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Biomedical subjects

David Gottlieb

Publications and source records attributed to David Gottlieb.

4 recordsLinked to original sources
PubMed2004

Bilateral leukemic orbital infiltration presenting as proptosis and narrow-angle glaucoma.

A 71-year-old man with acute myeloid leukemia presented with bilateral uveal and orbital leukemic infiltration presenting as tense bilateral proptosis, orbital inflammation, and acute-angle closure glaucoma. B-scan ultrasonography revealed uveoscleral thickening and anterior rotation of the ciliary body. Orbital CT and MRI showed bilateral proptosis with streaking of intraconal fat. Temporary pressure lowering occurred after lateral canthotomy and inferior cantholysis. Definitive treatment included systemic chemotherapy and steroids. Over a 2-week period, vision improved and proptosis resolved, and the intraocular pressure returned to normal. The patient died of cerebral complications of his illness after 6 weeks. This is the first reported case of orbital and ocular leukemic infiltration presenting simultaneously as tense proptosis and narrow-angle glaucoma.

Acute Disease↗
PubMed2003

Infection and injury of neurons by West Nile encephalitis virus.

West Nile virus (WNV) infects neurons and leads to encephalitis, paralysis, and death in humans, animals, and birds. We investigated the mechanism by which neuronal injury occurs after WNV infection. Neurons in the anterior horn of the spinal cords of paralyzed mice exhibited a high degree of WNV infection, leukocyte infiltration, and degeneration. Because it was difficult to distinguish whether neuronal injury was caused by viral infection or by the immune system response, a novel tissue culture model for WNV infection was established in neurons derived from embryonic stem (ES) cells. Undifferentiated ES cells were relatively resistant to WNV infection. After differentiation, ES cells expressed neural antigens, acquired a neuronal phenotype, and became permissive for WNV infection. Within 48 h of exposure to an exceedingly low multiplicity of infection (5 x 10(-4)), 50% of ES cell-derived neurons became infected, producing nearly 10(7) PFU of infectious virus per ml, and began to die by an apoptotic mechanism. The establishment of a tractable virus infection model in ES cell-derived neurons facilitates the study of the molecular basis of neurotropism and the mechanisms of viral and immune-mediated neuronal injury after infection by WNV or other neurotropic pathogens.

Animals↗
PubMed2002

Cytokine manipulation of the immune response in the treatment of human acute leukaemia.

Myeloid leukaemia cells are sensitive to attack by elements of the immune system as evidenced by the effects of T cell depletion, graft versus leukaemia and donor lymphocyte infusion on leukaemic recurrence. An implication is that the immune system can be manipulated to enhance anti-leukaemic effects by exogenous stimulation including the use of immunostimulatory cytokines. These could potentially be used in a controlled manner that avoids the clinical problems associated with graft-versus-host disease. The cytokine used most extensively to date is interleukin-2 (IL2), a molecule that induces T lymphocyte proliferation and the generation of MHC unrestricted cytotoxicity. Despite over 10 years of clinical experience, the data on efficacy in acute myeloid leukaemia remains unclear due to lack of adequate randomised trials. IL2 appears to be effective in patients with low level marrow infiltration by acute myeloid leukaemia (AML) blast cells. It is less effective when patients present or relapse with packed bone marrows. The logical assumption that IL2 treatment given during states of minimal residual disease will reduce the incidence or speed of disease recurrence remains to be adequately tested. IL2 administration is associated with characteristic clinical adverse effects and with specific immuno-haematological changes. The use of other cytokines for immune manipulation in patients with AML is so far essentially limited to the research laboratory. Potential uses include cytokine induced blast differentiation to dendritic cells and the use of irradiated cytokine gene transduced leukaemic cells as vaccines.

Clinical Trials as Topic↗