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Biomedical subjects

I W Flinn

Publications and source records attributed to I W Flinn.

26 records · Page 2Linked to original sources
PubMed1998

AIDS oncology.

New diagnostic approaches to primary central nervous system lymphoma have been developed that may make brain biopsy unnecessary in many instances. Reduced-dose chemotherapy for non-Hodgkin's lymphoma has been shown to be advantageous in a randomized controlled trial. New agents for the treatment of Kaposi's sarcoma are available. Adoptive cellular immunotherapy has been shown to be effective in the treatment and prevention of Epstein-Barr virus-associated B-cell lymphomas in bone marrow transplant recipients, and may have promise in AIDS patients.

Journal Article↗
PubMed1998

Bone marrow transplantation for chronic lymphocytic leukemia.

The use of bone marrow transplant (BMT) for patients with chronic lymphocytic leukemia (CLL) is a relatively new approach when compared to the use of this therapy for other hematologic malignancies. The long natural history of CLL and significant procedure-related mortality initially deterred the use of BMT for CLL. However, improvement in transplantation procedures and supportive care paved the way for the use of BMT in patients with CLL. There are now multiple reports showing complete remissions with both autologous and allogeneic BMT. The follow-up remains short, therefore, the durability of these remissions remains to be determined. Several innovative approaches to BMT for CLL are now being explored and include non-myeloablative preparative regimens for allogeneic transplants, purging autologous grafts, and induction of graft-versus-leukemia effects. Ultimately, however, long-term disease-free and overall survival will need to be shown before BMT for CLL will gain widespread acceptance.

Bone Marrow Purging↗
PubMed1996

AIDS primary central nervous system lymphoma.

The incidence of primary central nervous system lymphomas is increased several 1000-fold in AIDS patients. These are B-cell malignancies consistently associated with Epstein-Barr virus. They typically occur late in the course of HIV infection and are associated with a very short median survival. The pattern of Epstein-Barr virus gene expression is indicative of severe immunocompromise. Radiographic differentiation from toxoplasmosis remains a problem. Polymerase chain reaction amplification of Epstein-Barr virus DNA in cerebrospinal fluid, 18F-fluoro-deoxyglucose-positron emission tomography scanning, and 201-thallium single-photo emission CT are all promising noninvasive or minimally invasive diagnostic procedures that may obviate the need for brain biopsy in the future. Occasional patients have long remissions after therapy but most patients die within a few months. A possible role for combined modality therapy, including combination chemotherapy, is being explored.

Antigens, Viral↗
PubMed1991

Effects of chronic ethanol exposure on cardiac receptor-adenylyl cyclase coupling: studies in cultured embryonic chick myocytes and ethanol fed rats.

Ethanol effects in the brain appear to be mediated at least in part by an alteration in receptor-effector coupling via guanine nucleotide-binding regulatory proteins (G proteins). To test the hypothesis that a similar pathway participates in the cardiotoxic effects of ethanol, we assessed the effects of chronic ethanol on two commonly used experimental models: embryonic chick myocytes in culture and ventricular myocardium from chronically fed rats. Ethanol had no effect on either the function or quantity of G proteins as assessed by effector-stimulated adenylyl cyclase activity and the levels of ADP-ribosylation substrates. In contrast, effector-stimulated adenylyl cyclase activity was significantly altered in the liver of ethanol-fed rats. These results suggest that receptor-effector coupling via G proteins in our two cardiac models is insensitive to ethanol and that ethanol effects may be species or organ specific.

ADP-Ribosylation Factors↗
PubMedDate not supplied

Leptomeningeal involvement in chronic lymphocytic leukemia.

PURPOSE: This review and case report address the rare complication of leptomeningeal involvement in patients with chronic lymphocytic leukemia. OVERVIEW: Chronic lymphocytic leukemia is the most common form of leukemia, with more than 200,000 cases reported in the past 20 years. An uncommon complication of the disorder is central nervous system invasion. To date, only 21 cases have been reported, and their presenting symptoms have been heterogeneous and often nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia, nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or radiation alone. Prognosis is improved by prompt and aggressive therapy. In this case report, a 61-year-old man developed severe ataxia, vertigo, and occipital headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic leukemia. After treatment with both radiation to the head and neck and intrathecal methotrexate the patient achieved complete symptom resolution. Thus far, no additional systemic cytotoxic chemotherapy has been necessary. CLINICAL IMPLICATIONS: Because central nervous system invasion is uncommon in chronic lymphocytic leukemia, it may go undiagnosed and under-reported. Providers of patients with this disease need to be aware of possible central nervous system invasion when patients present with cranial nerve signs or symptoms and/or nonspecific neurologic manifestations. Early identification and prompt central nervous system-directed chemotherapy can affect morbidity and quality of life positively.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Carboxyamido-triazole (CAI)--a novel "static" signal transduction inhibitor induces apoptosis in human B-cell chronic lymphocytic leukemia cells.

Signal transduction is a key mechanism by which both proliferative and apoptotic processes of B-cell chronic lymphocytic leukemia (CLL) cells are mediated. Carboxyamido-triazole (CAI) is a cytostatic signal transduction inhibitor currently being tested in phase II clinical trials. Based on this, we investigated the in vitro activity of CAI in mononuclear cell isolates from patients with B-CLL (n=11). Viability, utilizing the MTT assay, was assessed at varying concentrations (0.01-100 microM) of CAI for 4 days. The CAI concentration required for 50% inhibition of cell viability (LC50), determined by the tetrazolium dye (MTT) assay, at 4 days was 53.5 microM (range 29-74.6; 95% CI+/-14.8). Cells from 6 of 11 patients (3 of whom were clinically fludarabine refractory) had a 27 percent (range 11-43) mean decline in viability at 10 microM after a 4 day drug exposure, a concentration readily attainable in humans. To assess if loss of viability was due to apoptosis, we incubated cells from 4 additional CLL patients with media or CAI (10 microM) for 4 days. Annexin-V/propidium iodine labeling subsequently demonstrated CAI significantly (p=0.049) induces apoptosis (40.1%; 95% CI+/-18.1) as compared to media matched control cells (18.3%; 95% CI+/-11.2). These data provide evidence that CAI can induce apoptosis in human CLL cells in vitro at drug concentrations attainable in vivo. These findings justify phase II studies of CAI in patients with B-CLL.

Antineoplastic Agents↗