Radiation dosimetry of 204Bi- and 206Bi-citrates.
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The absorbed-radiation doses from 204Bi- and 206Bi-citrates to humans are calculated from available nuclear and biologic data in order to evaluate the relative radiation risk of these radionuclides. The calculations reveal that the radiation dose to the kidneys is reduced by a factor of 8 if 204Bi replaces 206Bi. This reduction suggests that 204Bi should be investigated further as a possible soft-tissue scanning agent. (+info)
Efficacy and safety of single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole, for the eradication of Helicobacter pylori: an international multicentre study.
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BACKGROUND: The high prevalence of Helicobacter pylori resistance to metronidazole demands treatments more effective than standard bismuth-based triple therapy against these strains. AIM: To evaluate the H. pylori eradication rate in both metronidazole-sensitive and -resistant strains following quadruple therapy using single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole. METHODS: One hundred and seventy valid patients with duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were treated in eight centres located in five countries. H. pylori was confirmed at baseline using 13C-urea breath test, histology and/or culture. Patients received three single-triple capsules q.i.d. and omeprazole, 20 mg b.d., for 10 days. Each capsule contained bismuth biskalcitrate, 140 mg (as 40 mg Bi2O3 equivalent), metronidazole, 125 mg, and tetracycline, 125 mg. 13C-Urea breath test was repeated at least 4 and 8 weeks post-treatment. RESULTS: Overall eradication rates were 93% (158/170) by modified intention-to-treat analysis and 97% (142/146) by per protocol analysis. Eradication rates were 93% (40/43) and 95% (38/40) for strains resistant to metronidazole and 95% (82/86) and 99% (75/76) for strains sensitive to metronidazole by modified intention-to-treat and per protocol analysis, respectively. CONCLUSION: This omeprazole-bismuth biskalcitrate-metronidazole-tetracycline 10-day regimen is a very effective and well-tolerated treatment, which overcomes metronidazole resistance. (+info)
Selective T-cell ablation with bismuth-213-labeled anti-TCRalphabeta as nonmyeloablative conditioning for allogeneic canine marrow transplantation.
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Two major immunologic barriers, the host-versus-graft (HVG) and graft-versus-host (GVH) reactions, have to be overcome for successful allogeneic hematopoietic cell transplantation. T cells were shown to be primarily involved in these barriers in the major histocompatibility complex identical setting. We hypothesized that selective ablation of T cells using radioimmunotherapy together with postgrafting immunosuppression would suffice to ensure stable allogeneic engraftment. We had described a canine model of nonmyeloablative marrow transplantation in which host immune reactions were impaired by a single dose of 200 cGy total body irradiation (TBI), and both GVH and residual HVG reactions were controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Here, we substituted the alpha-emitter bismuth-213 (213Bi) linked to a monoclonal antibody (mAb) against T-cell receptor (TCR) alphabeta, using the metal-binding chelate diethylenetriaminepentaacetic acid (DTPA) derivative cyclohexyl-(CHX)-A", for 200 cGy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCRalphabeta mAb showed uptake primarily in blood, marrow, lymph nodes, spleen, and liver. Four dogs were treated with 0.13 to 0.46 mg/kg TCRalphabeta mAb labeled with 3.7 to 5.6 mCi/kg (137-207 MBq/kg) 213Bi. The treatment was administered in 6 injections on days -3 and -2 followed by transplantation of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF/CSP. The therapy was well tolerated except for elevations of transaminases that were transient in all but one of the dogs. No other organ toxicities or signs of graft-versus-host disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5% to 55% after more than 30 weeks of follow up. (+info)
Preclinical studies of targeted alpha therapy for breast cancer using 213Bi-labelled-plasminogen activator inhibitor type 2.
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The control of micrometastatic breast cancer remains problematic. To this end, we are developing a new adjuvant therapy based on (213)Bi-PAI2, in which an alpha-emitting nuclide ((213)Bi) is chelated to the plasminogen activator inhibitor-2 (PAI2). PAI2 targets the cell-surface receptor bound urokinase plasminogen activator (uPA), which is involved with the metastatic spread of cancer cells. We have successfully labelled and tested recombinant human PAI2 with the alpha radioisotope (213)Bi to produce (213)Bi-PAI2, which is highly cytotoxic towards breast cancer cell lines. In this study, the 2-day postinoculation model, using MDA-MB-231 breast cancer cells, was shown to be representative of micrometastatic disease. Our in vivo efficacy experiments show that a single local injection of (213)Bi-PAI2 can completely inhibit the growth of tumour at 2 days postcell inoculation, and a single systemic (i.p.) administration at 2 days causes tumour growth inhibition in a dose-dependent manner. The specific role of uPA as the target for (213)Bi-PAI2 therapy was determined by PAI2 pretreatment blocking studies. In vivo toxicity studies in nude mice indicate that up to 100 microCi of (213)Bi-PAI2 is well tolerated. Thus, (213)Bi-PAI2 is successful in targeting isolated breast cancer cells and preangiogenic cell clusters. These results indicate the promising potential of (213)Bi-PAI2 as a novel therapeutic agent for micrometastatic breast cancer. (+info)
Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images.
