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Single Infusion (single + infusion)
Selected AbstractsTiludronate infusion in the treatment of bone spavin: A double blind placebo-controlled trialEQUINE VETERINARY JOURNAL, Issue 5 2010M. R. GOUGH Summary Reasons for performing study: Tiludronate regulates bone remodelling through a decrease of the resorptive process and should therefore ameliorate the remodelling processes active in osteoarthritis of the distal tarsal joints (,bone spavin') and alleviate pain associated with abnormal bone lysis. Objective: To confirm the efficacy of tiludronate, administered as a single infusion at a dose of 1 mg/kg bwt, in the treatment of bone spavin in the horse. Methods: A double blind placebo controlled trial on 108 clinical cases of bone spavin was undertaken. The lameness score of the lamest limb was assessed following distal tarsal analgesia of the contralateral limb and followed-up using the same procedure throughout the study. Bone spavin in the lamest limb was confirmed by distal tarsal analgesia and radiography. Horses were treated at Day 0 and reassessed 60 days later after controlled exercise. A second nonblinded treatment was given to unresponsive horses and all horses were re-examined at Day 120. Exercise levels were recorded at each examination. Results: Eighty-seven horses completed the trial as per the protocol. The tiludronate horses were significantly less lame than the placebo horses (P = 0.0318). Horses treated at Day 60 with tiludronate showed further improvement in lameness at Day 120 (P = 0.0096 and P = 0.0034 for horses treated with tiludronate and placebo at Day 0, respectively). The only significant difference in radiographic findings between tiludronate and placebo was for presence of periarticular osteophytes (P = 0.006). Conclusions: Tiludronate treatment is proven to be effective in bone spavin in horses in association with a controlled exercise programme. Clinical relevance: Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin. [source] Data presented at the 49th Annual Meeting of the American Society of Hematology held in Atlanta, Georgia in December 2007, has demonstrated dramatic positive results for the treatment of advanced follicular lymphoma with a single infusion of a combined anti-CD20 monoclonal antibody and a radioisotope.FUTURE PRESCRIBER, Issue 1 2008Rhonda Siddall No abstract is available for this article. [source] Reformulated BeneFix®: efficacy and safety in previously treated patients with moderately severe to severe haemophilia BHAEMOPHILIA, Issue 3 2007T. LAMBERT Summary. BeneFix®, the only recombinant factor IX (FIX), has been reformulated. The reformulation involves a change in diluent and allows for more concentrated infusions of recombinant FIX. A double-blind, randomized, pharmacokinetic (PK) crossover study demonstrated that reformulated BeneFix was bioequivalent to original BeneFix and follow-up PK evaluation after 6 months of treatment demonstrated the PK stability of reformulated BeneFix after multiple exposures. Favourable efficacy and safety profiles, consistent with those already well-established for original BeneFix, were observed: 81.1% of haemorrhages resolved with only a single infusion; 85.3% of initial treatment response ratings were Excellent or Good; more than half of the subjects using reformulated BeneFix for routine prophylaxis (11 of 17, 64.7%) had no spontaneous haemorrhages during their 6,12 month course of prophylactic treatment, with an overall spontaneous bleeding rate of 0.72 year,1; and for the single surgical procedure (knee washing), treatment was rated Useful. In addition, there was no FIX inhibitor development, allergic-type manifestations, or thrombogenic complications with more than 1100 infusions (nearly 5.2 million IUs) administered in this trial. All efficacy and safety outcomes from this study were achieved with more concentrated recombinant protein infusions than that possible with original BeneFix, and utilization of the 2000 IU per vial dosage strength, newly introduced with the reformulated product, was high (>62%). The reformulation of BeneFix allows smaller delivery volumes and an increased choice of dosage strengths without altering the PK properties (including incremental recovery and half-life) or the established efficacy and safety profile of recombinant FIX. [source] Proposal of a standard approach to dental extraction in haemophilia patients.HAEMOPHILIA, Issue 5 2000A case-control study with good results We found no case,control studies on dental extraction in haemophilia patients in the literature even though the use of antifibrinolytic agents following a single infusion of factor VIII or IX has been accompanied by a lower number of