commonplace reality. For beta-emitting radionuclides, two physical features of importance are half-life and energy, with the latter determining the range. These features must be matched to the pharmacokinetics of the carrier and the distribution of the radionuclide, both macroscopically and microscopically. Alpha-particle emitters could be considered for cells that are readily accessible to the labeled antibody and for populations that uniformly and constantly display the targeted antigen or idiotype, e.g., trafficking cells such as T or B lymphocytes. For cells that concentrate the radioactive label, the use of low-energy electrons should be examined. If the radionuclide is translocated to the nucleus, the Auger effect can be particularly lethal because of the high LET-like biological response. 15 refs., 3 figs., 2 tabs

Criteria for the selection of radionuclides for tumor radioimmunotherapy

Energy Technology Data Exchange (ETDEWEB)

Srivastava, S.C.; Mausner, L.F.; Mease, R.C.

1991-01-01

The potential of utilizing monoclonal antibodies as carriers of radionuclides for the selective destruction of tumors (radioimmunotherapy, RIT) has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of RIT. This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Intermediate to high-energy beta emitters' (with and without gamma photons in their emission) are emphasized since they possess a number of advantages over alpha and Auger emitters. Factors relating to the production and availability of candidate radiometals as well as their stable chemical attachment to monoclonal antibodies are discussed. 34 refs., 4 tabs.

Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy

Science.gov (United States)

Martini, Petra; Pasquali, Micol

2017-01-01

Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872

Monoclonal antibodies to the pretargeting approach: Developments in the radiopharmaceuticals for radioimmunotherapy

International Nuclear Information System (INIS)

Chinol, M.

2001-01-01

In recent years, large experience has been accrued through the clinical application of radiolabelled monoclonal antibodies in the diagnosis and therapy of malignant disorders. While radioimmunoscintigraphy has established its role in the nuclear medicine practice, radioimmunotherapy has thus far gained limited acceptance mainly due to the low amount of radioactivity that can be targeted to the tumour and to the myelotoxicity which is typically the dose limiting factor. In an attempt to overcome the low uptake of label by the tumour and improve the tumour-to-blood ratio, various studies have examined the concept of tumour pretargeting based on the separate protocols, especially the 3-step approach, with respect to the use of directly labelled antibodies, lies in the lower toxicity observed which has allowed to administer high doses of therapeutic radionuclides, such as Y-90, without bone marrow toxicity. Pilot studies, applied to the treatment of advanced stage tumours, have shown that this approach interferes with the progression of tumours and produce tumours regression in patients no longer responsive to other conventional therapeutic modalities. The potency of pretargeting based on the avidin/biotin system may be exploited in the near future to convey a variety of cytotoxic substances, other than radioactivity, onto cancer cells. (author)

Study of in vivo generators Pb-212/Bi--212 and U-230/Th-226 for alpha radioimmunotherapy

International Nuclear Information System (INIS)

Le Du, A.

2011-01-01

Alpha-radioimmunotherapy is a promising cancer therapy that uses a-particles vectorized by monoclonal antibody to break down cancerous tumors. The notion of in vivo generator was introduced in 1989 by Leonard Mausner. The concept involves labeling of various molecular carriers (antibodies, peptides, etc) with intermediate half-life generator parents, which after accumulation in the desired tissue generate much shorter half-life daughter radionuclide. This thesis focuses on the study of two in vivo generators potentially interesting for alpha-radioimmunotherapy: Pb-212 / Bi-212 generator and U-230 / Th-226 generator. The first part of this work presents the Pb-212 / Bi-212 generator, two approaches allowing the vectorization. Chelation approach on a protein and an approach by encapsulation in liposomes have been proposed. This last approach appears to be the most interesting. In vitro stability studies have been performed on these labeling. The second part of this work presents the U-230 / Th-226 generator. Studies have first been made to achieve a theoretical model to describe the speciation of Th(IV) in human serum. The efficacy of DTPA as chelating agent for complexation of Th(IV) in human serum could thus be estimated. (author)

Development of 90Y-DOTA-nimotuzumab Fab fragment for radioimmunotherapy

International Nuclear Information System (INIS)

Alonso Martinez, L.M.; Marylaine Perez-Malo Cruz; Rene Leyva Montana; Calzada Falcon, V.N.; Minely Zamora Barrabi; Alejandro Arbesu Valdivia; Ignacio Hernandez Gonzalez; Mariela Leon Perez

2014-01-01

Yttrium-90-( 90 Y) labeled monoclonal antibodies prepared with a chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), have been used for radioimmunotherapy of cancer. In the present work, the Fab fragment of anti-EGFR monoclonal antibody nimotuzumab was prepared with high purity, integrity and biological activity. The Fab fragment with high specific recognition of EGFR in NCI-H125 human lung adenocarcinoma cells was derivatized with DOTA-NHS applying a simple procedure. DOTA-nimotuzumab Fab fragment was successfully radiolabeled with 90 Y with high radiochemical yield. The in vitro stability of labeled product was optimal over 24 h in buffered solution at 37 deg C. Biodistribution and pharmacokinetic studies correctly evaluated the in vivo non-tumor uptake, dosage regimen and excretion pathway in normal Wistar rats. (author)

Clinical application of antibody monoclonal humanized anti-EGFrnimotuzumab labeled

International Nuclear Information System (INIS)

Perera Pintado, Alejandro; Peña Quián, Yamilé; Batista Cuéllar, Juan F.; Prats Capote, Anaís; Torres Aroche, Leonel A.; Casacó Santana, Caridad; Sánchez Mendosa, Elvia L.; Sánchez González, Yolaine; Romero Collado, Susana; Quesada Pozo, Rodobaldo; Valladares Oviedo, Lourdes; Masquida García, Elsa M.; Leyva Montaña, René; Casacó, Angel; Ramos Suzarte, Mayra; Crombet, Tania

2016-01-01

Most malignant tumors are of epithelial origin. These are characterized by overexpression of the receptor of epidermal growth factor (EGFR), which the neoplastic cells escape the regulatory mechanisms are allowed, so its high concentration of membrane is generally associated with a poor prognosis . By binding an antibody specifically to this receptor, preventing binding of EGF latter and activation mechanism tyrosine kinase inhibiting cell mitosis and apoptosis causing tumor cell. For this reason, the EGFr has been considered as an attractive target for anti-tumor therapy. The humanized monoclonal antibody anti-EGFr nimotuzumab was developed by the Center of Molecular Immunology (Havana, Cuba). Numerous clinical trials have been developed in the Department of Clinical Research Center Isotopes (Cuba), in which it has been applied this antibody, both labeled with 99mTc for immuno gammagraphic detection of tumors, as labeled with 188 Re for radioimmunotherapy of gliomas high degree of malignancy. The aim of this paper is to show the experience of the Department of Clinical Research of CENTIS in various clinical trials with marking for both immuno gammagraphics detection of tumors, such as for radioimmunotherapy nimotuzumab. (author)

Radioimmunotherapy: Development of an effective approach. Progress report, 1987

Energy Technology Data Exchange (ETDEWEB)

1987-12-31

Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma

Directory of Open Access Journals (Sweden)

Caroline eBodet-Milin

2013-07-01

Full Text Available This manuscript reviews current advances in the use of radioimmunotherapy (RIT for the treatment of B-cell non-Hodgkin’s lymphoma (NHL. RIT has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (MAbs, and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved: 131I-tositumomab, (Bexxar® and 90Y-ibritumomab tiuxetan, (Zevalin®. 131I-tositumomab is available in the United States, and 90Y-ibritumumab tiuxetan in Europe, the United States, Asia, and Africa. RIT can be integrated in clinical practice using non-ablative activities for treatment of patients with relapsed or refractory follicular lymphoma (FL or as consolidation after induction chemotherapy in front-line treatment in FL patients. Despite the lack of phase III studies to clearly define the efficacy of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing refractory FL and transformed NHL, RIT as a monotherapy induces around 30% complete response with a possibility of durable remissions. RIT consolidation after induction therapy significantly improves the quality of the response. Dose-limiting toxicity of RIT is hematological, depending on bone marrow involvement and prior treatment. Non-hematological toxicity is generally low. Different studies have been published assessing innovative protocols of RIT or new indications, in particular treatment in patients with aggressive lymphomas. High-dose treatment, RIT as consolidation after different therapeutic induction modalities, RIT in first-line treatment or fractionated RIT showed promising results. New MAbs, in particular humanized MAbs, or combinations of naked and radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should be developed to determine

Radioimmunotherapy. Dose calculation and radionuclides used in treatment

International Nuclear Information System (INIS)

Savolainen, S.

1995-10-01

In radioimmunotherapy (RIT) monoclonal antibodies to cancer-associated antigens can be utilized for the transport of therapeutic radioisotopes to cancer cells. Intravenous administration of radiolabelled antibody is a potentially curative form of therapy in hematological amignancies as circulating antibodies have easy access to tumour sites. Intravenous RIT is less effective in the treatment of solid tumours because of the low fractional uptake of the injected dose, particularly in the central parts of tumours. In solid tumours more promising results have been achieved by local RIT applications. The choice of radiation - α, β or γ - will depend of the characteristics of the tumour. The importance of radiation delivered by Auger electrons has been largely underestimated in the past, but recent research has resulted in a remarkable reassessment of this issue significantly influencing the selection of radioisotopes for RIT. Research is now being focused on the therapeutic aspects of different isotopes and microdosimetric problems. There are now good prospects of RIT becoming an important form of cancer treatment before year 2000. (orig.) (78 refs., 3 figs., 1 tab.)

Positron emission tomography/computed tomography and radioimmunotherapy of prostate cancer

DEFF Research Database (Denmark)

Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

2009-01-01

of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, which targets the extracellular domain of prostate-specific membrane antigen, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. SUMMARY: PET......PURPOSE OF REVIEW: Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computed tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) as no effective therapies...... are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. RECENT FINDINGS: Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated...

Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

DEFF Research Database (Denmark)

Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger

2010-01-01

The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods....... Nude mice were intraperitoneally inoculated with ~1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given 400 kBq (211)At-MX35 F(ab')(2) as a single or as a repeated treatment of up to 6 times (n = 18 in each group). The fractionated treatments were given every...... seventh day. Control animals were treated with unlabeled MX35 F(ab')(2) (n = 12). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals...

Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-α

International Nuclear Information System (INIS)

Mutschler, J.; Reske, S.N.; Steinbach, G.; Bunjes, D.; Buchmann, I.

2009-01-01

Tumour necrosis factor-α (TNF-α) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188 Re-CD-66-mAb on changes on TNF-α serum levels. Patients, methods: In 18 patients we measured TNF-α before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-α we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-α after conditioning with 188 Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 ± 6.6 pg/ml) and chemotherapy (10.8 ± 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with 188 Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-α. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

Science.gov (United States)

2010-01-01

Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

Directory of Open Access Journals (Sweden)

Weichert Wilko

2010-11-01

Full Text Available Abstract Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%; 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.

Dosimetric considerations in radioimmunotherapy of patients with hepatoma

International Nuclear Information System (INIS)

Leichner, P.K.; Klein, J.L.; Order, S.E.

1986-01-01

Dosimetric studies of I-131 labeled antiferritin have provided the foundation for preparative and administrative aspects of radiolabeled antibody treatment of patients with hepatoma. Tumor response to I-131 labeled antiferritin IgG was encouraging and radioimmunotherapy with Y-90 labeled antiferritin IgG was recently initiated. For these patients, In-111 labeled antiferritin IgG was used as the imaging agent, with administered activities ranging from 0.8 - 7 mCi. Serial gamma camera imaging from 30 minutes to 6 days post injection demonstrated that 5-30% of the administered activity localized in hepatomas (8/12 patients). The mean value of the effective half-life in the tumor and liver was 2.8 d. Disappearance curves for the blood circulation, spleen, and other normal tissues were biphasic such that 50% of the activity disappeared within 24 hours post injection. The eight patients who demonstrated sufficient tumor localization where subsequently treated with Y-90 labeled antiferritin IgG. Administered activities were dependent on tumor volume and uptake of radiolabeled IgG and ranged from 8 - 20 mCi. The remaining patients were treated under other existing protocols. 10 references

Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach

International Nuclear Information System (INIS)

Riva, P.; Franceschi, G.; Riva, N.; Casi, M.; Santimaria, M.; Adamo, M.

2000-01-01

The high-grade malignant gliomas (anaplastic astrocytomas and glioblastoma) have a very bad prognosis since the available methods of treatment (surgery, radiotherapy and chemotherapy) are unable to control the progression of the disease for long. The use of specific monoclonal antibodies labelled with a suitable isotope (iodine-131 or yttrium-90) represents an effective approach to hamper tumour regrowth. Some authors have injected the antibodies intravenously, or have tried to increase the tumour/background ratio with the avidin/ biotin system. In many cases the labelled monoclonal antibodies were injected directly into the tumoral bed after the operation. The authors' experiences concern a quite large locoregional radioimmunotherapy study which was performed by using antitenascin antibodies labelled initially with 131 I and more recently with 90 Y. The clinical results demonstrate the ability of this technique to control, for a long time, the growth of these tumours. The glioblastoma median survival was prolonged to 25 months ( 131 I group) or 31 months ( 90 Y group). The response rate (which comprises PR, CR and NED) was 47.1% (glioblastoma 131 I group) or 40% (glioblastoma 90 Y group). In many cases a significant tumour shrinking effect was radiologically demonstrated. The use of 90 Y proved more favourable in bulky lesions, and reduced the radioprotection problems. (orig.)

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

International Nuclear Information System (INIS)

Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

2003-01-01

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

Use of Re-188 labelled anti-EGFr humanized monoclonal antibody h-R3 for radioimmunotherapy of gliomas

International Nuclear Information System (INIS)

Perera, A.; Torres, L.A.; Lopez, G.; Casaco, A.; Batista, J.F.; Pena, Y.; Coca, M.A.; Leyva, R.; Garcia, I.

2007-01-01

Full text: Locally administered monoclonal antibodies labelled with radioisotopes like 90Y, 131I, 186Re, 212Bi, 211At, 177Lu and others, constitute a viable and promising alternative for management different kind of malignancies. The development of 188W/188Re generator has given the possibility of having a radionuclide showing satisfactory features for radioimmunotherapy (Eb2.12 MeV, Eg155 keV, T1/2=16.9 h and easy to make labelling approaches, similar to used for 99mTc). Neuroepithelial-derived tumours show an increased expression of the EGF receptor with regard to adjacent normal tissue. This overexpression could be related with the autocrine stimulation of the neoplasm by EGF and TGFb. Humanized monoclonal antibody h-R3 has shown a high affinity for this EGF receptor, blocking the binding of EGF to it receptor and inducing apoptosis. Thus, it could be a good candidate for radioimmunotherapy of neuroepithelial malignancies. The aim of the present work was to label monoclonal antibody h-R3 with 188Re, to assess it in an animal model and evaluate its internal dosimetry and toxicity in patients with grade III-IV gliomas through a phase I clinical trial. Schwarz's direct labelling method was employed. Briefly, a 2000-fold molar excess of 2-mercaptoethanol was used to reduce bisulfide bonds of the antibody. The amount of sodium glucoheptonate, ascorbic acid and stannous fluoride were varied to achieve optimum labelling yield. 188Re-labeling yield was proportional to the volume of stannous glucoheptonate solution added to the formulation. Radiochemical purity of 188Re-h-R3 was 98.0±0.4%. Challenge against 300-fold molar excess of L-cysteine was made to assess the stability of the tracer. There was no significant difference between stability of 188Re-h-R3 and 99mTc-h-R3 against cysteine challenge up to 24 h. Animal biodistribution study was performed at 3 and 24 h after intravenous administration of 188Re-h-R3 through tale vein of Male Wistar rats. The results were

Use of PET volume determination by fuzzy logic in the follow up of lymphomas treated by radio-immunotherapy

International Nuclear Information System (INIS)

Esnault, J.M.; Steinling, M.; Huglo, D.; Vermandel, M.; Vermandel, M.; Steinling, M.; Huglo, D.; Morschhauser, F.

2007-01-01

Purposes: the aim of this study was to assess if the evaluation of tumoral volumes by fuzzy logic was workable for clinical use. This study was performed with patients followed up for radio-immunotherapy of non-Hodgkin's lymphomas with a comparison of the respective contributions of this quantification and Standardized Uptake Value (S.U.V.). Materials and methods: thirty patients underwent 18 F-FDG PET before treatment and then in an iterative way. The analysis of 217 lesions allowed to evaluate their volumes and S.U.V.. The evolution of these parameters of quantification was compared. Results: these two quantitative parameters did not statistically differ but there were important discrepancies in some examinations. The determination of volumes was sometimes limited by tumoral localization or junction of lesions. Conclusion: this study proved the feasibility of the determination of tumoral volumes by fuzzy method in clinical use. Quantification supplemented the subjective visual analysis, which in most cases was sufficient to appreciate the progression of the disease. This quantification, usually given by the value of the S.U.V., could be improved by the volume data either in a separated way, or combining intensity and volume (total lesion glycolysis). Further work is necessary to specify the predictive value of these parameters in this particular indication. (authors)

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Radioimmunotherapy of solid cancers. A review

International Nuclear Information System (INIS)

Kairemo, K.J.A.

1996-01-01

Depending on radionuclide characteristics, radioimmunotherapy (RIT) relies on radioactivity to destroy cells distant from immunotargeted cells. Therefore, even heterogeneous tumors (for antigen recognition) can be treated, because not all cells have to be targeted. Substantial complete response rates have been reported in patients with non-Hodgkin's lymphoma. Much more modest results have been reported for patients iwth bulky solid tumors, e.g. adenocarcinomas. The radiation doses delivered by targeting antibodies are generally too low to achieve major therapeutic responses. Dose escalation is limited by myelotoxicity, and higher doses need to be delivered to neoplasmas less radiosensitive than lymphomas. Various trials for both systematic and regional RIT have been reported on. Intraperitoneal adminostration has been applied for colorectal and ovarian carcinomas. Our own results indicate that, e.g., intraperitoneal pseudomyxoma can be treated with RIT. Myelotoxicity can be reduced by anti-antibody-enhancement, 2- and 3-step strategies, bispecific monoclonal antibodies (MABs), and extracorporeal immunoadsorption. The radionuclide has to be selected properly for each purpose; it can be a β-emitter, e.g. I-131, Y-90, Re-188, Re-186, Lu-177 or Sm-153, an α-emitter At-211 or Bi-212 or an Auger-emitter, e.g. I-125, I-123. One major problem with RIT, besides slow penetration rate into tumor tissue and low tumor-to-normal tissue ratio, is the HAMA response, which can be partly avoided by the use of humanized MAbs and immunosuppression. However, RIT will be, because of all the recent developments, an important form of cancer management. (orig.)

Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy

International Nuclear Information System (INIS)

Rhmer, V.; Murat, A.

2000-01-01

The screening for sporadic medullary thyroid carcinoma relies upon calcitoninemia level, basal or during pentagastrine stimulation test. MEN2 are associated with nearly the third of medullary thyroid carcinoma. In these cases, prognosis of thyroid carcinoma is mainly driven by the tumor status at the time of surgery. Up to date, diagnosis relies upon the genetic screening. Prophylactic thyroidectomy indication may take account of calcitoninemia. Most of the molecules that have been suggested for scintiscan lack of accuracy and large use cannot be recommended. Promising results have been obtained with monoclonal antibodies anti-CEA, particularly with dual targeting antiCEA antiDTPA. This last technique may also be used for radio-guided surgery. Its use for radio-immunotherapy is under investigation. (authors)

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

International Nuclear Information System (INIS)

Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

2013-01-01

Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

Phase II clinical development of new drugs

CERN Document Server

Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C

2017-01-01

This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

Bone marrow dosimetry using blood-based models for 131i-anti-cd20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Kwon, J. H.; Kim, H. G.; Choi, T. H.

2005-01-01

Accurate estimations of radiation absorbed dose are essential part of evaluating the risks and benefits associated with radiotherapy. Determination of red marrow dose is important because myelotoxicity is often dose limiting in radioimmunotherapy. The aim of this study is to set up the procedures of dosimetry with activities in the blood and whole-body and to estimate the dose of patients according to MIRD schema. Therapy activities of 131I (136, 185, 200 mCi) were administrated to patients (n=3). Blood activity concentrations and whole-body images by gamma camera were collected from patients with non-Hodgkin's lymphoma (5min, 6h, 24h, 48h, 72h, 2week). Two kinds of patient specific approaches based on Sgouros bone marrow dosimetry methodology were considered to estimate bone marrow dose. The mean effective half-life in blood and whole-body were 25.2h and 27.1h respectively and the mean absorbed dose to bone marrow was 0.48Gy (0.22∼0.93Gy). The dominant contribution of dose was found to be from bone marrow self-dose (over 60%). The procedures of dosimetry with blood and gamma camera image were established. These enable to estimate the radioimmunotherapy patient's dose retrospectively. Some parts of the procedures need to be elaborated to obtain more accurate dose in the near future

Clinical Benefits of Memantine Treatment for Alzheimer's Disease in the Okayama Memantine Study II (OMS II).

Science.gov (United States)

Matsuzono, Kosuke; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Koike, Makoto; Sato, Kota; Kono, Syoichiro; Deguchi, Kentaro; Nakano, Yumiko; Abe, Koji

2015-01-01

The clinical benefits of memantine, depending on the baseline cognitive and affective conditions in real world dementia clinics, have not been completely examined. We performed the "Okayama Memantine Study II (OMS II)" to retrospectively evaluate the clinical effects of memantine monotherapy (n = 38) in Alzheimer's disease (AD) patients using seven batteries to assess dementia at the baseline, at 3, 6, and 12 months. Additionally, we divided 163 AD patients treated with memantine into two subgroups depending on the baseline cognitive score of the Mini-Mental State Examination (MMSE): the MMSE OMS II showed that memantine monotherapy improved BPSD until 12 months. The higher baseline cognitive subgroup (MMSE ≥15) and the worse baseline BPSD subgroup were expected to show better effects with memantine.

Radioimmunotherapy: Development of an effective approach

International Nuclear Information System (INIS)

DeNardo, S.J.

1991-01-01

We plan to extend our success in treating B cell malignancies with 131 I labeled Lym-1 by a major effort in therapy with 67 Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the 111 In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the 111 In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N',N double-prime, N'double-prime-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of 67 Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry

Antibody conjugate radioimmunotherapy of superficial bladder cancer

International Nuclear Information System (INIS)

Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

2002-01-01

The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

International Nuclear Information System (INIS)

Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Daha, Fariba Johari

2010-01-01

Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of 177 Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 μg ml -1 , 177 Lu-Herceptin (surviving cells: 5±0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43±3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

International Nuclear Information System (INIS)

Illidge, T.M.

1999-06-01

Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations

Science.gov (United States)

Butler, Javed; Hamo, Carine E.; Udelson, James E.; O’Connor, Christopher; Sabbah, Hani N.; Metra, Marco; Shah, Sanjiv J.; Kitzman, Dalane W.; Teerlink, John; Bernstein, Harold S.; Brooks, Gabriel; Depre, Christophe; DeSouza, Mary M.; Dinh, Wilfried; Donovan, Mark; Frische-Danielson, Regina; Frost, Robert J.; Garza, Dahlia; Gohring, Udo-Michael; Hellawell, Jennifer; Hsia, Judith; Ishihara, Shiro; Kay-Mugford, Patricia; Koglin, Joerg; Kozinn, Marc; Larson, Christopher J.; Mayo, Martha; Gan, Li-Ming; Mugnier, Pierrre; Mushonga, Sekayi; Roessig, Lothar; Russo, Cesare; Salsali, Afshin; Satler, Carol; Shi, Victor; Ticho, Barry; van der Laan, Michael; Yancy, Clyde; Stockbridge, Norman; Gheorghiade, Mihai

2017-01-01

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions. PMID:28356300

Combination radioimmunotherapy approaches and quantification of immuno-PET

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Su [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2016-06-15

Monoclonal antibodies (mAbs), which play a prominent role in cancer therapy, can interact with specific antigens on cancer cells, thereby enhancing the patient' immune response via various mechanisms, or mAbs can act against cell growth factors and, thereby, arrest the proliferation of tumor cells. Radionuclide-labeled mAbs, which are used in radioimmunotherapy (RIT), are effective for cancer treatment because tumor associated-mAbs linked to cytotoxic radionuclides can selectively bind to tumor antigens and release targeted cytotoxic radiation. Immunological positron emission tomography (immuno-PET), which is the combination of PET with mAb, is an attractive option for improving tumor detection and mAb quantification. However, RIT remains a challenge because of the limited delivery of mAb into tumors. The transport and uptake of mAb into tumors is slow and heterogeneous. The tumor microenvironment contributed to the limited delivery of the mAb. During the delivery process of mAb to tumor, mechanical drug resistance such as collagen distribution or physiological drug resistance such as high intestinal pressure or absence of lymphatic vessel would be the limited factor of mAb delivery to the tumor at a potentially lethal mAb concentration. When α-emitter-labeled mAbs were used, deeper penetration of α-emitter-labeled mAb inside tumors was more important because of the short range of the α emitter. Therefore, combination therapy strategies aimed at improving mAb tumor penetration and accumulation would be beneficial for maximizing their therapeutic efficacy against solid tumors.

EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with 90Y-radiolabelled ibritumomab tiuxetan (Zevalin)

International Nuclear Information System (INIS)

Tennvall, Jan; Fischer, Manfred; Brans, Boudewijn; Bischof Delaloye, Angelika; Bombardieri, Emilio; Bodei, Lisa; Giammarile, Francesco; Lassmann, Michael; Oyen, Wim

2007-01-01

In January 2004, EMEA approved 90 Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin's lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease. (orig.)

Radioimmunotherapy with Tenarad, a {sup 131}I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma

Energy Technology Data Exchange (ETDEWEB)

Aloj, Luigi [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Medicina Nucleare, Napoli (Italy); D' Ambrosio, Laura; Aurilio, Michela; Morisco, Anna; Caraco' , Corradina; Di Gennaro, Francesca; Lastoria, Secondo [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa Medicina Nucleare, Napoli (Italy); Frigeri, Ferdinando; Capobianco, Gaetana; Pinto, Antonio [Istituto Nazionale Tumori ' ' Fondazione G. Pascale' ' - IRCCS, Struttura Complessa di Ematologia Oncologica, Napoli (Italy); Giovannoni, Leonardo; Menssen, Hans D. [Philogen, SpA, Siena (Italy); Neri, Dario [Institute of Pharmaceutical Sciences, ETH, Zurich (Switzerland)

2014-05-15

The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with {sup 131}I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ({sup 131}I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments. Eight patients (four men, four women; age range 19 - 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m{sup 2}) if tumour uptake was more than four times higher than that of muscle. All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 - 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients

Alpha radioimmunotherapy of multiple myeloma: study of feasibility of ex vivo medullary purge

International Nuclear Information System (INIS)

Couturier, O.; Filippovitch, I.V.; Sorokina, N.I.; Cherel, M.; Thedrez, P.; Faivre-Chauvet, A.; Chatal, J.F.

1997-01-01

The efficiency of the radioimmunotherapy (RIT) using beta emitters has been clinically proved in treatments of refractory forms of lymphoma. The alpha-emitting radioelements of short half-life are also good potential candidates for RIT, applicable to tumor targets accessible rapidly to the molecules of the radio-immuno-conjugates of size compatible with the short range of alpha particles (50 to 80 μm). The goal of this study is to demonstrate the feasibility of such an approach on a model of myeloma multiply targeted by specific antibodies (B-B4) coupled to bismuth-213 with a chelating agent (benzyl-DTPA). The efficiency of the alpha RIT was evaluated in vitro by means of different techniques analyzing the cellular mortality (the method of limited dilution), the effects on DNA (the testing of micro-nuclei), the analysis of radio-induced apoptosis (the test with acridine orange) and finally the study of non-specific irradiation on population of cells of hematopoietic system un-recognized by the B-B4 benzyl-DTPA) immuno-conjugate. The first results have shown besides the technical feasibility of the project a strong dose dependent cellular mortality with a survival falling rapidly from 28% to around 1 o/oo for a single doubling of the dose from 14.8 kBq / 10 5 cells (0.4 μCi) to 29.6 kBq/10 5 cells (0.8 μCi). The cellular mortality was total at 300 kBq/10 5 cells (8 μCi). The cells in an apoptosis state were evidenced at rates up to 40% for a dose of 7.4 kBq/10 5 cells (0.2 μ Ci). New experiments will permit confirming these first results and determining the irradiation range having in view a utilization in protocols of purging of the myeloma cells on pockets obtained after plasmaphereses

Aptamer-based radioimmunotherapy. The feasibility and prospect in cancer therapy

International Nuclear Information System (INIS)

Li Li; Hui Wang; Shujie Liao; Wei Li; Weina Zhang; Dan Liu; Bo Cao; Shixuan Wang; Ding Ma; Wei Wang; Nanfang Hospital, Southern Medical University, Guangzhou; Xiangshang Xu; Keng Shen

2011-01-01

Radioimmunotherapy (RIT) has emerged as an attractive and promising strategy for the management of malignant diseases. It has been proven to be quite effective in the treatment of numerous tumors, such as non-Hodgkin lymphoma, metastatic prostate cancer, melanoma, thyroid cancer, colon cancer and so on. The RIT currently used is mainly based on monoclonal antibodies to recognize target antigens. As antibodies are large molecules, this method of RIT has some limitations in in vivo use, such as the immunogenicity, the high costs and low efficiency of production. Aptamer is discovered and selected by SELEX technology. As specific recognizers and binders, aptamers and antibodies have such a close similarity as to be interchangeable to some extent. But, aptamers have many advantages over antibodies: higher affinity and specificity, smaller molecular weight, more easily synthesized and modified, more rapidly penetrating into tumors, higher tumor-to-blood distribution ratio and more easily to be cleared. In addition, since aptamer has almost no immunogenicity in vivo, it can be repeatedly administered. Thus, we believe that aptamer-based RIT will be a feasible and promising way to treat human cancers, and it might display better results in cancer treatment than antibody-based RIT. In conclusion, aptamer-based RIT is hopeful to become a key therapeutics in cancer radiotherapy in the near future. (author)

Pharmacokinetics and tumor targeting of 131I-labeled F(ab')2 fragments of the chimeric monoclonal antibody G250: preclinical and clinical pilot studies.

NARCIS (Netherlands)

Brouwers, A.H.; Mulders, P.F.A.; Oosterwijk, E.; Buijs, W.C.A.M.; Corstens, F.H.M.; Boerman, O.C.; Oyen, W.J.G.

2004-01-01

INTRODUCTION: Clinical and animal studies of chimeric monoclonal antibody G250 (moAb cG250) for the targeting of clear-cell renal cell carcinoma (RCC), to date, have been with the intact IgG form. To determine whether F(ab')2 fragments are more suited for radioimmunotherapy (RIT) than intact IgG,

Clinical evaluation of the Non-Contact Tonometer Mark II.

Science.gov (United States)

Chauhan, B C; Henson, D B

1988-09-01

The purpose of this investigation was to test the reliability of the American Optical Non-Contact Tonometer Mark II (NCT II) using the Goldmann Applanation Tonometer (GAT) as the validating instrument. The sample contained 102 consecutive patients from our University Eye Clinic, of whom one-half had 4 NCT II measurements first, followed by 4 GAT measurements; the other one-half had 4 GAT measurements first, followed by 4 NCT II measurements. No significant change in intraocular pressure (IOP) was noted over the measurement sequence with either instrument. There was no significant difference between paired NCT II and GAT readings when the NCT II was used first; however, a highly significant difference between paired readings was obtained when the GAT was used first, indicating that the GAT measurement produced a delayed reduction in the IOP. This effect did not occur with the NCT II. Although the NCT II is shown to have a good overall reliability when compared to the GAT in both protocols, the agreement between any two tonometers may be influenced greatly by the very process of taking a measurement and by the dynamic nature of the IOP.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (Head and neck cancer: ImmunoChemo and Radiotherapy with Erbitux) – a multicenter phase IV trial

International Nuclear Information System (INIS)

Habl, G; Potthoff, K; Haefner, MF; Abdollahi, A; Hassel, JC; Boller, E; Indorf, M; Debus, J

2013-01-01

In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel

Radioimmunotherapy. Dose calculation and radionuclides used in treatment; Radioimmunoterapia. Hoidon radionuklidit ja annoslaskenta

Energy Technology Data Exchange (ETDEWEB)

Savolainen, S [Helsinki Univ. (Finland). Dept. of Physics; Kairemo, K [Helsinki Univ. (Finland). Dept. of Clinical Chemistry; Liewendahl, K [Helsinki Univ. Central Hospital (Finland). Dept. of Isotopes; Rannikko, S [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland)

1995-10-01

In radioimmunotherapy (RIT) monoclonal antibodies to cancer-associated antigens can be utilized for the transport of therapeutic radioisotopes to cancer cells. Intravenous administration of radiolabelled antibody is a potentially curative form of therapy in hematological amignancies as circulating antibodies have easy access to tumour sites. Intravenous RIT is less effective in the treatment of solid tumours because of the low fractional uptake of the injected dose, particularly in the central parts of tumours. In solid tumours more promising results have been achieved by local RIT applications. The choice of radiation - {alpha}, {beta} or {gamma} - will depend of the characteristics of the tumour. The importance of radiation delivered by Auger electrons has been largely underestimated in the past, but recent research has resulted in a remarkable reassessment of this issue significantly influencing the selection of radioisotopes for RIT. Research is now being focused on the therapeutic aspects of different isotopes and microdosimetric problems. There are now good prospects of RIT becoming an important form of cancer treatment before year 2000. (orig.) (78 refs., 3 figs., 1 tab.).

Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

Energy Technology Data Exchange (ETDEWEB)

Illidge, T.M

1999-06-01

Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti

Type I-II laryngeal cleft: clinical course and outcome.

Science.gov (United States)

Slonimsky, Guy; Carmel, Eldar; Drendel, Michael; Lipschitz, Noga; Wolf, Michael

2015-04-01

Laryngeal cleft (LC) is a rare congenital anomaly manifesting in a variety of symptoms, including swallowing disorders and aspirations, dyspnea, stridor and hoarseness. The mild forms (types I-II) may be underdiagnosed, leading to protracted symptomatology and morbidity. To evaluate the diagnostic process, clinical course, management and outcome in children with type I-II laryngeal clefts. We conducted a retrospective case analysis for the years 2005-2012 in a tertiary referral center. Seven children were reviewed: five boys and two girls ranging in age from birth to 5 years. The most common presenting symptoms were cough, aspirations and pneumonia. Evaluation procedures included fiber-optic laryngoscopy (FOL), direct laryngoscopy (DL) and videofluoroscopy. Other pathologies were seen in three children. Six children underwent successful endoscopic surgery and one child was treated conservatively. The postoperative clinical course was uneventful in most of the cases. Types I-II LC should be considered in the differential diagnosis of children presenting with protracted cough and aspirations. DL is crucial for establishing the diagnosis. Endoscopic surgery is safe and should be applied promptly when conservative measures fail.

The SafeBoosC phase II clinical trial

DEFF Research Database (Denmark)

Riera, Joan; Hyttel-Sorensen, Simon; Bravo, María Carmen

2016-01-01

BACKGROUND: The SafeBoosC phase II randomised clinical trial recently demonstrated the benefits of a combination of cerebral regional tissue oxygen saturation (rStO2) by near-infrared spectroscopy (NIRS) and a treatment guideline to reduce the oxygen imbalance in extremely preterm infants. AIMS: ...

18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

International Nuclear Information System (INIS)

Salaun, Pierre-Yves; Robin, Philippe; Campion, Loic; Ansquer, Catherine; Mathieu, Cedric; Frampas, Eric; Bournaud, Claire; Vuillez, Jean-Philippe; Taieb, David; Rousseau, Caroline; Drui, Delphine; Mirallie, Eric; Borson-Chazot, Francoise; Goldenberg, David M.; Chatal, Jean-Francois; Barbet, Jacques; Kraeber-Bodere, Francoise

2014-01-01

PET is a powerful tool for assessing targeted therapy. Since 18 F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18 F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV max , location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV max (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC

Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

Directory of Open Access Journals (Sweden)

Dina Tsukrov

2016-09-01

Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

WIPR 2013 - Radiopharmaceuticals: from research to industry - Book of abstracts

International Nuclear Information System (INIS)

2015-01-01

This workshop aims at presenting the latest progress in the field of radioimmunotherapy: radiopharmaceutical production, radiochemistry, radiolabelling, nuclear imaging and clinical applications. The presentations have been divided into 4 sessions: 1) alpha or beta radioimmunotherapy, 2) peptides or antibodies, 3) the benefits from nuclear imaging, and multimodal imaging

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

Science.gov (United States)

Scott, B R; Dillehay, L E

1990-11-01

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

{sup 18}F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Salaun, Pierre-Yves; Robin, Philippe [University Hospital, Nuclear Medicine Department, Brest (France); Campion, Loic [ICO-Gauducheau Cancer Institute, Statistical Department, Nantes (France); Ansquer, Catherine; Mathieu, Cedric [University Hospital, Nuclear Medicine Department, Nantes (France); Frampas, Eric [University Hospital, Radiology Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); Bournaud, Claire [University Hospital, Nuclear Medicine Department, Lyon (France); Vuillez, Jean-Philippe [University Hospital, Nuclear Medicine Department, Grenoble (France); Taieb, David [University Hospital, Nuclear Medicine Department, Marseille (France); Rousseau, Caroline [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Drui, Delphine [University Hospital, Endocrinology Department, Nantes (France); Mirallie, Eric [University Hospital, Surgery Department, Nantes (France); Borson-Chazot, Francoise [University Hospital, Endocrinology Department, Lyon (France); Goldenberg, David M. [IBC Pharmaceuticals, Inc., and Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States); Chatal, Jean-Francois [GIP ARRONAX, Saint-Herblain (France); Barbet, Jacques [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); GIP ARRONAX, Saint-Herblain (France); Kraeber-Bodere, Francoise [University Hospital, Nuclear Medicine Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Hotel Dieu University Hospital, Nuclear Medicine Department, Nantes (France)

2014-08-15

PET is a powerful tool for assessing targeted therapy. Since {sup 18}F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated {sup 18}F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV{sub max}, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV{sub max} (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the

Experimental study on 211At labelled monoclonal antibody 3H11 and its Fab fragment radioimmunotherapy for human gastric cancer xenografts in nude mice

International Nuclear Information System (INIS)

Jin Jiannan; Liu Ning; Zhang Shuyuan; Zhang Shiyuan; Luo Deyuan; Zhou Maolun

1996-01-01

Experimental radioimmunotherapy investigation of α-emitting radionuclide 211 At labelled anti-gastric cancer monoclonal antibody 3H11 and its Fab fragment for nude mice carrying human gastric cancer xenografts was conducted. Three i.p. injections of 14.8 or 22.2 kBq/g mouse were given, once every 5 days. The results showed that the growth of tumor xenografts was inhibited efficiently. The most evident therapy effect was observed at 15 days after treatment, and the tumor inhibition rates were 65% and 72%, respectively. No radiation injury of important organs was found

Carrier-free 194Ir from an 194Os/194Ir generator - a new candidate for radioimmunotherapy

International Nuclear Information System (INIS)

Mirzadeh, S.; Rice, D.E.; Knapp, F.F. Jr.

1992-01-01

Iridium-194 (t 1/2 = 19.15 h) decays by beta-particle emission (E max = 2.236 MeV) and is a potential candidate for radioimmunotherapy. An important characteristic is availability of 194 Ir from decay of reactor-produced 194 Os (t 1/2 = 6y). We report the fabrication of the first 194 Os/ 194 Ir generator system using activated carbon. In addition, a novel gas thermochromatographic method was developed for the one step conversion of metallic Os to OsO 4 and subsequent separation and purification of OsO 4 . In this manner, the reactor irradiated enriched 192 Os target was converted to 194 OsO 4 , which was then converted to the K 2 OsCl 6 for generator loading. The yield and the elution profile of carrier-free 194 Ir, and 194 Os breakthrough were determined for a prototype generator which was evaluated over a 10-month period. (author)

Radioimmunotherapy for non-Hodgkin's lymphoma; positioning, safety, and efficacy of 90Y-Ibritumomab. 10 years of experience and follow-up.

Science.gov (United States)

Martínez, A; Martínez-Ramirez, M; Martínez-Caballero, D; Beneit, P; Clavel, J; Figueroa, G; Verdú, J

Radioimmunotherapy (RIT) is one of the therapies directed against molecular targets in non-Hodgkin's lymphoma (NHL). To evaluate the positioning, safety, and effectiveness of RIT with 90Y-Ibritumomab in NHL patients. A retrospective study was conducted on patients with NHL who received RIT with 90Y-Ibritumomab. An evaluation was made of the concordance with clinical guidelines, toxicity as rated by the Common Terminology Criteria for Adverse Events (CTCAE), and effectiveness was assessed based on response to treatment, overall survival (OS), and progression-free survival (PFS). RIT was requested in 26 patients, of whom 21 (11 women, mean age 56±10 years) were included in the study, with the following distribution: Follicular NHL, 67%, Mantle NHL, 14%, Diffuse large B-cell NHL, 9.5%, and Transformed NHL 9.5%. Twelve patients with refractory NHL, 7 for consolidation response, and 2 transplant conditioning, were treated. Adverse effects were observed in 71% of patients, which were usually manageable and transient, and with the most common being thrombocytopenia. At 3-4 months, overall response rate was 76.2% (71.4% complete and 4.8% partial response), and 19% had progression of disease. With a median follow up of 70 months, the OS was 96±8 months, and the PFS was 54±11 months. RIT showed a moderate correlation with clinical guidelines, and is probably underused. Adverse effects were common, mild, and manageable. The data show a high complete response rate and an increase in the OS and PFS. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Design of clinical trials Phase I and II with radiopharmaceuticals

International Nuclear Information System (INIS)

Giannone, C.A.; Soroa, V.E.

