Richard R. Streiff

A Comparative Evaluation of Iron Clearance Models

A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.

Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days in patients with advanced malignancies.

This was a dose escalation Phase 1 trial designed todetermine the maximum tolerated dose (MTD) and dose-limitingtoxicities (DLT) of DENSPM. Methods: Adult patientswith refractory solid tumors were treated with DENSPMadministered by intravenous infusion in 100 ml of normalsaline over 30 minutes. The daily dose of DENSPM was dividedinto three equal doses administered approximately every eighthours for six days. Courses were repeated every 28 days.Results: Twenty-eight patients were enrolled in thestudy. Dose levels of DENSPM explored were 25mg/m2/day (3 patients), 50 mg/m2/day (9patients), 60 mg/m2/day (5 patients), 75mg/m2/day (6 patients), 94 mg/m2/day (3patients) and 118 mg/m2/day (2 patients). The DLTfor DENSPM was central nervous system toxicity characterizedby aphasia, ataxia, dizziness, vertigo and slurred speechoccurring at dose levels ≥ 94 mg/m2/day, whichwas also the MTD. Safety: The most frequent drug-relatedadverse events were asthenia (9 patients), injection sitereaction (6 patients) and anemia (6 patients). One patient wasremoved from the study due to CNS toxicity. There were notreatment-related deaths. No trends were observed regardinghematologic toxicities, biochemical changes or changes invital signs. Efficacy: Nineteen of the 28 patients enrolled inthe study were assessed for response. No objective responseswere observed. Five patients had stable disease as the bestresponse to therapy. Conclusions: Because the DLT wasCNS and because of the relatively low doses that could besafely administered on this schedule as compared with aonce-a-day schedule, this regimen was not recommended forPhase 2.

Relationship between the oral contraceptive and folic acid metabolism: serum folate concentrations.

Abstract A study of women who developed severe megaloblastic anemia while receiving oral contraceptive agents prompted a hematologic investigation of individuals taking such drugs. A group of patients receiving two different oral contraceptives has been evaluated and compared to a control series. No subjects became folate deficient. There does not appear to be any significant relationship between the duration of therapy and the serum folate level. The exact interaction between folic acid and estrogen remains to be determined.

Cardiac transplantation in a patient with hereditary hemochromatosis: role of adjunctive phlebotomy and erythropoietin

We describe the case of a 36-year-old woman with hereditary hemochromatosis (HH) resulting in end-stage cardiomyopathy and treated successfully with orthotopic cardiac transplantation. Before and after transplantation, the patient underwent aggressive treatment with frequent phlebotomy. We used erythropoietin concomitantly to maintain adequate hematocrit to support continued phlebotomy. We believe that aggressive use of phlebotomy provided the patient hemodynamic benefit and hastened the return of endocrine function post-transplantation. We also believe that the patients history of high-dose vitamin C usage may have accelerated iron deposition in the heart and other vital organs.

Anemia and nutritional deficiency in the acutely ill hospitalized patients

Hospitalized patients may present with nutritional deficiencies or develop them during the hospitalization. The physician should remain alert to the presence of these readily correctable conditions.