Elliott F. Osserman

Effects of Dichloromethylene Diphosphonate on Skeletal Mobilization of Calcium in Multiple Myeloma

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of oestoclast activity, was evaluated for its ability to decrease the excessive mobilization of skeletal calcium that complicates multiple myeloma. Ten patients with active myeloma, wide-spread bone disease, and hypercalciuria were studied in a double-blind, placebo-controlled, crossover-designed trial in which they took Cl2MDP for eight weeks and placebos for eight weeks. Two patients died during the placebo phase; of eight patients who received Cl2MDP, seven had rapid, sustained, and highly significant (P less than 0.001) decreases in urinary excretion of calcium. Six also had significant decreases in hydroxyproline excretion, and five reported lessening of skeletal pain. On patient did not respond. Although the patients received concurrent chemotherapy during the study, concentrations of myeloma proteins actually increased or decreased only slightly, indicating the declines in hypercalciuria resulted from Cl2MDP and not from improvement in the underlying disease. We conclude that Cl2MDP is a potentially useful inhibitor of osteoclast-mediated bone erosion in multiple myeloma.

THE CLINICAL IMPLICATIONS OF HYPOGAMMAGLOBULINEMIA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND LYMPHOCYTIC LYMPHOSARCOMA

Excerpt Although many patients with agammaglobulinemia have been reported since 1952, there are few reports and surveys of serum gamma globulin depressions in association with chronic lymphocytic l...

Monoclonal IgMK antibody precipitating with chondroitin sulfate C from patients with axonal polyneuropathy and epidermolysis

We studied two patients with an axonal type of polyneuropathy, epidermolysis, and IgMK plasma cell dyscrasia. The IgMK was deposited in the dermis, was absorbed from the serum by axonal micelle preparations, and was precipitated with chondroitin sulfate in highly purified agarose in 0.15 M NaCl with 0.01 M phosphate buffer, pH 7.8. In contrast, we found none of these abnormalities in three patients with IgM plasma cell dyscrasia and demyelinating neuropathy. Of 78 other macroglobulinemic serum samples from patients without neuropathy, 7 precipitated with a sulfated polysaccharide. This reaction occurred at low ionic strength, 0.05 M barbital buffer, pH 8.1, but did not occur in the higher ionic strength of 0.01 M phosphate with 0.15 M NaCl (PBS). The interaction of the IgM with chondroitin sulfate at relatively high ionic strength could cause both the axonal polyneuropathy and the epidermolysis.

Lysozymuria and renal tubular dysfunction in monocytic and myelomonocytic leukemia

Abstract Monocytic or myelomonocytic leukemia is associated with lysozymuria. These patients often also have hypokalemia. In order to determine whether or not there is an association between lysozymuria and hypokalemia, balance studies were performed in three patients with this disorder and hypokalemia. The results indicate that all three patients had marked lysozymuria and inappropriately high rates of renal potassium loss. There was also limitation in titratable acid excretion in one patient and glycosuria and hyperuricosuria in another. Ammonium excretion following the administration of an ammonium chloride load was above the expected values at a given urine pH in two patients. All subjects had osteoporosis and fractures developed spontaneously or following minor trauma.

Motor neuron disease and plasma cell dyscrasia

In the years 1977 to 1984, 10 of 206 patients (4.8%) with motor neuron disease (MND) had M proteins; 4 had IgM and 6 had IgG. Among 100 control patients with other neurologic diseases, only 1 had an M protein. We later added six cases of MND and M proteins, as well as three with polyclonal IgM elevations and two with Bence-Jones proteins. Including other reports, there are now 37 known cases of MND with monoclonal and 5 with polyclonal gammopathy. There is evidence that plasma cell dyscrasia is often undetected; the actual incidence of serum immunoglobulin abnormality in patients with MND may be greater than our figure.

