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A Brumfield

Publications and source records attributed to A Brumfield.

6 recordsLinked to original sources

Heart rate variability: comparison among devices with different temporal resolutions.

Several devices based on ECG can acquire beat-to-beat intervals, and some of these devices may be used for heart rate variability (HRV) analysis. Most of these devices and their methods to acquire the beat-to-beat intervals need to be validated for HRV analysis by comparing them against traditional methods. Some of these methods have low temporal resolution, which may be sufficient for certain studies. HRV analysis parameters obtained from two methods differing in temporal resolution were compared to the HRV analysis parameters obtained from a referent method (ECG). One of the methods had a high resolution (<1 ms) and the other method had a low resolution (10 ms). Seven healthy male volunteers participated in the study. The beat-to-beat intervals were collected simultaneously from the three methods and the HRV parameters derived from them were used for our comparisons. The Pearson product-moment correlations were used, which demonstrated an excellent correlation (r > 0.99) in time domain, frequency domain and some non-linear HRV measures. The HRV measures were further analyzed using the one-way repeated-measures analysis of variance (ANOVA) and statistically significant differences were observed in some of the HRV parameters obtained from the low-resolution method, especially the mean RR (p < 0.001) and the mean heart rate (p < 0.001). Since the same software was used for HRV analysis of the three methods, any differences were due to the temporal resolution of the RR intervals measured by the methods. Overall, both the methods correlated very well with the referent method among healthy volunteers in resting conditions and may be used by researchers for HRV studies.

Adult↗

FLT3 ligand induces the generation of functionally active dendritic cells in mice.

FLT3 ligand (FL) is a recently described hematopoietic growth factor that stimulates the proliferation and differentiation of hematopoietic progenitors. We have investigated the effect of FL on murine hematopoiesis and dendritic cell (DC) generation and accumulation in lymphoid tissues and liver in vivo and in vitro evaluating the morphologic, phenotypic, and functional characteristics of these DC. We have observed extramedullary hematopoiesis in the mouse spleen with all lineages of hematopoietic cells represented after the administration of FL. Injection of FL results in a time-dependent and reversible accumulation of DC in the spleen, bone marrow, lymph nodes, and liver. Both flow cytometry and immunohistochemistry revealed a significant accumulation of DC in these tissues. Results of mixed leukocyte reaction suggested that these cells, isolated from murine bone marrow or spleen, were active as antigen presenting cells. Furthermore, cultivation of splenic and marrow cells with GM-CSF and IL-4 gave rise to large numbers of functionally active mature DC. Thus, the results of this study suggest that FL is a promising growth factor that stimulates the generation of large number of DC and may be a useful cytokine for the immunotherapy of cancer.

Animals↗

A comparison of locoregional depot and systemic preparations of 9-aminocamptothecin for treatment of liver metastases in a rat tumor model: superior antitumor activity of sustained-release preparation.

BACKGROUND: Locoregional therapy of hepatic-metastatic disease may overcome the limitations of systemic therapy by allowing tumor drug dose intensification without increasing systemic toxicity. This may result in improved efficacy. We have demonstrated that the novel topoisomerase I inhibitor 9-Aminocamptothecin (9-AC) when dissolved in Ethiodol acts as a sustained release preparation, with good antitumor activity. Its benefit as a depot hepatic intraarterial (i.a.) therapy for hepatic metastases was compared to systemic therapy with an aqueous colloidal dispersion (CD) preparation of 9-AC in a rat model, since a lack of demonstrable benefit of the locoregional therapy, would argue against further clinical evaluation. METHODS: Fisher rats underwent direct intraportal injection of 2 x 10(5) MADB106 adenocarcinoma cells and were treated 6 to 7 days later with: (a) bolus i.a. 9-AC (60 micrograms) in 60 microliters of Ethiodol; (b) bolus i.a. CD/9-AC (60 micrograms) in 200 microliters water; (c) bolus i.a. Ethiodol only (60 microliters), or (d) CD/9-AC (60 micrograms) in 200 microliters water, via a mini-osmotic pump pumping at 1 microliter/hr for 7 days intraperitoneally (i.p.). Livers were harvested 10 to 12 days later, and the number of metastases on the surface were counted blindly. RESULTS: Bolus hepatic i.a. 9-AC/Ethiodol was found to be significantly superior in reducing the number of hepatic metastases, when compared to the aqueous CD preparation administered in the same manner, or by continuous infusion via mini-osmotic pump i.p. (p < 0.01). Systemic therapy was also associated with substantial toxicity. CONCLUSIONS: These results suggest that locoregional therapy of hepatic neoplasms with 9-AC/Ethiodol would be associated with clinical efficacy far exceeding that associated with its systemic administration.

Animals↗

Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: interim results of a phase I trial.

BACKGROUND: Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensify therapy without associated toxicity. METHODS: The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC. RESULTS: In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients. CONCLUSIONS: This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.

Aged↗

Alterations in cell-surface carbohydrates of rat large granular lymphocytes associated with interleukin-2 activation.

The activation of large granular lymphocytes (LGLs)/natural killer (NK) cells with interleukin-2 (IL-2) has been shown to increase the ability of these cells to lyse NK-resistant tumor target cells. Activated LGLs, termed LAK (lymphokine-activated killer) cells, have been demonstrated to be of therapeutic value in vivo against metastatic tumors. The mechanism by which IL-2 induces broadened cytolytic capability, as well as the molecular basis of target recognition and killing by the activated cells has not yet been elucidated. Since carbohydrate moieties have been demonstrated to be of possible significance in the cytolytic cascade of a variety of effector cells, the current study was undertaken to determine if the activation of LGLs with IL-2 is accompanied by an alteration of cell-surface carbohydrates. Two-color flow cytometry was performed to identify LGL/NK cells in populations of nylon wool-nonadherent splenic mononuclear cells and to assess the binding of various lectins to activated as well as nonactivated LGLs. Increases were observed in the binding of four lectins to LGLs after IL-2 activation; Triticum vulgaris (wheat germ agglutinin), Phytolacca americana (pokeweed mitogen), Lycopersicon esculentum (tomato lectin), and Griffonia simplicifolia I-B4 (GSI-B4). The wheat germ, pokeweed, and tomato lectins recognize complex carbohydrates structure consisting of GlcNAc(Bl,4GlcNAc)n while GSI-B4 recognizes alpha-D-galactose terminal end groups. Lectin binding to the activated LGLs was homogenous (i.e., flow cytometry revealed only a single population of fluorescent cells). Lectin binding to LGLs prior to activation was more heterogeneous, however, the tomato lectin uniquely revealed a bimodal distribution of receptors. These data indicate that LGL/NK cells from the rat are heterogeneous in their ability to bind specific lectins, and that IL-2 activation of these cells results in altered expression of specific cell-surface carbohydrates.

Animals↗