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Biomedical subjects

E M Berkman

Publications and source records attributed to E M Berkman.

At least 19 recordsLinked to original sources
PubMed1996

Methods of isolation and cryopreservation of stem cells from cord blood.

Successful reconstitution of the hematopoietic system by umbilical cord blood (UCB) stem cells has sparked interest in large-scale banking of UCB. This would only be feasible if UCB samples could be frozen in small volumes. Early efforts to fractionate UCB produced significant losses of stem and progenitor cells. Several groups have proposed techniques to concentrate the stem/progenitor cell fraction of UCB, with good recovery. These are described, together with the principles of cryopreservation of stem cells. It seems feasible to store UCB samples on a large scale, although the different fractionation methods need to be compared, and the optimal, most efficient technique must be determined.

Antigens, CD↗
PubMed1995

Interleukin-6-associated anemia: determination of the underlying mechanism.

Recombinant human interleukin-6 (rhIL-6) is a pluripotent cytokine with proinflammatory, antitumor, and growth factor effects. Clinical investigations of rhIL-6 either alone as immunotherapy or as a colony-stimulating factor in conjunction with chemotherapy have shown a dose-dependent, rapid onset, and largely reversible decrease in venous hematocrit levels. In an effort to determine the mechanism for the rhIL-6-associated anemia, we measured red blood cell volume serially in patients receiving rhIL-6 at either 30 micrograms/kg/day as a 120-hour continuous intravenous infusion (renal cell carcinoma) or 100 micrograms/kg/d intravenously over 1 hour for 5 days (melanoma) as part of two separate phase II trials. Radioisotope dilution assays with 51Cr-labeled autologous red blood cells and hemolysis screens were performed on day 1 before the initiation of therapy and on day 5 shortly before the end of therapy. In the 6 patients studied, the mean decrease in hemoglobin concentration was 1.9 +/- 0.94 g/dL. The mean decrease in the hematocrit level was 6% +/- 2% and the mean increase in total blood volume was 731 +/- 337 mL. These changes were explained by a mean decrease in red blood mass of 106 +/- 109 mL and a mean increase in plasma volume of 743 +/- 289 mL. The decrease in red blood cell mass was largely explained by phlebotomy during the hospitalization, but was not statistically significant (paired t-test, P = .06). All other changes were statistically significant (P < .05). Simple regression analysis indicated that the decrease in hematocrit level and increase in plasma volume were related (y = -1.78 - .0066X; R = -.74). Measurements of lactate dehydrogenase, bilirubin, haptoglobin, and reticulocyte counts and serial stool hemoccults did not indicate hemolysis or blood loss. We conclude that the anemia caused by IL-6 is caused by an increase in plasma volume.

Adult↗
PubMed1995

Large-volume leukapheresis for collection of mononuclear cells for hematopoietic rescue in Hodgkin's disease.

BACKGROUND: Peripheral blood mononuclear cells (MNCs) collected by leukapheresis contain hematopoietic stem and progenitor cells that provide autologous hematopoietic rescue after high-dose chemotherapy, an approach that offers a significant benefit to patients with recurrent Hodgkin's disease. However, patients with low MNC counts may require 10 or more standard leukapheresis procedures for the collection of sufficient cells for hematopoietic rescue. STUDY DESIGN AND METHODS: The effectiveness of steady-state large-volume leukapheresis (LVL; 15-35 L blood processed) was evaluated as a method for collecting MNCs for hematopoietic rescue in seven patients with recurrent Hodgkin's disease. LVL was performed on 2 consecutive days per week to collect 7 x 10(8) MNCs per kg. The circulating MNC counts on the first day of LVL and the total numbers of LVL, of MNCs collected, and of liters of blood processed were determined per patient. After high-dose chemotherapy and MNC transfusion, days to granulocyte and platelet engraftment were recorded. RESULTS: On the first day of LVL, patients had median circulating MNCs of 1536 (range, 504-3950) x 10(6) per L. The median number of LVL procedures per patient was four (range, 1.25-6), and the median L per kg of blood processed was 1.57 (range, 0.38-4.03). Simple regression analysis plotting L per kg against initial MNCs gave a curve with the equation y = e(1.42-(6.31 x 10E-4)x) (correlation coefficient = -0.97, R2 = 0.95, exponential fit). Without posttransfusion growth-factor support, median days to granulocyte engraftment were 19 (range, 12-26) and those to platelet transfusion independence were 34.5 (range, 10-57). CONCLUSION: LVL provides a useful method of collecting MNCs for hematopoietic rescue in patients with Hodgkin's disease. The patient's baseline MNC count provides a useful estimate of the volume required for LVL.

