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Biomedical subjects

E M Berkman

Publications and source records attributed to E M Berkman.

At least 37 records · Page 2Linked to original sources

EDTA-dependent leukoagglutination.

Leukopenia (WBC 1.9 x 10(9)/L) was reported from an automated cell counter (TOA E-5,000, Symex) on a patient blood sample collected in ethylene diamine tetracetic acid (EDTA). Leukocyte aggregates of 30-50 cells were seen on the peripheral blood smear. Blood samples collected in heparin, citrate, and EDTA had white blood counts (WBC) of 8.1, 8.1, and 2.5 x 10(9)/L. A 0.3-mL aliquot of patient EDTA-plasma mixed with 0.3 mL normal packed cells (NPC) resulted in a WBC of 2.7 x 10(9)/L, a reduction of 58% from the control value. Increasing concentrations of EDTA (0.35-2.16 mg/mL), patient serum, and NPC resulted in a greater than 60% WBC reduction at EDTA concentrations greater than 0.96 mg/mL. Serial dilutions of patient serum in phosphate buffered saline (PBS) showed greater than 50% WBC reduction at a dilution of 1:4. Incubation (0, 1, and 2 hours) (0 degrees C, room temperature [RT], and 37 degrees C) of samples containing patient serum, EDTA, and NPC resulted in the greatest WBC reduction at 2 hours and at RT (60%). Incubation with 0.01 M dithiothreitol (DTT) abolished the ability of patient serum to decrease the WBC. These data suggest an EDTA-dependent, low titer IgM leukoagglutinin.

Adult↗

Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells.

The development of a goiter and hypothyroidism in a 28-year-old man in whom metastatic melanoma had been treated with interleukin-2 and lymphokine-activated killer cells (LAK cells) prompted us to assess thyroid function in patients undergoing this therapy. Thirty-four patients with advanced neoplasms who had received interleukin-2 and LAK cells were followed for at least four weeks after treatment. Seven patients (21 percent) had laboratory evidence of hypothyroidism, with a decline in the serum thyroxine concentration to below normal (less than or equal to 35 nmol per liter; normal, 65 to 148), a decline in the serum free thyroxine index, and a rise in the serum thyrotropin concentration (peak values, 7.2 to 166 mU per liter; normal, 0.5 to 5.5) 6 to 11 weeks after treatment. Two patients had elevated serum thyrotropin levels before treatment, which increased further after treatment. In two patients, these abnormal values returned to normal within 10 months. All five symptomatic patients had borderline or elevated serum antimicrosomal antibody titers after treatment; two had serum antibodies to thyroglobulin. Five of the seven patients with hypothyroidism (71 percent) but only 5 of the 27 euthyroid patients (19 percent) had evidence of tumor regression (P less than 0.02). None of 11 patients treated with interleukin-2 but not LAK cells had hypothyroidism. We conclude that treatment with interleukin-2 and LAK cells can cause hypothyroidism, possibly by exacerbating preexisting autoimmune thyroiditis, and that it may be associated with a favorable tumor response.

Adult↗

Cold hemagglutinin disease associated with IgG cold-reactive antibody.

Six patients with chronic idiopathic cold hemagglutinin disease were studied whose serum cold agglutinin was not inactivated or was incompletely inactivated with the IgM-reducing agent dithiothreitol. In five of these patients, isolation of the antibodies revealed that two patients had predominantly IgG cold-reactive antibody, which was associated with smaller amounts of IgM in one patient and with IgA in the other; two patients had predominantly IgM cold agglutinin with lesser amounts of cold-reactive IgG; and one patient had an IgG cold agglutinin only. Both patients with predominantly IgG cold-reactive antibodies were treated with splenectomy and subsequently had a rise in more than hemoglobin levels that has been maintained for over 36 months without additional therapy. Two of the other three patients were treated with glucocorticoids only and responded similarly. These data indicate that a subset of patients with cold hemagglutinin disease have IgG cold-reactive antibodies. In contrast to patients with typical cold agglutinin disease, this subset appears responsive to glucocorticoids and splenectomy.