Acute renal failure in patients with multiple myeloma

In the past, patients with multiple myeloma and acute renal failure have had a poor prognosis. Few patients recovered renal function and fewer still survived for prolonged time periods. This report describes the course of 10 patients with multiple myeloma and true acute renal failure treated during the decade 1970 to 1980, and reviews recent reports concerning this association. The use of radiographic contrast agents is no longer the primary predisposing factor to acute renal failure in the myeloma population. Rather, infection, hypercalcemia, and dehydration in the presence of light chain excretion are the major conditions precipitating the renal failure. Despite severe renal failure requiring dialysis, many patients may regain good renal function. Factors associated with a good or poor prognosis in this population are reviewed. The prognosis in patients with myeloma and acute renal failure has greatly improved in recent years, and prolonged survival may occur.

Structural Identity of Bence Jones and Amyloid Fibril Proteins in a Patient with Plasma Cell Dyscrasia and Amyloidosis

The partial amino acid sequence of the amyloid fibril protein isolated from the small intestine of a patient with plasma cell dyscrasia and associated amyloidosis has been determined and compared with the sequence of the kappa-type Bence Jones protein isolated from the urine of the same patient. Identical sequences were observed for the 27 amino-terminal residues that could be compared. The C-terminal tryptic peptide of the amyloid protein was identical with that of the Bence Jones protein. Apparent molecular weights and amino acid compositions of the Bence Jones and amyloid proteins were similar. It appears, therefore, that the predominant protein present in the amyloid deposits in this patient was an intact kappa-type light polypeptide chain that was identical with the urinary Bence Jones protein.

LOCALIZATION OF LYSOZYME IN NORMAL RAT TISSUES BY AN IMMUNOPEROXIDASE METHOD

The immoperoxidase-immunoglobulin bridge technique has been utilized for the localization of lysozyme (LZM) in the cells and tissue of the normal rat. Specific LZM staining was found in the proximal tubules of the kidney, Paneth cells of the small intestine and alveolar macrophages. LZM staining was also demonstrated in macrophages in the perifollicular sinusoids of an activated lymph node. The immunoperoxidase method appears to have significant advantages over previously described methods for LZM localization, and it should also be adaptable to electron microscopic studies.

Abnormal serum and urine proteins in thirty-five cases of multiple myeloma, as studied by filter paper electrophoresis

Abstract 1.1. Filter paper electrophoretic analysis of the serum and urine proteins in thirty-five cases of multiple myeloma has been carried out. In all thirty-five cases characteristic protein abnormalities were observed; seventeen cases showing homogeneous peaks in both the serum and urine, eleven cases in serum only, seven cases in urine only. 2.2. All urine samples showing a positive Bence-Jones protein reaction also displayed a characteristic electrophoretic abnormality. Eight of the twenty-four electrophoretically positive urine samples were Bence-Jones protein negative by the usual tests. Because of the relative simplicity of urine electrophoresis by the filter paper technic, this test is considered to be a practical clinical procedure. 3.3. Two cases are presented in detail because certain atypical clinicopathologic features of their disease patterns possibly assist in an understanding of the relationship of the plasma cell dyscrasias to chronic lymphatic leukemia and the lymphosarcomas. A third case, which demonstrates the value of serial electrophoretic studies in myeloma, is also presented. 4.4. Consideration is given to some of the physicochemical properties of the myeloma serum and urine proteins, and to the possible nature of their interrelationship.

Identical Twin Marrow Transplantation in Multiple Myeloma

We performed the first successful syngeneic bone marrow transplantation (BM Txp) in a patient with multiple myeloma. The patient and his normal identical twin are 50-year-old physicians. Prior to BM Txp, a partial remission was achieved with 1 year of continuous low dosage melphalan and prednisone therapy. Immediately before BM Txp, high dose cyclophosphamide and total body irradiation were administered in an attempt to eradicate the residual tumor. For 17 months after BM Txp, the patient was asymptomatic and hematologically normal although a low concentration of serum monoclonal IgGK persisted. In the 18th month, recurrence of bone pain and increase in the monoclonal IgG signalled exacerbation of the disease. Chemotherapy was resumed and again produced objective and subjective evidence of response. This study demonstrates the feasibility and potential usefulness of syngeneic BM Txp in myeloma.