2015-01-01

We presented some usual designs for clinical studies in Phase I and Phase II. For Phase I we considered the 3 + 3 Classic design, designs with accelerated titration and those with dose escalation schemes with overdose control (EWOC). For Phase II designs with efficacy outcomes are presented. The design proposed by Fleming is discussed as well as those with inclusion of patients in two stages: Gehan’s design and the Optimal two–stage Simon’s design. We also discussed the design of combined endpoints of efficacy and safety of Bryant and Day with an application example of therapeutically Lu-177. Finally some proposals for phase II trials with control group are considered. (authors) [es

Synthesis of Lutetium Phosphate/Apoferritin Core-Shell Nanoparticles for Potential Applications in Radioimmunoimaging and Radioimmunotherapy of Cancers

International Nuclear Information System (INIS)

Wu, Hong; Engelhard, Mark H.; Wang, Jun; Fisher, Darrell R.; Lin, Yuehe

2008-01-01

We report a novel approach for synthesizing LuPO4/apoferritin core-shell nanoparticles based on an apoferritin template, conjugated to the protein biotin. To prepare the nanoparticle conjugates, we used non-radioactive lutetium as a model target or surrogate for radiolutetium (177Lu). The central cavity, multi-channel structure, and chemical properties of apoferritin are well-suited for sequentially diffusing lutetium and phosphate ions into the cavity--resulting in a stable core-shell composite. We characterized the synthesized LuPO4/apoferritin nanoparticle using transmission electron microscopy (TEM) and x-ray photoelectron spectroscopy (XPS). We tested the pre-targeting capability of biotin-modified lutetium/apoferritin nanoparticle using streptavidin-modified magnetic beads and streptavidin-modified fluorescein isothiocyanate (FITC) tracer. This paper presents a simple, fast, and efficient method for synthesizing LuPO4/apoferritin nanoparticle conjugates with biotin for potential applications in radioimmunotherapy and radioimmunoimaging of cancer

The SafeBoosC Phase II Randomised Clinical Trial

DEFF Research Database (Denmark)

Pellicer, Adelina; Greisen, Gorm; Benders, Manon

2013-01-01

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO2) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO2 can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the bur...

Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

Energy Technology Data Exchange (ETDEWEB)

Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

2008-06-15

leukemic blasts. They enable the treatment of leukemia patients with a high medullar tumor load or extramedullar leukemic blast infiltration. Specific doses (Gy/GBq) for the {sup 90}Y-anti-CD45-mAb YAML568 are 6.4 {+-} 1.2 (bone marrow), 3.9 {+-} 1.4 (liver) and 1.1 {+-} 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of patients with multiple myeloma may markedly be improved using a combination of {alpha}- and {beta}-anti-CD45-mAbs. This review provides a systematic and critical overview of the currently used radionuclides and antibodies for the treatment of AML, MDS and multiple myeloma and summarizes the present literature on clinical trials of myeloablative radioimmunotherapies for conditioning before both, autologous and allogeneic stem cell transplantation. (orig.)

[Prescribed drug use for bipolar disorder type I and II in clinical practice].

Science.gov (United States)

Persson, Charlotte; Kardell, Mathias; Karanti, Alina; Isgren, Anniella; Annerbrink, Kristina; Landen, Mikael

2017-01-10

Prescribed drug use for bipolar disorder type I and II in clinical practice Practice guidelines based on available evidence and clinical consensus are available for the treatment of bipolar disorder. We surveyed to which extent those guidelines are implemented in clinical practice in Sweden. We analysed pharmacological treatment in patients with bipolar disorder in 2015 using the national quality register for bipolar disorder (BipoläR). We compared bipolar disorder type I (BDI) with type bipolar disorder type II (BDII). The vast majority of patients were prescribed a mood stabilizer either as monotherapy or as a part of combination therapy (BDI 87%, BDII 83%, pbipolar disorder.

Evaluating changes in stable chromosomal translocation frequency in patients receiving radioimmunotherapy

International Nuclear Information System (INIS)

Wong, Jeffrey Y.C.; Wang Jianyi; Liu An; Odom-Maryon, Tamara; Shively, John E.; Raubitschek, Andrew A.; Williams, Lawrence E.

2000-01-01

Purpose: The lack of any consistent correlation between radioimmunotherapy (RIT) dose and observed hematologic toxicity has made it difficult to validate RIT radiation dose estimates to marrow. Stable chromosomal translocations (SCT) which result after radiation exposure may be a biologic parameter that more closely correlates with RIT radiation dose. Increases in the frequency of SCT are observed after radiation exposure and are highly correlated with absorbed radiation dose. SCT are cumulative after multiple radiation doses and conserved through an extended number of cell divisions. The purpose of this study was to evaluate whether increases in SCT frequency were detectable in peripheral lymphocytes after RIT and whether the magnitude of these increases correlated with estimated radiation dose to marrow and whole body. Methods and Materials: Patients entered in a Phase I dose escalation therapy trial each received 1-3 intravenous cycles of the radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody, 90 Y-chimeric T84.66. Five mCi of 111 In-chimeric T84.66 was co-administered for imaging and biodistribution purposes. Blood samples were collected immediately prior to the start of therapy and 5-6 weeks after each therapy cycle. Peripheral lymphocytes were harvested after 72 hours of phytohemagglutinin stimulation and metaphase spreads prepared. Spreads were then stained by fluorescence in situ hybridization (FISH) using commercially available chromosome paint probes to chromosomes 3 and 4. Approximately 1000 spreads were evaluated for each chromosome sample. Red marrow radiation doses were estimated using the AAPM algorithm and blood clearance curves. Results: Eighteen patients were studied, each receiving at least one cycle of therapy ranging from 5-22 mCi/m 2 . Three patients received 2 cycles and two patients received 3 cycles of therapy. Cumulative estimated marrow doses ranged from 9.2 to 310 cGy. Increases in SCT frequencies were observed after

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

Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas

2017-01-01

Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...

The hypoxic cytotoxin SR 4233 increases the effectiveness of radioimmunotherapy in mice with human non-Hodgkin's lymphoma xenografts.

Science.gov (United States)

Wilder, R B; McGann, J K; Sutherland, W R; Waller, E K; Minchinton, A I; Goris, M L; Knox, S J

1994-01-01

To determine if either the hypoxic cell radiosensitizer etanidazole (SR 2508) or the hypoxic cytotoxin SR 4233 could improve the effectiveness of radioimmunotherapy. LC4 (an IgG1 monoclonal antibody directed toward malignant T cells) and MB-1 (an irrelevant isotype-matched control antibody) were injected intraperitoneally into severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts in order to determine the distribution of the antibodies in the tumors and normal tissues as a function of time. Computerized-pO2-histography was used to measure the median oxygen tension in the tumors. Tumor-bearing mice were treated with: (a) LC4; (b) 90Y-LC4; (c) 90Y-MB-1; (d) whole body irradiation delivered via an external 137Cs source; (e) etanidazole and 90Y-LC4; (f) SR 4233 and 90Y-LC4; (g) etanidazole; and (h) SR 4233. An additional group of mice received no treatment and served as controls. A tumor growth delay assay was used to assess the effectiveness of the different treatment regimens. LC4 accumulated in the tumors to a significantly greater extent than MB-1 (p LC4 by itself was able to produce a minor decrease in tumor size (control vs. LC4; p = 0.001). 90Y-LC4 produced greater tumor growth delay than LC4 alone (LC4 vs. 90Y-LC4; p = 0.01); however, the Yttrium-90 caused neutropenia and weight loss. The 90Y-labeled tumor-specific and non-specific antibodies both exerted greater tumor growth delay than externally delivered whole body irradiation (p LC4 (90Y-LC4 vs etanidazole and 90Y-LC4, p = 0.13). SR 4233, on the other hand, did enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs. SR 4233 and 90Y-LC4, p = 0.046). The neutropenia and weight loss caused by 90Y-LC4 were exacerbated slightly (< 10%) by the administration of SR 4233. A first generation hypoxic cytotoxin, SR 4233, was able to enhance the tumor growth delay produced by radioimmunotherapy in severe combined immunodeficient phenotype mice with human cutaneous T cell

A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

Directory of Open Access Journals (Sweden)

Jeffrey V. Leyton

2015-01-01

Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients

Directory of Open Access Journals (Sweden)

Caroline eBodet-Milin

2015-11-01

Full Text Available Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096 was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections.Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG humanized trivalent bispecific antibody (TF2 and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288, and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288. The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands.Results. TF2 pharmacokinetics (PK was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h. The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002. S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best

Clinical efficacy of terlipressin in treatment of type II hepatorenal syndrome

Directory of Open Access Journals (Sweden)

DING Xiaohong

2015-05-01

Full Text Available ObjectiveTo investigate the clinical efficacy of domestic terlipressin in the treatment of type II hepatorenal syndrome (HRS-II. MethodsA total of 25 HRS-II patients admitted to our hospital from November 2011 to June 2014 were recruited into the treatment group, and 28 HRS-II patients treated with dopamine before 2011 were recruited into the control group. Patients in the treatment group were randomly divided into two subgroups: one subgroup (n=12 was given terlipressin once every 8 h, and the other subgroup (n=13 was given terlipressin once every 12 h. Both groups received albumin (Alb infusion to expand the blood volume before treatment with terlipressin or dopamine, and the course of treatment was 7 days. The improvement in clinical symptoms, levels of blood urea nitrogen (BUN, serum creatinine and electrolytes, urine volume, changes in liver function, and ascites disappearance in the two groups before and after treatment were compared. Comparison of categorical data between the two groups was made by χ2 test, and comparison of continuous data was made by t test. ResultsPatients in the control group showed no obvious symptom relief, but those in the treatment group had varying degrees of improvement in clinical symptoms. Neither group had significant changes in liver function and serum sodium level after treatment. The treatment group had significantly more patients whose ascites volume had decreased from large to medium than the control group (χ2=5.705, P＜0.05. There was a slight but not significant decrease in the levels of BUN and serum creatinine in the control group after treatment with dopamine (all P＞0.05, whereas the urine volume showed significant difference after the treatment (t=15.534, P＜0.01. The treatment group showed significant differences in the levels of BUN and serum creatinine and urine volume after terlipressin treatment (t=11.535, 9.941, and 19.685, respectively; all P＜0.01, and significant differences in

Issues in the assessment of personality disorder and substance abuse using the Millon Clinical Multiaxial Inventory (MCMI-II).

Science.gov (United States)

Flynn, P M; McCann, J T; Fairbank, J A

1995-05-01

Substance abuse treatment clients often present other severe mental health problems that affect treatment outcomes. Hence, screening and assessment for psychological distress and personality disorder are an important part of effective treatment, discharge, and aftercare planning. The Millon Clinical Multiaxial Inventory-II (MCMI-II) frequently is used for this purpose. In this paper, several issues of concern to MCMI-II users are addressed. These include the extent to which MCMI-II scales correspond to DSM-III-R disorders; overdiagnosis of disorders using the MCMI-II; accuracy of MCMI-II diagnostic cut-off scores; and the clinical utility of MCMI-II diagnostic algorithms. Approaches to addressing these issues are offered.

Detecting comorbid Axis-II status among inpatients using the MMPI-2 Restructured Clinical Scales

NARCIS (Netherlands)

Kamphuis, J.H.; Arbisi, P.A.; Ben-Porath, Y.S.; McNulty, J.L.

2008-01-01

This study examined the differential diagnostic utility of the MMPI-2 Restructured Clinical Scales (RCS) and Clinical Scales (CS) in detecting a complex multivariate clinical phenomenon: that is, comorbid Axis-II status in two matched samples of inpatients. Psychiatric inpatients diagnosed with

[How to assess clinical practice guidelines with AGREE II: The example of neonatal jaundice].

Science.gov (United States)

Renesme, L; Bedu, A; Tourneux, P; Truffert, P

2016-03-01

Neonatal jaundice is a very frequent condition that occurs in approximately 50-70% of term or near-term (>35 GA) babies in the 1st week of life. In some cases, a high bilirubin blood level can lead to kernicterus. There is no consensus for the management of neonatal jaundice and few countries have published national clinical practice guidelines for the management of neonatal jaundice. The aim of this study was to assess the quality of these guidelines. We conducted a systematic review of the literature for national clinical practice guidelines for the management of neonatal jaundice in term or near-term babies. Four independent reviewers assessed the quality of each guideline using the AGREE II evaluation. For each of the clinical practice guidelines, the management modalities were analyzed (screening, treatment, follow-up, etc.). Seven national clinical practice guidelines were found (South Africa, USA AAP, UK NICE, Canada, Norway, Switzerland, and Israel). The AGREE II score showed widespread variation regarding the quality of these national guidelines. There was no major difference between the guidelines concerning the clinical management of these babies. The NICE guideline is the most valuable guideline regarding the AGREE II score. NICE showed that, despite a strong and rigorous methodology, there is no evidenced-based recommended code of practice (RCP). Comparing RCPs, we found no major differences. The NICE guideline showed the best quality. The AGREE II instrument should be used as a framework when developing clinical practice guidelines to improve the quality of the future guideline. In France, a national guideline is needed for a more standardized management of neonatal jaundice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

American tertiary clinic-referred bipolar II disorder versus bipolar I disorder associated with hastened depressive recurrence.

Science.gov (United States)

Dell'Osso, Bernardo; Shah, Saloni; Do, Dennis; Yuen, Laura D; Hooshmand, Farnaz; Wang, Po W; Miller, Shefali; Ketter, Terence A

2017-12-01

Bipolar disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000-2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan-Meier analyses assessed the relationships between bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.

Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

Science.gov (United States)

Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

2005-12-15

We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

Accessing the public MIMIC-II intensive care relational database for clinical research.

Science.gov (United States)

Scott, Daniel J; Lee, Joon; Silva, Ikaro; Park, Shinhyuk; Moody, George B; Celi, Leo A; Mark, Roger G

2013-01-10

The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database is a free, public resource for intensive care research. The database was officially released in 2006, and has attracted a growing number of researchers in academia and industry. We present the two major software tools that facilitate accessing the relational database: the web-based QueryBuilder and a downloadable virtual machine (VM) image. QueryBuilder and the MIMIC-II VM have been developed successfully and are freely available to MIMIC-II users. Simple example SQL queries and the resulting data are presented. Clinical studies pertaining to acute kidney injury and prediction of fluid requirements in the intensive care unit are shown as typical examples of research performed with MIMIC-II. In addition, MIMIC-II has also provided data for annual PhysioNet/Computing in Cardiology Challenges, including the 2012 Challenge "Predicting mortality of ICU Patients". QueryBuilder is a web-based tool that provides easy access to MIMIC-II. For more computationally intensive queries, one can locally install a complete copy of MIMIC-II in a VM. Both publicly available tools provide the MIMIC-II research community with convenient querying interfaces and complement the value of the MIMIC-II relational database.

Phase II cancer clinical trials for biomarker-guided treatments.

Science.gov (United States)

Jung, Sin-Ho

2018-01-01

The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

Real-time, in vivo measurement of radiation dose during radioimmunotherapy in mice using a miniature MOSFET dosimeter probe

International Nuclear Information System (INIS)

Gladstone, D.J.; Chin, L.M.

1995-01-01

This report presents the first real-time measurement of absorbed radiation dose during radioimmunotherapy in mice. Dose rate and total dose at the center of the tumor were measured after administration of 90 Y-labeled antibodies using a miniature metal oxide semiconductor field-effect transistor radiation dosimeter probe which was inserted into the center of the tumor volume. Continuous real-time measurements were made for as long as 23 h after injection of the radiolabeled antibodies. Comparison of the real-time dose-rate measurements with estimates based on the MIRD formalism indicates good agreement. The real-time measurements are further compared to measurements made in a second experiment in which groups of mice were sacrificed at individual times after injection of the same radiolabeled antibodies. The real-time measurements agree well with the measurements in excised tumors. The real-time measurements have greater time resolution and are much more efficient than traditional uptake measurements. 17 refs., 2 figs

Majewski osteodysplastic primordial dwarfism type II (MOPD II): natural history and clinical findings.

Science.gov (United States)

Hall, Judith G; Flora, Christina; Scott, Charles I; Pauli, Richard M; Tanaka, Kimi I

2004-09-15

A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family. Copyright 2004 Wiley-Liss, Inc.

Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies

International Nuclear Information System (INIS)

Shen, Shang; Forero, Andres; LoBuglio, Albert F.; Breitz, H.; Khazaeli, M. B.; Fisher, Darrell R.; Wang, W. Q.; Meredith, Ruby F.

2005-01-01

Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor (90)Y doses were calculated based on (111)In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. RESULTS: The (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean (90)Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body

Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

DEFF Research Database (Denmark)

Eriksson, Sophie E; Elgström, Erika; Bäck, Tom

2014-01-01

for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... The rats suffered from reversible myelotoxicity after treatment. CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect....

Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

Energy Technology Data Exchange (ETDEWEB)

Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

2009-07-01

Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

Two-year clinical evaluation of IPS Empress II ceramic onlays/inlays.

Science.gov (United States)

Tagtekin, D A; Ozyöney, G; Yanikoglu, F

2009-01-01

The stronger the ceramic material, the longer the restoration stays in the mouth. The current study evaluated the two-year clinical performance of a strong ceramic system, IPS Empress II, with increased strength on onlay/inlay restorations of molars. Teeth from 35 patients, including three premolars and 32 molars, were prepared for 28 onlay and seven inlay restorations with IPS Empress II ceramics. The restorations were cemented with a highly viscous, dual-curing luting composite cement (Bifix) and evaluated by two examiners using USPHS criteria at baseline (one week following insertion), six months, one year and two years. The baseline scores and recalls were assessed by Wilcoxon signed rank test. Statistically significant marginal discoloration at the Bravo level was found at the 12- and 24-month recalls (p=0.046). One debonding was statistically insignificant. No changes were observed with respect to anamnesis, such as any symptom from the TMJ or masticatory muscles. No restorations were replaced due to hypersensitivity or were missing at the two-year evaluation. Any wear on the restoration, antagonist tooth or any changes of proximal contacts were not observed. IPS Empress II Ceramics were found to be appropriate as onlay/inlay restorations for clinical use under the conditions of the current study.

Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

Science.gov (United States)

Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

2017-04-01

The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

Levels and clinical significance of serum IGF-II in patients with five kinds of malignant tumors

International Nuclear Information System (INIS)

Qi Falian; Xu Jun; Du Xiumin; Ke Bingkun; Yang Daoli

2002-01-01

Objective: To study the levels and clinical significance of serum IGF-II in patients with malignant tumor. Methods: Levels of serum IGF-II were detected in patients with gastric cancer, lung cancer, liver cancer, ovarian carcinoma and endometrial carcinoma by radioimmunoassay, levels in patients with hepatic cirrhosis, uterine myoma and normal controls were also determined for comparison. Results: The levels of serum IGF-II in patients with gastric cancer, lung cancer and liver cancer were significantly higher than those in normal controls (p 0.05). Conclusion: The determination of serum IGF-II has no clinical significance in patients with endometrial carcinoma, ovarian carcinoma and uterine myoma but it could be useful to judge the severity and evaluate the prognosis in patients with gastric cancer, lung cancer, liver cancer and cirrhosis

Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

Energy Technology Data Exchange (ETDEWEB)

Nestor, Marika, E-mail: marika.nestor@bms.uu.s [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden); Sundstroem, Magnus [Unit of Molecular Pathology, Department of Genetics and Pathology, Uppsala University (Sweden); Anniko, Matti [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden)

2011-01-15

Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ({sup 211}At-cMAb U36). Effects on {sup 211}At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with {sup 211}At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced {sup 211}At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

International Nuclear Information System (INIS)

Nestor, Marika; Sundstroem, Magnus; Anniko, Matti; Tolmachev, Vladimir

2011-01-01

Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ( 211 At-cMAb U36). Effects on 211 At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with 211 At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211 At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

Radioimmunotherapy for liver micrometastases in mice. Pharmacokinetics, dose estimation, and long-term effect

International Nuclear Information System (INIS)

Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

1999-01-01

The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0% injected dose (ID)/g on day 1 to 17.8% ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. (author)

The Value of the SYNTAX Score II in Predicting Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.

Science.gov (United States)

Ryan, Nicola; Nombela-Franco, Luis; Jiménez-Quevedo, Pilar; Biagioni, Corina; Salinas, Pablo; Aldazábal, Andrés; Cerrato, Enrico; Gonzalo, Nieves; Del Trigo, María; Núñez-Gil, Iván; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

2017-11-27

The predictive value of the SYNTAX score (SS) for clinical outcomes after transcatheter aortic valve implantation (TAVI) is very limited and could potentially be improved by the combination of anatomic and clinical variables, the SS-II. We aimed to evaluate the value of the SS-II in predicting outcomes in patients undergoing TAVI. A total of 402 patients with severe symptomatic aortic stenosis undergoing transfemoral TAVI were included. Preprocedural TAVI angiograms were reviewed and the SS-I and SS-II were calculated using the SS algorithms. Patients were stratified in 3 groups according to SS-II tertiles. The coprimary endpoints were all-cause death and major adverse cardiovascular events (MACE), a composite of all-cause death, cerebrovascular event, or myocardial infarction at 1 year. Increased SS-II was associated with higher 30-day mortality (P=.036) and major bleeding (P=.015). The 1-year risk of death and MACE was higher among patients in the 3rd SS-II tertile (HR, 2.60; P=.002 and HR, 2.66; P<.001) and was similar among patients in the 2nd tertile (HR, 1.27; P=.507 and HR, 1.05; P=.895) compared with patients in the 1st tertile. The highest SS-II tertile was an independent predictor of long-term mortality (P=.046) and MACE (P=.001). The SS-II seems more suited to predict clinical outcomes in patients undergoing TAVI than the SS-I. Increased SS-II was associated with poorer clinical outcomes at 1 and 4 years post-TAVI, independently of the presence of coronary artery disease. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Divergences between clinical and research methods for assessing personality disorders: implications for research and the evolution of axis II.

Science.gov (United States)

Westen, D

1997-07-01

The purpose of this study was to examine the extent to which instruments for assessing axis II diverge from clinical diagnostic processes. Subjects in the first study were 52 clinicians with experience in assessment and treatment of patients with personality disorders, who were surveyed about the methods they use in clinical practice to make diagnoses and other aspects of the diagnostic process. A second study replicated the major findings with a random national sample of 1,901 experienced psychiatrists and psychologists. Whereas current instruments rely primarily on direct questions derived from DSM-IV, clinicians of every theoretical persuasion found direct questions useful for assessing axis I disorders but only marginally so for axis II. They made axis II diagnoses, instead, by listening to patients describe interpersonal interactions and observing their behavior with the interviewer. In contrast to findings with current research instruments, most patients with personality disorders in clinical practice receive only one axis II diagnosis, and if they receive more than one, one is considered primary. Clinicians reported treating a substantial number of patients for enduring personality patterns that current axis II instruments do not assess, many of which meet neither axis I nor axis II criteria, notably problems with relatedness, work, self-esteem, and chronic subclinical depressive traits. Measurements of axis II were constructed by using a model derived from axis I instruments that diverges from clinical diagnostic procedures in a way that may be problematic for the assessment of personality disorders and the development of a more clinically and empirically sound taxonomy.

Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder: A naturalistic study.

Science.gov (United States)

Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas; Christensen, Ellen Margrethe; Kessing, Lars Vedel

2017-01-15

In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional level, the presence of comorbid personality disorders and coping strategies. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using the Functional Assessment Short Test. Cognitive complaints were assessed using the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, the presence of comorbid personality disorders using the Standardized Assessment of Personality - Abbreviated Scale and coping style using the Coping Inventory for Stressful Situations. In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders. Finally, they exhibited a trend towards using less adaptive coping styles. It cannot be omitted that some patients may have progressed from BD II to BD I. Most measures were based on patient self report. Overall, BD II was associated with a higher disease burden. Clinically, it is important to differentiate BD II from BD I and research wise, there is a need for tailoring and testing specific interventions towards BD II. Copyright © 2016 Elsevier B.V. All rights reserved.

MAJEWSKI OSTEODYSPLASTIC PRIMORDIAL DWARFISM TYPE II: CLINICAL FINDINGS AND DENTAL MANAGEMENT OF A CHILD PATIENT

OpenAIRE

Terlemez, Arslan; Altunsoy, Mustafa; Çelebi, Hakkı

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular prima...

Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients.

Science.gov (United States)

Bénichou, O D; Laredo, J D; de Vernejoul, M C

2000-01-01

Type II autosomal dominant osteopetrosis (ADO II, Albers-Schonberg disease) is a genetic condition characterized by generalized osteosclerosis predominating in some skeletal sites such as the spine and pelvis. ADO II is rare, and most available clinical descriptions are based on small numbers of patients. We report the clinical and radiological manifestations in 42 ADO II patients. To our knowledge, this is the largest series reported so far. Our inclusion criterion was presence on radiographs of the spine of vertebral endplate thickening, producing the classic sandwich vertebra appearance. We found various patterns of sandwich vertebra, of which we provide a description to assist physicians in diagnosing ADO II. The classic bone-within-bone appearance was present in most but not all skeletal sites. The radiological penetrance of the disease was high (90%) and increased after 20 years of age. As many as 81% of our patients experienced clinical manifestations. Fractures were common (78% of patients) and healed slowly. Hip osteoarthritis developed in 27% of patients and required arthroplasty in 9 of the 16 affected hips. Nonmandibular osteomyelitis occurred in 4 cases (11%). Twenty-four percent of patients had thoracic or lumbar scoliosis. Orthopedic surgery was performed in 52.8% of patients, of whom half had at least three surgical procedures for internal fracture fixation, arthroplasty, limb deformity correction, or treatment of surgical complications. There was a high rate of surgical complications including nonunion, infection, prosthesis loosening, and intraoperative fractures. Nearly two-thirds of patients (64%) had stomatologic manifestations, including mandibular osteomyelitis in 4 patients (11%). Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was present in 14 patients but was clearly attributable to ADO II in only 6 cases (16%). This large series sheds new light on several aspects of ADO II, most

Radiolabeling of trastuzumab with {sup 177}Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Rasaneh, Samira [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)], E-mail: hrajabi@modares.ac.ir; Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Salouti, Mojtaba [Department of Biology, School of Sciences, Islamic Azad University - Zanjan Branch, Zanjan (Iran, Islamic Republic of)

2009-05-15

Aim: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Material and Methods: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. Results: The radiochemical purity of the complex was 96{+-}0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93{+-}1.2% and 85{+-}3.5%, respectively. The immunoreactivity of the complex was 89{+-}1.4%. At a concentration of 1 nM, the complex killed 70{+-}3% of MCF7 cells. At 1.9 nM, 90{+-}5% of the cells were killed. Conclusions: The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.

Majewski osteodysplastic primordial dwarfism type II: clinical findings and dental management of a child patient.

Science.gov (United States)

Terlemez, Arslan; Altunsoy, Mustafa; Celebi, Hakki

2015-01-01

Majewski osteodysplastic primordial dwarfism type II (MOPD II) is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient's history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

MAJEWSKI OSTEODYSPLASTIC PRIMORDIAL DWARFISM TYPE II: CLINICAL FINDINGS AND DENTAL MANAGEMENT OF A CHILD PATIENT

Directory of Open Access Journals (Sweden)

Arslan Terlemez

2015-01-01

Full Text Available Majewski osteodysplastic primordial dwarfism type II (MOPD II is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient’s history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

International Nuclear Information System (INIS)

Casaco, A.

2009-01-01

tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human cancers has kept the subject controversial. For the first time, we described herein the 'in vivo' detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with 99mTc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. 'In vivo' immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy. In two phase II Clinical Trials including women with metastatic breast cancer (n=14) and patients with colon cancer (n=19) in all stages, the 14F7 monoclonal antibody (3 mg) labelled with 99mTc (30-40 mCi) was also able to detect distant metastasis over expressing the GM3(NeuGc) ganglioside. (author)

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

Science.gov (United States)

da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

2016-10-01

The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?

Science.gov (United States)

Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I

2002-04-01

Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.

Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

Science.gov (United States)

Day, Roger S

2010-02-01

In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

Reproducing a Prospective Clinical Study as a Computational Retrospective Study in MIMIC-II.

Science.gov (United States)

Kury, Fabrício S P; Huser, Vojtech; Cimino, James J

2015-01-01

In this paper we sought to reproduce, as a computational retrospective study in an EHR database (MIMIC-II), a recent large prospective clinical study: the 2013 publication, by the Japanese Association for Acute Medicine (JAAM), about disseminated intravascular coagulation, in the journal Critical Care (PMID: 23787004). We designed in SQL and Java a set of electronic phenotypes that reproduced the study's data sampling, and used R to perform the same statistical inference procedures. All produced source code is available online at https://github.com/fabkury/paamia2015. Our program identified 2,257 eligible patients in MIMIC-II, and the results remarkably agreed with the prospective study. A minority of the needed data elements was not found in MIMIC-II, and statistically significant inferences were possible in the majority of the cases.

A Prototype {sup 212}Pb Medical Dose Calibrator for Alpha Radioimmunotherapy

Energy Technology Data Exchange (ETDEWEB)

Mueller, W.F.; Patil, A.; Russ, W.R.; Newman, J. [CANBERRA Industries, Inc. (United States); Torgue, J. [AREVA Med (United States)

2015-07-01

AREVA Med, an AREVA group subsidiary, is developing innovative cancer-fighting therapies involving the use of {sup 212}Pb for alpha radioimmunotherapy. Canberra Industries, the nuclear measurement subsidiary of AREVA, has been working with AREVA Med to develop a prototype measurement system to assay syringes containing a {sup 212}Pb solution following production by an elution system. The relative fraction of emitted radiation from the source associated directly with the {sup 212}Pb remains dynamic for approximately 6 hours after the parent is chemically purified. A significant challenge for this measurement application is that the short half-life of the parent nuclide requires assay prior to reaching equilibrium with progeny nuclides. A gross counting detector was developed to minimize system costs and meet the large dynamic range of source activities. Prior to equilibrium, a gross counting system must include the period since the {sup 212}Pb was pure to calculate the count rate attributable to the parent rather than the progeny. The dynamic state is determined by solving the set of differential equations, or Bateman equations, describing the source decay behavior while also applying the component measurement efficiencies for each nuclide. The efficiencies were initially estimated using mathematical modeling (MCNP) but were then benchmarked with source measurements. The goal accuracy of the system was required to be within 5%. Independent measurements of the source using a high resolution spectroscopic detector have shown good agreement with the prototype system results. The prototype design was driven by cost, compactness and simplicity. The detector development costs were minimized by using existing electronics and firmware with a Geiger-Mueller tube derived from Canberra's EcoGamma environmental monitoring product. The acquisition electronics, communications and interface were controlled using Python with the EcoGamma software development kit on a Raspberry

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

International Nuclear Information System (INIS)

Syme, A M; McQuarrie, S A; Middleton, J W; Fallone, B G

2003-01-01

A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

Five-year safety and performance results from the Argus II Retinal Prosthesis System clinical trial

Science.gov (United States)

da Cruz, Lyndon; Dorn, Jessy D.; Humayun, Mark S.; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E.; Hafezi, Farhad; Safran, Avinoam B.; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V.; de Juan, Eugene; Duncan, Jacque L.; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C.; Ho, Allen C.; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V.; Arditi, Aries; Greenberg, Robert J.

2016-01-01

Purpose The Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) was developed to restore some vision to patients blind from retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception due to end-stage RP. Design The study is a prospective, multicenter, single-arm, clinical trial. Within-patient controls included the non-implanted fellow eye and patients' native residual vision compared to their vision when using the System. Subjects There were 30 subjects in 10 centers in the U.S. and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II System. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by three computer-based, objective tests. Secondary measures included functional vision performance on objectively-scored real-world tasks. Results Twenty-four out of 30 patients remained implanted with functioning Argus II Systems at 5 years post-implant. Only one additional serious adverse event was experienced since the 3-year time point. Patients performed significantly better with the System ON than OFF on all visual function tests and functional vision tasks. Conclusions The five-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. PMID:27453256

The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity

Directory of Open Access Journals (Sweden)

Toni Cristina

2008-11-01

Full Text Available Abstract Background Much of the literature on panic disorder (PD-bipolar disorder (BP cormorbidity concerns BP-I. This literature emphasizes the difficulties encountered in pharmacologic treatment and outcome when such comorbidity is present. The present report explores these issues with respect to BP-II. Methods The sample comprised 326 outpatients (aged 34.5 ± 11.5 years old; 222 females with Diagnostic and Statistical Manual of Mental Disorders 3rd edn, revised (DSM-III-R PD-agoraphobia; among them 52 subjects (16% were affected by lifetime comorbidity with BP-II. Patients were evaluated by means of the Structured Clinical Interview for DSM-IV (SCID, the Panic-Agoraphobia Interview, and the Longitudinal Interview Follow-up Examination (Life-Up and treated according to routine clinical practice at the University of Pisa, Italy, for a period of 3 years. Clinical and course features were compared between subjects with and without BP-II. All patients received the clinicians' choice of antidepressants and, in the case of the subsample with BP-II, mood stabilizers (for example, valproate, lithium were among the mainstays of treatment. Results In comparison to patients without bipolar comorbidity, those with BP-II showed a significantly greater frequency of social phobia, obsessive-compulsive disorder, alcohol-related disorders, and separation anxiety during childhood and adolescence. Regarding family history, a significantly greater frequency of PD and mood disorders was present among the BP-II. No significant differences were observed in the long-term course of PD or agoraphobic symptoms under pharmacological treatment or the likelihood of spontaneous pharmacological treatment interruptions. Conclusion Although the severity and outcome of panic-agoraphobic symptomatology appear to be similar in patients with and without lifetime bipolar comorbidity, the higher number of concomitant disorders in our PD patients with BP-II does indicate a greater

Cerebral near infrared spectroscopy oximetry in extremely preterm infants : Phase II randomised clinical trial

NARCIS (Netherlands)

Hyttel-Sorensen, Simon; Pellicer, Adelina; Alderliesten, Thomas; Austin, Topun; Van Bel, Frank; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Franz, Axel R.; Fumagalli, Monica; Gluud, Christian; Grevstad, Berit; Hagmann, Cornelia; Lemmers, Petra; Van Oeveren, Wim; Pichler, Gerhard; Plomgaard, Anne Mette; Riera, Joan; Sanchez, Laura; Winkel, Per; Wolf, Martin; Greisen, Gorm

2015-01-01

Objective: To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design: Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in

Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique.

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Savvidou, Christiana; Tsai, Tsu-Min

2015-06-01

The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.

Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

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Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

2016-04-01

Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

International Nuclear Information System (INIS)

Sato, Noriko; Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

2000-01-01

Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131 I-labeled anti-CEA monoclonal antibody (MAb) (24-38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72-115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P<0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P<0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. (author)

Clinical and Radiological Findings of Autosomal Dominant Osteopetrosis Type II: A Case Report

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Priyanka Kant

2013-01-01

Full Text Available Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton caused by the absence or malfunction of osteoclasts. Three distinct forms of the disease have been recognized, autosomal dominant osteopetrosis being the most common. Autosomal dominant osteopetrosis exhibits a heterogeneous trait with milder symptoms, often at later childhood or adulthood. The aim of this case report is to present the clinical and radiographic features of a 35-year-old female patient with autosomal dominant osteopetrosis type II who exhibited features of chronic generalised periodontitis, and the radiographs revealed generalised osteosclerosis and hallmark radiographic features of ADO type II, that is, “bone-within-bone appearance” and “Erlenmeyer-flask deformity.”

Trial Watch: Anticancer radioimmunotherapy.

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Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-09-01

Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

Preparation and biological evaluation of {sup 177}Lu conjugated PR81 for radioimmunotherapy of breast cancer

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Salouti, Mojtaba, E-mail: saloutim@yahoo.com [Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145 (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Biomolecule Laboratory, Radioisotope Department, Nuclear Science and Technology Research Institute, Tehran 14144-1339 (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of); Rasaee, Mohammad javad [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of)

2011-08-15

Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Materials and Methods: The radiochemical purity and in vitro stability of {sup 177}Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. Results: The radiochemical purity was 91.2{+-}3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1{+-}3.4% and 76.2{+-}3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4{+-}2.4%. The cell toxicity study showed that the complex inhibited 85.2{+-}3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. Conclusion: The results showed that one may consider {sup 177}Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.

Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

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Djidjik Réda

2012-08-01

Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

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Kwon Joong Yong

2016-05-01

Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

The experimental study on the radioimmunotherapy of the hepatoma in nude mice model with intratumoral injection of 131I-human anti-HBsAg Fab

International Nuclear Information System (INIS)

Luo Rongcheng; Wu Guichen; Han Huanxing; You Changxuan; Ding Xuemei; Li Aimin; Wang Chuanbin; Zhang Mingjiang

2001-01-01

Objective: To study the therapeutic efficacy of radioimmunotherapy of 131 I-human anti-HBsAg Fab via different routes of administration. Methods: The human hepatoma bearing nude mice we reinjected with 131 I-human anti-HBsAg Fab intra-tumor (IT) and intra-peritoneum (IP). Biodistribution was measured on the 5th day. The tumor growth inhibition rate was determined by measurement of tumor volume. Results: In the IT-treated mice, tumor uptake of 131 I-human anti-HBsAg Fab was four-fold greater than in the IP-treated mice, and normal organ uptake was half of that in the IP-treated mice. At the 3rd week after the infusion, the tumor growth inhibition rate in IT-treated mice was higher than that in the IP-treated mice. Conclusions: Intratumoral administration of 131 I-human anti-HBsAg Fab makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy

A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

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K Gita Malathi

2013-01-01

Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

Intraoperative boron neutron capture therapy for malignant gliomas. First clinical results of Tsukuba phase I/II trial using JAERI mixed thermal-epithermal beam

International Nuclear Information System (INIS)

Matsumura, A.; Yamamoto, T.; Shibata, Y.

2000-01-01

Since October 1999, a clinical trial of intraoperative boron neutron capture therapy (IOBNCT) is in progress at JRR-4 (Japan Research Reactor-4) in Japan Atomic Energy Research Institute (JAERI) using mixed thermal-epithermal beam (thermal neutron beam I: TNB-I). Compared to pure thermal beam (thermal neutron beam II: TNB-II), TNB-I has an improved neutron delivery into the deep region than TNB-II. The clinical protocol and the preliminary results will be discussed. (author)

Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

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Jahnavi Aluri

2018-02-01

Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

Preparation and characterization of a cysteine based DTPA derivative and its immunoconjugate for radioimmunotherapy

International Nuclear Information System (INIS)

Lee, S. Y.; Hong, Y. D.; Choi, S. J.

2007-01-01

Recently, radioimmunotherapy (RIT), which uses a monoclonal antibody in addition to a radionuclide to deliver radiation to the sites of a disease, has been extensively studied in this population. To label an antibody with radionuclides it is necessary to introduce a bifunctional chelating agent (BFCA) such a DTPA since it can not be directly labeled to a radionuclide. Therefore, developing a better BFCA for chelating biomolecule and radionuclide has been of major interest in developing radioimmunotherapeutic agents. Thereby, we describe the entantiospecific synthesis of a DTPA analogue which is derived from L-cysteine via bis N-alkylation. And the prepared DTPA derivative was conjugated with human Immunoglobulin G, and a characterization of the immunoconjugate was carried out. N, N-Bis[(tert-butoxycarbonyl)methyl]-2-ethanolamine, N, N-Bis[(tert-butoxycarbony)methyl]-2-bromoethyl-amine, 2-(4-N-Boc-aminophenyl) ethanol, 1-(4-N-Boc-aminophenyl)-2-bromoethane, S-((4-N-Boc-arninophenyl)-1-ethyl)-cysteine methylester, S-(N-Boc-aminophenyl)-Cys(tBu4-DTPA) methylester, -aminophenylethyl-Cys-DTPA, isothiocyanate-cysteine-DTPA, Immunoconjugation with IgG. The optimal molar DTPA derivative to IgG conjugation ratio was 1: 1. At higher amounts of DTPA derivative, amounts of unbounded DTPA derivative increased, and the immunoactivities of immunoconjugates reduced. Gel electrophoresis analysis of the immunoconjugates showed no degradation products or other impurities. This demonstrates the stability of the IgG in DTPA derivative. We established the preparation of an amino acid based DTPA by producing 4-Ethylaniline-DTPA-L-Cysteine. At the same molar this DTPA derivative to IgG, the immunoconjugate has stable molecular structure. In conclusion, 4-Ethylaniline-DTPA-L-Cysteine as a BFCA will show good properties for preparing a specific regional delivery system such as in radiopharmaceuticals, as a radiotracer, and NMR contrasting agents

Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review.

Science.gov (United States)

Bober, Michael B; Jackson, Andrew P

2017-04-01

This review will provide an overview of the microcephalic primordial dwarfism (MPD) class of disorders and provide the reader comprehensive clinical review with suggested care guidelines for patients with microcephalic osteodysplastic primordial dwarfism, type II (MOPDII). Over the last 15 years, significant strides have been made in the diagnosis, natural history, and management of MOPDII. MOPDII is the most common and well described form of MPD. The classic features of the MPD group are severe pre- and postnatal growth retardation, with marked microcephaly. In addition to these features, individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal dentition, and an increased risk for cerebrovascular disease and insulin resistance. Biallelic loss-of-function mutations in the pericentrin gene cause MOPDII, which is inherited in an autosomal recessive manner.