Adolescent↗

Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the POEMS syndrome.

A patient with osteosclerotic myeloma and POEMS syndrome, unresponsive to pulse prednisone and melphalan therapy, was admitted to the hospital for a trial of plasma exchange therapy. The presentation included IgG lambda monoclonal gammopathy, peripheral neuropathy, hepatosplenomegaly, hyperpigmentation and thickening of the skin, edema, and tense ascites. Laboratory tests confirmed hypothyroidism, hypogonadism, and adrenal insufficiency. Six exchange procedures failed to affect the clinical course, and the patient died. Greater-than-one-plasma-volume exchanges (patient's measured plasma volume, 2,703 cc) were performed. When IgG and cholesterol removal were compared to the predicted removal, based on the volume of plasma removed, significantly less reduction in concentration than predicted was measured. IgG concentrations increased postapheresis and, at 2 weeks, three-fourths of the removed IgG had reaccumulated. A reduced efficiency of removal of both IgG and cholesterol can be explained by postulating increased vascular permeability with free exchange of soluble substances from one compartment to another. If an abnormal product is produced by the disease and is responsible for the clinical syndrome, a more intensive schedule of plasma exchange therapy may be needed to achieve a sustained depletion of the responsible soluble substance. Alternatively, neither increased vascular permeability or the clinical manifestations are responsive to removal of a soluble substance or are caused by a soluble substance produced by the malignancy.

Adrenal Insufficiency↗

A combination of IgG and IgM autoantibodies in chronic cold agglutinin disease: immunologic studies and response to splenectomy.

A patient with chronic cold agglutinin disease and anti-I antibody was studied. The titer of the patient's serum at 4 degrees C was 700 with adult I RBC, 256 with cord RBC, 256 with adult i RBC. At room temperature the titers were decreased and the serum also reacted at a titer of 4,000 with enzyme treated adult I RBC. Dithiothreitol treatment of the serum and purified antibody decreased reactivity only slightly, indicating that the antibody was IgG. The heat eluate contained 1.2 mg/ml IgG kappa, but only 80 micrograms/ml IgM kappa. A hybridoma made by fusing the patient's peripheral blood lymphocytes with a human myeloma cell line contained only IgM kappa (30 micrograms/ml) anti-I activity. The IgM fraction of the heat eluate reacted similarly to the hybridoma supernatant. The IgG fraction resembled the serum and heat eluate. In this case study, IgG kappa and IgM kappa immunoglobulins, both possessing cold agglutinin activity, were present in the patient's serum. This finding is unusual in idiopathic cold agglutinin disease and in view of the predominance of an IgG cold agglutinin, splenectomy was recommended for treatment.

Adult↗

Plasmapheresis with immunosuppression in amyotrophic lateral sclerosis.

Four patients with amyotrophic lateral sclerosis and one with progressive muscular atrophy were treated with large-volume plasmapheresis combined with immunosuppression. Assessment of muscle strength and functional ability was performed during a period of time ranging from 6.2 to 13 months. Patients were compared with a clinically matched control group. Both treated and untreated patients continued to show similar deterioration. The results of this study failed to show any therapeutic benefit of plasmapheresis with immunosuppression in patients with amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗

Plasma exchange in autoimmune hemolytic anemia (AIHA).