bleeding complications in dental extractions. In this study we verified the incidence of bleeding complications after dental extraction in a group of 77 haemophilia patients. One hundred and eighty-four male patients requiring dental extraction represented the control group. All haemophilia patients received 20 mg kg,1 of tranexamic acid and a single infusion of factor VIII or IX to achieve a peak level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty-five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239 (46%) dental extractions in the control group were surgical ones. We registered two bleeding complications in the group of haemophilia patients (one late bleeding and one haematoma in the site of the anaesthetic injection) and one (a late bleeding) in the control group. The difference of bleeding complications in the two groups of patients were not statistically significant (P=0.2; OR 0.2; CI 0.01,2.22). The protocol proposed in this study, characterized by the feasibility and the number of haemorrhagic complications not different from normal population, make dental extractions in haemophilia patients possible on an out-patient basis with a cost reduction for the community and minor discomfort for the patients. [source] Clinical trial: colectomy after rescue therapy in ulcerative colitis , 3-year follow-up of the Swedish-Danish controlled infliximab studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. Gustavsson Aliment Pharmacol Ther 2010; 32: 984,989 Summary Background, The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim, To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method, In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results, Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion, The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy. [source] Clinically significant liver injury in patients treated with natalizumabALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010S. BEZABEH Aliment Pharmacol Ther,31, 1028,1035 Summary Background, Natalizumab is a recombinant monoclonal antibody approved for the treatment of patients with multiple sclerosis and patients with Crohn's disease. Because of its immunosuppressive effects, natalizumab has been associated with a number of atypical and opportunistic infections. Aim, To describe and summarize six spontaneously reported post-marketing cases of clinically significant drug induced-liver injury associated with natalizumab use. Methods, The FDA maintains a database of adverse event reports (AERS). We searched the AERS database for reports of serious liver injury associated with natalizumab use from November 2004, when the drug was approved, through 30 June 2008. Results, The search resulted in six spontaneously reported post-marketing cases of severe drug-induced liver injury. Four of six patients developed liver injury with elevations of serum transaminases and hyperbilirubinemia after only a single infusion of natalizumab. One of these patients experienced repeated increases of aminotransferases and bilirubin when natalizumab was re-administered. Conclusions, Serious hepatic injury may occur in association with natalizumab use. Health professionals should be alerted to possible serious liver injury in patients receiving natalizumab. [source] Mathematical modelling of the impact of haematopoietic stem cell-delivered gene therapy for HIVTHE JOURNAL OF GENE MEDICINE, Issue 12 2009John M. Murray Abstract Background Gene therapy represents a new treatment paradigm for HIV that is potentially delivered by a safe, once-only therapeutic intervention. Methods Using mathematical modelling, we assessed the possible impact of autologous haematopoietic stem cell (HSC) delivered, anti-HIV gene therapy. The therapy comprises a ribozyme construct (OZ1) directed to a conserved region of HIV-1 delivered by transduced HSC (OZ1+HSC). OZ1+HSC contributes to the CD4+ T lymphocyte and monocyte/macrophage cell pools that preferentially expand under the selective pressure of HIV infection. The model was used to predict the efficacy of OZ1 in a highly active antiretroviral therapy (HAART) naïve individual and a HAART-experienced individual undergoing two structured treatment operations. In the standard scenario, OZ1+HSC was taken as 20% of total body HSC. Results For a HAART-naïve individual, modelling predicts a reduction of HIV RNA at 1 and 2 years post-OZ1 therapy of 0.5 log10 and 1 log10, respectively. Eight years after OZ1 therapy, the CD4+ T-lymphocyte count was 271 cells/mm3 compared to 96 cells/mm3 for an untreated individual. In a HAART-experienced individual HIV RNA was reduced by 0.34 log10 and 0.86 log10 at 1 and 2 years. The OZ1 effect was maximal when both CD4+ T lymphocytes and monocytes/macrophages