The proposed research will use biomagnetic susceptometry - a method introduced and developed by our laboratories - to measure hepatic storage iron concentrations in patients with disorders of iron metabolism. At present, the results of non-invasive magnetic determinations and of the chemical analysis of hepatic tissue obtained by biopsy are quantitatively equivalent when body iron stores are normal or increased. With our new computer-enhanced, dual channel, superconducting quantum-interference device (SQUID) susceptometer, a computer controls the entire measurement procedure and automatically calculates the hepatic iron concentration. In effect, the susceptometric method provides an automated, safe, and non-invasive magnetic """"""""biopsy"""""""" of liver ferritin and hemosiderin iron that is well accepted by patients. In patients with iron overload, magnetic studies permit accurate, direct, reliable, and repeated measurements of hepatic iron that are not possible with any other available method. Clinically, hepatic magnetic measurements will be used for the detection and serial monitoring of patients with iron overload. In hereditary hemochromatosis, magnetic determinations of hepatic iron stores can identify affected individuals at an early precirrhotic stage when conventional indirect measures of iron status (serum, ferritin, transferrin saturation) may be unreliable and make possible early, preventive phlebotomy therapy. Magnetic measurements provide a new means for rapidly determining the effectiveness of treatment programs (chelation, transfusion) in transfusional iron overload (thalassemia major, other refractory anemia). Studies using the new dual channel instrument have already provided new quantitative insights that make possible the prescription of optimal individualized chelation regimens for patients with transfusional iron overload. Other studies are directed toward evaluating the toxicity of iron in patients with sickle cell anemia transfused for the prevention of recurrent stroke and in patients with iron-loading anemias with non-transfusional iron excess. In porphyria cutanea tarda, the relationship of clinical manifestations to hepatic iron content will be assessed during phlebotomy therapy. The prevalence and magnitude of iron overload in alcoholic cirrhosis and in patients requiring chronic hemodialysis will be examined in our hospital population. The goal of our studies is to determine directly the quantitative relationship between the level of iron stores and the pathophysiologic manifestations of disorders of iron metabolism.
| Brittenham, G M; Griffith, P M; Nienhuis, A W et al. (1994) Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331:567-73 |
| Brittenham, G M; Cohen, A R; McLaren, C E et al. (1993) Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 42:81-5 |
| Bacon, B R; Healey, J F; Brittenham, G M et al. (1986) Hepatic microsomal function in rats with chronic dietary iron overload. Gastroenterology 90:1844-53 |
| Bacon, B R; Park, C H; Brittenham, G M et al. (1985) Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload. Hepatology 5:789-97 |