Plasma exchange therapy in autoimmune hemolytic anemia (AIHA) was used in four patients (two with warm hemolytic anemia and two with cold hemolytic anemia). The size of each plasma exchange approximated 1 plasma volume; three consecutive daily exchanges removed 80-90% of the immunoglobulins--immunoglobulin G (IgG) and immunoglobulin M (IgM)-, complement (C3, C4), and reduced antibody titers. Transfusion requirements dramatically decreased after plasma exchange in each case. In two patients, red blood cell (RBC) survival studies were performed to more accurately assess the effect of plasma exchange therapy, since steroid and/or immunosuppressive therapy was given concomitantly. In one case of cold AIHA, homologous 51Cr-RBC were injected 4 days prior to plasma exchange and repeat injection (same donor) following completion of plasma exchange. The survival curve prior to plasma exchange therapy had a T 1/2 = 7.8 days (r = -0.988) and after plasma exchange therapy had a T 1/2 = 20.4 days (r = 0.925). RBC survival studies using homologous 51Cr-RBC were also performed in a patient with warm AIHA. The survival curve before plasma exchange had a T 1/2 = 2 days (r = -0.95), and postplasma exchange a T 1/2 = 1.8 days (r = -0.91). Plasma exchange therapy seems to have a beneficial effect in cold rather than warm autoimmune hemolytic anemia.

Adult↗

Angiotensin-1-converting enzyme (ACE) activity in human serum following plasma exchange.

Although angiotensin-1-converting enzyme (ACE), which catalyzes both the conversion of angiotensin 1 to angiotensin 2 and the hydrolysis of bradykinin, is known to be present in serum, little information is available about its source or turnover characteristics. We determined the removal and recovery characteristics of serum ACE for two normal subjects and 16 patients, with various diseases, who were undergoing partial plasma exchange. Cholesterol was removed as predicted, but the average actual removal of ACE, 70% of that originally present, was 28% greater than predicted. Recovery of serum levels of ACE after plasma exchange was 34% on Day 1, 62% on Day 3, 94% on Day 5, and 104% on Day 8, and the level remained relatively constant thereafter up to 28 days of study. The pattern of recovery of serum ACE is more compatible with a system of synthesis and release of ACE than with a simple exchange mechanism from sites on the plasma membrane of the endothelial cell or a shift of the enzyme from one space to another.

Cholesterol↗

Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents.

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48-72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.

Alanine Transaminase↗

Primary biliary cirrhosis and cold autoimmune hemolytic anemia: effect of partial plasma exchange.

The previously unreported occurrence of primary biliary cirrhosis with cold autoimmune hemolytic anemia is described. Red cell survival studies showed a t1/2 of 11.1 days. Partial plasma exchange increased red cell survival to 15.8 days. Concomitantly, alkaline phosphatase, SGOT, SGPT, and bilirubin was reduced in predictable amounts but rebounded to prepheresis levels quickly. Although partial plasma exchange was effective in increasing red cell survival and in reducing the level of selected abnormal plasma components, the patient died 3 mo after initiation of plasma exchange therapy. Partial plasma exchnage did not appear to have any long-term beneficial effects on either liver disease or the hemolytic process.

Agglutinins↗

Evidence for a silent or null gene in hereditary C2 deficiency.

Three generations of a family with hereditary C2 deficiency were studied, Six members heterozygous for C2 deficiency were identified by serum C2 levels that were approximately 50% of normal C2 values and the identity was supported by HLA analysis. All six members with low C2 levels had only a single electrophoretic variant. Two of four children did not have the variant found in the parent from whom they inherited the partial C2 deficiency. It is inferred that the low levels of C2 result from the inheritance of a silent or null gene, C2D allelic with the structural genes controlling the electrophoretic variants.

Antigens↗

Cytotoxins against a granulocyte antigen system: detection by a new method employing cytochalasin-B-treated cells.

A method for demonstrating granulocyte cytotoxins using a modified microdroplet dye exclusion technique and cytochalasin-B-treated cells is described. Cytochalasin-B-treated granulocytes were reacted against 223 sera from multitransfused pregnant and renal transplant patients. Incidence of granulocyte cytotoxins was 11.2%. Analysis (2 X 2 contingency tables) of the reactivity of GCT+ sera showed highly significant (p less than 0.001) positive associations among 5 sera and a significant (p less than 0.001) negative association with another serum. The data are consistent with the hypothesis that a granulocyte antigen system is detected by cytotoxins and that granulocyte antigens 'Grl' and 'Gr2' may be products of allelic genes.

Alleles↗