were protected from successful, productive infection by OZ1. Conclusions The modelling indicates a single infusion of HSC cell-delivered gene therapy can impact on HIV viral load and CD4 T-lymphocyte count. Given that gene therapy avoids the complications associated with HAART, there is significant potential for this approach in the treatment of HIV. Copyright © 2009 John Wiley & Sons, Ltd. [source] Thrombomodulin Improves Early Outcomes After Intraportal Islet TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009W Cui Primary islet nonfunction due to an instant blood mediated inflammatory reaction (IBMIR) leads to an increase in donor islet mass required to achieve euglycemia. In the presence of thrombin, thrombomodulin generates activated protein C (APC), which limits procoagulant and proinflammatory responses. In this study, we postulated that liposomal formulations of thrombomodulin (lipo-TM), due to its propensity for preferential uptake in the liver, would enhance intraportal engraftment of allogeneic islets by inhibiting the IBMIR. Diabetic C57BL/6J mice underwent intraportal transplantation with B10.BR murine islets. In the absence of treatment, conversion to euglycemia was observed among 29% of mice receiving 250 allo-islets. In contrast, a single infusion of lipo-TM led to euglycemia in 83% of recipients (p = 0.0019). Fibrin deposition (p < 0.0001), neutrophil infiltration (p < 0.0001), as well as expression TNF-, and IL-, (p < 0.03) were significantly reduced. Significantly, thrombotic responses mediated by human islets in contact with human blood were also reduced by this approach. Lipo-TM improves the engraftment of allogeneic islets through a reduction in local thrombotic and inflammatory processes. As an enzyme-based pharmacotherapeutic, this strategy offers the potential for local generation of APC at the site of islet infusion, during the initial period of elevated thrombin production. [source] Successful correction of murine sickle cell disease with reduced stem cell requirements reinforced by fractionated marrow infusionsBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2010Hady Felfly Summary Minimal criteria requirements of stem cell replacement, conditioning regimen and modalities of infusion essential for cure of sickle cell disease (SCD) by bone marrow(BM)/stem cell transplantation or gene therapy must be established prior to clinical trials. The threshold of normal BM/stem cells for therapeutic correction of this red blood cell disorder was evaluated in the SAD murine SCD model from peripheral donor white blood cells. From 11 groups of stable chimeric SAD mice (5,92%) analyzed over ,2 years, mice with ,16% normal donor stem cells showed improvement of haematological and erythroid responses. Mice in the 26% chimeric group and above demonstrated substantial amelioration of organ pathologies with generalized decreased iron deposits, fibrosis and reached normal lifespan. Subsequently, the minimal myelosuppression concurrently with number and timing of infusions and number of BM cells was determined to reach therapeutic threshold in SAD mice. Higher myelosuppression (2 Gy vs. 1 Gy) and cell number in single infusion led to increased chimerism. Importantly, administration of three-equivalent cell subdoses within 28 h of mild myelosuppression resulted in 100% recipient engraftment at therapeutic levels. These studies established the long-term therapeutic chimeric threshold of normal white blood cells at ,26% and determined the minimal fractionated BM/stem cell doses concomitant with mild myelosuppression for significant correction of SCD in SAD mice. [source] A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinomaCANCER SCIENCE, Issue 11 2006Junichi Sakamoto In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m2). Patients with locally advanced (UICC-TNM [International Union Against Cancer,tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of 131I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of 131I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting. (Cancer Sci 2006; 97: 1248,1254) [source] Pamidronate infusion in patients with systemic sclerosis results in changes in blood mononuclear cell cytokine profilesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006L. D. Carbone Summary A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-,, interleukin (IL)-10, transforming growth factor (TGF)-,1, tumour necrosis factor (TNF)-, and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-, and TNF-, and reduced levels of TGF-,1 for up to 24 weeks after the infusion. ,, T cells from patients with SSc were activated in vitro and produced increased IFN-,. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study. [source] | ||||||||||