{sup 124}I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of {sup 131}I-L19-SIP radioimmunotherapy

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Tijink, Bernard M.; Perk, Lars R.; Budde, Marianne; Stigter-van Walsum, Marijke; Leemans, C.R. [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, Amsterdam (Netherlands); Visser, Gerard W.M.; Kloet, Reina W. [VU University Medical Center, Nuclear Medicine and PET Research, Amsterdam (Netherlands); Dinkelborg, Ludger M. [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany); Neri, Dario [Swiss Federal Institute of Technology, Institute of Pharmaceutical Sciences, Zurich (Switzerland); Dongen, Guus A.M.S. van [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, Amsterdam (Netherlands); VU University Medical Center, Nuclear Medicine and PET Research, Amsterdam (Netherlands)

2009-08-15

The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with {sup 131}I-L19-SIP was recently started. In the present study, after GMP production of {sup 124}I and efficient production of {sup 124}I-L19-SIP, we aimed to demonstrate the suitability of {sup 124}I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical {sup 131}I-L19-SIP RIT. {sup 124}I was produced in a GMP compliant way via {sup 124}Te(p,n){sup 124}I reaction and using a TERIMO trademark module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected {sup 124}I- and {sup 131}I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while {sup 124}I PET images were obtained from mice with tumours of <50 to {proportional_to}700 mm{sup 3}. {sup 124}I was produced highly pure with an average yield of 15.4 {+-} 0.5 MBq/{mu}Ah, while separation yield was {proportional_to}90% efficient with <0.5% loss of TeO{sub 2}. Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for {sup 124}I-L19-SIP: {proportional_to}80, 99.9 and >90%, respectively. Tumour uptake was 7.3{+-}2.1, 10.8{+-}1.5, 7.8{+-}1.4, 5.3{+-}0.6 and 3.1{+-}0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i. Fully concordant labelling and biodistribution results were obtained with {sup 124}I- and {sup 131}I-L19-SIP. Immuno-PET with {sup 124}I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm{sup 3} and no adverse uptake in other organs. {sup 124}I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with {sup 124}I-L19-SIP appeared qualified for sensitive

Clinical significance of determination of changes of serum IGF-II, CRP levels after treatment in pediatric patients with broncho-pneumonia

International Nuclear Information System (INIS)

Chen Chuanbin

2006-01-01

Objective: To investigate the changes of serum insulin-like growth factor-II (IGF-II), CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II levels were measured with RIA and serum CRP levels with immune method both before and after treatment in 33 pediatric patients with bronchopneumonia and 35 controls. Results: Before treatment the serum levels of IGF-II, CRP were significantly higher in the patients than those in controls (P 0.05). Conclusion: Determination of serum IGF-II, CRP levels is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

Country report: Italy (Chinol). Pre-clinical evaluation of a new biotin-DOTA conjugate labeled with 90Y for application in pretargeting clinical protocols

International Nuclear Information System (INIS)

Chinol, Marco

2010-01-01

In the attempt to improve the therapeutic efficacy of radiolabeled mAbs in cancer radioimmunotherapy, various studies have examined the concept of tumor pretargeting. The so called three-step pretargeting technique, employing the avidin–biotin system, was applied in phase I-II clinical trials showing low toxicity and therapeutic efficacy. The final step of the pretargeting protocols consists in the systemic injection of radiolabeled biotin. The worldwide recognized “successful association” is between 90 Y and the tetraazamacrocycle DOTA chelator chemically bound to biotin. Improvements in the structure of the biotin-DOTA conjugate have been reported by our group following a novel approach which simplified the synthetic pattern by reducing the amide group to a methylene group, thus transforming the amide into a secondary amine without affecting the length of the biotin side arm. Preliminary in-vitro experiments, previously published by our group, indicated the potential of the new conjugate. Based on our previous experience with avidin-based pre-targeting followed 90 Y-DOTA-biotin in the locoregional treatment of peritoneal carcinomatosis and malignant glioma suggested that similar radionuclide therapy might be worth investigating as a partial replacement of external beam radiotherapy in breast cancer. We have developed IART® the Intra-operative Avidination for Radionuclide Therapy that relies on the avidin-biotin binding system. In fact, the “avidination” of the anatomical area of the tumor with native avidin, directly injected by the surgeon into and around the tumor bed, provides a target for the radiolabeled biotin intravenously (iv) injected one day later. In order to optimize the overall strategy, further efforts were needed to optimize the use of the labeled new biotin conjugate and to elucidate its chemical and biological properties. In the first 18 months of this CRP, the pre-clinical evaluation of this new reduced biotinamidohexylamine

Modern trends in radioimmunotherapy of cancer. Pre targeting strategies for the treatment of ovarian cancer

International Nuclear Information System (INIS)

Mcquarrie, S.A.; Xiao, Z.; Mercer, J. R.; Suresh, M. R.

2001-01-01

A review of published data on some of the problems associated in treating cancer using radioimmunotherapy is presented. Potential improvements for this type of therapy using pretargeting strategies are discussed and preliminary results on a novel multistep regimen to treat human ovarian cancer are presented. A pretargeting strategy using ovarian cancer are presented. A pretargeting strategy using a biotinylated, anti-CA 125 monoclonal antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of CA 125-expressing ovarian cancer cells, was employed. Confocal laser scanning microscopy and fluorescent labels were used to establish the biodistribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using 125 I labeled MAbs. No significant internalization of the MAb used in the pretargeting step was observed by 4 hrs. The antibody was gradually internalized starting at 6 hrs, and most of the labelled MAb was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the antigen-MAb complex was not significant for up to 6-hours following administration of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. It has been demonstrated that by a three-step pretargeting approach, biotinylated liposomes can be specifically delivered to cells pretargeted with biotinylated MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep pretargeting methods. A successful multistep linkage was established with the biotinylated MAb B27.1, streptavidin and biotinylated liposomes to OVCAR-3 cells, but not to SK-OV-3 cells

The therapeutic threesome, Iodine 131, Lutetium-111 and Rhenium-188 Radionuclide Trifecta

International Nuclear Information System (INIS)

Turner, J.H.

2007-01-01

Full text: Affordable, available, cost-effective, safe, efficacious therapeutic radiopharmaceuticals are required for clinical application throughout the world. In-house preparation of non-proprietary therapeutic radiopharmaceuticals at tertiary referral hospitals in all countries following appropriate technology transfer and training at key research and development centres can potentially supply this need. Illustrative examples of novel therapeutic radiopharmaceuticals currently under development in physician sponsored phase II clinical trials and candidates for contemplation of translation to developing countries include: (1) I-131 Rituximab radioimmunotherapy of relapsed/refractory and first-line treatment of non- Hodgkin's lymphoma; (2) Lu-177 octreotate radiopeptide therapy of neuroendocrine malignancy with capecitabine tumour radiosensitization; (3) Re-188 lipiodol intrahepatic arterial therapy of hepatocellular carcinoma. In addition to presentation of preliminary clinical results, the logistics and techniques of preparation, quality control and administration of each of these therapeutic radiopharmaceuticals will be described and the calculation of individual patient dosimetry and issues of radiation safety will also be addressed. 1. Iodine-131 rituximab: I-131 rituximab may be prepared in a hospital department of nuclear medicine equipped with a shielded fume cupboard, using commercially available single-use sterile pyrogen-free labelling kits (Go Medical Industries Pty Ltd, Subiaco, Australia) (1). Individualized prospective dosimetry is performed on each patient by quantitative whole body gamma imaging, to determine the therapeutic administered activity, to provide a maximum safe whole body radiation absorbed dose of 0.75 Gy, which equates to less than 2 Gy to red marrow (2). More than 200 patients with relapsed/refractory non-Hodgkin's lymphoma have been treated at Fremantle Hospital without infection or haemorrhagic incident. Myelosuppression is self

Efficacy of therapeutic nuclear medicine

International Nuclear Information System (INIS)

Hoefnagel, C.A.

1998-01-01

The following topics are discussed: (i) 131 I therapy of thyrotoxicosis; (ii) 131 I therapy of differentiated thyroid carcinoma; (iii) 32 P therapy of myeloproliferative disease; (iv) 131 MIBG therapy of neural crest tumors; (v) radiolabelled peptides in neuroendocrine tumors; (vi) radioimmunotherapy; (vii) palliative bone therapy of painful skeletal metastases; (viii) radiosynoviorthesis; (ix) alternative approaches; (x) side effects and long-term effects

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8, TNF-α levels after treatment in children with bronchopneumonia

International Nuclear Information System (INIS)

Feng Yue

2011-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and TNF-α levels after treatment in children with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 and TNF-α levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and TNF-α levels were significantly higher in the patients than those in the controls (P 0.05). Conclusions: Serum IGF-II, IL-6, IL-8 and TNF-α could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important. (authors)

Country report: Italy (Chinol). Pre-clinical evaluation of a new biotin-DOTA conjugate labeled with {sup 90}Y for application in pretargeting clinical protocols

Energy Technology Data Exchange (ETDEWEB)

Chinol, Marco

2010-07-01

In the attempt to improve the therapeutic efficacy of radiolabeled mAbs in cancer radioimmunotherapy, various studies have examined the concept of tumor pretargeting. The so called three-step pretargeting technique, employing the avidin–biotin system, was applied in phase I-II clinical trials showing low toxicity and therapeutic efficacy. The final step of the pretargeting protocols consists in the systemic injection of radiolabeled biotin. The worldwide recognized “successful association” is between {sup 90}Y and the tetraazamacrocycle DOTA chelator chemically bound to biotin. Improvements in the structure of the biotin-DOTA conjugate have been reported by our group following a novel approach which simplified the synthetic pattern by reducing the amide group to a methylene group, thus transforming the amide into a secondary amine without affecting the length of the biotin side arm. Preliminary in-vitro experiments, previously published by our group, indicated the potential of the new conjugate. Based on our previous experience with avidin-based pre-targeting followed {sup 90}Y-DOTA-biotin in the locoregional treatment of peritoneal carcinomatosis and malignant glioma suggested that similar radionuclide therapy might be worth investigating as a partial replacement of external beam radiotherapy in breast cancer. We have developed IART® the Intra-operative Avidination for Radionuclide Therapy that relies on the avidin-biotin binding system. In fact, the “avidination” of the anatomical area of the tumor with native avidin, directly injected by the surgeon into and around the tumor bed, provides a target for the radiolabeled biotin intravenously (iv) injected one day later. In order to optimize the overall strategy, further efforts were needed to optimize the use of the labeled new biotin conjugate and to elucidate its chemical and biological properties. In the first 18 months of this CRP, the pre-clinical evaluation of this new reduced biotinamidohexylamine

Targeting angiogenesis for radioimmunotherapy with a {sup 177}Lu-labeled antibody

Energy Technology Data Exchange (ETDEWEB)

Ehlerding, Emily B.; Hernandez, Reinier [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lacognata, Saige; Jiang, Dawei [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Ferreira, Carolina A. [University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); Goel, Shreya [University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States); Jeffery, Justin J. [University of Wisconsin - Madison, Small Animal Imaging Facility, Madison, WI (United States); Theuer, Charles P. [TRACON Pharmaceuticals, Inc., San Diego, CA (United States); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States)

2018-01-15

Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with {sup 177}Lu (t{sub 1/2} 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: {sup 177}Lu only, TRC105 only, {sup 177}Lu-DTPA-IgG (a nonspecific antibody), {sup 177}Lu-DTPA-TRC105 low-dose, and {sup 177}Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of {sup 177}Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose {sup 177}Lu-DTPA-TRC105. Biodistribution studies indicated steady uptake of {sup 177}Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. {sup 177}Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a

Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II

NARCIS (Netherlands)

Versyck, B.; Geffen, G.J. van; Houwe, P. Van

2017-01-01

STUDY OBJECTIVE: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. DESIGN: A prospective randomized double blind placebo-controlled study. SETTING:

Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

Science.gov (United States)

Gong, Fen; Niu, Junzhi; Pei, Xing

2016-11-02

Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

Clinical significance of measurement of changes of serum IGF-II, NO levels after treatment in pediatric patients with bronchial pneumonia

International Nuclear Information System (INIS)

Zhao Huajiang

2005-01-01

Objective: To study the clinical significance of changes of serum IGF-II and NO levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II (with RIA) and NO (with Biochemical method) levels were measured in 38 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, in the patients the serum IGF-II, and NO levels were significantly higher than those in controls (P 0.05). Conclusion: Serum IGF-II and NO levels changes could reflect the disease status of the patients as well as the progress of diseases. (authors)

Clinical significance of determination of serum insulin-like growth factor II levels in patients with chronic obstructive pulmonary diseases (COPD)

International Nuclear Information System (INIS)

Wu Changming

2006-01-01

Objective: To explore the clinical significance of the changes of serum insulinlike growth factor II (IGF-II) levels in patients with chronic obstruive pulmonary diseases (COPD). Methods: The serum IGF-II levels was determined with radioimmunoassay in 60 patients with COPD and 30 controls. Results: The serum IGF-II levels in patients with COPD were significantly higher than those in controls (0.65 ± 0.22μg/L vs 0.51±0.18μg/L, P<0.01). There were no significant differences among the levels in patients of different stages (stages I, II, III). Levels of IGF-II were significantly higher in patients succumbed to the dis- ease than those in patients recoverd (P<0.05). Conclusion: Serum IGF-II levels were significantly increased in patients with COPD, especially in those succumbed. (authors)

Clinical and genetic investigation of families with type II Waardenburg syndrome.

Science.gov (United States)

Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

2016-03-01

The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research.

Using AGREE II to Evaluate the Quality of Traditional Medicine Clinical Practice Guidelines in China.

Science.gov (United States)

Deng, Wei; Li, Le; Wang, Zixia; Chang, Xiaonan; Li, Rui; Fang, Ziye; Wei, Dang; Yao, Liang; Wang, Xiaoqin; Wang, Qi; An, Guanghui

2016-03-15

To evaluate/assess the quality of the Clinical Practice Guidelines (CPGs) of traditional medicine in China. We systematically searched the literature databases WanFang Data, VIP, CNKI and CBM for studies published between 1978 and 2012 to identify and select CPGs of traditional medicine. We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to evaluate these guidelines. A total of 75 guidelines were included, of which 46 guidelines (62%) were on Traditional Chinese Medicine, 19 (25%) on Chinese Integrated Medicine, and 10 (13%) on Uyghur Medicine. Most traditional medicine CPGs published in domestic journals scored medicine. In each domain of AGREE II, traditional Medicine CPGs performed clearly better than international CPGs. The same trend was seen in guidelines of Modern Medicine. An increasing amount of CPGs are being published, but their quality is low. Referring to the key points of international guidelines development, supervision through AGREE II, cooperating with international groups and exploring the strategy of guideline development could improve the quality of CPGs on traditional medicine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical significance of determination of serum NSE and plasma ET, IGF-II, CNP levels in patients with acute brain injury

International Nuclear Information System (INIS)

Chen Bo

2010-01-01

Objective: To investigate the clinical significance of changes of plasma ET, IGF-II, CNP and serum NSE contents in patients with acute brain injury. Methods: Serum contents of neuron specific enolase (NSE) were measured with chemiluminescence immunoassay and plasma endothelin (ET), insulin-like growth factor-II (IGF-II) and C-type natriuretic peptide (CNP) were measured with radioimmunoassay in 30 patients with acute brain injury and 35 controls. Results: Serum contents of NSE and plasma IGF-II, CNP were not much different in patients with mild brain injury from those in controls (P >0.05), but plasma contents of ET were already significantly higher in patients with mild brain injury than those in controls(P < 0.01). The serum NSE and plasma ET levels in patients with moderate and severe brain injury were significantly higher than those in patients with mild brain injury and controls (P < 0.01). Decrease of plasma levels of IGF-II and CNP was not significant in patients with mild brain injury (vs controls). However, the plasma levels of IGF-II and CNP were significantly lower in patients with moderate and severe brain injury than those in patients with mild brain injury and controls (P <0.01). As a whole, the magnitude of changes of these parameters was proportional to the severity of the injury. Conclusion: Changes of serum NSE and plasma IGF-II, ET and CNP levels were closely related to the pathological process of brain injury. Determination of these parameters was of clinical importance for evaluation of the severity of injury and outcome prediction. (authors)

Application of ICHD-II Criteria in a Headache Clinic of China

Science.gov (United States)

Dong, Zhao; Di, Hai; Dai, Wei; Liang, Jingyao; Pan, Meiyan; Zhang, Mingjie; Zhou, Zhibin; Li, Zheng; Liu, Ruozhuo; Yu, Shengyuan

2012-01-01

Background China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II). Methods and Results Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, Pheadache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria. PMID:23239993

Clinical dosimetry in molecular radiotherapy: protocol optimization and clinical implementation

International Nuclear Information System (INIS)

Ferrer, Ludovic

2011-01-01

Molecular radiotherapy (mrt) consists in destructing tumour targets by radiolabelled vectors. This nuclear medicine specialty is being considered with increasing interest for example via the success achieved in the treatment of non-Hodgkin lymphomas by radioimmunotherapy. One of the keys of mrt optimization relies on the personalising of absorbed doses delivered to the patient: This is required to ascertain that irradiation is focused on tumour cells while keeping surrounding healthy tissue irradiation at an acceptable - non-toxic - level. Radiation dose evaluation in mrt requires in one hand, the spatial and temporal localization of injected radioactive sources by scintigraphic imaging, and on a second hand, the knowledge of the emitted radiation propagating media, given by CT imaging. Global accuracy relies on the accuracy of each of the steps that contribute to clinical dosimetry. There is no reference, standardized dosimetric protocol to date. Due to heterogeneous implementations, evaluation of the accuracy of the absorbed dose is a difficult task. In this thesis, we developed and evaluated different dosimetric approaches that allow us to find a relationship between the absorbed dose to the bone marrow and haematological toxicity. Besides, we built a scientific project, called DosiTest, which aims at evaluating the impact of the various step that contribute to the realization of a dosimetric study, by means of a virtual multicentric comparison based on Monte-Carlo modelling. (author) [fr

Ultrasensitive detection of pepsinogen I and pepsinogen II by a time-resolved fluoroimmunoassay and its preliminary clinical applications

Energy Technology Data Exchange (ETDEWEB)

Huang Biao [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China) and Southern Yangzi University, Wuxi, Jiangsu Province 214036 (China)]. E-mail: huangbiao78@hotmail.com; Xiao Hualong [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Zhang Xiangrui [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Zhu, Lan [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Liu Haiyan [Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province 214063 (China); Jin Jian [Southern Yangzi University, Wuxi, Jiangsu Province 214036 (China)

2006-06-30

.8 {+-} 7.4 for the PG I/PG II ratio. The normal ranges of Serum PG I levels for healthy volunteers were 58.2-266.6 {mu}g L{sup -1}, and those of serum PG II levels were less than 25.3 {mu}g L{sup -1}. The availability of a highly sensitive, reliable, and convenient PG-TRFIA method for quantifying PG will allow investigations into the possible diagnostic value of this analysis in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastric ulcer and gastritis. The sensitivity and reproducibility of the assay were satisfactory for clinical applications.

Short-interval test-retest interrater reliability of the Dutch version of the structured clinical interview for DSM-IV personality disorders (SCID-II)

NARCIS (Netherlands)

Weertman, A; ArntZ, A; Dreessen, L; van Velzen, C; Vertommen, S

2003-01-01

This study examined the short-interval test-retest reliability of the Structured Clinical Interview (SCID-II: First, Spitzer, Gibbon, & Williams, 1995) for DSM-IV personality disorders (PDs). The SCID-II was administered to 69 in- and outpatients on two occasions separated by 1 to 6 weeks. The

Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review.

Science.gov (United States)

Cabarrou, B; Mourey, L; Dalenc, F; Balardy, L; Kanoun, D; Roché, H; Boher, J M; Rougé-Bugat, M E; Filleron, Thomas

2017-08-01

As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

Borderline personality disorder subscale (Chinese version) of the structured clinical interview for DSM-IV axis II personality disorders: a validation study in Cantonese-speaking Hong Kong Chinese.

Science.gov (United States)

Wong, H M; Chow, L Y

2011-06-01

Borderline personality disorder is an important but under-recognised clinical entity, for which there are only a few available diagnostic instruments in the Chinese language. None has been tested for its psychometric properties in the Cantonese-speaking population in Hong Kong. The present study aimed to assess the validity of the Chinese version of the Borderline Personality Disorder subscale of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis II Personality Disorders (SCID-II) in Cantonese-speaking Hong Kong Chinese. A convenience sampling method was used. The subjects were seen by a multidisciplinary clinical team, who arrived at a best-estimate diagnosis and then by application of the SCID-II rater using the Chinese version of the Borderline Personality Disorder subscale. The study was carried out at the psychiatric clinic of the Prince of Wales Hospital in Hong Kong. A total of 87 patients of Chinese ethnicity aged 18 to 64 years who attended the clinic in April 2007 were recruited. The aforementioned patient parameters were used to examine the internal consistency, best-estimate clinical diagnosis-SCID diagnosis agreement, sensitivity, and specificity of the Chinese version of the subscale. The Borderline Personality Disorder subscale (Chinese version) of SCID-II had an internal consistency of 0.82 (Cronbach's alpha coefficient), best-estimate clinical diagnosis-SCID diagnosis agreement of 0.82 (kappa), sensitivity of 0.92, and specificity of 0.94. The Borderline Personality Disorder subscale (Chinese version) of the SCID-II rater had reasonable validity when applied to Cantonese-speaking Chinese subjects in Hong Kong.

Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

DEFF Research Database (Denmark)

Lindegren, Sture; Andrade, Luciana N S; Bäck, Tom

2015-01-01

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual...

Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy

International Nuclear Information System (INIS)

Roscher, Mareike

2013-01-01

Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

Clinical evaluation of Dyslipidemia among type II diabetic patients at Public hospital Penang, Malaysia

Directory of Open Access Journals (Sweden)

Zaki Nada F

2010-11-01

Full Text Available Abstract Background Global views emphasize the need for early; effective intervention against the atherogenic dyslipidemia associated with type 2 diabetes and metabolic syndrome to reduce the risk of premature cardiovascular diseases. Our aim was to determine the clinical practices and compliance among dyslipidemia with type II diabetes and hypertension in multiracial society. Method(s Study was carried out in out-patient department of General hospital Penang over a period of ten months (Jan - Oct 2008. Study reflects the retrospective data collection covering a period of three years from Jan 2005 - Dec 2007. Universal sampling technique was used to select all the patients' undergone treatment for diabetes type II and dyslipidemia. All the concerned approvals were obtained from Clinical research Committee (CRC. Data was analyzed by using SPSS 15®. Result(s A total of 501 diabetes type 2 patients with dyslipidemia were identified in this study. The demographic data showed that 55.9% (n = 280 were female patients and 44.1% (n = 221 were males. Patients on combination therapy of metformin with other antidiabetic agent were 79%, while 21% were on monotherapy. Lovastatin was received as monotherapy in 83% of study population, while only 17% were on combination with gemfibrozil. Means of FPG and lipid profile were reduced from the initial (2005 to the latest level (2007 significantly (p Conclusion Metformin and lovastatin use among patients of type 2 diabetes and dyslipidemia is significantly improved the clinical outcomes. No significant association of metformin or lovastatin is found against the hypertension. Metformin and calcium channel blocker combination therapy was found to be the best choice in the co-treatment of diabetes and hypertension.

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

Advances in hepatitis E - II: Epidemiology, clinical manifestations, treatment and prevention.

Science.gov (United States)

Goel, Amit; Aggarwal, Rakesh

2016-09-01

Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. This infection, with fecal-oral transmission, was previously thought to be limited to humans residing in developing countries with poor sanitation, spreading via contaminated drinking water. In recent years, our understanding of epidemiology and clinical spectrum of this infection have changed markedly. This article reviews the epidemiology, including routes of transmission, and clinical manifestations of HEV infection around the world. In addition, recent findings on transmission-associated HEV infection, extrahepatic manifestations of hepatitis E and chronic infection with HEV, and treatment and prevention of this infection are discussed. Expert commentary: HEV infection has two distinct epidemiologic forms and clinical patterns of disease: (i) acute epidemic or sporadic hepatitis caused by fecal-oral (usually water-borne) transmission of genotype 1 and 2 HEV from a human reservoir in areas with poor hygiene and frequent water contamination, and (ii) infrequent sporadic hepatitis E caused by zoonotic infection, possibly from an animal source through ingestion of undercooked animal meal, of genotype 3 or 4 virus. In disease-endemic areas, pregnant women are at a particular risk of serious disease and high mortality. In less-endemic areas, chronic infection with HEV among immunosuppressed persons is observed. HEV can also be transmitted through Transfusion of blood and blood products. Ribivirin treatment is effective in chronic hepatitis E. Two efficacious vaccines have been tried in humans; one of these has received marketing approval in its country of origin.

Distinguishing bipolar II depression from major depressive disorder with comorbid borderline personality disorder: demographic, clinical, and family history differences.

Science.gov (United States)

Zimmerman, Mark; Martinez, Jennifer H; Morgan, Theresa A; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy

2013-09-01

Because of the potential treatment implications, it is clinically important to distinguish between bipolar II depression and major depressive disorder with comorbid borderline personality disorder. The high frequency of diagnostic co-occurrence and resemblance of phenomenological features has led some authors to suggest that borderline personality disorder is part of the bipolar spectrum. Few studies have directly compared patients with bipolar disorder and borderline personality disorder. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we compared these 2 groups of patients on demographic, clinical, and family history variables. From December 1995 to May 2012, 3,600 psychiatric patients presenting to the outpatient practice at Rhode Island Hospital (Providence, Rhode Island) were evaluated with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders. The focus of the present study is the 206 patients with DSM-IV major depressive disorder and borderline personality disorder (MDD-BPD) and 62 patients with DSM-IV bipolar II depression without borderline personality disorder. The patients with MDD-BPD were significantly more often diagnosed with posttraumatic stress disorder (P depression had a significantly higher morbid risk for bipolar disorder in their first-degree relatives than the MDD-BPD patients (P depression and major depressive disorder with comorbid borderline personality disorder differed on a number of clinical and family history variables, thereby supporting the validity of this distinction. © Copyright 2013 Physicians Postgraduate Press, Inc.

SU-C-201-05: Imaging 212Pb-TCMC-Trastuzumab for Alpha Radioimmunotherapy for Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Shen, S; Meredith, R; Azure, M; Yoder, D [University of Alabama, Birmingham, AL (United States); Torgue, J; Banaga, E [AREVA Med LLC, Bethesda, MD (United States)

2015-06-15

Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: {sup 212}Pb decays to {sup 212}Bi via beta emission. {sup 212}Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. There are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was <10%. For photopeak images, substantial scatter around phantom source extended to > 5 cm outside; scatter correction improved image contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01.

Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

Science.gov (United States)

Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

2018-07-01

Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Continuity Between DSM-5 Section II and III Personality Disorders in a Dutch Clinical Sample.

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Orbons, Irene M J; Rossi, Gina; Verheul, Roel; Schoutrop, Mirjam J A; Derksen, Jan L L; Segal, Daniel L; van Alphen, Sebastiaan P J

2018-05-14

The goal of this study was to evaluate the continuity across the Section II personality disorders (PDs) and the proposed Section III model of PDs in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013a ). More specifically, we analyzed association between the DSM-5 Section III pathological trait facets and Section II PDs among 110 Dutch adults (M age = 35.8 years, range = 19-60 years) receiving mental health care. We administered the Structured Clinical Interview for DSM-IV Axis II Disorders to all participants. Participants also completed the self-report Personality Inventory for DSM-5 (PID-5) as a measure of pathological trait facets. The distributions underlying the dependent variable were modeled as criterion counts, using negative binomial regression. The results provided some support for the validity of the PID-5 and the DSM-5 Section III Alternative Model, although analyses did not show a perfect match. Both at the trait level and the domain level, analyses showed mixed evidence of significant relationships between the PID-5 trait facets and domains with the traditional DSM-IV PDs.

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

International Nuclear Information System (INIS)

Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

2004-01-01

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131 I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P 131 I-A7 RIT displayed a marked therapeutic effect (n=8) (P 131 I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P 131 I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

[Verrucous pastern dermatitis syndrome in heavy draught horses. Part II: Clinical findings].

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Geburek, F; Deegen, E; Hewicker-Trautwein, M; Ohnesorge, B

2005-07-01

In the present field study the skin of the feet of 37 heavy draught horses of different breeds showing verrucous pastern dermatitis was examined clinically. Included were the degree of severity of the disease and the prevalence of anatomically normal structures associated with the skin: fetlock tufts of hair ("feathering"), ergots, chestnuts, bulges in the pastern region, cannon circumference. Each horse was examined for Chorioptes sp. skin mites. Information was also collected on the development of the skin alterations and housing conditions and feeding. These individual data were correlated with the clinical degree of severity of verrucous pastern dermatitis, which was evaluated using a numerical code (scoring system). In addition, punch biopsies were taken from the diseased skin of the feet and from healthy skin of the neck for comparative patho-histological examination (see Part III). Verrucous pastern dermatitis is a chronic disease which can be divided into four groups: scaling (group I), hyperkeratotic and hyperplastic plaque-like lesions (group II), tuberous skin masses (group III), and verrucous skin lesions with rugged surfaces (group IV). No correlation was found between the clinical degree of severity of the skin lesions and sex, breed, amount of work, use of stallions for breeding, grooming condition of the hair, white markings in the foot region, or Chorioptes sp. infestation. In regard to feeding it was found that the amount of maize and oats fed had some influence on the clinical degree of severity. Statistical analysis revealed a significant correlation between the clinical degree of severity and the age, the grooming condition of the hooves, and the mean cannon circumference. The prevalence of fetlock tufts of hair, chestnuts, ergots, and anatomically normal bulges in the pastern region also increased significantly with the clinical degree of severity. Furthermore the study revealed that the clinical degree of severity depended on the hygienic

Clinical significance of measurement of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis

International Nuclear Information System (INIS)

Gu Tao

2006-01-01

Objective: To study the clinical significance of changes of serum IGF-II and NO levels after treatment in elderly patients with chronic bronchitis. Methods: Serum IGF-II (with RIA) and NO (with Biochemical method) levels were measured in 42 elderly patients with chronic bronchitis both before and after treatment as well as in 30 controls. Results: Before treatment in the patients the serum IGF-II levels were significantly higher than those in controls (P<0.01), while the NO levels were significantly lower (P<0.01). After two weeks of treatment, the levels though dropped markedly, lemained higher than those in controls (P<0. 05). Conclusion: Serum IGF-II and NO levels changes could reflect the disease status as well as the progress of diseases. (authors)

Clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia

International Nuclear Information System (INIS)

Zhou Hong; Hu Yan; Wei Guoyu; Huang Jufeng

2011-01-01

Objective: To investigate the clinical significance of changes of serum IGF-II, IL-2 and SOD levels after treatment in pediatric patients with bronchial pneumonia. Methods: Serum IGF-II, IL-2 and SOD (with RIA) levels were measured in 33 pediatric patients with bronchial pneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II levels in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IGF-II, IL-2 and SOD levels both before and after treatment could reflect the diseases status of the patients as well as the progress of diseases, and might be of prognostic importance in pediatric patients with bronchial pneumonia. (authors)

Predictive value of SAPS II and APACHE II scoring systems for patient outcome in a medical intensive care unit

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Amina Godinjak

2016-11-01

Full Text Available Objective. The aim is to determine SAPS II and APACHE II scores in medical intensive care unit (MICU patients, to compare them for prediction of patient outcome, and to compare with actual hospital mortality rates for different subgroups of patients. Methods. One hundred and seventy-four patients were included in this analysis over a oneyear period in the MICU, Clinical Center, University of Sarajevo. The following patient data were obtained: demographics, admission diagnosis, SAPS II, APACHE II scores and final outcome. Results. Out of 174 patients, 70 patients (40.2% died. Mean SAPS II and APACHE II scores in all patients were 48.4±17.0 and 21.6±10.3 respectively, and they were significantly different between survivors and non-survivors. SAPS II >50.5 and APACHE II >27.5 can predict the risk of mortality in these patients. There was no statistically significant difference in the clinical values of SAPS II vs APACHE II (p=0.501. A statistically significant positive correlation was established between the values of SAPS II and APACHE II (r=0.708; p=0.001. Patients with an admission diagnosis of sepsis/septic shock had the highest values of both SAPS II and APACHE II scores, and also the highest hospital mortality rate of 55.1%. Conclusion. Both APACHE II and SAPS II had an excellent ability to discriminate between survivors and non-survivors. There was no significant difference in the clinical values of SAPS II and APACHE II. A positive correlation was established between them. Sepsis/septic shock patients had the highest predicted and observed hospital mortality rate.

Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

Energy Technology Data Exchange (ETDEWEB)

Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2011-02-15

Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

[Clinical Practice Guidelines for Management of Schizophrenia: Evaluation Using AGREE II].

Science.gov (United States)

de la Hoz Bradford, Ana María; Ávila, Mauricio J; Bohórquez Peñaranda, Adriana Patricia; García Valencia, Jenny; Arenas Borrero, Álvaro Enrique; Vélez Traslaviña, Ángela; Jaramillo González, Luis Eduardo; Gómez-Restrepo, Carlos

2014-01-01

Colombia is developing multiple national practice guidelines from a range of diseases. Clinical practice guidelines represent a very useful tool to be able to take decision over a patient care that is widely available for the clinician. In psychiatry there are a good number of international clinical guidelines for the treatment of schizophrenia nevertheless there is no article that evaluate them scientifically In the settings of developing a Colombian schizophrenia practice guideline, a systematic search was performed in multiple databases and the results were then evaluated by two trained persons. We present the results globally and by domains. We found 164 matches for possible guidelines. After screening 7 guidelines were evaluated with the AGREE II instrument. Globally and by the different domains, the National Institute for Health and Care Excellence (NICE) was the guideline that got the best score. From the guidelines that were reviewed, 4 were from Europe and only 2 were from Latin America. None of the guidelines used GRADE methodology for the recommendations. The diversity of the schizophrenia treatment guidelines does not allow an easy adoption of the recommendation by a psychiatrist in Colombia. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

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Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling

2015-02-21

Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity Y-86- or Lu-177-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

Science.gov (United States)

Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Lee, Sang-gyu; Punzalan, Blesida; Chalasani, Sandhya; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; Carrasquillo, Jorge A.; O’Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K. Dane; Cheung, Nai-Kong V.; Larson, Steven M.

2015-01-01

Purpose GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pre-targeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn (radiolanthanide metal) complex. Methods PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent (CA), and the C825-haptens 177Lu-or 86Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Results Using optimized PRIT, therapeutic indices (TIs) for tumor radiation absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI: 73), 6.3 (TI: 10), 6.6 (TI: 10), and 5.3 (TI: 12), respectively. Two cycles of PRIT treatment (66.6 or 111 MBq 177Lu-DOTA-Bn) were safe and effective, with 9/9 complete responses of established s.c. tumors (100–700 mm3) and 2/9 alive without recurrence >140 d. Tumor log kill in this model was estimated to be 2.1–3.0 based time to 500-mm3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA-hapten 86Y-DOTA-Bn. Conclusions We have developed anti-GPA33 PRIT, as a triple-step theranostic strategy for pre-clinical detection, dosimetry and safe targeted radiotherapy of established human colorectal mouse xenografts. PMID:26596724

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

International Nuclear Information System (INIS)

Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane; Dorrer, Holger; Zhernosekov, Konstantin; Koester, Ulli; Tuerler, Andreas; Schibli, Roger

2014-01-01

The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67 Cu- and 177 Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177 Lu and the potential alternative 161 Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched 160 Gd targets. 161 Tb and 177 Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of 177 Lu- and 161 Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. 177 Lu- and 161 Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161 Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the 177 Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the 161 Tb-DOTA-chCE7 than the 177 Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM 161 Tb RIT is more effective compared to 177 Lu RIT in ovarian cancer xenografts. These results suggest that 161 Tb is a promising candidate for future clinical

Serum insulin-like growth factor II (IGF-II) in chronic heart failure

International Nuclear Information System (INIS)

Tong Lijun; Chen Donghai; Ji Naijun; Fan Bifu; Wang Chengyao; Mei Yibin; Li Fuyuan; Kao Yan

2004-01-01

Objective: To investigate the clinical significance of changes of serum insulin-like growth factor II (IGF-II) levels in patients with chronic heart failure. Methods: Serum IGF-II levels were measured with RIA in 132 cases of chronic heart failure and 45 controls. Results: Serum IGF-II levels were significantly higher in patients with chronic heart failure than those in the controls (t=0.033, P<0.001). IGF-II levels were highest in grade IV CHF patients (vs grade II t=3.963, P<0.01; vs grade III, t=3.578, P<0.01). In the twelve patients died in hospital, the serum IGF-II levels were significantly higher than those patients recovered (t=7.141, P<0.01). Conclusion: Serum IGF-II levels were increased in CHF patients and were highest in the most severe cases. (authors)

Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA Gold 4 epitope and designed for radioimmunotherapy (RIT of colorectal cancers

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Pugnière Martine

2004-10-01

Full Text Available Abstract Background Human monoclonal antibodies (MAbs are needed for colon cancer radioimmunotherapy (RIT to allow for repeated injections. Carcinoembryonic antigen (CEA being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. Methods XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. Results Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g, close to that of 131I-X4 (21.7 ± 7.2%ID/g. At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g. At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of

Closure of the patent ductus arteriosus with the Amplatzer Duct Occluder II: a clinical experience.

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Karagöz, Tevfik; Akin, Alper; Ertuğrul, Ilker; Aykan, Hayrettin Hakan; Alehan, Dursun; Ozer, Sema; Ozkutlu, Süheyla

2012-12-01

The aim of our study was to share our clinical experience on cases with patent ductus arteriosus treated with the Amplatzer Duct Occluder II. Between 2008 and 2012, 26 of 31 patients with patent ductus arteriosus underwent successful transcatheter closure of patent ductus arteriosus using the Amplatzer Duct Occluder II. Mean age was 3.3 years and mean weight was 15.7 kilograms. The presence of a residual shunt, left pulmonary artery or aortic obstruction was explored by administering contrast material during the procedure. The patients were discharged 24 hours after the procedure. The procedure was successful in 26 of 31 patients and failed in five patients. According to the Krichenko classification, 26 patients had type A, one patient had type B and 4 patients had type C ductus. The mean narrowest ductus diameter was 3.2 mm and the mean ductus length was 6.7 mm. Complete angiographic occlusion occurred immediately after the procedure in 22 out of 26 patients in whom the ductus was closed successfully with the Amplatzer Duct Occluder II. Complete occlusion was achieved in the remaining patients with residual shunt one month after the procedure. The procedure was preceded by closure with an Amplatzer Duct Occluder I in two patients and an Amplatzer Vascular Plug I in one patient. Amplatzer Duct Occluder II is highly effective in transcatheter closure of patent ductus arteriosus. We think that an alternative closure device and alternative techniques can be attempted in patients with type C ductus. The success rate could increase with accumulating experience.

Application of ICHD-II criteria in a headache clinic of China.

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Zhao Dong

Full Text Available China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II.Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9-80 years and the female/male ratio of 1.67/1. The primary headaches (78.4% were classified as the following: migraine (39.1%, tension-type headache (32.5%, trigeminal autonomic cephalalgias (5.3% and other primary headache (1.5%. Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843 were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%, chronic tension-type headache (CTTH, 32.7% and chronic migraine (CM, 13.5%. The visual analogue scale (VAS score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001. The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004. The peak age at onset of TTH for male and female were both in the 3(rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2(nd decade for females and the 1(st decade for males.This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is

Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

Energy Technology Data Exchange (ETDEWEB)

Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

2014-08-15

Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

DEFF Research Database (Denmark)

Horwich, A.; Specht, L.; Ashley, S.

1997-01-01

relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

Clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF-α levels after treatment in children with acute nephritis

International Nuclear Information System (INIS)

Xu Xiaoyan; Zhou Hong; Xu Weiqin; Li Xinghua

2008-01-01

Objective: To explore the clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF- α levels after treatment in children with acute nephritis. Methods: Serum IGF-II, GM-CSF and TNF-α levels (with RIA) were measured in 31 pediatric patients with acute nephritis and 35 controls. Results: Before treatment, the serum IGF-II, GM-CSF and TNF-α levels in the patients were significantly higher than those in controls (P< O.01). After treatment for 3 months, the serum IGF-II, GM-CSF and TNF-α levels, though markedly corrected, remained significantly higher than those in controls (P<0.05). Conclusion: Determination of changes of serum IGF-II, GM-CSF and TNF-α contents after treatment might be of prognostic importance in pediatric patients with acute nephritis. (authors)

Clinical significance of measurement of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer

International Nuclear Information System (INIS)

Chen Jianlin

2010-01-01

Objective: To study the clinical significance of changes of serum IGF-II, EGF and CYFRA21-1 levels after chemotherapy in patients with lung cancer. Methods: Serum IGF-II, EGF (with RIA), and CYFRA21-1 (with ECLIA) levels were determined both before and after chemotherapy in 39 patients with lung cancer as well as once in 35 controls. Results: Before chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels were significantly higher in the patients than those in controls(P<0.01). Six months after chemotherapy, serum IGF-II, EGF and CYFRA21-1 levels dropped markedly, but remained significantly higher than those in controls(P<0.05). Conclusion: The development of lung cancer in patients was closely related to the serum IGF-II, EGF and CYFRA21-1 levels. (authors)

Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

Directory of Open Access Journals (Sweden)

Johnnie J Orozco

Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

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.)

