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Biomedical subjects

R F Branda

Publications and source records attributed to R F Branda.

64 records · Page 4Linked to original sources

Randomized study of nandrolone therapy for anemias due to bone marrow failure.

A prospective, randomized, double-blind study was designed to determine the effectiveness and toxicity of nandrolone phenpropionate in the treatment of anemias due to bone marrow failure. Twenty-four patients were initially entered; 21 now may be evaluated: seven with aplastic anemia, six with myelofibrosis, and eight with refractory anemia. Six patients improved, but only three were taking nandrolone, the other three placebo. Response did not correlate with type of anemia. No serious drug toxicity was noted. One patient with myelofibrosis improved dramatically with placebo therapy alone, no longer requiring frequent transfusions because of a hemoglobin level increase from 5.4 to 15.8 gm/100 ml. We conclude that no substantial improvement of anemia due to marrow failure can be ascribed to nandrolone as given, and that clinical trials in these conditions should be controlled to exclude spontaneous remissions as a cause of apparent improvement.

Adult↗

Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia.

Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.

Adult↗

The effect of T-lymphocyte 'clonality' on the calculated hprt mutation frequency occurring in vivo in humans.

The frequency of 6-thioguanine resistant (TGr) mutant T-lymphocytes arising in vivo in humans can be quantified with a cell cloning assay. However, the in vivo proliferation of T-lymphocytes that may include TGr mutant cells can distort the relationship between mutation events and the resulting frequency of mutant cells. The T-cell receptor (TCR) gene rearrangement pattern of T-cell colonies can be used as an independent measure of clonality. Analysis of T-cell 'clonality' in 413 wild type and 1736 TGr mutant isolates from 58 individuals shows that mutant clonality is a frequent occurrence (35/58 individuals = 60.3%). However, a major effect on the mutant frequency corrected for clonality (the calculated 'mutation frequency') was found only in nine samples all of which had mutant frequencies greater than 40 x 10(-6).

Autoimmune Diseases↗

Plasma exchange in the treatment of immune disease.

Plasma exchange was investigated as an alternative to the use of toxic drugs to remove unwanted antibody. Studies in rabbits immunized with bovine serum albumin demonstrate that exchange transfusion after a primary immunization results in a rebound of antibody to above preexchange levels. However, exchange transfusion seven, 11, or 18 days after secondary immunization results in permanent lowering of antibody levels. Plasma exchange with the continuous flow centrifuge was used in four patients with hematologic diseases. White cell isoantibodies were removed in a septic leukopenic patient, permitting white cell transfusions. Two patients with immune thrombocytopenia were exchanges; one showed prompt and permanent elevation of platelet count, while the other did not improve. A patient with immune hemolytic anemia had stabilization of hemoglobin levels and decreased Coombs reactivity following plasma exchange.

Adult↗

Specific removal of antibodies with an immunoadsorption system.

A continuous flow immunoadsorption system consisting of a cell separator, protein A-sepharose columns, and a semi-automatic elution component was developed to specifically remove circulating IgG. This system provides extensive absorption with an essentially unlimited column bed volume. Six dogs were treated a total of 19 times. In no case did fever, sepsis, or respiratory distress result from the treatment. Serial blood counts and tests of liver and renal function remained in the normal range. Ex vivo perfusion of one plasma volume caused an acute drop in IgG levels of approximately 50 percent. This was reflected in a similar decrease in specific antibody levels to sheep erythrocytes, bovine serum albumin, and canine parvovirus. Antibody kinetics following immunoadsorption were variable, but in several cases, antibody levels remained lowered. This immunoadsorptive system appears to be a safe and effective alternative to plasma exchange for removal of IgG antibodies.

Animals↗

Immunoadsorption of human plasma with protein A-sepharose columns.

Four patients with refractory acute leukemia were treated a total of 31 times with an immunoadsorption system consisting of protein A-sepharose columns, a cell separator, and an elution monitor to test its safety and capacity to remove immunoglobulins. The procedure was tolerated well, and acutely reduced plasma IgG levels by approximately 18 percent. When the procedure was repeated two to three times per week for 3 weeks, IgG levels dropped by 30 to 40 percent, but they gradually returned to pretreatment levels after completion of the course of treatment. Single columns became saturated with IgG after approximately 1500 ml of plasma had passed through the columns. The use of multiple columns sequentially provided continuous extraction of immunoglobulin. One patient regained responsiveness to platelet transfusions after removal of platelet antibodies. These preliminary studies suggest that this immunoadsorption system is effective for specifically removing IgG and that it merits further clinical testing.

Acute Disease↗