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The purpose of this study was to evaluate the therapeutic efficacy and limitations of alpha-particle-emitting radiolabeled compounds by means of 2-dimensional histological images and distribution of activity on a microscopic level. METHODS: A microdosimetric approach based on histological images is used to analyze the therapeutic effectiveness of alpha-particle-emitting (211)At and (213)Bi conjugated to 201B monoclonal antibody (mAb), which is reactive with murine lung blood vessels for the treatment of EMT-6 lung tumor colonies in nude mice. Autoradiography images were used to define the tissue morphology and activity distribution within lung tissues. Two animal groups were studied: Group A consisted of animals bearing small tumors (<130 micro m) and group B consisted of larger tumors (<600 micro m). Probability density functions (pdf) described the variability in average absorbed dose and survival probability among normal and tumor target cells and, in turn, were used to assess the survival fraction of tumor and normal tissue. RESULTS: The average absorbed dose to tumor cells per unit cumulated activity concentration for animals in group A was 1.10 x 10(-3) and 1.37 x 10(-3) Gy g MBq(-1) s(-1) for (211)At and (213)Bi, respectively, and for animals in group B was 3.8 x 10(-4) and 5.6 x 10(-4) Gy g MBq(-1) s(-1) for (211)At and (213)Bi, respectively. The fraction of tumor cells that received a zero absorbed dose for animals in group A was 0.04% for (213)Bi and 0.2% for (211)At and for animals in group B was 25% for (213)Bi and 31% for (211)At. Both (213)Bi- and (211)At-labeled 201B mAb were effective therapies for animals with small tumors, where predicted therapeutic effectiveness was consistent with experimental findings; however, they were ineffective for animals with larger tumors. CONCLUSION: Microdosimetric methods based on knowledge of tissue morphology and activity distribution on a small-scale level can be a useful tool for evaluating a priori the therapeutic efficacy and limitations of targeted alpha-particle endoradiotherapeutic strategies. (+info)
Therapeutic efficacy of ranitidine bismuth citrate with clarithromycin for seven days in the eradication of Helicobacter pylori in Brazilian peptic ulcer patients.
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CONTEXT: The curative treatment of peptic ulcer is made available nowadays through the eradication of the bacterium Helicobacter pylori, which is associated with it, but the best therapeutic regimen is yet to be determined. OBJECTIVE: To assess the efficacy of a therapeutic regimen with 400 mg ranitidine bismuth citrate associated with 500 mg clarithromycin given twice a day for seven days in a cohort of Brazilian patients with peptic ulcer. TYPE OF STUDY: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: One hundred and twenty nine outpatients, with active or healed peptic ulcers infected by Helicobacter pylori, diagnosed via endoscopy with confirmation via the urease test and histological examination, who had never undergone a regimen for the eradication of the bacterium. PROCEDURE: Administration of 400 mg ranitidine-bismuth and 500 mg clarithromycin twice a day, for seven days. MAIN MEASUREMENTS: Efficacy of the treatment, with a check on the cure done via another endoscopy eight weeks after drug administration. The eradication of the bacterium was determined via the urease test and histological examination. Patients who were negative for both were considered to be cured. RESULTS: Eight patients failed to complete the study. The eradication rate according to intention to treat was 81% (104/129) and per protocol was 86% (104/121). CONCLUSION: The bismuth ranitidine compound associated with clarithromycin used for one week was shown to be a simple, effective and well-tolerated therapeutic regimen for the eradication of Helicobacter pylori. (+info)
Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis.
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BACKGROUND: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first-line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first-line treatment. AIM: To compare triple vs. quadruple therapy for the first-line treatment of H. pylori infection. METHODS: An extensive literature search was performed to identify randomized trials comparing triple vs. quadruple therapy. Selected trials were included in a meta-analysis using Review Manager 4.1. RESULTS: Four studies met the inclusion criteria. Eradication rates with quadruple therapy were slightly higher in both the intention-to-treat (81% vs. 78%; odds ratio, 0.83; 95% confidence interval, 0.61-1.14) and per protocol (88% vs. 85%; odds ratio, 0.81; 95% confidence interval, 0.55-1.20) analysis, although the differences were not statistically significant. Nor were there significant differences in compliance or adverse effects between the therapies. CONCLUSION: Triple and quadruple therapies seem to be roughly equivalent in terms of effectiveness, compliance and side-effects profile when administered as first-line treatment for H. pylori infection. (+info)
Systematic review: Antacids, H2-receptor antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia.
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BACKGROUND: Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting. AIM: To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse. RESULTS: Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias. CONCLUSIONS: The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues. (+info)