Open-access MIMIC-II database for intensive care research.

Science.gov (United States)

Lee, Joon; Scott, Daniel J; Villarroel, Mauricio; Clifford, Gari D; Saeed, Mohammed; Mark, Roger G

2011-01-01

The critical state of intensive care unit (ICU) patients demands close monitoring, and as a result a large volume of multi-parameter data is collected continuously. This represents a unique opportunity for researchers interested in clinical data mining. We sought to foster a more transparent and efficient intensive care research community by building a publicly available ICU database, namely Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II). The data harnessed in MIMIC-II were collected from the ICUs of Beth Israel Deaconess Medical Center from 2001 to 2008 and represent 26,870 adult hospital admissions (version 2.6). MIMIC-II consists of two major components: clinical data and physiological waveforms. The clinical data, which include patient demographics, intravenous medication drip rates, and laboratory test results, were organized into a relational database. The physiological waveforms, including 125 Hz signals recorded at bedside and corresponding vital signs, were stored in an open-source format. MIMIC-II data were also deidentified in order to remove protected health information. Any interested researcher can gain access to MIMIC-II free of charge after signing a data use agreement and completing human subjects training. MIMIC-II can support a wide variety of research studies, ranging from the development of clinical decision support algorithms to retrospective clinical studies. We anticipate that MIMIC-II will be an invaluable resource for intensive care research by stimulating fair comparisons among different studies.

Clinical results of Hi-tech Knee II total knee arthroplasty in patients with rheumatoid athritis: 5- to 12-year follow-up

Directory of Open Access Journals (Sweden)

Yamanaka Hajime

2012-02-01

Full Text Available Abstract Background Total knee arthroplasty (TKA is a common form of treatment to relieve pain and improve function in cases of rheumatoid arthritis (RA. Good clinical outcomes have been reported with a variety of TKA prostheses. The cementless Hi-Tech Knee II cruciate-retaining (CR-type prosthesis, which has 6 fins at the anterior of the femoral component, posterior cruciate ligament (PCL retention, flat-on-flat surface component geometry, all-polyethylene patella, strong initial fixation by the center screw of the tibial base plate, 10 layers of titanium alloy fiber mesh, and direct compression molded ultra high molecular weight polyethylene (UHMWPE, is appropriate for TKA in the Japanese knee. The present study was performed to evaluate the clinical results of primary TKA in RA using the cementless Hi-Tech Knee II CR-type prosthesis. Materials and methods We performed 32 consecutive primary TKAs using cementless Hi-Tech Knee II CR-type prosthesis in 31 RA patients. The average follow-up period was 8 years 3 months. Clinical evaluations were performed according to the American Knee Society (KS system, knee score, function score, radiographic evaluation, and complications. Results The mean postoperative maximum flexion angle was 115.6°, and the KS knee score and function score improved to 88 and 70 after surgery, respectively. Complications, such as infection, occurred in 1 patient and revision surgery was performed. There were no cases of loosening in this cohort, and prosthesis survival rate was 96.9% at 12 years postoperatively. Conclusion These results suggest that TKA using the cementless Hi-Tech Knee II CR-type prosthesis is a very effective form of treatment in RA patients at 5 to 12 years postoperatively. Further long-term follow-up studies are required to determine the ultimate utility of this type of prosthesis.

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

Science.gov (United States)

Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

2015-01-01

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

[The external patello-tibial transfixation (EPTT). Part II: Clinical application and results].

Science.gov (United States)

Ishaque, B; Gotzen, L; Ziring, E; Petermann, J

1999-07-01

In part I of the paper the biomechanical and technical background of the EPTT using the MPT fixator and the indications for this procedure have been described. In part II we report about the clinical application of the EPTT in 67 patients with a wide spectrum of repairs and reconstructions of the extensor mechanism. 48 patients had fresh injuries, 18 of them with severe concomitant knee lesions and 19 patients had neglected rsp. unsuccessfully operated injuries. There were 4 deep infections, two of them related to the MPT fixator. In the patients with uneventful healing the fixator remained in place for 7.3 weeks in average. The clinical, isokinetic and radiological results were reviewed in 17 patients with an average follow-up time of 37.3 months. There were 5 patients with partial patellectomy and tendon reattachment because of lower patella pole comminution and 12 patients with tendon reattachment ruptured at the inferior patella pole or suture repair in midsubstance rupture. The clinical results according to the IKDC score were rated in 3 patients as normal, in 10 patients as nearly normal and in 4 patients as abnormal. This rating was highly dependend on the subjective judgement by the patients who considered their operated knees not as normal as the contralateral knees. From our clinical experiences and results we can derive that the EPTT enables the surgical management of extensor mechanism disruptions with a minimum of internal fixation material and provides a safe protection of the repairs and reconstructions during the healing period. The EPTT allows immediate unrestricted functional rehabilitation and early walking without crutches. Thus the EPTT represents an effective alternative to the patello-tibial cerclage with a wire or synthetic ligaments.

Mixed-state bipolar I and II depression: time to remission and clinical characteristics.

Science.gov (United States)

Shim, In Hee; Woo, Young Sup; Jun, Tae-Youn; Bahk, Won-Myong

2014-01-01

We compared the time to achieve remission and the clinical characteristics of patients with bipolar depressive mixed state and those with bipolar depressive non-mixed state. The subjects (N=131) were inpatients diagnosed between 2006 and 2012 with bipolar I or II disorder, depression and were classified into the following three groups: "pure depressive state" (PD, n=70), "sub-threshold mixed state" (SMX, n=38), and "depressive mixed state" (DMX, n=23). Diagnosis of a DMX was in accordance with Benazzi's definition: three or more manic symptoms in a depressive episode. The subjects' charts were retrospectively reviewed to ascertain the time to achieve remission from the index episode and to identify other factors, such as demographic and clinical characteristics, specific manic symptoms, and pharmacological treatment, that may have contributed to remission. The time to achieve remission was significantly longer in the DMX (p=0.022) and SMX (p=0.035) groups than in the PD group. Adjustment for covariates using a Cox proportional hazards model did not change these results. Clinically, subjects with a DMX were more likely to have manic symptoms in the index episode, especially inflated self-esteem and psychomotor agitation than those in the PD. We investigated only inpatients and therefore could not comment on outpatients. These findings showed that sub-syndromal manic symptoms in bipolar depression had different clinical characteristics and a more severe illness course, including a longer time to achieve remission, than did a pure depressive state. © 2013 Elsevier B.V. All rights reserved.

Comparative clinical evaluation of removable partial dentures made of two different materials in Kennedy Applegate class II partially edentulous situation.

Science.gov (United States)

Hundal, Maninder; Madan, Rajesh

2015-12-01

Cast Chromium Cobalt alloy has been the material of choice for fabricating Removable Partial Dentures (RPDs) but has certain drawbacks. Newer materials like the flexible Nylon based Super Polyamide have been introduced to overcome these drawbacks. The present study has compared the above two materials for nine clinical parameters. The study was carried out on 30 patients presenting with a Kennedy Applegate class II partially edentulous situation who were divided into two equal groups and clinically assessed. Statistically significant results were obtained in favor of flexible RPDs, in the parameters of 'aesthetics' and 'overall patient satisfaction'. Both groups showed more or less similar values for 'frequency of fracture of the prosthesis during usage' with the incidence being slightly higher for patients wearing the cast RPDs. The clinical parameters of 'oral soft tissue tolerance', 'gingival health', 'periodontal health' and 'adaptability in areas with undercut' were statistically at par for all the 30 patients thus suggesting the comparable biocompatibility of the two materials. The highlight of this study was the relative ease in fabrication of the flexible RPDs as compared to the cast RPDs. Based on the favorable clinical results of this study, it can be summarized that the flexible RPDs is a viable alternative to cast RPDs in Kennedy Applegate class II partially edentulous situation in the short term.

Trichorhinophalangeal syndrome II, expanding the clinical spectrum

African Journals Online (AJOL)

Rabah M. Shawky

2014-06-17

Jun 17, 2014 ... an autosomal dominant fashion, most cases of TRPS II are sporadic [1]. TRPS III, is a form of brachydactyly due to short metacarpals and severe .... and broad on both sides (black asterisk), the fifth metacarpal bone has similar yet less pronounced appearance (white asterisk). Langer–Giedion syndrome. 91 ...

Three-year randomized controlled clinical study of a one step universal adhesive and a two-step self-etch adhesive in Class II resin composite restorations

DEFF Research Database (Denmark)

van Dijken, Jan WV; Pallesen, Ulla

2017-01-01

Purpose: To evaluate in a randomized clinical evaluation the 3-year clinical durability of a one-step universal adhesive bonding system and compare it intraindividually with a 2-step self-etch adhesive in Class II restorations. Materials and Methods: Each of 57 participants (mean age 58.3 yr......) received at least two, as similar as possible, extended Class II restorations. The cavities in each of the 60 individual pairs of cavities were randomly distributed to the 1-step universal adhesive (All Bond Universal: AU) and the control 2-step self-etch adhesive (Optibond XTR: OX). A low shrinkage resin......) success rates (p>0.05). Annual failure rates were 1.8% and 2.6%, respectively.The main reason for failure was resin composite fracture. Conclusion: Class II resin composite restorations placed with a one-step universal adhesive showed good short time effectiveness....

Is 'subthreshold' bipolar II disorder more difficult to differentiate from borderline personality disorder than formal bipolar II disorder?

Science.gov (United States)

Bayes, Adam; Graham, Rebecca K; Parker, Gordon B; McCraw, Stacey

2018-06-01

Recent research indicates that borderline personality disorder (BPD) can be diagnostically differentiated from the bipolar disorders. However, no studies have attempted to differentiate participants with sub-threshold bipolar disorder or SubT BP (where hypomanic episodes last less than 4 days) from those with a BPD. In this study, participants were assigned a SubT BP, bipolar II disorder (BP II) or BPD diagnosis based on clinical assessment and DSM-IV criteria. Participants completed self-report measures and undertook a clinical interview which collected socio-demographic information, a mood history, family history, developmental history, treatment information, and assessed cognitive, emotional and behavioural functioning. Both bipolar groups, whether SubT BP or BP II, differed to the BPD group on a number of key variables (i.e. developmental trauma, depression correlates, borderline personality scores, self-harm and suicide attempts), and compared to each other, returned similar scores on nearly all key variables. Borderline risk scores resulted in comparable classification rates of 0.74 (for BPD vs BP II) and 0.82 (for BPD vs sub-threshold BP II). Study findings indicate that both SubT BP and BP II disorder can be differentiated from BPD on a set of refined clinical variables with comparable accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

Radiosensitizing efficacy of iso-metronidazole after intravesical application in bladder cancer. A clinical phase II study

International Nuclear Information System (INIS)

Kob, D.; Lilienthal, A.; Bauhardt, H.; Merkle, K.; Schroeder, E.; Schroeder, E.; Hentschel, M.

1991-01-01

The radiosensitizing efficacy of iso-Metronidazole, a 4-Nitroimidazole derivative, was evaluated in a prospective clinical phase II study. The results of combined radiotherapy of 25 patients with bladder cancer were compared with those of a control group of 25 patients treated with radiotherapy only. Tumor regression six months after radiotherapy was used as an endpoint. The surgical procedure was performed as double TUR. Evaluating the local tumor control after additional application of iso-Metronidazole a gain factor of 1.2 is obtained. (orig.) [de

Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

Science.gov (United States)

Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

2018-05-01

Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

Science.gov (United States)

Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

2017-07-11

To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Radioimmunotherapy of indolent non-Hodgkin's lymphoma with Yttrium-90 labeled anti-CD20 monoclonal antibody therapy does not preclude subsequent chemotherapy or autologous hematologic stem cell transplantation therapy in most patients

International Nuclear Information System (INIS)

Wiseman, G.A.; Witzig, T.E.; Ansell, S.M.; Ristow, K.M.

2002-01-01

Introduction: Yttrium-90 (Y-90) labeled anti-CD20 monoclonal antibody (ibritumomab tiuxetan or Zevalin TM ) is a novel therapy for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (NHL). Patients treated with Zevalin radioimmunotherapy (RIT) are limited from higher doses due to transient and reversible platelet and neutrophil suppression. Patients with indolent NHL who relapse or are refractory to chemotherapy have a 70-80% overall response rate and a 20-30% complete response rate when treated with Zevalin RIT. Therefore additional treatment is required in a minority of patients shortly after Zevalin therapy and in many others at relapse. Relapsed patients are generally treated with chemotherapy alone or high dose chemotherapy followed by autologous transplantation. We wanted to evaluate the ability of patients to tolerate subsequent therapy given at relapse following Zevalin RIT. Methods: We had 58 patients who relapsed after receiving Zevalin RIT and later received additional therapy. The clinical records and lab results were reviewed and compared with a matched control group of patients treated prior to Zevalin availability who received chemotherapy without prior Zevalin RIT. Results: The toxicity in 58 patients treated with Zevalin RIT and subsequent therapy was not significantly different from the control group who did not receive Zevalin RIT. Patients had a median of two subsequent therapies (range, 1-7) after Zevalin. Twenty eight percent required blood cell growth factor support with subsequent chemotherapy and 2 patients required reductions from the standard chemotherapy doses due to prolonged myelosuppression. Eight patients subsequently had successful autologous hematologic stem cell transplant with cells collected after Zevalin. Thirteen of the 58 patients (28%) treated with standard dose chemotherapy were hospitalized for neutropenic fever or thrombocytopenia. Conclusions: Chemotherapy or high dose chemotherapy with autologous transplantation

Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

Directory of Open Access Journals (Sweden)

Ardeshir Lafzi

2013-03-01

Full Text Available Background and aims. Plasma rich in growth factors (PRGF is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods. In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD, vertical clinical attachment level (V-CAL, horizontal clinical attachment level (H-CAL, location of gingival margin (LGM, surgically exposed horizontal probing depth of bony defect (E-HPD, vertical depth of bone crest (V-DBC, vertical depth of the base of bony defect (V-DBD, and length of the intrabony defect (LID. After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results. After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion. Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed.

Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

Science.gov (United States)

Lafzi, Ardeshir; Shirmohammadi, Adileh; Faramarzi, Masoumeh; Jabali, Sahar; Shayan, Arman

2013-01-01

Background and aims Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD), vertical clinical attachment level (V-CAL), horizontal clinical attachment level (H-CAL), location of gingival margin (LGM), surgically exposed horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest (V-DBC), vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect (LID). After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed. PMID:23486928

Clinical significance of estimation of changes in serum IGF-II, TNF-α and TSGF levels after chemotherapy in patients with acute leukemia

International Nuclear Information System (INIS)

Liu Huijie

2011-01-01

Objective: To explore the clinical significance of changes in serum IGF-II, TNF-α and TSGF levels after chemotherapy in patients with acute leukemia. Methods: Serum IGF-II, TNF-α (with RIA) and TSGF (with biochemistry) levels were determined in 33 patients with acute leukemia both before and after chemotherapy as well as in 35 normal healthy Controls. Results: Before chemotherapy, serum IGF-II, TNF-α and TSGF levels in the patients were significantly higher than those in controls (P<0.01), 6 months after chemotherapy the levels in 28 patients without recurrence dropped markedly and approached those in controls. However, in the 5 eases with recurrence, the levels after return again, approaching those before chemotherapy. Conclusion: Changes of serum levels on IGF-II, TNF-α and TSGF might be useful as indicative parameters for diagnosis and curative effect in patients with acute leukemia. (authors)

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

Energy Technology Data Exchange (ETDEWEB)

England, Christopher G. [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); Rui, Lixin [University of Wisconsin School of Medicine and Public Health, Department of Medicine, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); Cai, Weibo [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

2017-03-15

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

International Nuclear Information System (INIS)

England, Christopher G.; Rui, Lixin; Cai, Weibo

2017-01-01

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

Energy Technology Data Exchange (ETDEWEB)

Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

2014-10-15

The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

Phase II drugs under clinical investigation for the treatment of chronic constipation.

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Mozaffari, Shilan; Didari, Tina; Nikfar, Shekoufeh; Abdollahi, Mohammad

2014-11-01

Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability. The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract. At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.

[Evaluation of serum PIVKA-II by Lumipulse PrestoII assay].

Science.gov (United States)

Hiramatsu, Kumiko; Tanaka, Yasuhito; Takagi, Kazumi; Kani, Satomi; Goto, Takaaki; Takasaka, Yoshimitsu; Matsuura, Kentaro; Sugauchi, Fuminaka; Moriyama, Kazushige; Murakami, Hiroshi; Kitajima, Sachiko; Mizokami, Masashi

2009-03-01

Measurements of serum concentrations of Des-gamma-carboxy Prothrombin (PIVKA-II) are widely used for diagnosing hepatocellular carcinoma (HCC). Recently, in Lumipulsef assay, it was reported that antibodies against alkaline phosphatase (ALP) derived from anti bleeding sheets led false high values of PIVKA-II in the patients with HCC resection. To improve the previous issue, newly developed Lumipulse PrestoII assay was examined. (1) The assay was reliable and positively correlated with the previous assays (Lumipulse f and Picolumi, R = 0.997 and 0.994 (n=115), respectively). (2) Eleven cases, which had false high values of PIVKA-II by the Lumipulsef assay, were examined by the PrestoII assay with excess of inactive ALP. The false high values of 10 cases were improved, but only one was still high. False reactivity of this case was stronger than other cases, more effective adsorption was required. (3) Comparing the absorbent activity of inactive ALP among 6 different kinds, we found inactive ALP with much higher adsorbent activity. When this inactive ALP was applied to assay, false high values of PIVKA-II were improved in all 11 cases. In conclusion, the PrestoII assay, which applies the inactive ALP with high activity, is reliable and useful for clinical screening.

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

International Nuclear Information System (INIS)

Wang Guanghui; Chen Chuanbing; Wang Xianwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Wiseman, G.A.; Dunn, W.L.; White, C.A.; Berlfein, J.R.; Ding, E.; Grillo-Lopez, A.J.; Stabin, M.; Erwin, W.; Spies, S.; Dahlbom, M.; Silverman, D.H.S.; Raubitschek, A.; Karvelis, K.; Schultheiss, T.; Witzig, T.E.; Belanger, R.

2000-01-01

Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90 Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90 Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received 111 In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of 90 Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of 111 In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T 1/2 , blood AUC

Antisocial Personality Disorder Subscale (Chinese Version) of the Structured Clinical Interview for the DSM-IV Axis II disorders: validation study in Cantonese-speaking Hong Kong Chinese.

Science.gov (United States)

Tang, D Y Y; Liu, A C Y; Leung, M H T; Siu, B W M

2013-06-01

OBJECTIVE. Antisocial personality disorder (ASPD) is a risk factor for violence and is associated with poor treatment response when it is a co-morbid condition with substance abuse. It is an under-recognised clinical entity in the local Hong Kong setting, for which there are only a few available Chinese-language diagnostic instruments. None has been tested for its psychometric properties in the Cantonese-speaking population in Hong Kong. This study therefore aimed to assess the reliability and validity of the Chinese version of the ASPD subscale of the Structured Clinical Interview for the DSM-IV Axis II Disorders (SCID-II) in Hong Kong Chinese. METHODS. This assessment tool was modified according to dialectal differences between Mainland China and Hong Kong. Inpatients in Castle Peak Hospital, Hong Kong, who were designated for priority follow-up based on their assessed propensity for violence and who fulfilled the inclusion criteria for the study, were recruited. To assess the level of agreement, best-estimate diagnosis made by a multidisciplinary team was compared with diagnostic status determined by the SCID-II ASPD subscale. The internal consistency, sensitivity, and specificity of the subscale were also calculated. RESULTS. The internal consistency of the subscale was acceptable at 0.79, whereas the test-retest reliability and inter-rater reliability showed an excellent and good agreement of 0.90 and 0.86, respectively. Best-estimate clinical diagnosis-SCID diagnosis agreement was acceptable at 0.76. The sensitivity, specificity, positive and negative predictive values were 0.91, 0.86, 0.83, and 0.93, respectively. CONCLUSION. The Chinese version of the SCID-II ASPD subscale is reliable and valid for diagnosing ASPD in a Cantonese-speaking clinical population.

Comparison between radioimmunotherapy and external beam radiation therapy for patients with hepatocellular carcinoma

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Zeng, Zhao-Chong [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 (China); Tang, Zhao-You; Yang, Bing-Hui; Liu, Kang-Da; Wu, Zhi-Quan; Fan, Jia; Qin, Lun-Xiu; Sun, Hui-Chuan; Zhou, Jian [Liver Cancer Institute, Fudan University, Shanghai (China); Jiang, Guo-Liang [Department of Radiation Oncology, Cancer Hospital. Fudan University, Shanghai (China)

2002-12-01

It has previously been observed in animal studies that, at equivalent doses, radioimmunotherapy (RIT) is 2.5 times more effective than multiple fractions of external beam radiation therapy (EBRT) in inhibiting tumour growth. In this study, we compared the use of RIT and EBRT in patients with hepatocellular carcinoma (HCC), treated during the past 10 years. Of 67 patients without extrahepatic involvement, 32 were treated with hepatic artery ligation combined with RIT (the RIT group) while 35 were treated with a combination of hepatic arterial chemo-embolisation and EBRT (the EBRT group). The patients in the RIT group received {sup 131}I-Hepama-1 monoclonal antibody, which was infused through the hepatic artery catheter. The patients in the EBRT group received transcatheter arterial chemo-embolisation and limited-field EBRT using a linear accelerator. Parameters observed include tumour response, alpha-fetoprotein (AFP) level in serum, human anti-murine antibody (HAMA) assay, T lymphocyte subsets, survival rates, routine parameters, sequential resection rates and histopathological status of the resection specimens. The sequential resection rates were 53% (17/32) and 23% (8/35), and tumour response rates were 72% (23/32) and 86% (30/35) in the RIT and EBRT groups, respectively. The main side-effects in the RIT group were mild allergic reactions. The most common toxicity in the EBRT group was an increase in liver enzymes. The liver tissue in the target volume was injured by EBRT. The injured liver tissue revealed a low-attenuation area adjacent to the hepatic tumour within the target volume on follow-up computed tomography studies after EBRT. On pathological evaluation, the low-attenuation area revealed hyperaemia, distended hepatic sinusoids packed with erythrocytes and hepatic cell loss. The sequential resection specimens from both the RIT and the EBRT group showed residual cancer tissue located at the edge of the mass. The residual cancer cells presented as giant

Evaluation of the quality of the reporting of phase II clinical trials in oncology: A systematic review.

Science.gov (United States)

Rivoirard, Romain; Langrand-Escure, Julien; Oriol, Mathieu; Tinquaut, Fabien; Chauvin, Franck; Rancoule, Chloé; Magné, Nicolas; Bourmaud, Aurélie

2018-05-01

To describe the current state of knowledge concerning the quality of reporting in phase II clinical trials in oncology and to describe the various methods published allowing this quality evaluation. databases including MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the quality of the reporting of phase II trials in oncology were included. Descriptive analysis of the results was performed. Thirteen publications were retained. Only 2 publications adopted a systematic approach of evaluation of the quality of reporting by overall scores. The Key Methodological Score (KMS), proposed by Grellety et al., gathering 3 items, seemed adapted for such an evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analysed by this score. The other reviews used a qualitative analysis to evaluate the reporting, via an analysis of a single criterion, generally the statistical plan of the study. This item was considered as having been correctly reported in less than 50% of the analysed articles. The quality of reporting in phase II trials in oncology is a field that has been investigated very little (13 publications). When it is studied, the estimated level of quality is not satisfactory, whatever the method employed. The use of an overall score of evaluation is a path which should be pursued, in order to get reliable results. It also seems necessary to propose strong recommendations, which would create a consensus for the methodology and the reporting of these studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Physical activity in type II Diabetes Mellitus, an effective therapeutic element: review of the clinical impact

Directory of Open Access Journals (Sweden)

Pedro Iván Arias-Vázquez

2015-07-01

Full Text Available A review was conducted in databases (PubMed, PEDro of type studies clinical trial, cohort study, systematic reviews, meta-analysis and clinical practice guidelines based on evidence they have studied the benefits of physical activity in the prevention , treatment and decreased risk of complications and death in patients with Type II Diabetes Mellitus. Realization regular physical activity is associated with a decreased risk of developing Diabetes Mellitus; likewise was associated with decrease in glycated hemoglobin percentage A1C values. Diabetic patients undergoing high levels of physical activity had decreased risk of complications and death from cardiovascular disease and all causes. At present the scientific evidence on the impact of physical activity in the prevention and treatment of Diabetes Mellitus is solid, so it must be emphasized promoting physical activity as a fundamental part of the therapeutic regimens for this disease.

Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

International Nuclear Information System (INIS)

Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

2006-01-01

Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells

International Nuclear Information System (INIS)

Li, Xiao-Feng; Kinuya, Seigo; Yokoyama, Kunihiko; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

2002-01-01

The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, 131 I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on 131 I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or 131 I-A7 RIT significantly suppressed metastasis growth (P 131 I-A7 RIT. Combination of AT and 131 I-A7 RIT more effectively suppressed the growth to 0.28±0.32 g (P 131 I-HPMS-1 RIT, which suppressed metastasis growth to 2.25±0.88 g, was significant in comparison with the control (P 131 I-HPMS-1 RIT (which suppressed growth to 1.41±0.68 g) was far less effective than the combination of AT and 131 I-A7 RIT. AT did not decrease 131 I-A7 accumulation in metastases. AT did not affect RIT myelotoxicity. The results of this study demonstrating the combined effects of AT and 131 I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease. (orig.)

Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a Phase II clinical protocol

International Nuclear Information System (INIS)

Noyes, William R.; Bastin, Kenneth; Edwards, Scott A.; Buchler, Dolores A.; Stitt, Judith A.; Thomadsen, Bruce R.; Fowler, Jack F.; Kinsella, Timothy J.

1995-01-01

Purpose: In September 1989, a postoperative Phase II high dose rate (HDR) brachytherapy protocol was started for International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial adenocarcinoma. This review reports the overall survival, local control, and complication rates for the initial 63 patients treated in this Phase II study. Methods and Materials: High dose rate brachytherapy was delivered using an Iridium-192 HDR remote afterloader. Sixty-three patients were entered into the Phase II protocol, each receiving two vaginal cuff treatments 1 week apart (range 4-12 days) with vaginal ovoids (diameter 2.0-3.0 cm). No patient received adjuvant external beam radiation. A dose of 32.4 Gy in two fractions was prescribed to the ovoid surface in 63 patients. The first three patients treated at our institution received 15, 16.2, and 29 Gy, respectively, to determine acute effects. Results: At a median follow-up of 1.6 years (range 0.75-4.3 years) no patient has developed a vaginal cuff recurrence. One regional recurrence (1.6%) occurred at 1.2 years at the pelvic side wall. This patient is alive and without evidence of disease 7 months after completion of salvage irradiation, which resulted in the only vaginal stenosis (1.6%). Fourteen patients (22%) experienced vaginal apex fibrosis by physical exam, which was clinically symptomatic in four patients. Two patients reported stress incontinence; however, these symptoms were noted prior to their HDR therapy. One patient died 2.4 years after HDR therapy due to cardiovascular disease without evidence of cancer at autopsy. Conclusion: Preliminary results of our phase II HDR vaginal cuff protocol for postoperative FIGO Stage IA, Grade 3 or Stage IB, Grade 1-2 patients demonstrate that 32.4 Gy in two fractions is well tolerated by the vaginal cuff mucosa. Local control appears comparable to our prior experience and others with low dose rate (LDR) brachytherapy. Additional patient accrual and further follow

Long term results of mantle irradiation(MRT) alone in 261 patients with clinical stage I-II supradiaphragmatic Hodgkin's disease

International Nuclear Information System (INIS)

Wirth, A.; Byram, D.; Chao, M.; Corry, J.; Davis, S.; Kiffer, J.; Laidlaw, C.; Quong, G.; Ryan, G.; Liew, K.

1997-01-01

Purpose: We report our results using MRT for clinical stage I-II HD and assess the value of published prognostic criteria in our study population. Pts and Methods: Between 1969 and 1994, 261 pts were treated with MRT alone for clinical stage I-II supradiaphragmatic HD. Pt characteristics: median age-30; M-54%/F-46%; stage IA-52%, IB-2%, IIA-37%, IIB-8%; histology LP-21%, NS-51%, MC-23%, other 5%; median ESR 18. CT abdomen and LAG were performed in 61% and 60% respectively. No pt had prior staging laparotomy. No pt received infradiaphragmatic RT. Central axis dose was 32 Gy-36 Gy. Univariate analysis was performed for prognostic factors for progression-free (PFS) and overall survival(OS). Outcome was assessed in favourable subsets as defined by: EORTC (v. favourable: CSIA, LP or NS histology, age < 40, female, no bulk, ESR < 50; favourable: CSI-II, age < 50, < 4 sites, no bulky mediastinal mass, ESR < 50 with no B symptoms or ESR < 30 with B symptoms); Princess Margaret Hospital (PMH) (IA-IIA, LP or NS histology, ESR < 40, age < 50, no large mediastinal mass, no E lesion). Results: 261 pts completed RT, with 5% requiring treatment interruption for toxicity. Significant factors (P<0.05) for PFS were stage, performance status, histology, B symptoms, number of sites, ESR and bulk. Significant factors (P<0.05) for OS were age, performance status, histology and B symptoms. (The results of a multivariate analysis will be presented.) Results in our study population using published prognostic criteria (in %): Thirty-six percent progressed following RT: 8% in-field; 24% out of field only (including 10% in the paraaortic/splenic region alone); 4% marginal; Fifty-seven percent of relapsed pts remain progression free after subsequent salvage treatment. Two cases of acute leukaemia, 8 cases of non-Hodgkin's lymphoma and 14 (non-skin) carcinomas occurred, of which 11 were in-field. Seventy pts have died. The cause was: HD 41%; other malignancy 20%; cardiovascular 17%; other 15

Clinical nuclear medicine applications in Turkey and specific renal studies

International Nuclear Information System (INIS)

Erbas, B.

2004-01-01

Full text: Nuclear cardiology, nuclear oncology, pediatric nuclear medicine and nuclear endocrinology are the main application areas of clinical nuclear medicine in Turkey. Not only imaging studies, but also therapeutic application of radiopharmaceuticals is also performed at many institutes, such as hyperthyroidism treatment with radioiodine, thyroid cancer ablation and metastases treatment with radioiodine, radio synovectomy, metastatic pain therapy, and recently radioimmunotherapy of lymphomas. Almost all radionuclides and radiopharmaceuticals are obtained commercially from European countries, except 18-FDG which is obtained from two cyclotrons in Turkey. More than 30.000 renal procedures are performed at the University hospitals in a year. Pediatric age groups is approximately % 55 of patients. 99mTc-DTPA (%44), 99mTc-DMSA (%37), 99mTc-MAG3 (%17) and 99mTc-EC (%2) are the most commonly used radiopharmaceuticals for renal imaging. More than 6.000 vials of several pharmaceuticals are used for renal cortical scintigraphy (%35), dynamic renal imaging (%34), renal scintigraphy with diuretic (%27) and captopril scintigraphy (%4). Most common indication for renal cortical scintigraphy is detection of cortical scarring (%53). In addition, using single plasma sample method or gamma-camera method renal clearance measurements with 99mTc-MAG3 99mTc-DTPA have been used at some institutions

Clinical nuclear medicine applications in Turkey and specific renal studies

International Nuclear Information System (INIS)

Erbas, B.

2004-01-01

Nuclear cardiology, nuclear oncology, pediatric nuclear medicine and nuclear endocrinology are the main application areas of clinical nuclear medicine in Turkey. Not only imaging studies, but also therapeutic application of radiopharmaceuticals is also performed at many institutes, such as hyperthyroidism treatment with radioiodine, thyroid cancer ablation and metastases treatment with radioiodine, radio synovectomy, metastatic pain therapy, and recently radioimmunotherapy of lymphomas. Almost all radionuclides and radiopharmaceuticals are obtained commercially from European countries, except 18-FDG which is obtained from two cyclotrons in Turkey. More than 30.000 renal procedures are performed at the University hospitals in a year. Pediatric age groups is approximately % 55 of patients. 99m Tc-DTPA (%44), 99m Tc-DMSA (%37), 99m Tc-MAG3 (%17) and 99m Tc-EC (%2) are the most commonly used radiopharmaceuticals for renal imaging. More than 6.000 vials of several pharmaceuticals are used for renal cortical scintigraphy (%35), dynamic renal imaging (%34), renal scintigraphy with diuretic (%27) and captopril scintigraphy (%4). Most common indication for renal cortical scintigraphy is detection of cortical scarring (%53). In addition, using single plasma sample method or gamma-camera method renal clearance measurements with 99m Tc-MAG3 99m Tc-DTPA have been used at some institutions. (author)

An Immature Type II Dens Invaginatus in a Mandibular Lateral Incisor with Talon’s Cusp: A Clinical Dilemma to Confront

Directory of Open Access Journals (Sweden)

Anshul Gangwar

2014-01-01

Full Text Available Dens invaginatus (DI is a malformation of teeth probably resulting from an infolding of the dental papilla during tooth development. DI is classified as type I, II, and III by Oehlers depending on the severity of malformation. The maxillary lateral incisor is the most commonly affected tooth. Structural defects do exist in the depth of the invagination pits, and as a consequence, the early development of caries and the subsequent necrosis of the dental pulp, as well as abscess and cyst formation are clinical implications associated with DI. Occasionally, we can see more than one developmental anomaly occurring in a single tooth. In such cases it becomes important to identify the anomalies and initiate a proper treatment plan for good prognosis. In this paper, an unusual case of DI which clinically presented as a huge talons cusp affecting a mandibular lateral incisor tooth is described. This case report illustrates grinding of the talons cusp followed by nonsurgical endodontic management of dens invaginatus type II with an immature apex and periapical lesions, in which Mineral Trioxide Aggregate (MTA shows a complete periapical healing with bone formation at the site of the lesions.

MHC class II deficiency: Report of a novel mutation and special review.

Science.gov (United States)

Farrokhi, S; Shabani, M; Aryan, Z; Zoghi, S; Krolo, A; Boztug, K; Rezaei, N

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Clinical utility of the DSM-5 alternative model for borderline personality disorder: Differential diagnostic accuracy of the BFI, SCID-II-PQ, and PID-5.

Science.gov (United States)

Fowler, J Christopher; Madan, Alok; Allen, Jon G; Patriquin, Michelle; Sharp, Carla; Oldham, John M; Frueh, B Christopher

2018-01-01

With the publication of DSM 5 alternative model for personality disorders it is critical to assess the components of the model against evidence-based models such as the five factor model and the DSM-IV-TR categorical model. This study explored the relative clinical utility of these models in screening for borderline personality disorder (BPD). Receiver operator characteristics and diagnostic efficiency statistics were calculated for three personality measures to ascertain the relative diagnostic efficiency of each measure. A total of 1653 adult inpatients at a specialist psychiatric hospital completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews, SCID-II Questionnaire (SCID-II-PQ) and the Big Five Inventory (BFI), while Sample 2 (n=1,000) completed the SCID-II interviews, Personality Inventory for DSM5 (PID-5) and the BFI. BFI measure evidenced moderate accuracy for two composites: High Neuroticism+ low agreeableness composite (AUC=0.72, SE=0.01, ptrait constellation for diagnosing BPD. Limitations of the study include the single inpatient setting and use of two discrete samples to assess PID-5 and SCID-II-PQ. Copyright © 2017 Elsevier Inc. All rights reserved.

Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised clinical trial.

Science.gov (United States)

Schrøder, Cecilie Piene; Skare, Øystein; Reikerås, Olav; Mowinckel, Petter; Brox, Jens Ivar

2017-12-01

Labral repair and biceps tenodesis are routine operations for superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their efficacy is lacking. We evaluated the effect of labral repair, biceps tenodesis and sham surgery on SLAP lesions. A double-blind, sham-controlled trial was conducted with 118 surgical candidates (mean age 40 years), with patient history, clinical symptoms and MRI arthrography indicating an isolated type II SLAP lesion. Patients were randomly assigned to either labral repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100. Secondary outcomes were Oxford Instability Shoulder Score, change in main symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications. There were no significant between-group differences at any follow-up in any outcome. Between-group differences in Rowe scores at 2 years were: biceps tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no differences between groups-were found for WOSI scores. Postoperative stiffness occurred in five patients after labral repair and in four patients after tenodesis. Neither labral repair nor biceps tenodesis had any significant clinical benefit over sham surgery for patients with SLAP II lesions in the population studied. ClinicalTrials.gov identifier: NCT00586742. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

Science.gov (United States)

Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

2014-09-01

To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

Science.gov (United States)

Wiehle, Ronald D; Fontenot, Gregory K; Wike, Jenny; Hsu, Kuang; Nydell, Jennifer; Lipshultz, Larry

2014-09-01

To determine the effect of enclomiphene citrate in men with secondary hypogonadism. Phase II clinical trial. Community dwelling men making visits to physician offices. Men with secondary hypogonadism. Oral administration of enclomiphene citrate or 1% topical T gel. Luteinizing hormone, FSH, T, and semen analysis. Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. NCT01270841 (ClinicalTrials.gov Identifier NCT01270841). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Diagnostic Efficiency among Psychiatric Outpatients of a Self-Report Version of a Subset of Screen Items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II)

Science.gov (United States)

Germans, Sara; Van Heck, Guus L.; Masthoff, Erik D.; Trompenaars, Fons J. W. M.; Hodiamont, Paul P. G.

2010-01-01

This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective analyses of 495 SCID-II interviews. The…

Inflammation's Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder.

Directory of Open Access Journals (Sweden)

Sheng-Yu Lee

Full Text Available Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117 diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0% patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7 and triglyceride (P = 0.005 levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (P = 8.2E-6, cholesterol (P = 0.004, and triglyceride (P = 0.006 levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003 levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006 and TNF-α (P = 0.039 levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology

Four-year clinical evaluation of Class II nano-hybrid resin composite restorations bonded with a one-step self-etch and a two-step etch-and-rinse adhesive

DEFF Research Database (Denmark)

van Dijken, Jan W V; Pallesen, Ulla

2011-01-01

The objective of this prospective clinical trial was to evaluate the 4-year clinical performance of an ormocer-based nano-hybrid resin composite (Ceram X; Dentsply/DeTrey) in Class II restorations placed with a one-step self-etch (Xeno III; Dentsply/DeTrey) and two-step etch-and-rinse adhesive (I...

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

Science.gov (United States)

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

[New intensifying screens in clinical radiology. II. Examinations in clinical practice].

Science.gov (United States)

Freyschmidt, J; Saure, D; Hagemann, G

1976-09-01

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.

Clinical Trials

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Full Text Available ... Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of your treatment ... phase II clinical trials. The risk of side effects might be even greater for ... treatments. Health insurance and health care providers don't always ...

Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

Science.gov (United States)

JENABIAN, Niloofar; HAGHANIFAR, Sina; MABOUDI, Avideh; BIJANI, Ali

2013-01-01

Objective Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. Material and Methods In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were recorded before the first and re-entry surgery (six months later): vertical clinical attachment level (VCAL), gingival index (GI), plaque index (PI), horizontal probing depth (HPD), vertical probing depth (VPD), gingival recession (GR), furcation vertical component (FVC), furcation to alveolar crest (FAC), fornix to base of defect (FBD), and furcation horizontal component (FHC) were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant. Results Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups. Conclusion The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone material

Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

Directory of Open Access Journals (Sweden)

Niloofar Jenabian

2013-09-01

Full Text Available OBJECTIVE: Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. MATERIAL AND METHODS: In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group or Biocollagen and Bio-Gen (control group. The following parameters were recorded before the first and re-entry surgery (six months later: vertical clinical attachment level (VCAL, gingival index (GI, plaque index (PI, horizontal probing depth (HPD, vertical probing depth (VPD, gingival recession (GR, furcation vertical component (FVC, furcation to alveolar crest (FAC, fornix to base of defect (FBD, and furcation horizontal component (FHC were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant. RESULTS: Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups. CONCLUSION: The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone

Hearing loss in Usher syndrome type II is nonprogressive.

Science.gov (United States)

Reisser, Christoph F V; Kimberling, William J; Otterstedde, Christian R

2002-12-01

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-88 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity

Energy Technology Data Exchange (ETDEWEB)

Kozak, R.W.; Raubitschek, A.; Mirzadeh, S.; Brechbiel, M.W.; Junghaus, R.; Gansow, O.A.; Waldmann, T.A. (Center for Biologics Evaluation and Research, FDA, Bethesda, MD (USA))

1989-05-15

One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B.

4. Berder Meeting - Biology of ionizing radiation - Booklet

International Nuclear Information System (INIS)

2013-01-01

This conference has been organized around 5 sessions: 1) radioimmunotherapy and signaling, 2) external radiotherapy and signaling, 3) dosimetry and radiobiology, 4) early events induced by radiation, and 5) radiotherapy and tumor response. This document gathers 50 short papers the 2 first are dedicated respectively to the presentation of the 'Canceropole Grand Ouest' and the story of radioimmunotherapy

Late-onset Bartter syndrome type II.

