John R. Wright

Normal Serum Ferritin Concentrations in Precirrhotic Hemochromatosis

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Familial hemochromatosis: Characteristics of the pre-cirrhotic stage in a large kindred

Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.

Arthritis, Vasculitis, and Cryoglobulinemia Associated with Relapsing Hepatitis A Virus Infection

Hepatitis A virus, unlike hepatitis B virus, has rarely been associated with extrahepatic features. Two patients developed relapsing hepatitis A complicated by arthritis in both cases and cutaneous vasculitis in one. Both patients had cryoglobulinemia, with cryocrit values of 4.3% and 8.6%. Serologic studies showed that the cryoglobulin consisted of polyclonal IgM and IgG. The washed cryoglobulin was analyzed by sucrose density gradient ultracentrifugation under neutral (pH 7.4) and acidic (pH 2.8) conditions. Enzyme-linked immunosorbent assay techniques were used to characterize the native and dissociated cryoglobulin. The cryoglobulin contained acid-dissociable IgG complexes greater than 19S, and high molecular weight rheumatoid factors of both IgG and IgM isotypes that could be dissociated to 7S and 19S forms, respectively. Dissociation of the cryoglobulin augmented 7S anti-hepatitis A virus IgG 2.27-fold, but augmented total 7S IgG only 1.12-fold, suggesting enrichment of antiviral antibody in the cryoglobulin.

Amyloidosis and multiple myeloma. A reevaluation using a control population.

Abstract To explore the possible influence of multiple myeloma on age-related amyloid accumulation, the frequency, extent and distribution of amyloid deposition in 35 patients who died of multiple myeloma was compared to that observed in 138 patients of comparable age but without myeloma (controls). The presence of multiple myeloma did not appear to enhance the development of age-related amyloid. Amyloid deposition in the patients with myeloma could be distinguished from that in the patients without myeloma by the occasional finding of amyloid in the bone marrow. In addition, material having the tinctorial and ultrastructural characteristics of amyloid was found in the renal tubular casts of 15 patients with myeloma but in none of the controls. The results suggest that although the appearance of amyloid in certain locations appears to be characteristic of multiple myeloma, the presence of amyloid in the heart or vascular system, even in considerable amounts, in a patient with multiple myeloma does not necessarily imply that the two conditions are related.

Renal Transplantation in Multiple Myeloma: A Case Report

A patient with plasma cell myeloma presented in severe renal failure but was otherwise considered a good risk candidate for chemotherapy. Supported by hemodialysis she received intensive cyclophosphamide chemotherapy, resulting in a stabilization of all overt manifestations of her disease except for the renal failure. After 11 1/2 months of follow-up without showing any further progression of the myeloma process, she received a successful cadaveric renal transplant, which functioned well until the time of her death 15 months later. No evidence of recurrent myeloma kidney disease was found at postmortem examination.

Influence of rheumatoid arthritis on amyloidosis of aging. Comparison of 47 rheumatoid patients with 47 controls matched for age and sex.

Abstract Amyloidosis, both human and experimental, is allied with a multiplicity of predisposing factors. This study was designed to determine whether the presence of one such factor, rheumatoid arthritis, would enhance the tendency for amyloid accumulation in aged persons. With the use of sensitive histologic methods, the autopsy prevalence of amyloidosis in 47 patients with documented severe rheumatoid arthritis was compared to that in 47 nonrheumatoid subjects appropriately matched for sex and age. Contrary to expectations, the frequency and, with one exception, the distribution and amount of amyloid deposition were identical. Only one rheumatoid patient exhibited secondary amyloidosis. In this study, the rheumatoid patients exhibited an unexpectedly high frequency of gallstones and relatively low frequency of cancer in comparison to the control group.

Amyloid and Aging — An Hypothesis Involving So-Called Amyloid Degrading Activity (ADA)

Many studies have now documented amyloid accumulation as an almost universal tissue change in aging man. Although this accumulation differs in many respects from that observed in the classic forms of systemic amyloidosis and, with a few notable exceptions, its clinical significance is open to question, an understanding of amyloid deposition in the elderly may advance not only general amyloid research but may provide important insight into the basic biology of aging itself.