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Biomedical subjects

C Rodger

Publications and source records attributed to C Rodger.

9 recordsLinked to original sources

Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice.

The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti-epileptic drugs were also examined. In both models, the anticonvulsant effects of small doses or carbamazepine and phenytoin were enhanced by flunarizine and the effects of small doses of ethosuximide were enhanced by nifedipine. The effects of large doses of the anti-epileptic drugs were not further enhanced by either flunarizine or nifedipine. It is possible that these findings in mice are relevant to the variability of the responses to calcium antagonists as add-on therapy for epilepsy in man.

Animals↗

The concentration of IgG in the serum is a major determinant of Fc-dependent reticuloendothelial function.

Defective Fc receptor-specific reticuloendothelial (RE) function has been reported in certain patients with a variety of immunologic and nonimmunologic diseases. The mechanism responsible for the impaired RE function is uncertain, but it could be caused by immune complexes that are present in many of these disorders. Alternatively, the impaired RE function could be a secondary effect of the high concentrations of monomeric IgG in the serum of these patients, since monomeric IgG can compete with complexed IgG for macrophage receptors in vitro. We studied the Fc-dependent RE function in 30 healthy control subjects and 27 patients using IgG-coated radiolabeled autologous red cells. There was a significant relationship between the concentration of IgG in the serum and the rate of clearance of antibody-sensitized cells (r = 0.51, P less than .01). Patients with hypergammaglobulinemia had the slowest Fc-dependent clearance, whereas those with hypogammaglobulinemia had the most rapid clearance. Immune complexes (Raji or polyethylene glycol) could not be shown to contribute to Fc-dependent RE clearance above the effect of the IgG in the serum. The unusually rapid clearance in a patient with hypogammaglobulinemia could be returned to normal by raising the concentration of IgG in the serum. This study supports the concept that serum (monomeric) IgG competes with immune complexed IgG for macrophage Fc receptors in vivo. The competition for Fc receptors determines the level of competence of Fc-dependent RE function. Based on the results of this study, one can predict that a number of disorders characterized by hypergammaglobulinemia also will have impaired Fc-dependent RE function.

Agammaglobulinemia↗

The relationship among platelet-associated IgG, platelet lifespan, and reticuloendothelial cell function.

Platelet-associated IgG (PAIgG) has been reported to be elevated in nonthrombocytopenic patients who have a normal platelet lifespan. This has been interpreted as indicating that PAIgG is a nonspecific finding in these patients and not a determinant of platelet survival. It is important to recognize that the reticuloendothelial (RE) system plays an important role in the clearance of antibody-sensitized cells. In this study, we related the level of PAIgG and the platelet lifespan to the RE function in patients with: (A) idiopathic thrombocytopenic purpura (ITP), and (B) five patients with elevated levels of PAIgG yet normal or near-normal platelet counts. RE function was assessed by measuring the clearance of autologous chromium-labeled red cells sensitized with a precise amount of alloantibody (2,000-3,600 molecules of IgG/cell). Eight patients with immune thrombocytopenia had significantly shortened platelet survivals (less than 2-113 hr). In contrast, the five patients with elevated PAIgG, yet normal or near-normal platelet counts, all had normal autologous platelet survivals (186-222 hr). These patients also had significantly impaired clearance of IgG-sensitized red cells, with an average of 85% of the infused red cells remaining in the circulation at 60 min (normal 42% +/- 14%, n = 10). In this study, every patient with elevated PAIgG and normal RE function had a shortened platelet lifespan. Those patients with elevated PAIgG and impaired RE function did not invariably have a shortened platelet lifespan. The observation that the PAIgG is elevated in some patients whose platelet survival is normal does not indicate that PAIgG is not biologically relevant. It indicates that these patients may have RE blockade and do not clear IgG-sensitized cells.

Blood Platelets↗