Science.gov (United States)

Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik

2017-10-01

Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

Clinical significance of measurement of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma of uterine cervix

International Nuclear Information System (INIS)

Kuang Lei

2010-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, SCC and CYFRA21-1 levels after operation in patients with carcinoma uterine cervix. Methods: Serum levels of IGF-II, SCC and CYFRA21-1 were determined with RIA repeatedly in 31 patients with carcinoma of uterine cervix (before operation 1 month after operation and 6 month after operation) and once in 35 controls. Results: Before operation,serum levels of IGF-II, SCC and CYFRA21-1 in the patients were significantly higher than those in the controls (P<0.01). One month after operation all the serum levels were approaching normal. Six month later,the levels in the patients without recurrence remained normal. However, the levels in the 6 patients with recurrence returned to those before operation again. Conclusion: Changes of serum IGF-II, SCC and CYFRA21-1 levels are closely related to the tumor burden and may be of prognostic importance. (authors)

Eradication of colon cancer cells before tumour formation in the peritoneal cavity of mice treated with intraperitoneal Re-186 radioimmunotherapy

International Nuclear Information System (INIS)

Kinuya, S.; Hiramatsu, T.; Michigishi, T.

2006-01-01

A treatment adjuvant to surgical resection of the primary lesion has been proven to be beneficial in improving the prognosis of patients with high risks of peritoneal dissemination of colon cancer. This study was performed to determine the comparative efficacy of intraperitoneal radioimmunotherapy (RIT) using Re-186 or I-131 labeled murine antibodies in the extermination of cancer cells. A murine anti-colorectal IgG1, A7 monoclonal antibody, was radio-labeled either with I-131 (by the chloramine-T method) or Re-186 (by the MAG3 pre-chelated method). A total number of 16 mice were subjected to RIT with Re-186 A7 (N=8) or I-131 A7 (N=8) at equitoxic doses in Balb/c bu/nu mice 10 min after intraperitoneal injection of LS180 human colon cancer cells. A third group of mice were subjected to chemotherapy with 5-fluorouracil at 30 mg/kg for 4 consecutive days following the intraperitoneal injection of the same LS180 human colon cancer cells. There were 19 mice in the control group who were not subjected to any form of therapy. The results revealed that the mean survival of mice in the control (N-19), I-131 A7 RIT (N=8) and Chemotherapy (N=6) groups were 33.8 ± 1.0, 80.1 ± 2.5 and 49.3 ± 5.3 days respectively. The eight mice who were subjected to Re-186 A7 RIT showed much better survival compared to the other groups. Two of the eight mice from this group died at 105 and 111 days following Re-186 A7 RIT. Other six mice were sacrificed at 172 days, and autopsy revealed no macroscopic peritoneal tumor growth. Based on this pilot study we concluded that individual tumor cells in the peritoneal cavity would be effectively exterminated by intraperitoneal RIT with Re-186 A7. (author)

Evaluation of glycodendron and synthetically-modified dextran clearing agents for multi-step targeting of radioisotopes for molecular imaging and radioimmunotherapy

Science.gov (United States)

Cheal, Sarah M.; Yoo, Barney; Boughdad, Sarah; Punzalan, Blesida; Yang, Guangbin; Dilhas, Anna; Torchon, Geralda; Pu, Jun; Axworthy, Don B.; Zanzonico, Pat; Ouerfelli, Ouathek; Larson, Steven M.

2014-01-01

A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific anti-tumor antibody (scFv4) streptavidin (SA) fusion protein (scFv4-SA) in vivo, to improve tumor to normal tissue concentration ratios for targeted radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with average molecular weight (MW) of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogs (e.g. CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of 124I-labelled-scFv4-SA clearance and dual-label biodistribution studies following multi-step targeting (MST) directed at subcutaneous (s.c.) human colon adenocarcinoma xenografts in mice. The MST protocol consists of three injections: first, a bispecific antibody specific for an anti-tumor associated glycoprotein (TAG-72) single chain genetically-fused with SA (scFv4-SA); second, CA16 or other clearing agent; and third, radiolabeled biotin. We observed using PET imaging of 124I-labelled-scFv4-SA clearance that the spatial arrangement of ligands conjugated to NAG (i.e. biotin) can impact the binding to antibody in circulation and subsequent liver uptake of the NAG-antibody complex. Also, NAGB CA32-LC or CA16-LC can be utilized during MST to achieve comparable tumor- to-blood ratios and absolute tumor uptake seen previously with CA16. Finally, DEXB was equally effective as NAGB CA32-LC at lowering scFv4-SA in circulation, but at the expense of reducing absolute tumor uptake of radiolabeled biotin. PMID:24219178

Aase-Smith Syndrome type II

International Nuclear Information System (INIS)

Soker, Murat; Ayyildiz, Orhan; Isikdogan, Abdurrahman

2004-01-01

Aase-Smith syndrome type II is a rare in childhood and there a few reported cases. Here, we report an 8-months-old boy with congenital red cell aplasia and triphalangeal thumbs. In addition to thumb anomalies. He presented with growth failure, hypertelorism and novel osseous radiologic abnormalities, large fontanelles and micrognathia as extraordinary. Some clinical symptoms had complete clinical remission with deflazacort treatment. (author)

A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis.

Science.gov (United States)

Wada, Koichiro; Uehara, Shinya; Ishii, Ayano; Sadahira, Takuya; Yamamoto, Masumi; Mitsuhata, Ritsuko; Takamoto, Atsushi; Araki, Motoo; Kobayashi, Yasuyuki; Watanabe, Masami; Watanabe, Toyohiko; Hotta, Katsuyuki; Nasu, Yasutomo

2016-08-01

Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants.

Bone radioisotope scanning: usefulness in the evaluation and observation of patients with breast cancer in clinical stage II, III, IV

International Nuclear Information System (INIS)

Cano P, R.A.

1995-01-01

The clinical records of 420 patients with diagnosis of breast cancer well documented by the pathological anatomy in clinical stage II, III and IV were reviewed. In each one of them has been done at least a bone scanning during the diagnosis. In 52 cases carried out sericeous dosages of CA 15-3 and in some cases it was necessary to administer Samarium-153 EDTMP as palliative therapy of bone pain. The presence of secondary gamma-graphic focuses was 0/84 cases (0%) in clinical stage II, 54/265 cases (20%) in III and 41/91 cases (45%) in IV. The one focus appeared in 6.7% of the cases. In 7 of the 52 cases that received sericeous dosages of CA 15-3 were detected secondary osseous lesions, and 5 of them presented a marker elevation. The bone scanning has shown in many cases the presence of getters focuses in singular places of skeleton, urinary excretory system or mammary tissue. The gamma rays from Sm-153 allowed us to get some appropriate basal views post-therapy of the secondary lesions. The results show that the great incidence of secondary lesions in the skeleton occurred in cases of stages III and IV unlike other countries. The serial repetition of the radioisotope scanning. The presence of one focus in the skeleton of a patient with a well-known neoplasia makes us to do a careful evaluation of the focus nature. The presence of tracer accumulation in the kidney, ureter and bladder allows us to infer the pathology of excretory system that is the first evidence of its presence in many cases. (author). 71 refs., 7 figs., 6 tabs

Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.

Science.gov (United States)

Zohar, Sarah; Chevret, Sylvie

2003-02-01

We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

Science.gov (United States)

Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

2013-07-15

Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

Bloqueio do nervo supraescapular: procedimento importante na prática clínica. Parte II Suprascapular nerve block: important procedure in clinical practice. Part II

Directory of Open Access Journals (Sweden)

Marcos Rassi Fernandes

2012-08-01

Full Text Available O bloqueio do nervo supraescapular é um método de tratamento reprodutível, confiável e extremamente efetivo no controle da dor no ombro. Esse método tem sido amplamente utilizado por profissionais na prática clínica, como reumatologistas, ortopedistas, neurologistas e especialistas em dor, na terapêutica de enfermidades crônicas, como lesão irreparável do manguito rotador, artrite reumatoide, sequelas de AVC e capsulite adesiva, o que justifica a presente revisão (Parte II. O objetivo deste estudo foi descrever as técnicas do procedimento e suas complicações descritas na literatura, já que a primeira parte reportou as indicações clínicas, drogas e volumes utilizados em aplicação única ou múltipla. Apresentamse, detalhadamente, os acessos para a realização do procedimento tanto direto como indireto, anterior e posterior, lateral e medial, e superior e inferior. Diversas são as opções para se realizar o bloqueio do nervo supraescapular. Apesar de raras, as complicações podem ocorrer. Quando bem indicado, este método deve ser considerado.The suprascapular nerve block is a reproducible, reliable, and extremely effective treatment method in shoulder pain control. This method has been widely used by professionals in clinical practice such as rheumatologists, orthopedists, neurologists, and pain specialists in the treatment of chronic diseases such as irreparable rotator cuff injury, rheumatoid arthritis, stroke sequelae, and adhesive capsulitis, which justifies the present review (Part II. The objective of this study was to describe the techniques and complications of the procedure described in the literature, as the first part reported the clinical indications, drugs, and volumes used in single or multiple procedures. We present in details the accesses used in the procedure: direct and indirect, anterior and posterior, lateral and medial, upper and lower. There are several options to perform suprascapular nerve block

Clinical effects of fixed functional Herbst appliance in the treatment of class II/1 malocclusion

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Nedeljković Nenad

2009-01-01

Full Text Available Introduction. Sagittal mandible deficiency is the most common cause of skeletal Class II malocclusion. Treatment objective is to stimulate sagittal mandible growth. Fixed functional Herbst appliance use is beneficial for shortening the time required for treatment and does not depend on patient compliance. Case outline. A 13-year-old girl was referred to the Clinic of Orthodontics, School of Dentistry in Belgrade following previous unsuccessful treatment of her skeletal Class II malocclusion using an activator. The patient's poor cooperation had led to failure of the treatment. Patient was subjected to the Herbst treatment for 6 months followed by fixed appliance for another 8 months. Lateral cephalograms before and after the treatment was performed. The remodelation of condylar and fossal articulation was assessed by superimposition of pre- and post-treatment temporomandibular joint tomograms. The promotion of oral hygiene and fluoride use was performed because orthodontic treatment carries a high caries risk and risk for periodontal disease. Skeletal and dental changes were observed after treatment (correction [Max+Mand]: molar relation 7 mm, overjet 8 mm, skeletal relation 5 mm, molars 2 mm, incisors 3 mm. Combination of Herbst and fixed appliances was effective in the treatment of dental and skeletal irregularities for a short period of time. Conclusion . In the retention period, 14 months after treatment, occlusal stability exists. Follow-up care in oral prevention is based on regular recalls at the dental office and supervision at home by the parents.

SU-E-J-35: Clinical Performance Evaluation of a Phase II Proton CT Scanner

International Nuclear Information System (INIS)

Mandapaka, A; Ghebremedhin, A; Farley, D; Giacometti, V; Vence, N; Bashkirov, V; Patyal, B; Schulte, R; Plautz, T; Zatserklyaniy, A; Johnson, R; Sadrozinski, H

2014-01-01

Purpose: To develop the methodology to evaluate the clinical performance of a Phase II Proton CT scanner Methods: Range errors on the order of 3%-5% constitute a major uncertainty in current charged particle treatment planning based on Hounsfield Unit (HU)-relative stopping power (RSP) calibration curves. Within our proton CT collaboration, we previously developed and built a Phase I proton CT scanner that provided a sensitive area of 9 cm (axial) × 18 cm (in-plane). This scanner served to get initial experience with this new treatment planning tool and to incorporate lessons learned into the next generation design. A Phase II scanner was recently completed and is now undergoing initial performance testing. It will increase the proton acquisition rate and provide a larger detection area of 9 cm x 36 cm. We are now designing a comprehensive evaluation program to test the image quality, imaging dose, and range uncertainty associated with this scanner. The testing will be performed along the lines of AAPM TG 66. Results: In our discussion of the evaluation protocol we identified the following priorities. The image quality of proton CT images, in particular spatial resolution and low-density contrast discrimination, will be evaluated with the Catphan600 phantom. Initial testing showed that the Catphan uniformity phantom did not provide sufficient uniformity; it was thus replaced by a cylindrical water phantom. The imaging dose will be tested with a Catphan dose module, and compared to a typical cone beam CT dose for comparable image quality. Lastly, we developed a dedicated dosimetry range phantom based on the CIRS pediatric head phantom HN715. Conclusion: A formal evaluation of proton CT as a new tool for proton treatment planning is an important task. The availability of the new Phase II proton CT scanner will allow us to perform this task. This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the NIH under award number R01

Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II ...

Indian Academy of Sciences (India)

Unknown

Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N RAMAN*, Y PITCHAIKANI RAJA and A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001, India e-mail: ra_man@123india.com.

EVIDENCE-BASED MEDICINE – II. CLINICAL USE AND CRITICS

Directory of Open Access Journals (Sweden)

Angela Čuk

2004-01-01

Full Text Available Background. Evidence-based medicine employs systematic searching, evaluation and use of current research findings as the basis for clinical decision-making. However, there are some problems and uncertainties hindering introduction and spreading of the use of the method in clinical practice. Physicians often have no time for literature searching and for use of the method in practice. For certain questions in clinical practice there are no answers in medical literature. Most of the evidences in medical literature are only available in English. Introduction of the method is hampered also by the fact that clinical decision-making is complex and does not allow procedures prescribed in advance. Rigidity and universality of decisions resulting from the evidence may appear impersonal and may affect the relationship between the physician and the patient. Trends towards evidence based medicine are followed also by big multinational pharmaceutical corporations. They carry out large and expensive clinical trials using the results for promotional purposes. In this way, they get the competitive advantage and influence the objectivity of physicians’ clinical decision-making.Conclusions. With introduction of evidence based medicine into clinical practice physicians acquire new information and use a new form of continuing education by following new developments in their field. This way, new findings from medical literature get into clinical practice faster and more efficiently. In addition, physicians get more professional satisfaction and quality in clinical practice is higher.

Biologically active new Fe(II, Co(II, Ni(II, Cu(II, Zn(II and Cd(II complexes of N-(2-thienylmethylenemethanamine

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C. SPÎNU

2008-04-01

Full Text Available Iron(II, cobalt(II, nickel (II, copper (II, zinc(II and cadmium(II complexes of the type ML2Cl2, where M is a metal and L is the Schiff base N-(2-thienylmethylenemethanamine (TNAM formed by the condensation of 2-thiophenecarboxaldehyde and methylamine, were prepared and characterized by elemental analysis as well as magnetic and spectroscopic measurements. The elemental analyses suggest the stoichiometry to be 1:2 (metal:ligand. Magnetic susceptibility data coupled with electronic, ESR and Mössbauer spectra suggest a distorted octahedral structure for the Fe(II, Co(II and Ni(II complexes, a square-planar geometry for the Cu(II compound and a tetrahedral geometry for the Zn(II and Cd(II complexes. The infrared and NMR spectra of the complexes agree with co-ordination to the central metal atom through nitrogen and sulphur atoms. Conductance measurements suggest the non-electrolytic nature of the complexes, except for the Cu(II, Zn(II and Cd(II complexes, which are 1:2 electrolytes. The Schiff base and its metal chelates were screened for their biological activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and the metal chelates were found to possess better antibacterial activity than that of the uncomplexed Schiff base.

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.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

Science.gov (United States)

Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

2002-03-01

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria

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Yongjun Wang

2016-04-01

Full Text Available Antimicrobial peptides have been accepted as excellent candidates for developing novel antibiotics against drug-resistant bacteria. Recent studies indicate that spider venoms are the source for the identification of novel antimicrobial peptides. In the present study, we isolated and characterized an antibacterial peptide named lycosin-II from the venom of the spider Lycosa singoriensis. It contains 21 amino acid residue lacking cysteine residues and forms a typical linear amphipathic and cationic α-helical conformation. Lycosin-II displays potent bacteriostatic effect on the tested drug-resistant bacterial strains isolated from hospital patients, including multidrug-resistant A. baumannii, which has presented a huge challenge for the infection therapy. The inhibitory ability of lycosin-II might derive from its binding to cell membrane, because Mg2+ could compete with the binding sites to reduce the bacteriostatic potency of lycosin-II. Our data suggest that lycosin-II might be a lead in the development of novel antibiotics for curing drug-resistant bacterial infections.

Complexes of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and dioxouranium(II) with thiophene-2-aldehydethiosemicarbazone

International Nuclear Information System (INIS)

Singh, Balwan; Misra, Harihar

1986-01-01

Metal complexes of thiosemicarbazides have been known for their pharmacological applications. Significant antitubercular, fungicidal and antiviral activities have been reported for thiosemicarbazides and their derivatives. The present study describes the systhesis and characterisation of complexes of Co II , Cu II , Zn II ,Cd II and UO II with thiosemicarbazone obtained by condensing thiophene-2-aldehyde with thiosemicarbazide. 17 refs., 2 tables. (author)

Clinical Trials

Medline Plus

Full Text Available ... new treatments in small groups of people for safety and side effects. Phase II clinical trials look at how well treatments work and further review these treatments for safety. Phase ...

[Clinical efficacy of alprostan in combination with "Bioptron-II" rays and iruxol-miramistin in the treatment of the diabetic foot complicated by atherosclerosis].

Science.gov (United States)

Tomashuk, I P; Tomashuk, I I

2001-08-01

Experience of clinical treatment of 9 patients with diabetes mellitus and diabetic angiopathy using alprostan in combination with rays "Bioptron-II" and iruxol-miramistinum in conditions of polyclinic was summarized. Antidiabetic preparations, mainly insulin, were administered to all patients together with abovementioned treatment. Optimal scheme of treatment constitutes daily slow (no less than 6 h) dropper intravenous infusion of alprostan in 0.1 mg dosage in 150-200 ml isotonic solution of sodium chloride during 15 days. Before and after infusion of alprostan ulcer was locally irradiated using "Bioptron-II" lamp from 5 cm distance during 6 min, bandage with iruxol-miramistinum ointment was applied in ratio 1:1. In 6 patients pain in lower extremities disappeared, ulcers epithelized, in 3--ulcers reduced by 50%.

Symptoms of depression as possible markers of bipolar II disorder.

Science.gov (United States)

Benazzi, Franco

2006-05-01

Underdiagnosis and misdiagnosis of bipolar-II disorder (BP-II) as a major depressive disorder (MDD) are frequently reported. The study aim was to find which symptoms of depression could be possible cross-sectional markers of BP-II, in order to reduce underdiagnosing BP-II. Consecutive 379 BP-II and 271 MDD major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Inside-MDE hypomanic symptoms (elevated mood and increased self-esteem always absent by definition) were systematically assessed. Mixed depression was defined as an MDE plus 3 or more inside-MDE hypomanic symptoms, a definition validated by Akiskal and Benazzi. The MDE symptoms significantly more common in BP-II versus MDD were weight gain, increased eating, hypersomnia, psychomotor agitation, worthlessness, and diminished ability to concentrate. The inside-MDE hypomanic symptoms significantly more common in BP-II were distractibility, racing/crowded thoughts, irritability, psychomotor agitation, more talkativeness, increased risky and goal-directed activities. Multiple logistic regression showed that hypersomnia, racing/crowded thoughts, irritability, and psychomotor agitation were independent predictors of BP-II. Irritability had the most balanced combination of sensitivity and specificity predicting BP-II. Psychomotor agitation had the highest specificity but the lowest sensitivity. Racing/crowded thoughts had the highest sensitivity but the lowest specificity. These symptoms had a similar positive predictive value (PPV) for BP-II, which was around 70% (PPV is more clinically useful than sensitivity and specificity), which in turn was similar to the PPV of mixed depression and atypical depression (two diagnostic clinical markers of BP-II). All possible combinations of these symptoms had a PPV similar to that of the individual symptoms. The

Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families.

Science.gov (United States)

Willems, M; Geneviève, D; Borck, G; Baumann, C; Baujat, G; Bieth, E; Edery, P; Farra, C; Gerard, M; Héron, D; Leheup, B; Le Merrer, M; Lyonnet, S; Martin-Coignard, D; Mathieu, M; Thauvin-Robinet, C; Verloes, A; Colleaux, L; Munnich, A; Cormier-Daire, V

2010-12-01

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or mild mental retardation. Seckel syndrome is associated with defective ATR dependent DNA damage signalling. In 2008, loss-of-function mutations in the pericentrin gene (PCNT) have been identified in 28 patients, including 3 SCKL and 25 MOPDII cases. This gene encodes a centrosomal protein which plays a key role in the organisation of mitotic spindles. The aim of this study was to analyse PCNT in a large series of SCKL-MOPD II cases to further define the clinical spectrum associated with PCNT mutations. Among 18 consanguineous families (13 SCKL and 5 MOPDII) and 6 isolated cases (3 SCKL and 3 MOPD II), 13 distinct mutations were identified in 5/16 SCKL and 8/8 MOPDII including five stop mutations, five frameshift mutations, two splice site mutations, and one apparent missense mutation affecting the last base of exon 19. Moreover, we demonstrated that this latter mutation leads to an abnormal splicing with a predicted premature termination of translation. The clinical analysis of the 5 SCKL cases with PCNT mutations showed that they all presented minor skeletal changes and clinical features compatible with MOPDII diagnosis. It is therefore concluded that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of-function of pericentrin.

Phase II clinical trial of robotic stereotactic body radiosurgery for metastatic gynecologic malignancies

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Charles eKunos

2012-12-01

Full Text Available Background Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT in women with metastatic gynecologic cancers. Methods A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4 metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses. Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0. SBRT target responses were recorded following RECIST criteria (version 1.0. Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to control for prognostic variables.Findings SBRT was safely delivered, with 49 (98% of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%, nausea (8% and diarrhea (4%. One (2% grade 4 hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients. A 6-month clinical benefit was recorded in 34 (68% [95% CI, 53.2, 80.1] patients. No SBRT-targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62% patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6. Median overall survival was 20.2 months (95% CI, 10.9, 29.5.Interpretation SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway.Funding Case Comprehensive Cancer Center

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

Energy Technology Data Exchange (ETDEWEB)

Kunos, Charles A.; Brindle, James [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, School of Medicine, Cleveland, OH (United States); Waggoner, Steven; Zanotti, Kristine; Resnick, Kimberly; Fusco, Nancy; Adams, Ramon; Debernardo, Robert, E-mail: charles.kunos@uhhospitals.org [Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospitals Case Medical Center and Case Western Reserve University, School of Medicine, Cleveland, OH (United States)

2012-12-05

Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

International Nuclear Information System (INIS)

Kunos, Charles A.; Brindle, James; Waggoner, Steven; Zanotti, Kristine; Resnick, Kimberly; Fusco, Nancy; Adams, Ramon; Debernardo, Robert

2012-01-01

Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

DEFF Research Database (Denmark)

Specht, L.; Horwich, A.; Ashley, S.

1994-01-01

patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology......PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681...

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

Science.gov (United States)

Vogel, Moritz; Bayi, Pierre F; Ruf, Marie-Thérèse; Bratschi, Martin W; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

2016-02-01

Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. ISRCT 72102977. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Mn(II), Zn(II) and VO(II) Schiff

Indian Academy of Sciences (India)

Home; Journals; Journal of Chemical Sciences; Volume 113; Issue 3. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N Raman Y Pitchaikani Raja A Kulandaisamy. Inorganic Volume 113 Issue 3 June 2001 pp 183-189 ...

DEGRO 2017. Abstracts

Energy Technology Data Exchange (ETDEWEB)

NONE

2017-06-15

The volume includes abstracts of the Annual DEGRO Meeting 2017 covering lectures and poster sessions with the following issues: lymphoma, biology, physics, radioimmunotherapy, sarcomas and rare tumors, prostate carcinoma, lung tumors, benign lesions and new media, mamma carcinoma, gastrointestinal tumors, quality of life, care science and quality assurance, high-technology methods and palliative situation, head-and-neck tumors, brain tumors, central nervous system metastases, guidelines, radiation sensitivity, radiotherapy, radioimmunotherapy.

Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival.

Science.gov (United States)

Yang, Jia-Cheng; Risch, Eric; Zhang, Meiqin; Huang, Chan; Huang, Huatian; Lu, Lingeng

2017-09-01

To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. Patients with NSUN2 high IGF-II low had significantly superior overall and disease progression-free survival, followed by NSUN2 low IGF-II low , NSUN2 high IGF-II high and NSUN2 low IGF-II high (p IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

From academy to industry

International Nuclear Information System (INIS)

Chatal, J.F.

2015-01-01

Full text of publication follows. Clinical efficacy of radioimmunotherapy (RIT) has been clearly documented in the consolidation situation, such as first line treatment of indolent Non Hodgkin Lymphoma after induction chemotherapy [1] or after salvage resection of liver metastases from colon carcinoma [2], when tumor targets have a small, preferably microscopic, size. In this favorable situation RIT, which is a targeted therapy with toxicity limited to hematological toxicity, has a great potential and could be competitive with chemotherapy in particular for solid tumors. Such potential has been recently demonstrated in prostate cancer [3]. A lot of academic preclinical studies have been performed using multiple antibodies and antibody formats labeled with varied beta-emitting and more recently alpha particle-emitting radionuclides. With regard to other targeted therapies, the efficacy of RIT has been fully recognized and academic preclinical studies have been extended to a lot of clinical phase I/II studies but a limited number of phase II studies. Paradoxically, despite quite encouraging results, the number of industrially implemented phase III studies has been limited to the fingers of one hand illustrating a gap between academy and industry. For the last ten years only 2 ARCs (Antibody Radio Conjugates) (Zevalin and Bexxar) have been approved. The reasons for such a gap are complex and multiple but they could be summarized in one word: Money. The cost for a phase III study, enrolling hundreds of patients, exceeds the financial capabilities of most radiopharmaceutical companies and, up to now, Big Pharmas did not dare to invest in this field of RIT in part because they are not familiar with the use of radionuclides and prefer to develop ADCs (Antibody Drug Conjugates) even if they are generally more toxic and no more efficient than ARCs. For the future of RIT it is crucial to succeed in convincing Big Pharmas to invest in this field of ARCs. For this purpose it

Clinical significance of combined determination of the changes of serum IGF-II, CA19-9 and AFP levels after intervention therapy in patients with primary hepatic cancer

International Nuclear Information System (INIS)

Wang Zhong

2007-01-01

Objective: To investigate the clinical significance of changes of serum IGF-II, CA19-9 and AFP levels after intervention therapy in patients with primary hepatic cancer. Methods: Serum levels of IGF-II, CA19-9 and AFP (with RIA) were repeatedly determined in 35 patients with primary hepatic cancer before intervention therapy, 1 month after intervention therapy and 6 months after intervention therapy as well as in 30 controls. Results: Before intervention therapy, serum levels of IGF-II, CA19-9 and AFP in the patients were significantly higher than those in the controls (P <0.01 ). One month after intervention therapy, all the serum levels were approaching normal. Six months later, the levels in the patients without recurrence remained normal. However, the levels in the 6 patients with recurrence returued to those before intervention therapy again. Conclusion: Changes of serum IGF-II, CA19-9 and AFP levels are closely related to the tumor burden and may reflect the presence of recurrence. (authors)

Are the MDS-UPDRS-based composite scores clinically applicable?

Science.gov (United States)

Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert

2018-02-28

The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Early changes of serum insulin-like growth factor-II (IGF-II) levels in patients with acute brain injury

International Nuclear Information System (INIS)

Liu Cegang; Zhang Xinlu; Tao Jin; Xu Anding; Xu Shanshui; Huang Zhenpeng

2003-01-01

Objective: To investigate the early changes and clinical significance of serum Insulin-like growth factor-II (IGF-II) levels in patients with acute brain injury. Methods: Radioimmunoassay was used for measurement of the serum IGF-II concentration in 30 controls and 29 acute brain injury patients before and after treatment (within 1 day, at 3 and 7 days). Results: The serum IGF-II levels in brain injury patients at 1 day, 3 day 7 days after injury were 0.131 ± 0.047 ng/ml, 0.117 ± 0.046 ng/ml and 0.123 ±0.050 ng/ml respectively and were significantly lower than those in controls 0.44 ± 0.014 ng/ml, p<0.01. Differences among the values of the three days were not significant. Conclusion: IGF-II might play important role in the pathophysiological process of early acute brain injury

Clinical Trials

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Full Text Available ... small groups of people for safety and side effects. Phase II clinical trials look at how well ... confirm how well treatments work, further examine side effects, and compare new treatments with other available treatments. ...

Significance of determination of the serum levels of homocysteine (Hcy) and insulin-like growth factor-II (IGF-II) in patients with cerebrovascular diseases

International Nuclear Information System (INIS)

Tong Haijiang; Wang Yaling; Wang Lin; Xia Weiren; Shi Min; Lu Yaling

2006-01-01

Objective: To investigate the clinical significance of the changes of homocysteine (Hcy) and insulin-like growth factor H (IGF-II) in patients with cerebrovascular diseases (CVD). Methods: The serum Hcy (with CLIA) and IGF-II (with RIA) levels were measured in 123 patients with CVD (cerebral infarction 69 and cerebral hemorrhage 54) and 43 controls. Results: The levels of Hcy and IGF-II in patients with CVD were significantly higher than those in the controls (P 0.05). Conclusion: The serum Hcy and IGF-II levels in patients with CVD are elevated, Hcy and IGF-II may be involved in the development and pathogenesis of CVD. (authors)

Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial.

Science.gov (United States)

Montero-Odasso, Manuel; Muir-Hunter, Susan W; Oteng-Amoako, Afua; Gopaul, Karen; Islam, Anam; Borrie, Michael; Wells, Jennie; Speechley, Mark

2015-01-01

Gait deficits are prevalent in people with dementia and increase their fall risk and future disability. Few treatments exist for gait impairment in Alzheimer's disease (AD) but preliminary studies have shown that cognitive enhancers may improve gait in this population. To determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic activity, on gait in older adults newly diagnosed with AD. Phase II clinical trial in 43 seniors with mild AD who received donepezil. Participants had not previously received treatment with cognitive enhancers. Primary outcome variables were gait velocity (GV) and stride time variability (STV) under single and dual-task conditions measured using an electronic walkway. Secondary outcomes included attention and executive function. After four months of treatment, participants with mild AD improved their GV from 108.4 ± 18.6 to 113.3 ± 19.5 cm/s, p = 0.010; dual-task GV from 80.6 ± 23.0 to 85.3 ± 22.3 cm/s, p = 0.028. Changes in STV were in the expected direction although not statistically significant. Participants also showed improvements in Trail Making Tests A (p = 0.030), B (p = 0.001), and B-A (p = 0.042). Donepezil improved gait in participants with mild AD. The enhancement of dual-task gait suggests the positive changes achieved in executive function as a possible causal mechanism. This study yielded a clinically significant estimate of effect size; as well, the findings are relevant to the feasibility and ethics considerations for the design of a Phase III clinical trial.

Adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II), and As(V) on bacterially produced metal sulfides.

Science.gov (United States)

Jong, Tony; Parry, David L

2004-07-01

The adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II) and As(V) onto bacterially produced metal sulfide (BPMS) material was investigated using a batch equilibrium method. It was found that the sulfide material had adsorptive properties comparable with those of other adsorbents with respect to the specific uptake of a range of metals and, the levels to which dissolved metal concentrations in solution can be reduced. The percentage of adsorption increased with increasing pH and adsorbent dose, but decreased with increasing initial dissolved metal concentration. The pH of the solution was the most important parameter controlling adsorption of Cd(II), Cu(II), Fe(II), Ni(II), Pb(II), Zn(II), and As(V) by BPMS. The adsorption data were successfully modeled using the Langmuir adsorption isotherm. Desorption experiments showed that the reversibility of adsorption was low, suggesting high-affinity adsorption governed by chemisorption. The mechanism of adsorption for the divalent metals was thought to be the formation of strong, inner-sphere complexes involving surface hydroxyl groups. However, the mechanism for the adsorption of As(V) by BPMS appears to be distinct from that of surface hydroxyl exchange. These results have important implications to the management of metal sulfide sludge produced by bacterial sulfate reduction.

Memorial—John A. Washington II, M.D.▿

OpenAIRE

2010-01-01

John A. Washington II, M.D., former Head of Clinical Microbiology at the Mayo Clinic from 1972 to 1986 and Chairman of the Department of Microbiology at the Cleveland Clinic from 1986 to 1992, died on 5 September 2010 at the age of 74. John was an internationally recognized, widely respected leader in the disciplines of clinical microbiology and infectious diseases, authoring more than 450 scientific articles, books, and book chapters and training scores of pathology residents and clinical mi...

Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children

Directory of Open Access Journals (Sweden)

Gregory K Friedman

Full Text Available Oncolytic engineered herpes simplex viruses (HSVs possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy.

A New Clinical HIFU System (Teleson II)

Science.gov (United States)

Ma, Yixin; Symonds-Tayler, Richard; Rivens, Ian H.; ter Haar, Gail R.

2007-05-01

Previous clinical trials with our first prototype HIFU system (Teleson I) for the treatment of liver tumors, demonstrated a major challenge to be treatment of those tumors located behind the ribs. We have designed a new multi-element transducer for rib sparing. Initial simulation and experimental results (using a single channel power amplifier) are very encouraging. A new clinical HIFU system which can drive the multi-element transducer and control each channel independently is being designed and constructed. This second version of a clinical prototype HIFU system consists of a 3D motorised gantry, a multi-channel signal generator, a multi-channel power amplifier, a user interface PC, an embedded controller and auxiliary circuits for real-time interleaving/synchronization control and a to-be-implemented safety monitoring and data logging unit. For multi-element transducers, each element can be individually switched on and off for rib sparing, and phase and amplitude modulated for potential phased array applications. The multi-channel power amplifier can be switched on/off very rapidly at required intervals to interleave with ultrasound B-Scan imaging for HIFU monitoring or radiation force elastography imaging via a dedicated interleaving/timing module. The gantry movement can also be synchronised with power amplifier on/off and phase/amplitude updating for lesion generation under a wide variety of conditions including single lesions, lesion arrays and lesions "tracks" created whilst translating the active transducer. Results from testing the system using excised tissue will be presented.

Prevalence of cystic macular lesions in patients with Usher II syndrome.

Science.gov (United States)

Walia, S; Fishman, G A; Hajali, M

2009-05-01

To evaluate the prevalence of cystic macular lesions in patients with Usher II syndrome. All Usher type II patients seen in the inherited eye disease clinic at the University of Illinois at Chicago between January 2002 and December 2007 were included (n=76). Each participating patient underwent a detailed clinical examination, including best-corrected visual acuity, slit-lamp biomicroscopy and dilated fundus examination. The presence of cystoid lesions was determined by optical coherence tomography (OCT), fundus fluorescein angiogram (FFA), fundus photographs and/or clinical examination. A cystic-appearing macular change was observed in at least one eye in 19 out of the 76 patients (25%), 13 on the basis of OCT, five using FFA (two solely with the use of FFA and three based on clinical notes and FFA findings) and one based solely on clinical notes. Of the 18 patients with CME, determined by OCT or FFA, five (27.8%) showed either a funduscopically normal-appearing macula (n=4) or an atrophic appearing macular change (n=1). One-fourth of our total cohort of Usher II patients had cystic macular lesions. Moreover, a funduscopically normal-appearing macula was observed in 22% (n=4) of our 18 patients with cystic-appearing macular lesions on OCT and/or FFA testing. On the basis of the reasonably high prevalence of cystic macular lesions in our cohort, it would seem prudent to evaluate Usher II patients for the presence of cystoid macular oedema.

The SafeBoosC Phase II Randomised Clinical Trial : A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

NARCIS (Netherlands)

Pellicer, Adelina; Greisen, Gorm; Benders, Manon; Claris, Olivier; Dempsey, Eugene; Fumagalli, Monica; Gluud, Christian; Hagmann, Cornelia; Hellstroem-Westas, Lena; Hyttel-Sorensen, Simon; Lemmers, Petra; Naulaers, Gunnar; Pichler, Gerhard; Roll, Claudia; van Bel, Frank; van Oeveren, Wim; Skoog, Maria; Wolf, Martin; Austin, Topun

2013-01-01

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rSto(2)) reflects venous oxygen saturation. If cerebral metabolism is stable, rSto(2) can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the

α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

Energy Technology Data Exchange (ETDEWEB)

Frost, Sophia; Miller, Brian W.; Back, Tom; Santos, E. B.; Hamlin, Donald K.; Knoblaugh, E.; Frayo, Shani; Kenoyer, Aimee L.; Storb, Rainer; Press, O. W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, B. M.

2015-09-03

Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

Synthesis and spectroscopic studies of biologically active tetraazamacrocyclic complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II

Directory of Open Access Journals (Sweden)

Monika Tyagi

2014-01-01

Full Text Available Complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II were synthesized with the macrocyclic ligand, i.e., 2,3,9,10-tetraketo-1,4,8,11-tetraazacycoletradecane. The ligand was prepared by the [2 + 2] condensation of diethyloxalate and 1,3-diamino propane and characterized by elemental analysis, mass, IR and 1H NMR spectral studies. All the complexes were characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II, Co(II and Ni(II complexes in DMF correspond to non electrolyte nature, whereas Pd(II and Pt(II complexes are 1:2 electrolyte. On the basis of spectral studies an octahedral geometry has been assigned for Mn(II, Co(II and Ni(II complexes, whereas square planar geometry assigned for Pd(II and Pt(II. In vitro the ligand and its metal complexes were evaluated against plant pathogenic fungi (Fusarium odum, Aspergillus niger and Rhizoctonia bataticola and some compounds found to be more active as commercially available fungicide like Chlorothalonil.

New modalities (setting, fractionation) of radioimmunotherapy by 90Y-ibritumomab tiuxetan (90Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach

International Nuclear Information System (INIS)

Morschhauser, F.

2008-12-01

Rationale: radioimmunotherapy (R.I.T.) with 90 Y-ibritumomab tiuxetan ([ 90 Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [ 90 Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with 90 Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with Zevalin in patient

The Bipolar II Depression Questionnaire: A Self-Report Tool for Detecting Bipolar II Depression.

Directory of Open Access Journals (Sweden)

Chi Ming Leung

Full Text Available Bipolar II (BP-II depression is often misdiagnosed as unipolar (UP depression, resulting in suboptimal treatment. Tools for differentiating between these two types of depression are lacking. This study aimed to develop a simple, self-report screening instrument to help distinguish BP-II depression from UP depressive disorder. A prototype BP-II depression questionnaire (BPIIDQ-P was constructed following a literature review, panel discussions and a field trial. Consecutively assessed patients with a diagnosis of depressive disorder or BP with depressive episodes completed the BPIIDQ-P at a psychiatric outpatient clinic in Hong Kong between October and December 2013. Data were analyzed using discriminant analysis and logistic regression. Of the 298 subjects recruited, 65 (21.8% were males and 233 (78.2% females. There were 112 (37.6% subjects with BP depression [BP-I = 42 (14.1%, BP-II = 70 (23.5%] and 182 (62.4% with UP depression. Based on family history, age at onset, postpartum depression, episodic course, attacks of anxiety, hypersomnia, social phobia and agoraphobia, the 8-item BPIIDQ-8 was constructed. The BPIIDQ-8 differentiated subjects with BP-II from those with UP depression with a sensitivity/specificity of 0.75/0.63 for the whole sample and 0.77/0.72 for a female subgroup with a history of childbirth. The BPIIDQ-8 can differentiate BP-II from UP depression at the secondary care level with satisfactory to good reliability and validity. It has good potential as a screening tool for BP-II depression in primary care settings. Recall bias, the relatively small sample size, and the high proportion of females in the BP-II sample limit the generalization of the results.

Bipolar Treatment: Are Bipolar I and Bipolar II Treated Differently?

Science.gov (United States)

... The diagnosis and management of bipolar I and bipolar II disorders: Clinical practice update. Mayo Clinic Proceedings. 2017;92:1532. Haynes PL, et al. Social rhythm therapies for mood disorders: An update. Current Psychiatry Reports. ...

A clinical trial of Empress II porcelain inlays luted to vital teeth with a dual-curing adhesive system and a self-curing resin cement.

Science.gov (United States)

Fabianelli, Andrea; Goracci, Cecilia; Bertelli, Egidio; Davidson, Carel L; Ferrari, Marco

2006-12-01

The aim of the study was to clinically evaluate Empress II inlays cemented with a dual-curing bonding agent and a self-curing luting system. Forty patients were selected to receive one Empress II inlay. Empress II is a heat-pressed glass ceramic containing lithium disilicate and lithium orthophosphate crystals, purported to provide higher stress resistance and improved strength. The restorations were placed between March and May 2000. Recalls were performed after 6, 12, 24, and 36 months. At the 3-year recall, 7 patients were lost to follow-up. Inlays were evaluated for postoperative sensitivity, marginal integrity, marginal leakage, color stability, surface staining, retention, and surface crazing (microcracks). At the 3-year recall, all the restorations were in place and only one showed postoperative sensitivity (at the first recall, 1 week after placement). Only 3 inlays showed slight marginal staining, and 4 inlays showed gaps, with little surface staining or microcracks. No inlay debonded or fractured during theobservation period. All the evaluated inlays were in place and acceptable.

