Biomedical subjects

Daniel C Adelman

Publications and source records attributed to Daniel C Adelman.

3 recordsLinked to original sources

PubMed2003

Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.

BACKGROUND: Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. METHODS AND RESULTS: An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. CONCLUSIONS: This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Adult↗

PubMed2002

Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium.

Photodynamic therapy (PDT) has been approved as a tissue-specific light-activated cytotoxic therapy for many diseases. The ability of PDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque. Biotechnology has developed a new generation of selective photosensitizers and catheter-based technological advances in light delivery have allowed the introduction of PDT into the vasculature. The largest experience to date is with motexafin lutetium (MLu, Antrin), an expanded porphyrin (texaphyrin) that accumulates in plaque. The combination of the motexafin lutetium and endovascular illumination, or Antrin phototherapy, has been shown to reduce plaque in animal models. Antrin phototherapy generates cytotoxic singlet oxygen that has been shown to induce apoptosis in macrophages and smooth muscle cells. The safety, tolerability, and preliminary efficacy of Antrin phototherapy has been assessed in a phase 1 dose-ranging clinical trial in subjects with peripheral artery disease and is currently being examined in a phase 1 study in subjects with lesions of the native coronary arteries undergoing stent implantation. The preliminary results suggest that Antrin phototherapy is safe, well tolerated, and nontraumatic.

Animals↗

PubMed2002

Pharmacological approaches.

Treatment of moderate to severe atopic disease may require multidrug regimens, reflecting the multifaceted nature of allergic inflammation. Furthermore, despite the central role of Th2 inflammation in allergic rhinitis (15), asthma (14), and atopic dermatitis (11), specific mediator antagonists may not be uniformly successful in the treatment of all atopic disorders. For example, antihistamines are very effective treatment for the symptoms of allergic rhinitis (41), but have minimal benefit in the treatment of asthma (42-44). Current research efforts are ongoing to identify and develop therapies aimed at critical junctures in the immunopathological process. For example, animal studies have suggested that IL-4 and IL-13 are two cytokines that are pivotal in the generation of airway allergic inflammation. Blocking the action of these cytokines may markedly decrease the allergic inflammation (17,125).

Anti-Allergic Agents↗