The fitness for the Ageing Brain Study II (FABS II: protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Directory of Open Access Journals (Sweden)

Ames David

2010-12-01

Full Text Available Abstract Background Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II study is a multicentre randomized controlled clinical trial (RCT aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods. Methods/Design The study will recruit 230 community-dwelling participants diagnosed with Alzheimer's disease. Participants will be randomly allocated to two treatment groups: usual care group or 24-week home-based program consisting of 150 minutes per week of tailored moderate physical activity. The primary outcome measure of the study is cognitive decline as measured by the change from baseline in the total score on the Alzheimer's disease Assessment Scale-Cognitive section. Secondary outcomes of interest include behavioral and psychological symptoms, quality of life, functional level, carer burden and physical function (strength, balance, endurance, physical activity. Primary endpoints will be measured at six and twelve months following the baseline assessment. Discussion This RCT will contribute evidence regarding the potential benefits of a systematic program of physical activity as an affordable and safe intervention for people with Alzheimer's disease. Further, if successful, physical activity in combination with usual care has the potential to alleviate the symptoms of Alzheimer's disease and improve its management and the quality of life of patients and their carers. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12609000755235

Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

Science.gov (United States)

Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

2008-06-15

Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.

Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.

Science.gov (United States)

Isobe, Aki; Takeda, Takashi; Sakata, Masahiro; Miyake, Asako; Yamamoto, Toshiya; Minekawa, Ryoko; Nishimoto, Fumihito; Oskamoto, Yoko; Walker, Cheryl Lyn; Kimura, Tadashi

2008-02-01

Although uterine leiomyomas or fibroids are the most common gynecological benign tumor and greatly affect reproductive health and well-being, the pathophysiology and epidemiology of uterine leiomyomas are poorly understood. Elevated blood pressure has an independent, positive association with risk for clinically detected uterine leiomyoma. Angiotensin II (Ang II) is a key biological peptide in the renin-angiotensin system that regulates blood pressure. In this study, we investigated the potential role of Ang II (1-1000 nM) in the proliferation of rat ELT-3 leiomyoma cells in vitro. RT-PCR and western blot analysis with cell proliferation and DNA transfection assays were performed to determine the mechanism of action of Ang II. Ang II induced ELT-3 leiomyoma cell proliferation (P estradiol-induced cell proliferation (P < 0.01). AT(1)R, but not AT(2)R, plays a role in Ang II-induced ELT-3 cell proliferation. These experimental findings in vitro highlight the potential role of Ang II in the proliferation of leiomyoma cells.

Differential association of the N-propeptide of collagen IIA (PIIANP) and collagen II C-telopeptide (CTX-II) with synovitis and erosions in early and longstanding rheumatoid arthritis

DEFF Research Database (Denmark)

Christensen, A F; Lottenburger, T; Lindegaard, H

2009-01-01

OBJECTIVES: To determine the N-terminal propeptide of collagen IIA (PIIANP) in early and established rheumatoid arthritis (RA) and to study the association with collagen II degradation assessed by its C-telopeptide (CTX-II), x-ray status and disease activity measures. METHODS: Two cohorts of RA......-ray progression (p=0.84). There was no correlation between PIIANP and CTX-II. CONCLUSION: Declining PIIANP with increasing RA duration and persistently increased CTX-II indicate that cartilage anabolic and degradative pathways are unbalanced from clinical RA onset. Furthermore, that collagen II depletion in RA...... is both mediated by anti-anabolic effects unassociated with synovitis (decreased PIIANP) and by excess collagen II degradation linked to synovitis (increased CTX-II)....

Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013.

Science.gov (United States)

Al-Niemat, Sahar I; Aljbouri, Tareq M; Goussous, Lana S; Efaishat, Rania A; Salah, Rehab K

2014-07-01

To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children's Hospital at Royal Medical Services in Amman, Jordan. The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs) were also measured. Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85%) when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60%) of the total prescribed antibiotics and (83%) of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin) were the leading class among them. Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

Clinically Effective Treatment of Fibromyalgia Pain With High-Definition Transcranial Direct Current Stimulation: Phase II Open-Label Dose Optimization.

Science.gov (United States)

Castillo-Saavedra, Laura; Gebodh, Nigel; Bikson, Marom; Diaz-Cruz, Camilo; Brandao, Rivail; Coutinho, Livia; Truong, Dennis; Datta, Abhishek; Shani-Hershkovich, Revital; Weiss, Michal; Laufer, Ilan; Reches, Amit; Peremen, Ziv; Geva, Amir; Parra, Lucas C; Fregni, Felipe

2016-01-01

Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. Registered in Clinicaltrials.gov under registry number NCT01842009. In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

New basic science initiatives with the angiotensin II receptor blocker valsartan

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Marc de Gasparo

2000-06-01

Full Text Available Summary Angiotensin II (Ang II plays a key role in the regulation of blood pressure and fluid homeostasis. Valsartan is a highly selective Ang II receptor blocker that specifically and selectively blocks Ang II at the AT1-receptor. In animal models, valsartan has shown positive effects on vasoconstriction, proliferation, remodelling, endothelial function and thrombogenesis, inflammation and atherosclerosis. These data are likely to be confirmed by the results of current clinical trials and valsartan is set to provide improved cardiovascular therapy in the future.

Physicochemical properties of 3,4,5-trimethoxybenzoates of Mn(II, Co(II, Ni(II and Zn(II

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W. FERENC

2005-09-01

Full Text Available The complexes of Mn(II, Co(II, Ni(II, Cu(II and Zn(II with 3,4,5-trimethoxybenzoic acid anion of the formula: M(C10H11O52·nH2O, where n = 6 for Ni(II, n = 1 for Mn(II, Co(II, Cu(II, and n = 0 for Zn, have been synthesized and characterized by elemental analysis, IR spectroscopy, X–ray diffraction measurements, thermogravimetry and magnetic studies. They are crystalline compounds characterized by various symmetry. They decompose in various ways when heated in air to 1273 K. At first, they dehydrate in one step and form anhydrous salts. The final products of decomposition are oxides of the respective metals (Mn2O3, Co3O4, NiO, CuO, ZnO. The solubilities of the analysed complexes in water at 293 K are in the orders of 10-2 – 10-4 mol dm-3. The magnetic susceptibilities of the Mn(II, Co(II, Ni(II and Cu(II complexes were measured over the range of 76–303 K and the magnetic moments were calculated. The results show that the 3,4,5-trimethoxybenzoates of Mn(II, Co(II and Ni(II are high-spin complexes but that of Cu(II forms a dimer [Cu2(C10H11O54(H2O2]. The carboxylate groups bind as monodentate or bidentate chelating or bridging ligands.

Evaluation of APACHE II system among intensive care patients at a teaching hospital

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Paulo Antonio Chiavone

Full Text Available CONTEXT: The high-complexity features of intensive care unit services and the clinical situation of patients themselves render correct prognosis fundamentally important not only for patients, their families and physicians, but also for hospital administrators, fund-providers and controllers. Prognostic indices have been developed for estimating hospital mortality rates for hospitalized patients, based on demographic, physiological and clinical data. OBJECTIVE: The APACHE II system was applied within an intensive care unit to evaluate its ability to predict patient outcome; to compare illness severity with outcomes for clinical and surgical patients; and to compare the recorded result with the predicted death rate. DESIGN: Diagnostic test. SETTING: Clinical and surgical intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: The study involved 521 consecutive patients admitted to the intensive care unit from July 1998 to June 1999. MAIN MEASUREMENTS: APACHE II score, in-hospital mortality, receiver operating characteristic curve, decision matrices and linear regression analysis. RESULTS: The patients' mean age was 50 ± 19 years and the APACHE II score was 16.7 ± 7.3. There were 166 clinical patients (32%, 173 (33% post-elective surgery patients (33%, and 182 post-emergency surgery patients (35%, thus producing statistically similar proportions. The APACHE II scores for clinical patients (18.5 ± 7.8 were similar to those for non-elective surgery patients (18.6 ± 6.5 and both were greater than for elective surgery patients (13.0 ± 6.3 (p < 0.05. The higher this score was, the higher the mortality rate was (p < 0.05. The predicted death rate was 25.6% and the recorded death rate was 35.5%. Through the use of receiver operating curve analysis, good discrimination was found (area under the curve = 0.80. From the 2 x 2 decision matrix, 72.2% of patients were correctly classified (sensitivity = 35.1%; specificity = 92.6%. Linear

Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir.

Science.gov (United States)

Wyles, David; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Martin, Ross; Afdhal, Nezam H; Kowdley, Kris V; Lawitz, Eric; Brainard, Diana M; Miller, Michael D; Mo, Hongmei; Gane, Edward J

2017-04-01

Ledipasvir/sofosbuvir combination treatment in phase III clinical trials resulted in sustained viral suppression in 94-99% of patients. This study characterized drug resistance in treatment failures, which may help to inform retreatment options. We performed NS5A and NS5B deep sequencing of hepatitis C virus (HCV) from patients infected with genotype (GT) 1 who participated in ledipasvir/sofosbuvir phase II and III clinical trials. Fifty-one of 2144 (2.4%) (42 GT1a and 9 GT1b) treated patients met the criteria for resistance analysis due to virologic failure following the end of treatment. The majority of patients with virologic failure (38 of 51; 74.5%) had detectable ledipasvir-specific resistance-associated substitutions (RASs) at the time of virologic failure (1% deep sequencing cut-off). The percent of patients with NS5A RASs at virologic failure were 37.5%, 66.7%, 94.7% and 100% in patients treated for 6, 8, 12 and 24weeks, respectively. The common substitutions detected at failure were Q30R/H, and/or Y93H/N in GT1a and Y93H in GT1b. At failure, 35.3% (18/51) of virologic failure patients' viruses had two or more NS5A RASs and the majority of patients harbored NS5A RASs conferring a 100-1000-fold (n=10) or >1000-fold (n=23) reduced susceptibility to ledipasvir. One patient in a phase II study with a known ledipasvir RAS at baseline (L31M) developed the S282T sofosbuvir (NS5B) RAS at failure. In GT1 HCV-infected patients treated with ledipasvir/sofosbuvir±ribavirin, virologic failure was rare. Ledipasvir resistance in NS5A was selected or enhanced in most patients with virologic failure, one of whom also developed resistance to sofosbuvir. Clinical studies have shown that combination treatment with ledipasvir/sofosbuvir efficiently cures most patients with genotype 1 hepatitis C infection. For the few patients failing treatment, we show that resistance to ledipasvir was observed in most patients, whereas resistance to sofosbuvir was less common. This has

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

International Nuclear Information System (INIS)

Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A.; Martin, H.; Bergmann, L.

2001-01-01

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ( 188 Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2±2.1 (range 6.9-15.8) GBq 188 Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4±5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188 Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

Morphological caracteristics of malocclusion class II

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Pavlović J.

2015-01-01

Full Text Available Class II malocclusion are complex anomalies of the skeletal and dental systems. The aim of this study is that the rengenkefalometrics analysis closer determine the morphological characteristics of this malocclusion. For this study were used 30 patients aged 18-30, previously clinically diagnosed class II, before the planned orthodontic treatment. The results analisis lateral cephalometric radiographs were compared with the 30 patients with class I malocclusion. Analyzed three linear and two angular cranial base dimensions and nine angular and four linear measures from the facial skeleton. The Results show: No statistically significant differensis in cranial base angle (SNBa and anterior cranial base length (S-N between class II and control Class I. Angle maxillar prognathism ( SNA is no signifikant different between class I and Class II but SNB angle were signifikant smaller. The length of maxillary base (A'-SnP is longer and the length of mandibule (Pg'-MT1/MT is signifficantly smaller. The gonial angle (ArGo-Me was smaller with open articular angle (GoArSN. Morphological characteristics of class II malocclusion are , retrognathic and smaller mandibular ligth, normognathic and longer maxilla, open articular angle with vertical tendency of the craniofacial growth pattern.

Synthesis and spectral studies of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) complexes of 4-oxo-4H-1-benzopyran-3-carboxaldehyde hydrazone derivatives

International Nuclear Information System (INIS)

Nawar, N.; Khattab, M.A.; Bekheit, M.M.; El-Kaddah, A.H.

1996-01-01

A few complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-chlorobenzylhydrazone) (BCBH) and 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-methylbenzylhydrazone) (BMBH) have been synthesised and characterized by elemental analysis, molar conductivities, magnetic measurements and infrared (IR) and visible spectral studies. The IR spectra show that BCBH and BMBH behave as bidentate ligands either in the keto or enol form. (author). 24 refs., 2 tabs

Synthesis, Characterization, and Biological Activity of Mn(II, Fe(II, Co(II, Ni(II, Cu(II, Zn(II, and Cd(II Complexes of N-Thiophenoyl-N′-Phenylthiocarbohydrazide

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M. Yadav

2013-01-01

Full Text Available Mn(II, Fe(II, Co(II, Ni(II, Cu(II, Zn(II, and Cd(II complex of N-thiophenoyl -N′-phenylthiocarbohydrazide (H2 TPTH have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, infrared, NMR, electronic, and ESR spectral studies. The complexes were found to have compositions [Mn(H TPTH2], [Co(TPTH (H2O2], [Ni(TPTH (H2O2], [Cu(TPTH], [Zn(H TPTH], [Cd(H TPTH2], and [Fe(H TPTH2(EtOH]. The magnetic and electronic spectral studies suggest square planar geometry for [Cu(TPTH], tetrahedral geometry for [Zn(TPTH] and [Cd(H TPTH2], and octahedral geometry for rest of the complexes. The infrared spectral studies of the 1 : 1 deprotonated complexes suggest bonding through enolic oxygen, thiolato sulfur, and both the hydrazinic nitrogens. Thus, H2TPTH acts as a binegative tetradentate ligand. H2 TPTH and its metal complexes have been screened against several bacteria and fungi.

Measurement of DSM-5 section II personality disorder constructs using the MMPI-2-RF in clinical and forensic samples.

Science.gov (United States)

Anderson, Jaime L; Sellbom, Martin; Pymont, Carly; Smid, Wineke; De Saeger, Hilde; Kamphuis, Jan H

2015-09-01

In the current study, we evaluated the associations between the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) scale scores and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) Section II personality disorder (PD) criterion counts in inpatient and forensic psychiatric samples from The Netherlands using structured clinical interviews to operationalize PDs. The inpatient psychiatric sample included 190 male and female patients and the forensic sample included 162 male psychiatric patients. We conducted correlation and count regression analyses to evaluate the utility of relevant MMPI-2-RF scales in predicting PD criterion count scores. Generally, results from these analyses emerged as conceptually expected and provided evidence that MMPI-2-RF scales can be useful in assessing PDs. At the zero-order level, most hypothesized associations between Section II disorders and MMPI-2-RF scales were supported. Similarly, in the regression analyses, a unique set of predictors emerged for each PD that was generally in line with conceptual expectations. Additionally, the results provided general evidence that PDs can be captured by dimensional psychopathology constructs, which has implications for both DSM-5 Section III specifically and the personality psychopathology literature more broadly. (c) 2015 APA, all rights reserved.

MRI findings in central nervous system of neurofibromatosis-II

International Nuclear Information System (INIS)

Chen Maoen; Huang Suiqiao; Shen Jun; Hong Guobin; Wu Zhuo; Lin Xiaofeng

2007-01-01

Objective: To investigate the diagnostic value of MR imaging in central nervous system involvement of neurofibromatosis II. Methods: 7 patients with surgically and pathologically proved neurofibromatosis II were included. Their MR imaging findings and clinical features were retrospectively analyzed. Results: The main findings of 7 cases of neurofibraomaosis II on MR imaging included bilateral acoustic neurilemoma, multiple neurofibroma, meningioma and schwannoma. Among the 7 patients, Tl-weighted imaging after contrast enhancement displayed additional lesions which had been ignored on un-enhanced scan. Conclusion: MR imaging has advantages in the detection of central nervous sys- tem involvement of neurofibromatosis II with regard to its ability to show the lesions well, meanwhile displaying the size, morphology and signal features clearly. (authors)

Platelet GP II b/III a inhibitors in neurointervention therapeutics

International Nuclear Information System (INIS)

Wang Kuizhong; Huang Qinghai; Liu Jianmin

2007-01-01

The platelet glucoprotein (GP) II b/III a inhibitors prossess inhibiting platelet aggregation effectly. As new drugs of antiplatelet, they are different in mechanism with action, application and dosage between the II b/III a inhibitors and other tradional antiplatelet drugs such as aspirin or clopidogrel. In familiar with the pharmacologic action and clinical application of II b/III a inhibitors is important for endovascular interventional radiology, especially with important significance for obtaining high quality neuro-endovascular stenting in the perioperative period. (authors)

PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

DEFF Research Database (Denmark)

Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J

2011-01-01

disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer...

Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

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Rachael E Hawtin

2010-04-01

Full Text Available Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research.Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more potent.As a first-in-class anticancer

Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

International Nuclear Information System (INIS)

Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

2015-01-01

Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

Science.gov (United States)

Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical

Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

Science.gov (United States)

Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

2014-12-18

To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II binary complexes of l-methionine in 1,2-propanediol-water mixtures

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M. Padma Latha

2007-04-01

Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-methionine in 0.0-60 % v/v 1,2-propanediol-water mixtures maintaining an ionic strength of 0.16 M at 303 K has been studied pH metrically. The active forms of ligand are LH2+, LH and L-. The predominant species detected are ML, MLH, ML2, ML2H, ML2H2 and MLOH. Models containing different numbers of species were refined by using the computer program MINIQUAD 75. The best-fit chemical models were arrived at based on statistical parameters. The trend in variation of complex stability constants with change in the dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces.

Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients

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Calzavara-Pinton Pier

2009-11-01

Full Text Available Abstract Background Loeys-Dietz syndrome (LDS is a rare autosomal dominant disorder showing the involvement of cutaneous, cardiovascular, craniofacial, and skeletal systems. In particular, LDS patients show arterial tortuosity with widespread vascular aneurysm and dissection, and have a high risk of aortic dissection or rupture at an early age and at aortic diameters that ordinarily are not predictive of these events. Recently, LDS has been subdivided in LDS type I (LDSI and type II (LDSII on the basis of the presence or the absence of cranio-facial involvement, respectively. Furthermore, LDSII patients display at least two of the major signs of vascular Ehlers-Danlos syndrome. LDS is caused by mutations in the transforming growth factor (TGF beta-receptor I (TGFBR1 and II (TGFBR2 genes. The aim of this study was the clinical and molecular characterization of two LDS patients. Methods The exons and intronic flanking regions of TGFBR1 and TGFBR2 genes were amplified and sequence analysis was performed. Results Patient 1 was a boy showing dysmorphic signs, blue sclerae, high-arched palate, bifid uvula; skeletal system involvement, joint hypermobility, velvety and translucent skin, aortic root dilatation, tortuosity and elongation of the carotid arteries. These signs are consistent with an LDSI phenotype. The sequencing analysis disclosed the novel TGFBR1 p.Asp351Gly de novo mutation falling in the kinase domain of the receptor. Patient 2 was an adult woman showing ascending aorta aneurysm, with vascular complications following surgery intervention. Velvety and translucent skin, venous varicosities and wrist dislocation were present. These signs are consistent with an LDSII phenotype. In this patient and in her daughter, TGFBR2 genotyping disclosed in the kinase domain of the protein the novel p.Ile510Ser missense mutation. Conclusion We report two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with LDS and showing marked

A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

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Hamid Omid

2011-11-01

Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

Nuclear medicine therapy of neuroblastoma

International Nuclear Information System (INIS)

Hoefnagel, C.A.

1999-01-01

Specific targeting of radionuclides to neuroblastoma, a neural crest tumor occurring predominantly in young children and associated with a relatively poor prognosis, may be achieved via the metabolic route (Mibg), receptor binding (peptides) or immunological approach (antibodies). The clinical role of 1 31 I -Mibg therapy and radioimmunotherapy in neuroblastoma is discussed. In recurrent or progressive metastatic disease after conventional treatment modalities have failed, 1 31 I -Mibg therapy, with an overall objective response rate of 35%, is probably the best palliative treatment, as the invasiveness and toxicity of this therapy compare favourably with that of chemotherapy, immunotherapy and external beam radiotherapy. In patients presenting with inoperable stage III and IV neuroblastoma, 1 31 I -Mibg therapy at diagnosis is at least as effective as combination chemotherapy but is associated with much less toxicity. In patients with recurrent disease 1 31 I -Mibg therapy in combination with hyperbaric oxygen therapy proved feasible and encouraging effects on survival have ben observed. Attempts to intensify the treatment in relapsed patients by combination of 1 31 I -Mibg therapy with high dose chemotherapy and/or total body irradiation have met with considerable toxicity. Developments in Mibg therapy aiming at improving the therapeutic index are mentioned. Early results of radioimmunotherapy using 1 31 I -UJ13A or 1 31 I -3F8 monoclonal antibodies have shown moderate objective response and considerable side effects in patients with stage IV neuroblastoma, who had relapsed or failed conventional therapy. New developments in radioimmunotherapy of neuroblastoma include the use of chimeric antibodies, the enhancement of tumor uptake by modulation of antigen expression or by increasing the tumor perfusion/vascularity/permeability, the use of other labels and multistep targeting techniques, e.g. using bispecific monoclonal antibodies

Nuclear medicine and thyroid disease - part II

International Nuclear Information System (INIS)

Chatterton, B.E.

2005-01-01

Part 1 of this article discussed the anatomy, physiology and basic pathology of the thyroid gland. Techniques of thyroid scanning and a few clinical examples are shown part II Copyright (2005) The Australian and New Zealand Society Of Nuclear Medicine Inc

Effect of NonSurgical Periodontal Therapy on Plasma Levels of IL-17 in Chronic Periodontitis Patients with Well Controlled Type-II Diabetes Mellitus—A Clinical Study

Directory of Open Access Journals (Sweden)

Vishnu Jayakumar Sunandhakumari

2018-06-01

Full Text Available For years the pathogenesis of periodontitis was under an immunological Th1/Th2 paradigm. Th1 cells are considered to afford protection against the intracellular pathogens. These cells produce the interferons (IFN that are involved in macrophage activation, which, in turn, plays an important role in phagocytosis, complement fixation, and opsonization. Th2 cells are thought to have evolved as a form of protection against parasitic helminthes. Th17 subset of CD4Not Necessary+ T cells was identified in the year 2005, which added greater complexity to Th function and are pro inflammatory in nature. Interleukins (ILs have the ability to alter immunological changes and they also possess the ability to regulate lymphocyte differentiation and haemopoietic stem cells, cell proliferation, and motility, which are classified as pro-inflammatory and anti-inflammatory. There are numerous studies that reported IL-17 levels associated with chronic periodontitis (CP development. Type II diabetes mellitus (DM is considered a risk factor for the development of periodontal diseases because the incidence, progression, and severity of periodontal diseases are more common with Type II DM than without DM. This study was aimed at evaluating whether non-surgical periodontal therapy had any effect on plasma concentrations of Interleukin-17 in systemically healthy chronic periodontitis patients and in chronic periodontitis patients with well controlled Type II Diabetes mellitus. Patients were divided into the two groups including the chronic periodontitis group (20 subjects and the chronic periodontitis with well-controlled Type II Diabetes mellitus group (20 subjects. The Gingival Index and Plaque Index as well as the clinical Attachment Level (CAL were taken from all the patients of two groups after evaluating fasting blood sugar, post prandial blood sugar, and the Glycated Hemoglobin Level (HbA1c. Then 5 mL blood samples were collected from each patient and plasma was

Randomized 3-year Clinical Evaluation of Class I and II Posterior Resin Restorations Placed with a Bulk-fill Resin Composite and a One-step Self-etching Adhesive

DEFF Research Database (Denmark)

van Dijken, Jan Wv; Pallesen, Ulla

2015-01-01

PURPOSE: To evaluate the 3-year clinical durability of the flowable bulk-fill resin composite SDR in Class I and Class II restorations. MATERIALS AND METHODS: Thirty-eight pairs of Class I and 62 pairs of Class II restorations were placed in 44 male and 42 female patients (mean age 52.4 years......). Each patient received at least two extended Class I or Class II restorations that were as similar as possible. In all cavities, a one-step self-etching adhesive (XenoV+) was applied. One of the cavities of each pair was randomly assigned to receive the flowable bulk-fill resin composite SDR...... in increments up to 4 mm as needed to fill the cavity 2 mm short of the occlusal cavosurface. The occlusal part was completed with an ormocer-based nanohybrid resin composite (Ceram X mono+). In the other cavity, only the resin composite CeramX mono+ was placed in 2 mm increments. The restorations were...

Eight-year randomized clinical evaluation of Class II nanohybrid resin composite restorations bonded with a one-step self-etch or a two-step etch-and-rinse adhesive

DEFF Research Database (Denmark)

van Dijken, Jan WV; Pallesen, Ulla

2015-01-01

(13.5 %) and nine in the two-step etch-and-rinse group (13.0 %). This resulted in nonsignificant different annual failure rates of 1.69 and 1.63 %, respectively. Fracture of restoration was the main reason for failure. Conclusion: Good clinical performance was shown during the 8-year evaluation....... Results: One hundred and fifty-eight restorations were evaluated after 8 years. Three participants with five restorations (three Xeno III, two Excite) were registered as dropouts. Twenty-one failed restorations (13.3 %) were observed during the follow-up. Twelve in the one-step self-etch adhesive group...... and no significant difference in overall clinical performance between the two adhesives. Fracture was the main reason for failure. Clinical relevance: The one-step self-etch adhesive showed a good long-term clinical effectiveness in combination with the nanohybrid resin composite in Class II restorations....

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

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L John Hoffer

Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Science.gov (United States)

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

cobalt (ii), nickel (ii)

African Journals Online (AJOL)

DR. AMINU

Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

Genetic heterogeneity of Usher syndrome type II.

OpenAIRE

Pieke Dahl, S; Kimberling, WJ; Gorin, MB; Weston, MD; Furman, JM; Pikus, A; Moller, C

1993-01-01

Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis ...

21 CFR 880.2920 - Clinical mercury thermometer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical mercury thermometer. 880.2920 Section 880... Devices § 880.2920 Clinical mercury thermometer. (a) Identification. A clinical mercury thermometer is a... mercury. (b) Classification. Class II (special controls). The device is exempt from the premarket...

Effect of green tea catechins in patients with high-grade prostatic intraepithelial neoplasia: Results of a short-term double-blind placebo controlled phase II clinical trial

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Salvatore Micali

2017-10-01

Full Text Available Background and study objective: Several studies suggest a protective role of green tea catechins against prostate cancer (PCa. In order to evaluate the efficacy of green tea catechins for chemoprevention of PCa in patients with high-grade prostate intraepithelial neoplasia (HG-PIN we performed a phase II clinical trial. Methods: Sixty volunteers with HG-PIN were enrolled to carry out a double-blind randomized placebo-controlled phase II clinical trial. Treated group took daily 600 mg of green tea catechins (Categ Plus® for 1 year. Patients were screened at 6 and 12 months through prostatic biopsy and measurements of prostate-specific antigen (PSA. Results: Despite the statistically significant reduction of PSA observed in subjects who received green tea catechins for 6 and 12 months, we did not find any statistical difference in PCa incidence between the experimental groups neither after 6 nor after 12 months. However, throughout the one-year follow- up we observed very limited adverse effects induced by green tea catechins and a not significant improvement in lower urinary tract symptoms and quality of life. Conclusions: Although the small number of patients enrolled in our study and the relatively short duration of intervention, our findings seems to deny the efficacy of green tea catechins. However, results of our clinical study, mainly for its low statistical strength, suggest that the effectiveness of green tea catechins should be evaluated in both a larger cohort of men and longer trial.

Evaluation of dentoskeletal effects of Farmand functional appliance (Fa II on class II malocclusion

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Yassaei S.

2007-07-01

Full Text Available Background and Aim: Functional appliances refer to a variety of removable or fixed appliances designed to alter the mandibular position both sagitally and vertically, resulting in orthodontic and orthopedic changes. Despite the long history of functional appliances, there is still much controversy related to their effectiveness and mode of action. The aim of this study was to evaluate dental and skeletal effects of Fa II in patients with class II malocclusion due to mandibular deficiency.Materials and Methods: In this before-after clinical trial, 35 patients with class II div I malocclusion were selected. These samples were under treatment with Fa II appliance for 11 months. The range of age of females was 10-13 years and males 11-14 years. Combination analysis was used to determine skeletal and dental effects. Paired t-test was used to compare the differences of mean value pre and post treatment. P<0.05 was considered as the level of significance. Results: There was significant difference between pre and post treatment in respect to posterior and anterior facial height, eruption of upper and lower posterior teeth, eruption of upper anterior teeth, mandibular body length, ANB angle, IMPA and 1 to SN. No significant difference was observed between pre and post treatment regarding facial growth.Conclusion: Treatment with Fa II functional appliance leads to significant alterations in dental and skeletal elements of craniofacial complex and improvement of dental and jaws relationship.

Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013

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Sahar I. Al-Niemat

2014-07-01

Full Text Available Objective: To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children’s Hospital at Royal Medical Services in Amman, Jordan. Methods: The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs were also measured. Results: Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85% when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60% of the total prescribed antibiotics and (83% of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin were the leading class among them. Conclusion: Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

Autosomal recessive type II hereditary motor and sensory neuropathy with acrodystrophy.

Science.gov (United States)

Thomas, P K; Claus, D; King, R H

1999-02-01

A family is described with presumed autosomal recessive inheritance in which three siblings developed a progressive neuropathy that combined limb weakness and severe distal sensory loss leading to prominent mutilating changes. Electrophysiological and nerve biopsy findings indicated an axonopathy. The disorder is therefore classifiable as type II hereditary motor and sensory neuropathy (HMSN II). The clinical features differ from those reported in previously described cases of autosomal recessive HMSN II. This disorder may therefore represent a new variant.

International Literature Review on WHODAS II (World Health Organization Disability Assessment Schedule II

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Federici, Stefano

2009-06-01

Full Text Available This review is a critical analysis regarding the study and utilization of the World Health Organization Disability Assessment Schedule II (WHODAS II as a basis for establishing specific criteria for evaluating relevant international scientific literature.The WHODAS II is an instrument developed by the World Health Organisation in order to assess behavioural limitations and restrictions related to an individual’s participation, independent from a medical diagnosis. This instrument was developed by the WHO’s Assessment, Classification and Epidemiology Group within the framework of the WHO/NIH Joint Project on Assessment and Classification of Disablements. To ascertain the international dissemination level of for WHODAS II’s utilization and, at the same time, analyse the studies regarding the psychometric validation of the WHODAS II translation and adaptation in other languages and geographical contests. Particularly, our goal is to highlight which psychometric features have been investigated, focusing on the factorial structure, the reliability, and the validity of this instrument. International literature was researched through the main data bases of indexed scientific production: the Cambridge Scientific Abstracts – CSA, PubMed, and Google Scholar, from 1990 through to December 2008.The following search terms were used:“whodas”, in the field query, plus “title” and “abstract”.The WHODAS II has been used in 54 studies, of which 51 articles are published in international journals, 2 conference abstracts, and one dissertation abstract. Nevertheless, only 7 articles are published in journals and conference proceedings regarding disability and rehabilitation. Others have been published in medical and psychiatric journals, with the aim of indentifying comorbidity correlations in clinical diagnosis concerning patients with mental illness. Just 8 out of 51 articles have studied the psychometric properties of the WHODAS II. The

Portable digital assistants (PDAs) in dentistry: part II--pilot study of PDA use in the dental clinic.

Science.gov (United States)

Reynolds, P A; Harper, J; Dunne, S; Cox, M; Myint, Y K

2007-04-28

To describe a simple technical evaluation of the access, security issues and uses of wireless networked PDAs in a dental clinic and report a pilot study investigating students' educational use of PDAs to access a Virtual Learning Environment (VLE) in a dental clinic. To undertake a technical evaluation of wireless networking to PDAs focusing on security issues, robustness of the system and accessibility particularly to educational resources. To evaluate the impact of using a PDA on undergraduate students in the dental clinic and at home. Part II describes the technical and educational evaluation of PDAs used by one group of 12 undergraduate fourth year students in the Primary Dental Care clinic. A cross over trial of six students with PDAs and six without was carried out during one semester of 12 weeks. Technical issues such as secure internet access using wireless connectivity were addressed. An assessment of the general and educational use and the students' attitudes towards using PDAs was undertaken using online questionnaires and focus group discussions. Over 90% of participants wanted PDAs as part of their dental kit. The potential of PDA use in dental training was demonstrated by a good to excellent response by over 75% of participants to having access to online support materials, particularly videos, being able to make notes for individual study and to keep a diary of their commitments to teaching sessions. Recreational use included a 100% good to excellent response to playing games and keeping a diary. The PDA proved to be a convenient and versatile mode of access to online education. Technical solutions enabled a substantial proportion of the functionality of WebCT (Web Course Tools) to be accessed by the students in a clinical environment. Both novice and experienced users were able to appreciate the use of the PDA and the less able considered that their ICT skills had improved. However, further research is needed to determine how students use a range of

Coronally positioned flap with or without acellular dermal matrix graft in the treatment of class II gingival recession defects: A randomized controlled clinical study

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Sunitha Jagannathachary

2010-01-01

Full Text Available The aim of the randomized controlled single blind study is to evaluate the treatment of Miller′s class II gingival recessions by coronally positioned flap (CPF with or without acellular dermal matrix allograft (ADMA. Ten patients with 20 sites with maxillary bilateral Miller′s class II facial recession defects were selected randomly into two groups of test (ADMA+CPF and control (CPF alone group with each group having 10 recession defects to be treated. The clinical parameters included plaque index (PI, gingival index (GI, probing pocket depth (PPD, clinical attachment level (CAL, recession height (RH, recession width (RW, height of the keratinized tissue (HKT, and thickness of the keratinized tissue (TKT. These measurements were recorded at baseline and after 6 months post-surgery. Statistical analysis was made by the paired "t" test for intragroup and intergroup comparison was done by the unpaired "t" test. The percentage of root coverage for both the experimental and control groups were 82.2% and 50%, respectively. The changes from baseline to 6 months were significant in both the groups for PD, CAL, and RH; however, for parameters such as RW, HKT, and TKT significance was seen only in the experimental group. On comparison between two groups, only TKT showed statistically significance. It can be concluded that the amount of root coverage obtained with ADMA + CPF was superior compared to CPF alone.

Design of Phase II Non-inferiority Trials.

Science.gov (United States)

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

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Seung Ha Lee

2017-01-01

Full Text Available Objective Patients with drug-induced parkinsonism (DIP may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. Methods Forty-one DIP patients were classified into normal and abnormal [18F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. Results Twenty-eight patients had normal (Group I and 13 patients had abnormal (Group II scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040. Three patients of Group I and six of Group II had hyposmia (p = 0.018. After drug withdrawal, Group I showed greater improvement in Unified Parkinson’s Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. Conclusion None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

The SafeBoosC II randomized trial

DEFF Research Database (Denmark)

Plomgaard, Anne M; van Oeveren, Wim; Petersen, Tue Hvass

2016-01-01

BACKGROUND: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group...

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients.

Science.gov (United States)

Viggiani, Valentina; Palombi, Sara; Gennarini, Giuseppina; D'Ettorre, Gabriella; De Vito, Corrado; Angeloni, Antonio; Frati, Luigi; Anastasi, Emanuela

2016-10-01

As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

Cr(III,Mn(II,Fe(III,Co(II,Ni(II,Cu(II and Zn(II Complexes with Diisobutyldithiocarbamato Ligand

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Mohammad Tarique

2011-01-01

Full Text Available The synthesis of sulphur and nitrogen containing dithiocarbamato ligand derived from diisobutylamine as well as its coordination compounds with 3d series transition metals is presented. These synthesized compounds were characterized on the basis of elemental analysis, conductometric measurements and IR spectral studies. The analytical data showed the stoichiometry 1:2 and 1:3 for the compounds of the types ML2 {M=Mn(II, Co(II, Ni(II, Cu(II and Zn(II} and M'L3{M'=Cr(III and Fe(III} respectively. The conductometric measurements proved the non-electrolytic behaviour of all the compounds. The bidentate nature of dithiocarbamato moiety was confirmed on the basis of IR spectral data.

22. Annual meeting of the German Radiation Oncology Society. Abstracts; 22. Jahrestagung der Deutschen Gesellschaft fuer Radioonkologie. Abstractband

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

The volume on the 22th annual meeting of the German Radiation Oncology Society includes abstracts on the following issues: Brain/ central nervous system, biology, oligo-metastases, head and neck tumors, mammary carcinoma, physics, innovations, life quality, high individual doses, lung tumors, colorectal tumors, clinical studies, young DEGRO, translational research, prostate, brachytherapy. The poster abstracts cover the following issues: prostate, mammary glands, lungs, head and neck, colorectum, brain - central nervous system, innovations concerning percutaneous and interventional radiotherapy, radiotherapy with high single doses, radioimmunotherapy, knowledge-based radiotherapy, life quality, demand planning.

Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease

OpenAIRE

Hidenori Urata

2000-01-01

Summary Chymase is a potent and specific angiotensin II (Ang II)-forming enzyme in vitro. There is also strong evidence to suggest its importance in vivo. Recent clinical studies have suggested that high serum cholesterol levels are associated with increased vascular chymase activity and this may assist in the development of atherosclerosis. This clinical finding has been reproduced in hamster models. Studies with transgenic mice overexpressing the human chymase gene suggest a direct associat...

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

Science.gov (United States)

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours.

Science.gov (United States)

Molenaar, Remco J; Coelen, Robert J S; Khurshed, Mohammed; Roos, Eva; Caan, Matthan W A; van Linde, Myra E; Kouwenhoven, Mathilde; Bramer, Jos A M; Bovée, Judith V M G; Mathôt, Ron A; Klümpen, Heinz-Josef; van Laarhoven, Hanneke W M; van Noorden, Cornelis J F; Vandertop, W Peter; Gelderblom, Hans; van Gulik, Thomas M; Wilmink, Johanna W

2017-06-10

High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2 -mutated cancer cells produce the oncometabolite D -2-hydroxyglutarate ( D -2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine. We describe a dose-finding phase Ib/II clinical trial, in which patients with IDH1/2 -mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma are treated with a combination of metformin and chloroquine. Dose escalation is performed according to a 3+3 dose-escalation scheme. The primary objective is to determine the maximum tolerated dose to establish the recommended dose for a phase II clinical trial. Secondary objectives of the study include (1) determination of pharmacokinetics and toxic effects of the study therapy, for which metformin and chloroquine serum levels will be determined over time; (2) investigation of tumour responses to metformin plus chloroquine in IDH1/2 -mutated cancers using CT/MRI scans; and (3) whether tumour responses can be measured by non-invasive D -2HG measurements (mass spectrometry and magnetic resonance spectroscopy) of tumour tissue, serum, urine, and/or bile or next-generation sequencing of circulating tumour DNA (liquid biopsies). This study may open a novel treatment avenue for IDH1/2 -mutated high-grade chondrosarcoma, glioma and intrahepatic cholangiocarcinoma by repurposing the combination of two inexpensive drugs that are already approved for other indications. This study has been approved by the medical-ethical review committee of the Academic Medical Center, Amsterdam, The Netherlands. The report

Computer augumented modelling studies of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-glutamic acid in 1,2-propanediol–water mixtures

Directory of Open Access Journals (Sweden)

MAHESWARA RAO VEGI

2008-12-01

Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-glutamic acid was studied at 303 K in 0–60 vol. % 1,2-propanediol–water mixtures, whereby the ionic strength was maintained at 0.16 mol dm-3. The active forms of the ligand are LH3+, LH2 and LH–. The predominant detected species were ML, ML2, MLH, ML2H and ML2H2. The trend of the variation in the stability constants with changing dielectric constant of the medium is explained based on the cation stabilizing nature of the co-solvents, specific solvent–water interactions, charge dispersion and specific interactions of the co-solvent with the solute. The effect of systematic errors in the concentrations of the substances on the stability constants is in the order alkali > > acid > ligand > metal. The bioavailability and transportation of metals are explained based on distribution diagrams and stability constants.

Comparative clinical characteristics of depression in bipolar affective disorders types I and II

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N. A. Tyuvina

2016-01-01

Full Text Available Objective: to investigate the clinical features of depression within bipolar affective disorders types I and II (BADI and BADII.Patients and methods. An examination was made in 100 depressive patients, including 25 with BADI, 37 with BADII, and 38 with recurrent depressive disorder (RDD (a comparison group. The patients' status was evaluated in accordance with the ICD-10 and DSM-V affective disorder criteria, by using a specially developed questionnaire.Results. BAD-related depression has features distinguishing it from RDD: sexual preference (men; an earlier age of disease onset; a shorter duration, but a higher frequency of exacerbations; a greater tendency for the continuum; a more marked decrease in social and family adaptation; development in people with predominantly hyperthymic premorbid; more frequently a family history of affective disorders, schizophrenia, and alcoholism; high comorbidity with metabolic diseases and psychoactive substance abuse; worse health more commonly in autumn and winter; a predominant anxious affect and an obviously decreasing interest in the structure of depression; a higher incidence of atypical sleep, appetite, and weight disorders; high suicidal activity; higher motor retardation (in BADI; relatively small involvement of somatic complaints in BAD I and frequent panic attacks in BADII.Conclusion. Knowledge of the specific features of BAD-related depression will be able to make a more accurate differential diagnosis and to perform more effective treatment in these patients.

Resveratrol: A novel type of topoisomerase II inhibitor.

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Lee, Joyce H; Wendorff, Timothy J; Berger, James M

2017-12-22

Resveratrol, a polyphenol found in various plant sources, has gained attention as a possible agent responsible for the purported health benefits of certain foods, such as red wine. Despite annual multi-million dollar market sales as a nutriceutical, there is little consensus about the physiological roles of resveratrol. One suggested molecular target of resveratrol is eukaryotic topoisomerase II (topo II), an enzyme essential for chromosome segregation and DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent dimerization interface in topo II to block enzyme activity. Based on this similarity, we hypothesized that resveratrol may antagonize topo II by a similar mechanism. Using a variety of biochemical assays, we find that resveratrol indeed acts through the ICRF-187 binding locus, but that it inhibits topo II by preventing ATPase domain dimerization rather than stabilizing it. This work presents the first comprehensive analysis of the biochemical effects of both ICRF-187 and resveratrol on the human isoforms of topo II, and reveals a new mode for the allosteric regulation of topo II through modulation of ATPase status. Natural polyphenols related to resveratrol that have been shown to impact topo II function may operate in a similar manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Guided tissue regeneration and platelet rich growth factor for the treatment of Grade II furcation defects: A randomized double-blinded clinical trial - A pilot study

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Niloofar Jenabian

2017-01-01

Results: Eight patients were finally enrolled for this study. Overly, general and specific clinical and furcation parameters were improved except REC that was deteriorated insignificantly and FAC improved not significantly. Intergroup comparison revealed better improvement of FHC in GTR/PRGF group (P = 0.02. Conclusion: A significant improvement in the Grade II furcation defects treated with either GTR or PRGF/GTR was noticed. Further large-scale trials are needed to reveal differences of mentioned treatment in more details.

Synthesis and characterization of heterobimetallic complexes of the type [Cu(pn2][MCl4] where M = Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II

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Seema Yadav

2016-11-01

Full Text Available A series of new bimetallic transition metal complexes of the type [Cu(pn2] [MCl4] have been synthesized (where M = Co(II, Ni(II, Cu(II, Zn(II, Cd(II and Hg(II, pn = 1,3-diaminopropane and characterized by elemental analysis, molar conductance, TGA, IR and electronic spectra. All the compounds are 1:1 electrolyte in DMF. The Cu(II ion is square-planar while metal ions in the anionic moiety acquire their usual tetrahedral arrangement. On the basis of these studies it is concluded that anionic moiety is electrically stabilized by its cationic counterpart.

Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

International Nuclear Information System (INIS)

Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

2002-01-01

unequivocal CD22 expression, as compared with one of four patients with weak expression, exhibited OR. Tumour CD22 assessments before and during therapy were made in three patients, indicating down regulation of CD22. Conclusion: Radioimmunotherapy using a 2-4 weekly injection schedule with 90 Y-epratuzumab can result in durable OR in patients with various subtypes of B-cell lymphoma. Three weekly infusions 185 MBq/m 2 resulted in only minor haematological toxicity. Unequivocally CD22 expressing lymphoma seems more responsive. Low toxicity as well as evidence of down regulation of CD22 expression during therapy make fractionated treatment with 90 Y-epratuzumab warrants further study

Pre-clinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

Science.gov (United States)

2014-12-01

Aim 3: Secure FDA approval of a phase I/II clinical trial plan and obtain an amended IND in preparation for initiating human clinical testing in TBI...Neurology 6:193–201. Raineri M, Gonzalez B, Goitia B, Garcia-Rill E, Krasnova IN, Cadet JL, Urbano FJ, Bisagno V. 2012. Modafinil abrogates

E-READING II: words database for reading by students from Basic Education II.

Science.gov (United States)

Oliveira, Adriana Marques de; Capellini, Simone Aparecida

2016-01-01

To develop a database of words of high, medium and low frequency in reading for Basic Education II. The words were taken from the teaching material for Portuguese Language, used by the teaching network of the State of São Paulo in the 6th to the 9th year of Basic Education. Only nouns were selected. The frequency with which each word occurred was recorded and a single database was created. In order to classify the words as of high, medium and low frequency, the decision was taken to work with the distribution terciles, mean frequency and the cutoff point of the terciles. In order to ascertain whether the words of high, medium and low frequency corresponded to this classification, 224 students were assessed: G1 (6th year, n= 61); G2 (7th year, n= 44); G3 (8th year, n= 65); and G4 (9th year, n= 54). The lists of words were presented to the students for reading out loud, in two sessions: 1st) words of high and medium frequency and 2nd) words of low-frequency. Words which encompassed the exclusion criteria, or which caused discomfort or joking on the part of the students, were excluded. The word database was made up of 1659 words and was titled 'E - LEITURA II' ('E-READING II', in English). The E-LEITURA II database is a useful resource for the professionals, as it provides a database which can be used for research, educational and clinical purposes among students of Basic Education II. The professional can choose the words according to her objectives and criteria for elaborating evaluation or intervention procedures involving reading.

Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

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Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

2013-04-01

Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Beating the odds: Successful establishment of a Phase II/III clinical research trial in resource-poor Liberia during the largest-ever Ebola outbreak

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J. Doe-Anderson

2016-12-01

Full Text Available It has been argued that a country such as Liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. However, as Liberia, Sierra Leone, and Guinea were being ravaged by the largest and most devastating Ebola Virus Disease (EVD outbreak ever recorded, the topic of conducting clinical trials of experimental vaccine and treatment candidates in these resource-poor countries generated the keen interest and concern of scientists, researchers, physicians, bioethicists, philanthropists, and even politicians. Decisive action on behalf of the Liberian government, and a timely positive and supportive response from the United States (U.S. government, led to the formation of PREVAIL (Partnership for Research on Ebola Vaccines in Liberia – a clinical research partnership between the two governments. Within a span of 12 weeks, this partnership accomplished the unimaginable: the successful initiation of a Phase II/III vaccine clinical trial for EVD in Liberia. This paper will discuss the dynamics of the research collaboration, barriers encountered, breakthroughs realized, key elements of success, and lessons learned in the process.

Small Diameter Bomb Increment II (SDB II)

Science.gov (United States)

2015-12-01

Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-439 Small Diameter Bomb Increment II (SDB II) As of FY 2017 President’s Budget Defense... Bomb Increment II (SDB II) DoD Component Air Force Joint Participants Department of the Navy Responsible Office References SAR Baseline (Production...Mission and Description Small Diameter Bomb Increment II (SDB II) is a joint interest United States Air Force (USAF) and Department of the Navy

Synthesis and structural characterization of nickel(II), cobalt(II), Zinc(II), manganese(II), cadmium(II) and uranium(VI) complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazone

International Nuclear Information System (INIS)

Patel, P.S.; Patel, M.M.; Ray, R.M.

1993-01-01

A few metal complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazones (OAOATS)/(OAPATS) with Ni(II), Co(II), Zn(II), Mn(II), Hg(II), Cd(II) and UO 2 (II) have been prepared and characterized by elemental analyses, conductivity, differential scanning calorimetry study, thermogravimetric analyses and infrared and electronic spectral measurements in conjunction with magnetic susceptibility measurements at room temperature. They have also been tested for their antimicrobial activities. (author). 24 refs., 2 tabs

Clinical evaluation of the Byk LIA-mat CA125 II assay: discussion of a reference value.

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Bonfrer, J M; Korse, C M; Verstraeten, R A; van Kamp, G J; Hart, G A; Kenemans, P

1997-03-01

The Byk LIA-mat CA125 II assay was compared with the Centocor IRMA CA125 II. Serum samples studied (n = 1012) were obtained from 652 apparently healthy females, 61 pregnant women, and 299 patients with benign and malignant gynecological tumors. The CA125 II assay value at the 95th percentile of the total healthy group was 29 kU/L for the LIA-mat and 32 kU/L for the Centocor assay. For the LIA-mat assay the 95th percentile was 31 kU/L (Centocor 36 kU/L) for the group 55 years of age. By using ROC curves we found the optimal pretreatment Byk LIA-mat CA125 II value differentiating between benign and malignant ovarian tumors to be 95 kU/L. Pretreatment CA125 values > 1000 kU/L were detected in serum samples of patients with advanced epithelial ovarian cancer.

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

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Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag

International Nuclear Information System (INIS)

Xue Yongjie; Hou Haobo; Zhu Shujing

2009-01-01

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01 M NaNO 3 . In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84 mM in the single element system and 0.21 mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH 50 (the pH at which 50% adsorption occurs) was found to follow the sequence Zn > Cu > Pb > Cd in single-element systems, but Pb > Cu > Zn > Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag

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Xue Yongjie [School of Resource and Environment Science, Wuhan University, Hubei, Wuhan (China); Wuhan Kaidi Electric Power Environmental Protection Co. Ltd., Hubei, Wuhan (China)], E-mail: xueyj@mail.whut.edu.cn; Hou Haobo; Zhu Shujing [School of Resource and Environment Science, Wuhan University, Hubei, Wuhan (China)

2009-02-15

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01 M NaNO{sub 3}. In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84 mM in the single element system and 0.21 mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH{sub 50} (the pH at which 50% adsorption occurs) was found to follow the sequence Zn > Cu > Pb > Cd in single-element systems, but Pb > Cu > Zn > Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag.

Science.gov (United States)

Xue, Yongjie; Hou, Haobo; Zhu, Shujing

2009-02-15

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01M NaNO(3). In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84mM in the single element system and 0.21mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH(50) (the pH at which 50% adsorption occurs) was found to follow the sequence Zn>Cu>Pb>Cd in single-element systems, but Pb>Cu>Zn>Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.

Diagnostic performance of increased overjet in Class II division 1 malocclusion and incisor trauma.

Science.gov (United States)

Baccetti, Tiziano; Giuntini, Veronica; Vangelisti, Andrea; Darendeliler, M Ali; Franchi, Lorenzo

2010-01-01

The objectives of this study were: 1) to evaluate the associations between an increased overjet (IO) and other dentoskeletal characteristics of Class II division 1 malocclusions in the mixed dentition; 2) to assess whether Class II division 1 malocclusions or rather an increased overjet per se is a risk factor for upper incisor trauma (UIT). A sample of 900 mixed dentition subjects, was observed by clinical inspection, analysis of dental casts, and lateral cephalograms. The diagnostic performance of IO (overjet ≥ 7 mm) was evaluated in relation to other Class II dentoskeletal features (Class II molar and canine relationships, and skeletal Class II relationships). Secondly, the diagnostic performance of IO and of the other Class II dentoskeletal components was tested with regard to the prevalence of UIT. Diagnostic performance was assessed by odds ratio and positive likelihood ratio. The diagnostic performance of IO with regard to the other dentoskeletal components of Class II malocclusions was not significant. The only Class II features associated significantly with an increased risk of UIT was IO. When used as an isolated occlusal feature, IO is not a valid diagnostic indicator for Class II division 1 malocclusions. An increased overjet per se, and not Class II malocclusions, appears to be a significant risk factor for UIT. These findings recommend discrimination between clinical conditions showing an isolated IO from comprehensive Class II malocclusions during diagnosis, analysis of treatment outcomes, and evaluation of the risk of upper incisor trauma. Copyright © 2010 Società Italiana di Ortodonzia SIDO. Published by Elsevier Srl. All rights reserved.

Preparation of Schiff s base complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) and their spectroscopic, magnetic, thermal, and antifungal studies

International Nuclear Information System (INIS)

Parekh, H.M.; Patel, M.N.

2006-01-01

The potassium salt of salicylidene-DL-alanine (KHL), bis(benzylidene)ethylenediamine (A 1 ), thiophene-o-carboxaldene-p-toluidine (A 2 ), and its metal complexes of the formula [(M II (L)(A)(H 2 O)] (M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II); A = A 1 or A 2 ) are prepared. They are characterized by elemental analysis, magnetic susceptibility measurements, thermogravimetric analysis, and infrared and electronic spectral studies. The electronic spectral and magnetic moment data suggest an octahedral geometry for the complexes. All of these complexes, metal nitrates, fungicides (bavistin and emcarb), and ligands are screened for their antifungal activity against Aspergillus niger, Fusarium oxysporum, and Aspergillus flavus using a plate poison technique. The complexes show higher activity than those of the free ligands, metal nitrate, and the control (DMSO) and moderate activity against bavistin and emcarb [ru

A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

Science.gov (United States)

Hirano, Shigeru; Kawamoto, Atsuhiko; Tateya, Ichiro; Mizuta, Masanobu; Kishimoto, Yo; Hiwatashi, Nao; Kawai, Yoshitaka; Tsuji, Takuya; Suzuki, Ryo; Kaneko, Mami; Naito, Yasushi; Kagimura, Tatsuo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi

2018-04-01

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus. Copyright © 2017 John Wiley & Sons, Ltd.

The Latent Symptom Structure of the Beck Depression Inventory-II in Outpatients with Major Depression

Science.gov (United States)

Quilty, Lena C.; Zhang, K. Anne; Bagby, R. Michael

2010-01-01

The Beck Depression Inventory-II (BDI-II) is a self-report instrument frequently used in clinical and research settings to assess depression severity. Although investigators have examined the factor structure of the BDI-II, a clear consensus on the best fitting model has not yet emerged, resulting in different recommendations regarding how to best…

Clinical impact of the temporal relationship between depression and type 2 diabetes: the Fremantle diabetes study phase II.

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David G Bruce

Full Text Available BACKGROUND: The clinical features of type 2 diabetes may differ depending on whether first depression episode precedes or follows the diagnosis of diabetes. METHODS: Type 2 patients from the observational community-based Fremantle Diabetes Study Phase II underwent assessment of lifetime depression using the Brief Lifetime Depression Scale (developed and validated for this study supplemented by information on current depression symptoms (Patient Health Questionnaire, 9-item version and use of antidepressants. Patients were categorized as never depressed (Group 1, having had depression before diabetes diagnosis (Group 2, diagnosed with depression and diabetes within 2 years of each other (Group 3 and having depression after diabetes diagnosis (Group 4. RESULTS: Of 1391 patients, 20.8% were assigned to Group 2, 6.0% to Group 3 and 14.5% to Group 4. In Group 2, depression occurred a median 15.6 years before diabetes onset at age 37.2±14.7 years. These patients had similar clinical characteristics to never depressed patients except for reduced self-care behaviours and having more symptomatic peripheral arterial disease. In Group 4, depression occurred a median 9.9 years after diabetes onset at age 59.8±13.0 years. These patients had long duration diabetes, poor glycaemic control, more intensive management and more diabetic complications. Group 4 patients had more current depression than Group 2 but were less likely to be receiving antidepressants. CONCLUSIONS/INTERPRETATION: The clinical features of depression and type 2 diabetes are heterogeneous depending on their temporal relationship. There may be corresponding differences in the pathogenesis of depression in diabetes that have implications for diagnosis and management.

Cu(II) AND Zn(II)

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SYNTHESIS OF 2,2-DIMETHYL-4-PHENYL-[1,3]-DIOXOLANE USING ZEOLITE. ENCAPSULATED Co(II), Cu(II) AND Zn(II) COMPLEXES. B.P. Nethravathi1, K. Rama Krishna Reddy2 and K.N. Mahendra1*. 1Department of Chemistry, Bangalore University, Bangalore-560001, India. 2Department of Chemistry, Government ...

Metabolic and clinical effects of Ramadan fasting in patients with type II diabetes

International Nuclear Information System (INIS)

Yarahmadi, S.; Larijani, B.; Bastanhagh, M.H.; Pajouhi, M.; Bardar, J. R.; Zahedi, F.; Zendehdel, K.; Akrami, S.M.

2003-01-01

Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes. Results: Daily cholesterol intake increased in all subjects (p 0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p < 0.05), C-peptide (p < 0.01) and insulin resistance (p < 0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study. Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavorably altered due to changes in both diet and biochemical response to starvation. (author)

An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency.

Science.gov (United States)

Melek, Engin; Bulut, Fatma Derya; Atmış, Bahriye; Yılmaz, Berna Şeker; Bayazıt, Aysun Karabay; Mungan, Neslihan Önenli

2017-02-01

Carnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

Waardenburg syndrome: clinical differentiation between types I and II.

Science.gov (United States)

Pardono, Eliete; van Bever, Yolande; van den Ende, Jenneke; Havrenne, Poti C; Iughetti, Paula; Maestrelli, Sylvia R P; Costa F, Orozimbo; Richieri-Costa, Antonio; Frota-Pessoa, Oswaldo; Otto, Paulo A

2003-03-15

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the

Spectroscopic and thermal degradation behavior of Mg(II, Ca(II, Ba(II and Sr(II complexes with paracetamol drug

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Moamen S. Refat

2017-05-01

Full Text Available Complexes of Mg(II, Ca(II, Ba(II and Sr(II with paracetamol drug were synthesized and characterized by elemental analysis, conductivity, UV–Vis, IR, and 1H NMR spectroscopy and thermal analysis, as well as screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as paracetamol behaves as a neutral bidentate ligand coordinated to the metal ions via the lone pair of electrons of nitrogen and carbonyl-O atoms of the amide group. From the microanalytical data, the stoichiometry of the complexes reacts with Mg(II, Ca(II, Ba(II and Sr(II by molar ratios (2:1 (paracetamol:metal ion. The thermal behavior (TG/DTG of the complexes was studied. The ligand and their metal complexes were screened against both of antibacterial and fungicidal activities.

Is the development of Modic changes associated with clinical symptoms?

DEFF Research Database (Denmark)

Jensen, Rikke Krüger; Leboeuf-Yde, Charlotte; Wedderkopp, Niels

2012-01-01

/or the pathological type of MCs were associated with changes in clinical symptoms in a cohort of patients with persistent LBP and MCs. METHODS: Information on LBP intensity and detailed information from MRI on the presence, type and size of MCs was collected at baseline and follow-up. Changes in type (Type I, II, III...... developmental path from Type I (here Type I or I/II) to Type II (here Type II or II/III) or Type I to Type I/II. In general, the bigger the size of the MC at baseline, the more likely it was that it remained unchanged in size after 14 months. Patients who had MC Type I at both baseline and 14-month follow......PURPOSE: Modic changes (MCs) have been suggested to be a diagnostic subgroup of low back pain (LBP). However, the clinical implications of MCs remain unclear. For this reason, the aims of this study were to investigate how MCs developed over a 14-month period and if changes in the size and...

Compound heterozygous mutations in electron transfer flavoprotein dehydrogenase identified in a young Chinese woman with late-onset glutaric aciduria type II

OpenAIRE

Xue, Ying; Zhou, Yun; Zhang, Keqin; Li, Ling; Kayoumu, Abudurexiti; Chen, Liye; Wang, Yuhui; Lu, Zhiqiang

2017-01-01

Background Glutaric aciduria type II (GA II) is an autosomal recessive disorder affecting fatty acid and amino acid metabolism. The late-onset form of GA II disorder is almost exclusively associated with mutations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Till now, the clinical features of late-onset GA II vary widely and pose a great challenge for diagnosis. The aim of the current study is to characterize the clinical phenotypes and genetic basis of a late-onset GAII ...

Bone radioisotope scanning: usefulness in the evaluation and observation of patients with breast cancer in clinical stage II, III, IV; Gammagrafia osea: utilidad en la evaluacion y seguimiento de pacientes con cancer de mama en estadio clinico II, III, IV

Energy Technology Data Exchange (ETDEWEB)

Cano P, R A

1996-12-31

The clinical records of 420 patients with diagnosis of breast cancer well documented by the pathological anatomy in clinical stage II, III and IV were reviewed. In each one of them has been done at least a bone scanning during the diagnosis. In 52 cases carried out sericeous dosages of CA 15-3 and in some cases it was necessary to administer Samarium-153 EDTMP as palliative therapy of bone pain. The presence of secondary gamma-graphic focuses was 0/84 cases (0%) in clinical stage II, 54/265 cases (20%) in III and 41/91 cases (45%) in IV. The one focus appeared in 6.7% of the cases. In 7 of the 52 cases that received sericeous dosages of CA 15-3 were detected secondary osseous lesions, and 5 of them presented a marker elevation. The bone scanning has shown in many cases the presence of getters focuses in singular places of skeleton, urinary excretory system or mammary tissue. The gamma rays from Sm-153 allowed us to get some appropriate basal views post-therapy of the secondary lesions. The results show that the great incidence of secondary lesions in the skeleton occurred in cases of stages III and IV unlike other countries. The serial repetition of the radioisotope scanning. The presence of one focus in the skeleton of a patient with a well-known neoplasia makes us to do a careful evaluation of the focus nature. The presence of tracer accumulation in the kidney, ureter and bladder allows us to infer the pathology of excretory system that is the first evidence of its presence in many cases. (author). 71 refs., 7 figs., 6 tabs.

A critical appraisal of chronic kidney disease mineral and bone disorders clinical practice guidelines using the AGREE II instrument.

Science.gov (United States)

Sekercioglu, Nigar; Al-Khalifah, Reem; Ewusie, Joycelyne Efua; Elias, Rosilene M; Thabane, Lehana; Busse, Jason W; Akhtar-Danesh, Noori; Iorio, Alfonso; Isayama, Tetsuya; Martínez, Juan Pablo Díaz; Florez, Ivan D; Guyatt, Gordon H

2017-02-01

Patients with chronic kidney disease mineral and bone disorders (CKD-MBD) suffer high rates of morbidity and mortality, in particular related to bone and cardiovascular outcomes. The management of CKD-MBD remains challenging. The objective of this systematic survey is to critically appraise clinical practice guidelines (CPGs) addressing CKD-MBD. Data sources included MEDLINE, EMBASE, the National Guideline Clearinghouse, Guideline International Network and Turning Research into Practice up to May 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and subsequently appraised the guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE). Sixteen CPGs published from 2003 to 2015 addressing the diagnosis and management of CKD-MBD in adult patients (11 English, two Spanish, one Italian, one Portuguese and one Slovak) proved eligible. The National Institute for Health and Care Excellence guideline performed best with respect to AGREE II criteria; only three other CPGs warranted high scores on all domains. All other guidelines received scores of under 60% on one or more domains. Major discrepancies in recommendations were not, however, present, and we found no association between quality of CPGs which was not associated with resulting recommendations. Most guidelines assessing CKD-MBD suffer from serious shortcomings using AGREE criteria although limitations with respect to AGREE criteria do not necessarily lead to inappropriate recommendations.

Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub-analysis from a prospective multicenter study.

Science.gov (United States)

Yan, Cunling; Hu, Jian; Yang, Jia; Chen, Zhaoyun; Li, Huijun; Wei, Lianhua; Zhang, Wei; Xing, Hao; Sang, Guoyao; Wang, Xiaoqin; Han, Ruilin; Liu, Ping; Li, Zhihui; Li, Zhiyan; Huang, Ying; Jiang, Li; Li, Shunjun; Dai, Shuyang; Wang, Nianyue; Yang, Yongfeng; Ma, Li; Soh, Andrew; Beshiri, Agim; Shen, Feng; Yang, Tian; Fan, Zhuping; Zheng, Yijie; Chen, Wei

2018-04-01

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects. This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method. The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P < 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females. The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Reduction in chlorhexidine efficacy against multi-drug-resistant Acinetobacter baumannii international clone II.

Science.gov (United States)

Hayashi, M; Kawamura, K; Matsui, M; Suzuki, M; Suzuki, S; Shibayama, K; Arakawa, Y

2017-03-01

Nosocomial infections caused by Acinetobacter baumannii international clone II (IC II) can cause severe clinical outcomes. Differential evaluation of bactericidal efficacy of chlorhexidine gluconate (CHX) and benzethonium chloride (BZT) disinfectants against IC II and non-IC II isolates. Minimum inhibitory concentrations (MICs) of CHX and BZT were determined for 137 A. baumannii IC II, 99 non-IC II and 69 non-baumannii isolates, further classified according to MIC values into disinfectant-reduced susceptible (DRS) and disinfectant-susceptible (DS) groups. Time-kill curves and minimum bactericidal concentrations (MBCs) were evaluated for representative isolates in each group. CHX and BZT MIC 90 s for IC II isolates were 100 and 175mg/L, respectively, but those for non-IC II and non-baumannii isolates were <100mg/L. Nevertheless, time-kill curves indicated that CHX and BZT reduced live bacterial cell number by 5 log 10 for IC II and non-IC II isolates within 30s when used at 1000mg/L, comparable to practical use concentrations. CHX MBC at 30s was 1000mg/L for IC II and non-IC II isolates, and was not influenced by addition of 3% bovine serum albumin (BSA); BZT MBC at 30s was 100mg/L without BSA and increased up to 500mg/L upon addition of BSA. No significant differences in BSA were found between DRS and DS isolates. CHX and BZT were effective against Acinetobacter spp. including IC II at a concentration of 1000mg/L and exposure for at least 30s, but their concentrations should be considered carefully to ensure sufficient effects in both clinical and healthcare settings. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Solar photocatalytic removal of Cu(II), Ni(II), Zn(II) and Pb(II): Speciation modeling of metal-citric acid complexes

International Nuclear Information System (INIS)

Kabra, Kavita; Chaudhary, Rubina; Sawhney, R.L.

2008-01-01

The present study is targeted on solar photocatalytic removal of metal ions from wastewater. Photoreductive deposition and dark adsorption of metal ions Cu(II), Ni(II), Pb(II) and Zn(II), using solar energy irradiated TiO 2 , has been investigated. Citric acid has been used as a hole scavenger. Modeling of metal species has been performed and speciation is used as a tool for discussing the photodeposition trends. Ninety-seven percent reductive deposition was obtained for copper. The deposition values of other metals were significantly low [nickel (36.4%), zinc (22.2%) and lead (41.4%)], indicating that the photocatalytic treatment process, using solar energy, was more suitable for wastewater containing Cu(II) ions. In absence of citric acid, the decreasing order deposition was Cu(II) > Ni(II) > Pb(II) > Zn(II), which proves the theoretical thermodynamic predictions about the metals

Cd(II), Cu(II)

African Journals Online (AJOL)

user

Depending on the way goethite was pretreated with oxalic acid, affinity for Cd(II) varied ...... Effects and mechanisms of oxalate on Cd(II) adsorption on goethite at different ... precipitation, surfactant mediation, hydrothermal and micro-emulsion.

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial.

Science.gov (United States)

Prajna, N Venkatesh; Krishnan, Tiruvengada; Rajaraman, Revathi; Patel, Sushila; Srinivasan, Muthiah; Das, Manoranjan; Ray, Kathryn J; O'Brien, Kieran S; Oldenburg, Catherine E; McLeod, Stephen D; Zegans, Michael E; Porco, Travis C; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer

2016-12-01

To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis. Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. The primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use. A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some

The Clinical and Economic Impact of Generic Locking Plate Utilization at a Level II Trauma Center.

Science.gov (United States)

Mcphillamy, Austin; Gurnea, Taylor P; Moody, Alastair E; Kurnik, Christopher G; Lu, Minggen

2016-12-01

In today's climate of cost containment and fiscal responsibility, generic implant alternatives represent an interesting area of untapped resources. As patents have expired on many commonly used trauma implants, generic alternatives have recently become available from a variety of sources. The purpose of this study was to examine the clinical and economic impact of a cost containment program using high quality, generic orthopaedic locking plates. The implants available for study were anatomically precontoured plates for the clavicle, proximal humerus, distal radius, proximal tibia, distal tibia, and distal fibula. Retrospective review. Level II Trauma center. 828 adult patients with operatively managed clavicle, proximal humerus, distal radius, proximal tibia, tibial pilon, and ankle fractures. Operative treatment with conventional or generic implants. The 414 patients treated with generic implants were compared with 414 patients treated with conventional implants. There were no significant differences in age, sex, presence of diabetes, smoking history or fracture type between the generic and conventional groups. No difference in operative time, estimated blood loss or intraoperative complication rate was observed. No increase in postoperative infection rate, hardware failure, hardware loosening, malunion, nonunion or need for hardware removal was noted. Overall, our hospital realized a 56% reduction in implant costs, an average savings of $1197 per case, and a total savings of $458,080 for the study period. Use of generic orthopaedic implants has been successful at our institution, providing equivalent clinical outcomes while significantly reducing implant expenditures. Based on our data, the use of generic implants has the potential to markedly reduce operative costs as long as quality products are used. Therapeutic Level III.

Early Experience with the Amplatzer Vascular Plug II for Occlusive Purposes in Arteriovenous Hemodialysis Access

International Nuclear Information System (INIS)

Powell, Steven; Narlawar, Ranjeet; Odetoyinbo, Tolulola; Littler, Peter; Oweis, Deyana; Sharma, Ajay; Bakran, Ali

2010-01-01

The Amplatzer Vascular Plug Type II (AVP II) has proven effective in the therapeutic embolization of various vascular lesions. It benefits from very rapid occlusion of the target lesion and can be deployed, retrieved, and redeployed if required. There is no literature available on use of the AVP II in the maintenance, closure, and management of complicated arteriovenous access in hemodialysis patients. In this series, we present our clinical experience with the use of the AVP II for embolization of problematic hemodialysis access. The AVP II is a self-expandable Nitinol wire-mesh device. Mounted on a delivery wire it has the capability to be deployed, recaptured, and redeployed. In total seven patients (four males: one diabetic, all nonsmokers), with ages ranging from 44 to 81 years (mean, 63 years), were treated between July 2008 and January 2009. One patient had not started dialysis. The remaining six patients had varied histories, with the time on hemodialysis ranging from 1 to 21 years. Retrospective review of clinical notes revealed patient demographics, type of access, device size, deployment site, and outcomes. Indications for embolization included steal syndrome (one patient), high-flow tributaries (two patients), and limb swelling (four patients). All patients had clinical and sonographical follow-up to 3 months. Surgical ligation had either failed, was considered a contraindication due to concerns regarding wound healing, or was considered difficult due to complex venous anatomy. Only one device was used in each patient, ranging from 6 to 16 mm in diameter. Immediate technical success was seen in 100%. All these patients were followed up clinically in the vascular access radiology clinic at 4 weeks and 3 months. Occlusion of the treated vessel and resolution of symptoms were reconfirmed in 100% of cases at 3 months. It was also noted whether patients were having successful dialysis, if required. There were no complications. Average procedural time was 19

Feedback in Clinical Education, Part II: Approved Clinical Instructor and Student Perceptions of and Influences on Feedback

Science.gov (United States)

Nottingham, Sara; Henning, Jolene

2014-01-01

Context: Approved Clinical Instructors (ACIs; now known as preceptors) are expected to provide feedback to athletic training students (ATSs) during clinical education experiences. Researchers in other fields have found that clinical instructors and students often have different perceptions of actual and ideal feedback and that several factors may influence the feedback exchanges between instructors and students. However, understanding of these issues in athletic training education is minimal. Objective: To investigate the current characteristics and perceptions of and the influences on feedback exchanges between ATSs and ACIs. Design: Qualitative study. Setting: One entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants: Four ACIs and 4 second-year ATSs. Data Collection and Analysis: Individual, semistructured interviews were conducted with participants and integrated with field notes and observations for analysis. We used the constant comparative approach to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results: Participants described that feedback plays an important role in clinical education and has several purposes related to improving performance. The ACIs and ATSs also discussed several preferred characteristics of feedback. Participants identified 4 main influences on their feedback exchanges, including the ACI, the ATS, personalities, and the learning environment. Conclusions: The ACIs and ATSs had similar perceptions of ideal feedback in addition to the actual feedback that was provided during their clinical education experiences. Most of the preferences for feedback were aligned with recommendations in the literature, suggesting that existing research findings are applicable to athletic training clinical education. Several factors influenced the

Sequestration of Cu(II), Ni(II), and Co(II) by ethyleneimine immobilized on silica

International Nuclear Information System (INIS)

Arakaki, Luiza N.H.; Alves, Ana Paula M.; Silva Filho, Edson C. da; Fonseca, Maria G.; Oliveira, Severino F.; Espinola, Jose Geraldo P.; Airoldi, Claudio

2007-01-01

Thermodynamic data on interaction of Cu(II), Ni(II), and Co(II) with silica modified with ethyleneimine are obtained by calorimetric titration. The amount of ethyleneimine anchored on silica surface was estimated to be 0.70 mmol g -1 . The enthalpies of binding Ni(II), Cu(II) and Co(II), are -3.59 ± 0.001, -4.88 ± 0.001, and -7.75 ± 0.003 kJ mol -1 , respectively

Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology

Directory of Open Access Journals (Sweden)

Kazanji Mirdad

2003-01-01

Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

Electrodiagnostic evaluation of median nerve conduction in Type II ...

African Journals Online (AJOL)

MJP

2015-12-29

Dec 29, 2015 ... Type II diabetes mellitus patients that were asymptomatic for peripheral neuropathy: a case control study. Owolabi LF 1*, Adebisi S2, ... degree of abnormality and monitoring the clinical course of the disease. Symptoms of DN ...

Insulin-Like growth factor-II (IGF-II) prevents proinflammatory cytokine-induced apoptosis and significantly improves islet survival after transplantation.

Science.gov (United States)

Hughes, Amy; Mohanasundaram, Daisy; Kireta, Svjetlana; Jessup, Claire F; Drogemuller, Chris J; Coates, P Toby H

2013-03-15

The early loss of functional islet mass (50-70%) due to apoptosis after clinical transplantation contributes to islet allograft failure. Insulin-like growth factor (IGF)-II is an antiapoptotic protein that is highly expressed in β-cells during development but rapidly decreases in postnatal life. We used an adenoviral (Ad) vector to overexpress IGF-II in isolated rat islets and investigated its antiapoptotic action against exogenous cytokines interleukin-1β- and interferon-γ-induced islet cell death in vitro. Using an immunocompromised marginal mass islet transplant model, the ability of Ad-IGF-II-transduced rat islets to restore euglycemia in nonobese diabetic/severe combined immunodeficient diabetic recipients was assessed. Ad-IGF-II transduction did not affect islet viability or function. Ad-IGF-II cytokine-treated islets exhibited decreased cell death (40% ± 2.8%) versus Ad-GFP and untransduced control islets (63.2% ± 2.5% and 53.6% ± 2.3%, respectively). Ad-IGF-II overexpression during cytokine treatment resulted in a marked reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (8.3% ± 1.4%) versus Ad-GFP control (41% ± 4.2%) and untransduced control islets (46.5% ± 6.2%). Western blot analysis confirmed that IGF-II inhibits apoptosis via activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. Transplantation of IGF-II overexpressing islets under the kidney capsule of diabetic mice restored euglycemia in 77.8% of recipients compared with 18.2% and 47.5% of Ad-GFP and untransduced control islet recipients, respectively (Pislet transplant outcomes in vivo. Antiapoptotic gene transfer is a potentially powerful tool to improve islet survival after transplantation.

Comparison of (211)At-PRIT and (211)At-RIT of Ovarian Microtumors in a Nude Mouse Model

DEFF Research Database (Denmark)

Frost, Sofia H L; Bäck, Tom; Chouin, Nicolas

2013-01-01

Abstract Purpose: Pretargeted radioimmunotherapy (PRIT) against intraperitoneal (i.p.) ovarian microtumors using avidin-conjugated monoclonal antibody MX35 (avidin-MX35) and (211)At-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PL(suc)) was compared with conventional...... radioimmunotherapy (RIT) using (211)At-labeled MX35 in a nude mouse model. Methods: Mice were inoculated i.p. with 1×10(7) NIH:OVCAR-3 cells. After 3 weeks, they received PRIT (1.0 or 1.5 MBq), RIT (0.9 MBq), or no treatment. Concurrently, 10 additional animals were sacrificed and examined to determine disease...

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.

Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity.

Science.gov (United States)

Stewart, Alesha C; Bethel, Christopher R; VanPelt, Jamie; Bergstrom, Alex; Cheng, Zishuo; Miller, Callie G; Williams, Cameron; Poth, Robert; Morris, Matthew; Lahey, Olivia; Nix, Jay C; Tierney, David L; Page, Richard C; Crowder, Michael W; Bonomo, Robert A; Fast, Walter

2017-12-08

Use and misuse of antibiotics have driven the evolution of serine β-lactamases to better recognize new generations of β-lactam drugs, but the selective pressures driving evolution of metallo-β-lactamases are less clear. Here, we present evidence that New Delhi metallo-β-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites. Each of the clinical variants is shown to be progressively more thermostable and to bind zinc(II) more tightly than NDM-1, but a selective enhancement of penam turnover at low zinc(II) concentrations indicates that most of the improvement derives from catalysis rather than stability. X-ray crystallography of NDM-4 and NDM-12, as well as bioinorganic spectroscopy of dizinc(II), zinc(II)/cobalt(II), and dicobalt(II) metalloforms probe the mechanism of enhanced resistance and reveal perturbations of the dinuclear metal cluster that underlie improved catalysis. These studies support the proposal that zinc(II) scarcity, rather than changes in antibiotic structure, is driving the evolution of new NDM variants in clinical settings.

Clinical significance of nuclide renal dynamic imaging and urine microalbumin inspection of type II diabetic patients

International Nuclear Information System (INIS)

Wang Ying; Jin Yaoge; Shi Xueying; Gao Yong

2011-01-01

To investigate clinical value of glomerular filtration rate (GFR) and urine microalbumin in early diagnosis of diabetic nephropathy, GFR in 60 patients with type II diabetes mellitus and a control group of 20 were determined using 99 Tc m DTPA renal dynamic imaging and urine microalbumin. The following results were obtained.Among the 60 patients with diabetes, 5 patients had increased GFRs of, 142.0±13.6 mg/min, which was 35% higher than that of controls and differed significantly from the control (P<0.01); 20 patients had GFRs of 102.2±10.2 mg/min, which differed little from the control; and 35 patients had declined GFRs of 57.2±18.0 mg/min, which was 54.3% lowered than the control and differed significantly from the control (P<0.01). The urine microalbumin in diabetes patients was significantly higher than the control. In conclusion, the GFR is a good index of the early kidney injury in diabetic patients. The combined detection of GFR and urine microalbumin can improve the early diagnosis of diabetic nephropathy, and may help to monitor the treatment response and assess prognosis. (authors)

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

International Nuclear Information System (INIS)

Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M.; Xu, Hong; Guo, Hong-fen; Chalasani, Sandhya; Carrasquillo, Jorge A.; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; O'Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K.D.; Cheung, Nai-Kong V.

2016-01-01

GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens 177 Lu-or 86 Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq 177 Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm 3 ) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm 3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten 86 Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

Solid-phase extraction of Mn(II), Co(II), Ni(II), Cu(II), Cd(II) and Pb(II) ions from environmental samples by flame atomic absorption spectrometry (FAAS)

Energy Technology Data Exchange (ETDEWEB)

Duran, Celal [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Gundogdu, Ali [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Bulut, Volkan Numan [Department of Chemistry, Giresun Faculty of Art and Science, Karadeniz Technical University, 28049 Giresun (Turkey); Soylak, Mustafa [Department of Chemistry, Faculty of Art and Science, Erciyes University, 38039 Kayseri (Turkey)]. E-mail: soylak@erciyes.edu.tr; Elci, Latif [Department of Chemistry, Faculty of Art and Science, Pamukkale University, 20020 Denizli (Turkey); Sentuerk, Hasan Basri [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Tuefekci, Mehmet [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey)

2007-07-19

A new method using a column packed with Amberlite XAD-2010 resin as a solid-phase extractant has been developed for the multi-element preconcentration of Mn(II), Co(II), Ni(II), Cu(II), Cd(II), and Pb(II) ions based on their complex formation with the sodium diethyldithiocarbamate (Na-DDTC) prior to flame atomic absorption spectrometric (FAAS) determinations. Metal complexes sorbed on the resin were eluted by 1 mol L{sup -1} HNO{sub 3} in acetone. Effects of the analytical conditions over the preconcentration yields of the metal ions, such as pH, quantity of Na-DDTC, eluent type, sample volume and flow rate, foreign ions etc. have been investigated. The limits of detection (LOD) of the analytes were found in the range 0.08-0.26 {mu}g L{sup -1}. The method was validated by analyzing three certified reference materials. The method has been applied for the determination of trace elements in some environmental samples.

Use of Antihypertensive Drugs and Ischemic Stroke Severity - Is There a Role for Angiotensin-II?

NARCIS (Netherlands)

Hwong, Wen Yea; Bots, Michiel L.; Selvarajah, Sharmini; Aziz, Zariah Abdul; Sidek, Norsima Nazifah; Spiering, Wilko; Kappelle, L. Jaap; Vaartjes, Ilonca

2016-01-01

BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of

HTLV-I/II prevalence in different geographic locations

NARCIS (Netherlands)

Vrielink, Hans; Reesink, Henk W.

2004-01-01

Human T-cell lymphotropic virus (HTLV) type I (HTLV-I) is the etiological agent of adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-II is a closely related virus, and this infection is not clearly associated with clinical disease, although

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

Science.gov (United States)

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell

A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

Science.gov (United States)

DiMasi, J A; Hermann, J C; Twyman, K; Kondru, R K; Stergiopoulos, S; Getz, K A; Rackoff, W

2015-11-01

We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision-making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine-learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four-factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence-related measure) had high sensitivity and specificity for predicting regulatory marketing approval. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Synergistic anti-cancer response to chemotherapy and 177Lu-labelled APOMABR radioimmunotherapy in a preclinical model of lung cancer

International Nuclear Information System (INIS)

Staudacher, A.H.; Brown, M.P.

2015-01-01

after chemotherapy. However, combination of chemotherapy and 177 Lu-labelled APOMAB R had a synergistic response, resulting in a significant decrease in tumour growth and increased survival of tumour-bearing mice. Bio-distribution analysis revealed that radio-labelled APOMAB R targeted tumour tissue, and chemotherapy specifically increased tumour uptake of radio-labelled APOMAB R . Importantly, chemotherapy was not associated with increased normal tissue uptake of radio-labelled APOMAB R . Conclusions: We have demonstrated both in vitro and in vivo that APOMAB R is a dead tumour-cell specific antibody, and that 177 Lu-labelled APOMAB R is a safe and effective anti-cancer treatment when combined with chemotherapy. Given the safety and efficacy of a single cycle of β-radioimmunotherapy, multiple cycles of treatment, the substitution of an alpha-emitting radionuclide, or both, may provide further benefit and increase the anti-tumour response. (authors)

Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Penkowa, M; Espejo, C; Martínez-Cáceres, E M

2003-01-01

Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

Structure and Chromosomal Organization of Yeast Genes Regulated by Topoisomerase II.

Science.gov (United States)

Joshi, Ricky S; Nikolaou, Christoforos; Roca, Joaquim

2018-01-03

Cellular DNA topoisomerases (topo I and topo II) are highly conserved enzymes that regulate the topology of DNA during normal genome transactions, such as DNA transcription and replication. In budding yeast, topo I is dispensable whereas topo II is essential, suggesting fundamental and exclusive roles for topo II, which might include the functions of the topo IIa and topo IIb isoforms found in mammalian cells. In this review, we discuss major findings of the structure and chromosomal organization of genes regulated by topo II in budding yeast. Experimental data was derived from short (10 min) and long term (120 min) responses to topo II inactivation in top-2 ts mutants. First, we discuss how short term responses reveal a subset of yeast genes that are regulated by topo II depending on their promoter architecture. These short term responses also uncovered topo II regulation of transcription across multi-gene clusters, plausibly by common DNA topology management. Finally, we examine the effects of deactivated topo II on the elongation of RNA transcripts. Each study provides an insight into the particular chromatin structure that interacts with the activity of topo II. These findings are of notable clinical interest as numerous anti-cancer therapies interfere with topo II activity.

Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma

Energy Technology Data Exchange (ETDEWEB)

Heo, Young Jin [Inje University, Busan Paik Hospital, Department of Radiology, Busan (Korea, Republic of); Park, Ji Eun; Kim, Ho Sung; Lee, Ji Ye; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Nam, Soo Jeong [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

2017-07-15

To determine if gemistocytic grade II astrocytoma (GemA) and its MR imaging characteristics are associated with a shorter time-to-progression (TTP) compared with non-gemistocytic grade II astrocytoma (non-GemA). We enrolled 78 patients who were followed up more than 5 years (29 pathologically proven GemA and 49 non-GemA) during a 10-year period. Contrast-enhanced T1-weighted, diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC), and MR spectroscopy (MRS) and clinical data were retrospectively reviewed. Clinical and MR imaging features were analyzed as possible prognostic factors of high-grade transformation, and multivariate analysis of TTP was performed using Cox proportional modeling. GemA showed more frequent high-grade features than non-GemA, including diffusion restriction (P <.001), increased choline/creatine (P =.02), and increased choline/NAA ratio (P =.015). Patients with GemA had a significantly shorter median TTP (53.1 vs 68 months; P <.001). A gemistocytic histopathology (hazard ratio = 3.42; P =.015) and low ADC (hazard ratio = 3.61; P =.001) were independently associated with a shorter TTP. GemA can present with MR imaging findings mimicking high-grade glioma at initial diagnosis and transforms to high-grade disease earlier than non-GemA. Low ADC on DWI might be useful in stratifying the risk of progression in patients with grade II astrocytoma. (orig.)

Quality assessment of recent evidence-based clinical practice guidelines for management of type 2 diabetes mellitus in adults using the AGREE II instrument.

Science.gov (United States)

Anwer, Muhammad A; Al-Fahed, Ousama B; Arif, Samir I; Amer, Yasser S; Titi, Maher A; Al-Rukban, Mohammed O

2018-02-01

Type 2 diabetes mellitus (T2DM) is a worldwide and national public health problem that has a great impact on the population in Saudi Arabia. High-quality clinical practice guidelines (CPGs) are cornerstones in improving the health care provided for patients with diabetes. This study evaluated the methodological rigour, transparency, and applicability of recently published CPGs. Our group conducted a systematic search for recently published CPGs for T2DM. The searching and screening for Source CPGs were guided by tools from the ADAPTE methods with specific inclusion/exclusion criteria. Five reviewers using the second version of the Appraisal of Guidelines for Research and Evaluation (AGREE II) Instrument independently assessed the quality of the retrieved Source CPGs. Domains of Scope and purpose and Clarity of presentation received the highest scores in all CPGs. Most of the assessed CPGs (86%) were considered with high overall quality and were recommended for use. Rigour of development and applicability domains were together highest in 3 CPGs (43%). The overall high quality of DM CPGs published in the last 3 years demonstrated the continuous development and improvement in CPG methodologies and standards. Health care professionals should consider the quality of any CPG for T2DM before deciding to use it in their daily clinical practice. Three CPGs have been identified, using the AGREE criteria, as high-quality and trustworthy. Ideally, the resources provided by the AGREE trust including the AGREE II Instrument should be used by a clinician to scan through the large number of published T2DM CPGs to identify the CPGs with high methodological quality and applicability. © 2017 John Wiley & Sons, Ltd.

Average [O II] nebular emission associated with Mg II absorbers: dependence on Fe II absorption

Science.gov (United States)

Joshi, Ravi; Srianand, Raghunathan; Petitjean, Patrick; Noterdaeme, Pasquier

2018-05-01

We investigate the effect of Fe II equivalent width (W2600) and fibre size on the average luminosity of [O II] λλ3727, 3729 nebular emission associated with Mg II absorbers (at 0.55 ≤ z ≤ 1.3) in the composite spectra of quasars obtained with 3 and 2 arcsec fibres in the Sloan Digital Sky Survey. We confirm the presence of strong correlations between [O II] luminosity (L_{[O II]}) and equivalent width (W2796) and redshift of Mg II absorbers. However, we show L_{[O II]} and average luminosity surface density suffer from fibre size effects. More importantly, for a given fibre size, the average L_{[O II]} strongly depends on the equivalent width of Fe II absorption lines and found to be higher for Mg II absorbers with R ≡W2600/W2796 ≥ 0.5. In fact, we show the observed strong correlations of L_{[O II]} with W2796 and z of Mg II absorbers are mainly driven by such systems. Direct [O II] detections also confirm the link between L_{[O II]} and R. Therefore, one has to pay attention to the fibre losses and dependence of redshift evolution of Mg II absorbers on W2600 before using them as a luminosity unbiased probe of global star formation rate density. We show that the [O II] nebular emission detected in the stacked spectrum is not dominated by few direct detections (i.e. detections ≥3σ significant level). On an average, the systems with R ≥ 0.5 and W2796 ≥ 2 Å are more reddened, showing colour excess E(B - V) ˜ 0.02, with respect to the systems with R < 0.5 and most likely trace the high H I column density systems.

Clinical practice guidelines and consensus statements in oncology--an assessment of their methodological quality.

Directory of Open Access Journals (Sweden)

Carmel Jacobs

Full Text Available Consensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.Thirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored

Automated measurement of serum thyroxine with the ''AIRA II,'' as compared with competitive protein binding and radioimmunoassay

International Nuclear Information System (INIS)

Reese, M.G.; Johnson, L.V.R.

1978-01-01

Two conventional serum thyroxine assays, run in separate laboratories, one by competitive protein binding and one by radioimmunoassay, were used to evaluate the automated ARIA II (Becton Dickinson Immunodiagnostics) serum thyroxine assay. Competitive protein binding as compared to ARIA II with 111 clinical serum samples gave a slope of 1.04 and a correlation coefficient of 0.94. The radioimmunoassay comparison to ARIA II with 53 clinical serum samples gave a slope of 1.05 and a correlation coefficient of 0.92. The ARIA II inter-assay coefficient of variation for 10 replicates of low, medium, and high thyroxine serum samples was 6.2, 6.0, and 2.9%, respectively, with an inter-assay coefficient of variation among 15 different assays of 15.5, 10.1, and 7.9%. The automated ARIA II, with a 2.2-min cycle per sample, gives results that compare well with those by manual methodology

Potential Clinical Implications of the Urotensin II Receptor Antagonists

Directory of Open Access Journals (Sweden)

Emilie Kane

2011-07-01

Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

The bipolar II disorder personality traits, a true syndrome?

Science.gov (United States)

Gudmundsson, Einar

2015-06-01

The author was struck by the similarities and commonality of complaints, aside from mood swings, made by Bipolar II patients and started registrating these complaints. This registrational work eventually led to the development of The Bipolar II Syndome Checklist. The aim of this work was to understand how widely the Bipolar II disorder affects the personality, and what disturbing personality traits are the most common? Deliberately, no attempt was made to diagnose psychiatric comorbidities, in the hope that one would get a clearer view of what symptoms, if any, could be considered a natural part of the Bipolar II Disorder. As far as the author knows this is a novel approach. 105 Bipolar II patients completed the Bipolar II Syndrome Checklist. The answers to the 44 questions on the list are presented in tables. Symptoms like anxiety, low self esteem, paranoia, extreme hurtfulness, migraine, Post Partum Depression, obsessive traits, alcoholism in the family are amongst the findings which will be presented in greater detail. No control group. Bipolar I patients excluded. The Bipolar II Syndrome Checklist has not been systematically validated. The results show that Bipolar II Disorder causes multiple symptoms so commonly that it may be justified to describe it as a syndrome, The Bipolar II Syndrome. Also these disturbances commonly lie in families of Bipolar II patients and are in all likelihood, greatly underdiagnosed. The clinical relevance of this study lies in increasing our knowledge and understanding of the nature of the Bipolar II Disorder, which in all probability will increase the diagnostic and treatment accuracy, since clinicians are more likely to scan for other symptoms needing treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural information on the coordination compounds formed by manganese(II), cobalt(II), nickel(II), zinc(II), cadmium(II) and mercury(II) thiocyanates with 4-cyanopyridine N-oxide from their magnetic moments, electronic and infrared spectra

Science.gov (United States)

Ahuja, I. S.; Yadava, C. L.; Singh, Raghuvir

1982-05-01

Coordination compounds formed by the interaction of 4-cyanopyridine. N-oxide (4-CPO), a potentially bidentate ligand, with manganese(II), cobalt(II), nickel(II), zinc(II), cadmium(II) and rnercury(II) thiocyanates have been prepared and characterized from their elemental analyses, magnetic susceptibilities, electronic and infrared spectral studies down to 200 cm -1 in the solid state. The compounds isolated are: Mn(4-CPO) 2(NCS) 2, Co(4-CPO) 2(NCS) 2,Ni(4-CPO) 2(NCS) 2,Zn(4-CPO) 2(NCS) 2, Cd(4-CPO)(NCS) 2 and Hg(4-CPO) 2(SCN) 2. It is shown that 4-CPO acts as a terminal N-oxide oxygen bonded monodentate ligand in all the metal(II) thiocyanate complexes studied. Tentative stereochemistries of the complexes in the solid state are discussed. The ligand field parameters 10 Dq, B, β and λ calculated for the manganese(II), cobalt(II) and nickel(II) complexes are consistent with their proposed stereochemistries.

Macrocyclic receptor showing extremely high Sr(II)/Ca(II) and Pb(II)/Ca(II) selectivities with potential application in chelation treatment of metal intoxication.

Science.gov (United States)

Ferreirós-Martínez, Raquel; Esteban-Gómez, David; Tóth, Éva; de Blas, Andrés; Platas-Iglesias, Carlos; Rodríguez-Blas, Teresa

2011-04-18

Herein we report a detailed investigation of the complexation properties of the macrocyclic decadentate receptor N,N'-Bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6) toward different divalent metal ions [Zn(II), Cd(II), Pb(II), Sr(II), and Ca(II)] in aqueous solution. We have found that this ligand is especially suited for the complexation of large metal ions such as Sr(II) and Pb(II), which results in very high Pb(II)/Ca(II) and Pb(II)/Zn(II) selectivities (in fact, higher than those found for ligands widely used for the treatment of lead poisoning such as ethylenediaminetetraacetic acid (edta)), as well as in the highest Sr(II)/Ca(II) selectivity reported so far. These results have been rationalized on the basis of the structure of the complexes. X-ray crystal diffraction, (1)H and (13)C NMR spectroscopy, as well as theoretical calculations at the density functional theory (B3LYP) level have been performed. Our results indicate that for large metal ions such as Pb(II) and Sr(II) the most stable conformation is Δ(δλδ)(δλδ), while for Ca(II) our calculations predict the Δ(λδλ)(λδλ) form being the most stable one. The selectivity that bp18c6(2-) shows for Sr(II) over Ca(II) can be attributed to a better fit between the large Sr(II) ions and the relatively large crown fragment of the ligand. The X-ray crystal structure of the Pb(II) complex shows that the Δ(δλδ)(δλδ) conformation observed in solution is also maintained in the solid state. The Pb(II) ion is endocyclically coordinated, being directly bound to the 10 donor atoms of the ligand. The bond distances to the donor atoms of the pendant arms (2.55-2.60 Å) are substantially shorter than those between the metal ion and the donor atoms of the crown moiety (2.92-3.04 Å). This is a typical situation observed for the so-called hemidirected compounds, in which the Pb(II) lone pair is stereochemically active. The X-ray structures of the Zn(II) and Cd(II) complexes show that

TcI, TcII and TcVI Trypanosoma cruzi samples from Chagas disease patients with distinct clinical forms and critical analysis of in vitro and in vivo behavior, response to treatment and infection evolution in murine model.

Science.gov (United States)

Oliveira, Maykon Tavares de; Branquinho, Renata Tupinambá; Alessio, Gláucia Diniz; Mello, Carlos Geraldo Campos; Nogueira-de-Paiva, Nívia Carolina; Carneiro, Cláudia Martins; Toledo, Max Jean de Ornelas; Reis, Alexandre Barbosa; Martins-Filho, Olindo Assis Martins; Lana, Marta de

2017-03-01

The clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association between parasite's genetic, biological behavior and possibly the clinical aspects of Chagas disease in patients from whom they were isolated. This study intended to characterize a range of biological properties of TcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biological features were evaluated, including in vitro epimastigote-growth, "Vero"cells infectivity and growth, along with in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis and response to treatment by nifurtimox during the acute and chronic murine infection. The global results showed that the in vitro essays (acellular and cellular cultures) TcII parasites showed higher values for all parameters (growth and infectivity) than TcVI, followed by TcI. In vivo TcII parasites were more virulent and originated from patients with severe disease. Two TcII isolates from patients with severe pathology were virulent in mice, while the isolate from a patient with the indeterminate form of the disease caused mild infection. The only TcVI sample, which displayed low values in all parameters evaluated, was also originated of an indeterminate case of Chagas disease. Response to nifurtimox was not associated to parasite genetic and biology, as well as to clinical aspects of human disease. Although few number of T. cruzi samples have been analyzed, a discreet correlation between parasite genetics, biological behavior in vitro and in vivo (murine model) and the clinical form of human disease from whom the samples were isolated was verified. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of qnr, intI, and intII genes in extendedspectrum beta ...

African Journals Online (AJOL)

Purpose: To investigate the prevalence of qnr, intI, and intII genes in extended spectrum betalactamase (ESBL)-producing Escherichia coli isolated from clinical samples in Kerman, Iran. Methods: A total of 127 E. coli were collected from clinical samples in Kerman hospitals. The antibiotic susceptibility test was performed ...

Inducement of radionuclides targeting therapy by gene transfection

International Nuclear Information System (INIS)

Luo Quanyong

2001-01-01

The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

Accentuated hyperparathyroidism in type II Bartter syndrome.

Science.gov (United States)

Landau, Daniel; Gurevich, Evgenia; Sinai-Treiman, Levana; Shalev, Hannah

2016-07-01

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 ± 85.8 vs. 92.5 ± 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 ± 0.71 vs. 0.01 ± 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 ± 1.25 vs. 4.36 ± 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

Does temperamental instability support a continuity between bipolar II disorder and major depressive disorder?

Science.gov (United States)

Benazzi, F

2006-06-01

The current categorical split of mood disorders in bipolar disorders and depressive disorders has recently been questioned. Two highly unstable personality features, i.e. the cyclothymic temperament (CT) and borderline personality disorder (BPD), have been found to be more common in bipolar II (BP-II) disorder than in major depressive disorder (MDD). According to Kraepelin, temperamental instability was the "foundation" of his unitary view of mood disorders. The aim was to assess the distributions of the number of CT and borderline personality items between BP-II and MDD. Finding no bi-modal distribution (a "zone of rarity") of these items would support a continuity between the two disorders. an outpatient psychiatry private practice. Interviewer: A senior clinical and mood disorder research psychiatrist. A consecutive sample of 138 BP-II and 71 MDD remitted outpatients. Assessment instruments: The structured clinical interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV), the SCID-II Personality Questionnaire for self-assessing borderline personality traits (BPT) by patients, the TEMPS-A for self-assessing CT by patients. Interview methods: Patients were interviewed with the SCID-CV to diagnose BP-II and MDD, and then patients self-assessed the questions of the Personality Questionnaire relative to borderline personality, and the questions of the TEMPS-A relative to CT. As clinically significant distress or impairment of functioning is not assessed by the SCID-II Personality Questionnaire, a diagnosis of BPD could not be made, but BPT could be assessed (i.e. all BPD items but not the impairment criterion). The distribution of the number of CT and BPT items was studied by Kernel density estimate. CT and BPT items were significantly more common in BP-II versus MDD. The Kernel density estimate distributions of the number of CT and BPT items in the entire sample had a normal-like shape (i.e. no bi-modality). The expected finding, on the basis of previous

Test Review: Review of the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II)

Science.gov (United States)

McCrimmon, Adam W.; Smith, Amanda D.

2013-01-01

The Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II; Wechsler, 2011), published by Pearson, is a newly updated abbreviated measure of cognitive intelligence designed for individuals 6 to 90 years of age. Primarily used in clinical, psychoeducational, and research settings, the WASI-II was developed to quickly and accurately…

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

Science.gov (United States)

Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

2017-06-01

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Solid Phase Extraction of Trace Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) Ions in Beverages on Functionalized Polymer Microspheres Prior to Flame Atomic Absorption Spectrometric Determinations.

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Berber, Hale; Alpdogan, Güzin

2017-01-01

In this study, poly(glycidyl methacrylate-methyl methacrylate-divinylbenzene) was synthesized in the form of microspheres, and then functionalized by 2-aminobenzothiazole ligand. The sorption properties of these functionalized microspheres were investigated for separation, preconcentration and determination of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions using flame atomic absorption spectrometry. The optimum pH values for quantitative sorption were 2 - 4, 5 - 8, 6 - 8, 4 - 6, 2 - 6 and 2 - 3 for Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II), respectively, and also the highest sorption capacity of the functionalized microspheres was found to be for Cu(II) with the value of 1.87 mmol g -1 . The detection limits (3σ; N = 6) obtained for the studied metals in the optimal conditions were observed in the range of 0.26 - 2.20 μg L -1 . The proposed method was successfully applied to different beverage samples for the determination of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions, with the relative standard deviation of <3.7%.

[The effectiveness of magnetic therapy of grade I-II radiation pneumofibrosis].

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Grushina, T I

2014-01-01

Radiation therapy of malignant tumours of the chest organs may result in radiation damage of the lungs. To prevent and reduce radiation-induced lung injuries, new types of radiation therapy have been developed, a number of various modifiers investigated, the methods of pharmacotherapy and physiotherapy proposed. The present study involved 37 patients presenting with radiation pneumofibrosis, including 7 ones with lung cancer and 30 patients with breast cancer. Based on the results of clinical, radiographic, and functional investigations, grade 1 and II pneumofibrosis was diagnosed in 20 and 17 patients respectively. After the application of an alternating magnetic field during 15 days, all the patients experience the overall regression of clinical symptoms and disorders of respiratory biomechanics. However, it seems premature to draw a definitive conclusion about the effectiveness of magnetic therapy of grade 1 and II radiation pneumofibrosis before the extensive in-depth investigations are carried out based on a large clinical material including the results of long-term follow-up studies and continuous monitoring.

Clinical significance of measurement of serum insulin-like growth factor II and adrenomedulion levels in patients with essential hypertension

International Nuclear Information System (INIS)

Fan Bifu; Ji Naijun; Mei Yibin; Wang Chengyao; Chen Donghai; Li Fuyuan; Guan Lihua; Gao Meiying

2003-01-01

Objective: To investigate the changes of serum levels of insulin-like growth factor II (IGF II) and adrenomedullin (ADM) in patients with essential hypertension. Methods: Serum IGF II and ADM levels were measured in 62 cases of hypertension and 40 controls with RIA. Results: Serum IGF II and ADM levels were significantly bigger in hypertensive patients than those in the controls (t = 4.454, p < 0.01; t = 3.992, p < 0.01). The serum IGF II level was significantly positively correlated to the serum ADM levels (r = 0.379, p < 0.05) and both were significantly positively correlated to the mean arterial pressure (r = 0.346, r = 0.353, p < 0.05) but not with BMI. Serum ADM levels increased gradually as the disease progressed from stage I to stage III (p < 0.05) with levels in stage III markedly higher than those in stage I (p < 0.01). In EH patients with heart and/or brain and/or renal complications the serum ADM levels were significantly higher than those in EH patients without complications (t = 2.050, p < 0.05). Such differences did not exist in the case of IGF II. Conclusion: Serum IGF II and ADM levels were increased markedly in hypertensive patients. These two factors were mutually positively correlated and both were positively correlated to mean arterial pressure. ADM levels increased gradually as the disease progressing but IGF II levels remained stable

Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity

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Simona Crea

2017-05-01

Full Text Available Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients.Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy, the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle as secondary outcomes.Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days and after (3–4 months follow-up the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the

Phase-II Clinical Validation of a Powered Exoskeleton for the Treatment of Elbow Spasticity.

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Crea, Simona; Cempini, Marco; Mazzoleni, Stefano; Carrozza, Maria Chiara; Posteraro, Federico; Vitiello, Nicola

2017-01-01

Introduction: Spasticity is a typical motor disorder in patients affected by stroke. Typically post-stroke rehabilitation consists of repetition of mobilization exercises on impaired limbs, aimed to reduce muscle hypertonia and mitigate spastic reflexes. It is currently strongly debated if the treatment's effectiveness improves with the timeliness of its adoption; in particular, starting intensive rehabilitation as close as possible to the stroke event may counteract the growth and postpone the onset of spasticity. In this paper we present a phase-II clinical validation of a robotic exoskeleton in treating subacute post-stroke patients. Methods: Seventeen post-stroke patients participated in 10 daily rehabilitation sessions using the NEUROExos Elbow Module exoskeleton, each one lasting 45 min: the exercises consisted of isokinetic passive mobilization of the elbow, with torque threshold to detect excessive user's resistance to the movement. We investigated the safety by reporting possible adverse events, such as mechanical, electrical or software failures of the device or injuries or pain experienced by the patient. As regards the efficacy , the Modified Ashworth Scale, was identified as primary outcome measure and the NEEM metrics describing elbow joint resistance to passive extension (i.e., maximum extension torque and zero-torque angle) as secondary outcomes. Results: During the entire duration of the treatments no failures or adverse events for the patients were reported. No statistically significant differences were found in the Modified Ashworth Scale scores, between pre-treatment and post-treatment and between post-treatment and follow-up sessions, indicating the absence of spasticity increase throughout (14 days) and after (3-4 months follow-up) the treatment. Exoskeleton metrics confirmed the absence of significant difference in between pre- and post-treatment data, whereas intra-session data highlighted significant differences in the secondary outcomes

The clinical reasoning process in randomized clinical trials with patients with non-specific neck pain is incomplete: A systematic review.

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Maissan, Francois; Pool, Jan; de Raaij, Edwin; Mollema, Jürgen; Ostelo, Raymond; Wittink, Harriet

2018-06-01

Primarily to evaluate the completeness of the description of the clinical reasoning process in RCTs with patients with non-specific neck pain with an argued or diagnosed cause i.e. an impairment or activity limitation. Secondly, to determine the association between the completeness of the clinical reasoning process and the degree of risk of bias. Pubmed, Cinahl and PEDro were systematically searched from inception to July 2016. RCTs (n = 122) with patients with non-specific neck pain receiving physiotherapy treatment published in English were included. Data extraction included study characteristics and important features of the clinical reasoning process based on the Hypothesis-Oriented Algorithm for Clinicians II (HOAC II)]. Thirty-seven studies (30%) had a complete clinical reasoning process of which 8 (6%) had a 'diagnosed cause' and 29 (24%) had an 'argued cause'. The Spearmans rho association between the extent of the clinical reasoning process and the risk of bias was -0.2. In the majority of studies (70%) the described clinical reasoning process was incomplete. A very small proportion (6%) had a 'diagnosed cause'. Therefore, a better methodological quality does not necessarily imply a better described clinical reasoning process. Copyright © 2018 Elsevier Ltd. All rights reserved.

Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method.

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Goodman, Karyn A; Patton, Caroline E; Fisher, George A; Hoffe, Sarah E; Haddock, Michael G; Parikh, Parag J; Kim, John; Baxter, Nancy N; Czito, Brian G; Hong, Theodore S; Herman, Joseph M; Crane, Christopher H; Hoffman, Karen E

2016-01-01

To summarize results of a Clinical Practice Statement on radiation therapy for stage II-III rectal cancer, which addressed appropriate customization of (neo)adjuvant radiation therapy and use of non-surgical therapy for patients who are inoperable or refuse abdominoperineal resection. The RAND/University of California, Los Angeles, Appropriateness Method was applied to combine current evidence with multidisciplinary expert opinion. A systematic literature review was conducted and used by the expert panel to rate appropriateness of radiation therapy options for different clinical scenarios. Treatments were categorized by median rating as Appropriate, May Be Appropriate, or Rarely Appropriate. In the neoadjuvant setting, chemoradiation was rated Appropriate and the ratings indicated short-course radiation therapy, chemotherapy alone, and no neoadjuvant therapy are potential options in selected patients. However, neoadjuvant endorectal brachytherapy was rated Rarely Appropriate. For adjuvant therapy, chemoradiation (plus ≥4 months of chemotherapy) was rated Appropriate and chemotherapy alone May Be Appropriate for most scenarios. For medically inoperable patients, definitive external beam radiation therapy and chemotherapy alone were rated May Be Appropriate, whereas endorectal brachytherapy and chemoradiation plus endorectal brachytherapy were possible approaches for some scenarios. The last option, definitive chemoradiation, was rated Appropriate to May Be Appropriate based on performance status. Finally, for patients with low-lying tumors refusing abdominoperineal resection, definitive chemoradiation alone, chemoradiation plus endorectal brachytherapy, and chemoradiation plus external beam radiation therapy were all rated Appropriate. This Clinical Practice Statement demonstrated the central role of radiation therapy in stage II-III rectal cancer management and evaluated ways to better individualize its use in the neoadjuvant, adjuvant, and definitive settings

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

Science.gov (United States)

Saavedra Salinas, Miguel Ángel; Barrera Cruz, Antonio; Cabral Castañeda, Antonio Rafael; Jara Quezada, Luis Javier; Arce-Salinas, C Alejandro; Álvarez Nemegyei, José; Fraga Mouret, Antonio; Orozco Alcalá, Javier; Salazar Páramo, Mario; Cruz Reyes, Claudia Verónica; Andrade Ortega, Lilia; Vera Lastra, Olga Lidia; Mendoza Pinto, Claudia; Sánchez González, Antonio; Cruz Cruz, Polita Del Rocío; Morales Hernández, Sara; Portela Hernández, Margarita; Pérez Cristóbal, Mario; Medina García, Gabriela; Hernández Romero, Noé; Velarde Ochoa, María Del Carmen; Navarro Zarza, José Eduardo; Portillo Díaz, Verónica; Vargas Guerrero, Angélica; Goycochea Robles, María Victoria; García Figueroa, José Luis; Barreira Mercado, Eduardo; Amigo Castañeda, Mary Carmen

2015-01-01

Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The World Health Organisation Disability Assessment Scale (WHODAS II: Links between self-rated health and objectively defined and clinical parameters in the population of spinal cord injury

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Steinerte V.

2016-01-01

Full Text Available There are many clinical and objectively defined parameters that are used to evaluate a person's disability. Since the World Health Organisation has presented the WHODAS II as a means of objectively measuring subjectively defined functions, greater attention has been focused on self-rated health. Only a few studies, however, have been conducted about differences between self-rated health and objectively defined parameters. The survey for this study was conducted on the basis of WHODAS II and the population in Latvia with spinal cord injury. Respondents were between 18 and 65, and 98 questionnaires were analysed. The results show that people with spinal cord injury on average rate their functioning as limited (33–40 points of 100. Most respondents have been declared to be disabled, which is defined as very serious or severe functional disorders. More than 40% have paid jobs, while one-third do not work for reasons of health. The research shows that there is a close coherence (p< 0.05 between individual, objectively and clinically defined indicators on the one hand and the aspects of the questionnaire in which physical functioning was an important factor on the other hand. In order to understand the real functional abilities of patients and the individual factors that influence those abilities, it is necessary to define functional self-rated health in addition to objectively defined indicators.

Transarterial Embolization of Type II Endoleaks after EVAR: The Role of Ethylene Vinyl Alcohol Copolymer (Onyx)

International Nuclear Information System (INIS)

Müller-Wille, René; Wohlgemuth, Walter A.; Heiss, Peter; Wiggermann, Philipp; Güntner, Oliver; Schreyer, Andreas G.; Hoffstetter, Patrick; Stroszczynski, Christian; Zorger, Niels

2013-01-01

Purpose: To determine the feasibility and efficacy of transarterial endoleak embolization using the liquid embolic agent ethylene vinyl alcohol copolymer (Onyx). Methods: Over a 7-year period eleven patients (6 women, 5 men; mean age 68 years, range 37–83 years) underwent transarterial embolization of a type II endoleak after endovascular aortic aneurysm repair using the liquid embolic agent Onyx. Two patients (18 %) had a simple type II endoleak with only one artery in communication with the aneurysm sac, whereas 9 patients (82 %) had a complex type II endoleak with multiple communicating vessels. We retrospectively analyzed the technical and clinical success of transarterial type II endoleak embolization with Onyx. Complete embolization of the nidus was defined as technical success. Embolization was considered clinically successful when volume of the aneurysm sac was stable or decreased on follow-up CT scans. Result: Mean follow-up time was 26.0 (range 6–50) months. Clinical success was achieved in 8 of 11 patients (73 %). Transarterial nidus embolization with Onyx was technically successful in 6 of 11 patients (55 %). In three cases the nidus was embolized without direct catheterization from a more distal access through the network of collateral vessels. Conclusion: Onyx is a favorable embolic agent for transarterial endoleak embolization. To achieve the best clinical results, complete occlusion of the nidus is mandatory

Transarterial Embolization of Type II Endoleaks after EVAR: The Role of Ethylene Vinyl Alcohol Copolymer (Onyx)

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Mueller-Wille, Rene, E-mail: rene.mueller-wille@ukr.de; Wohlgemuth, Walter A., E-mail: walter.wohlgemuth@ukr.de; Heiss, Peter, E-mail: peter.heiss@ukr.de; Wiggermann, Philipp, E-mail: philipp.wiggermann@ukr.de; Guentner, Oliver, E-mail: oliverguentner@yahoo.de; Schreyer, Andreas G., E-mail: andreas.schreyer@ukr.de; Hoffstetter, Patrick, E-mail: p.hoffstetter@asklepios.com; Stroszczynski, Christian, E-mail: christian.stros@ukr.de [University Medical Center Regensburg, Department of Radiology (Germany); Zorger, Niels, E-mail: niels.zorger@barmherzige-regensburg.de [Krankenhaus Barmherzige Brueder Regensburg, Department of Radiology (Germany)

2013-10-15

Purpose: To determine the feasibility and efficacy of transarterial endoleak embolization using the liquid embolic agent ethylene vinyl alcohol copolymer (Onyx). Methods: Over a 7-year period eleven patients (6 women, 5 men; mean age 68 years, range 37-83 years) underwent transarterial embolization of a type II endoleak after endovascular aortic aneurysm repair using the liquid embolic agent Onyx. Two patients (18 %) had a simple type II endoleak with only one artery in communication with the aneurysm sac, whereas 9 patients (82 %) had a complex type II endoleak with multiple communicating vessels. We retrospectively analyzed the technical and clinical success of transarterial type II endoleak embolization with Onyx. Complete embolization of the nidus was defined as technical success. Embolization was considered clinically successful when volume of the aneurysm sac was stable or decreased on follow-up CT scans. Result: Mean follow-up time was 26.0 (range 6-50) months. Clinical success was achieved in 8 of 11 patients (73 %). Transarterial nidus embolization with Onyx was technically successful in 6 of 11 patients (55 %). In three cases the nidus was embolized without direct catheterization from a more distal access through the network of collateral vessels. Conclusion: Onyx is a favorable embolic agent for transarterial endoleak embolization. To achieve the best clinical results, complete occlusion of the nidus is mandatory.

Biological behavior of 188Re-biotin chelate for multistep therapy with the avidin-biotin system

International Nuclear Information System (INIS)

Choi, T. H.; Ahn, S. H.; Choi, C. W.; Woo, K. S.; Jung, W. S.; Lim, S. J.; Lim, S. M.

1999-01-01

The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin for radioimmunotherapy (RAIT). Three-step pretargetting can potentially decreases harmful radiation to normal tissues in radioimmunotherapy. 188 Re from 188 W- 188 Re generator, is recently introduced in therapeutic nuclear medicine and made it possible to use whenever needed. We studied biotin-chelates MGB for use in the avidin/biotin pretargetting system. Chelates that hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to non-target cells. We synthesized MAG 2 GABA-Biocytin (MGB), labeled with 188 Re and evaluated biological behavior of 188 Re-MGB. biotinyl MAG 2 GABA bind the therapeutic radiometal 188 Re with excellent in vitro stability and have the required physiological properties for pretargetted therapy. In normal mice, 188 Re-MGB was excreted via hepatobiliary pathway, %ID/g of GI tract was 52.1 at 120min. In Raji cells tumor bearing nude mice, liver and colon were higher than those of normal mouse. Tumor uptake at 120min was 0.05%ID/g. 188 Re-MGB may have a role in pretargetted radioimmunotherapy

Intensive inpatient treatment for bulimia nervosa: Statistical and clinical significance of symptom changes.

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Diedrich, Alice; Schlegl, Sandra; Greetfeld, Martin; Fumi, Markus; Voderholzer, Ulrich

2018-03-01

This study examines the statistical and clinical significance of symptom changes during an intensive inpatient treatment program with a strong psychotherapeutic focus for individuals with severe bulimia nervosa. 295 consecutively admitted bulimic patients were administered the Structured Interview for Anorexic and Bulimic Syndromes-Self-Rating (SIAB-S), the Eating Disorder Inventory-2 (EDI-2), the Brief Symptom Inventory (BSI), and the Beck Depression Inventory-II (BDI-II) at treatment intake and discharge. Results indicated statistically significant symptom reductions with large effect sizes regarding severity of binge eating and compensatory behavior (SIAB-S), overall eating disorder symptom severity (EDI-2), overall psychopathology (BSI), and depressive symptom severity (BDI-II) even when controlling for antidepressant medication. The majority of patients showed either reliable (EDI-2: 33.7%, BSI: 34.8%, BDI-II: 18.1%) or even clinically significant symptom changes (EDI-2: 43.2%, BSI: 33.9%, BDI-II: 56.9%). Patients with clinically significant improvement were less distressed at intake and less likely to suffer from a comorbid borderline personality disorder when compared with those who did not improve to a clinically significant extent. Findings indicate that intensive psychotherapeutic inpatient treatment may be effective in about 75% of severely affected bulimic patients. For the remaining non-responding patients, inpatient treatment might be improved through an even stronger focus on the reduction of comorbid borderline personality traits.

A simplified suite of methods to evaluate chelator conjugation of antibodies: effects on hydrodynamic radius and biodistribution

International Nuclear Information System (INIS)

Al-Ejeh, Fares; Darby, Jocelyn M.; Thierry, Benjamin; Brown, Michael P.

2009-01-01

Introduction: Antibodies covalently conjugated with chelators such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) are required for radioimmunoscintigraphy and radioimmunotherapy, which are of growing importance in cancer medicine. Method: Here, we report a suite of simple methods that provide a preclinical assessment package for evaluating the effects of DOTA conjugation on the in vitro and in vivo performance of monoclonal antibodies. We exemplify the use of these methods by investigating the effects of DOTA conjugation on the biochemical properties of the DAB4 clone of the La/SSB-specific murine monoclonal autoantibody, APOMAB (registered) , which is a novel malignant cell death ligand. Results: We have developed a 96-well microtiter-plate assay to measure directly the concentration of DOTA and other chelators in antibody-chelator conjugate solutions. Coupled with a commercial assay for measuring protein concentration, the dual microtiter-plate method can rapidly determine chelator/antibody ratios in the same plate. The biochemical properties of DAB4 immunoconjugates were altered as the DOTA/Ab ratio increased so that: (i) mass/charge ratio decreased; (ii) hydrodynamic radius increased; (iii) antibody immunoactivity decreased; (iv) rate of chelation of metal ions and specific radioactivity both increased and in vivo, (v) tumor uptake decreased as nonspecific uptake by liver and spleen increased. Conclusion: This simplified suite of methods readily identifies biochemical characteristics of the DOTA-immunoconjugates such as hydrodynamic diameter and decreased mass/charge ratio associated with compromised immunotargeting efficiency and, thus, may prove useful for optimizing conjugation procedures in order to maximize immunoconjugate-mediated radioimmunoscintigraphy and radioimmunotherapy.

Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment

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van Maldegem Annemiek M

2012-01-01

Full Text Available Abstract Background High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years. Results We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures. Conclusion Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into

Fibromyalgia in the adult Danish population: II. A study of clinical features

DEFF Research Database (Denmark)

Prescott, E; Jacobsen, S; Kjøller, M

1993-01-01

Clinical characteristics of fibromyalgia have so far been based mainly on patients identified in rheumatologic settings. This paper offers the clinical findings in fibromyalgia based on a national health interview survey, in which 123 persons fulfilled preset criteria for widespread pain. Clinical......, headache, difficulty in stair-climbing, and poorer self-evaluated health with more tender points was found. Contrary to that which was expected, fibromyalgia subjects did not suffer from sleep disturbances, irritable bowels or morning stiffness. Our findings indicate that clinical characteristics...... of fibromyalgia in the general population may differ from those found in rheumatological settings....

Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models.

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Aya Sugyo

Full Text Available Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR, is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT with 90Y-TSP-A01 in pancreatic cancer mouse models.TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2 was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02 were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted.MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced.90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further

Assessment of depression in medical patients: a systematic review of the utility of the Beck Depression Inventory-II.

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Wang, Yuan-Pang; Gorenstein, Clarice

2013-09-01

To perform a systematic review of the utility of the Beck Depression Inventory for detecting depression in medical settings, this article focuses on the revised version of the scale (Beck Depression Inventory-II), which was reformulated according to the DSM-IV criteria for major depression. We examined relevant investigations with the Beck Depression Inventory-II for measuring depression in medical settings to provide guidelines for practicing clinicians. Considering the inclusion and exclusion criteria seventy articles were retained. Validation studies of the Beck Depression Inventory-II, in both primary care and hospital settings, were found for clinics of cardiology, neurology, obstetrics, brain injury, nephrology, chronic pain, chronic fatigue, oncology, and infectious disease. The Beck Depression Inventory-II showed high reliability and good correlation with measures of depression and anxiety. Its threshold for detecting depression varied according to the type of patients, suggesting the need for adjusted cut-off points. The somatic and cognitive-affective dimension described the latent structure of the instrument. The Beck Depression Inventory-II can be easily adapted in most clinical conditions for detecting major depression and recommending an appropriate intervention. Although this scale represents a sound path for detecting depression in patients with medical conditions, the clinician should seek evidence for how to interpret the score before using the Beck Depression Inventory-II to make clinical decisions.

Synthesis, characterization and thermal studies of nickel (II), copper (II), zinc (II) and cadmium (II) complexes with some mixed ligands

International Nuclear Information System (INIS)

Mitra, Samiran; Kundu, Parimal; Singh, Rajkumar Bhubon

1998-01-01

Dichloro-(DCA) and trichloroacetate(TCA) -cyclic ligand morpholine (Morph)/thiomorpholine (Tmorph)/methylmorpholine (Mmorph)/dimethyl-piperazine (DMP) complexes of nickel (II), copper (II), zinc (II) and cadmium (II) with the compositions [Ni(tmorph) 2 (DCA) 2 ], [Ni(tmorph) 2 (TCA) 2 ].2H 2 O, [Cu(DMP) 2 (TCA) 2 ],[ML 2 X 2 ].nH 2 O where M=Zn II or Cd II , L=Morph, DMP or tmorph and X=DCA or TCA and n=O except in case of [Cd (Morph) 2 (TCA) 2 ] where n=1 have been synthesised. Some intermediate complexes have been isolated by temperature arrest technique (pyrolysis) and characterised. Configurational and conformational changes have been studied by elemental analyses, IR and electronic spectra, magnetic moment data (in the case of Ni(II) and Cu(II) complexes) and thermal analysis. E a * , ΔH, and ΔS for the decomposition reaction of these complexes are evaluated and the stability of the complexes with respect to activation energy has also been compared. The linear correlation has been found between E a * and ΔS for the decomposition of the complexes. (author)

The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

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