Adult↗
PubMed1995

Vascular erosion caused by a double-lumen central venous catheter during therapeutic plasma exchange.

BACKGROUND: The use of large-bore double-lumen dialysis catheters has simplified the procedure of therapeutic plasma exchange, but these catheters are associated with unusual and possibly life-threatening complications. CASE REPORT: A 46-year-old black man was admitted to the hospital with acute onset of paresthesia and weakness. A diagnosis of Guillain-Barré syndrome was made. Plasma exchange therapy was instituted by peripheral venous access. After three such exchanges, a double-lumen central venous catheter was placed via the left subclavian vein on hospital Day 7. The patient experienced a sudden onset of severe chest pain and dyspnea during the fourth plasma exchange. He became diaphoretic and hypotensive and experienced tachycardia. The apheresis procedure was stopped. Because of worsening respiratory distress, endotracheal intubation was performed. A chest x-ray revealed a large right pleural effusion. The central venous catheter was removed. A chest tube was placed, and a large amount of bloody fluid was drained. Several days later, the endotracheal and chest tubes were removed. CONCLUSION: An unusual complication of the use of a central venous catheter, erosion of the superior vena cava, occurred during therapeutic plasma exchange. Prompt recognition of this complication and appropriate therapy can be life-saving.

Blood Component Removal↗
PubMed1994

Waldenström's macroglobulinemia with an IgM paraprotein that is both a cold agglutinin and a cryoglobulin and has a suppressive effect on progenitor cell growth.

BACKGROUND: A patient with Waldenström's macroglobulinemia was admitted to the hospital with fever, leg pain, and dyspnea. The patient had gas gangrene of the left leg that required above-the-knee amputation. Plasmapheresis was instituted to treat hyperviscosity. STUDY DESIGN AND METHODS: The patient's serum contained an IgM-kappa paraprotein, a cryoglobulin, and a cold agglutinin. The serum was studied. RESULTS: The patient's red cells typed as A1, Rh-positive. The direct antiglobulin test was negative. The serum contained a cold agglutinin with anti-Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sample was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline resulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g per L. These results indicate that the cryoglobulin and the cold agglutinin are the same paraprotein. Serum protein electrophoresis using agarose gel and immunofixation of the serum revealed an IgM-kappa monoclonal band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhibition of burst-forming units-erythroid and colony-forming units-granulocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenström's macroglobulinemia did not suppress progenitor cell growth. The patient's serum inhibited colony formation in a dose-response fashion. CONCLUSION: Reports of cryoprecipitable cold agglutinins are rare. This case is unusual because the IgM-kappa paraprotein was also a cold agglutinin with anti-Pr specificity and erythroid and granulocyte-macrophage progenitor cell-suppressive properties.

Agglutinins↗
PubMed1992

Immune hemolysis, disseminated intravascular coagulation, and serum sickness after large doses of immune globulin given intravenously for Kawasaki disease.

One week after treatment with intravenously administered immune globulin and aspirin, a child with Kawasaki disease had persistent fever and an increase in coronary artery diameter to greater than 3 mm. Two additional doses of immune globulin were given intravenously. Rapid hemolysis occurred, followed by disseminated intravascular coagulation and serum sickness. Clinicians should be aware that immune globulin preparations contain antibodies to blood-type antigens that may cause significant hemolysis and disseminated intravascular coagulation.

ABO Blood-Group System↗
PubMed1992

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma.

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.

Adolescent↗
PubMed1992

Large-volume leukapheresis for peripheral blood stem cell collection in patients with hematologic malignancies.

Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for bone marrow rescue following high-dose chemotherapy. The target cell count was 7 x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components were collected from them as four sequential samples. Total MNCs collected averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU-GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout the three consecutive planned days of 5-hour LVL. An average of three LVL procedures per patient was performed (range, 1.25-4), and an average of 27 L (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1 with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p < 0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19 percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗
PubMed1991

Trisomy 13q in a case of acute leukemia with lineage inconsistency.

A case of acute leukemia has two distinct immature blast lines, lineage inconsistency with CD 4 positivity, and trisomy 13q as the effective cytogenetic abnormality. This case represents another instance of trisomy 13 with acute leukemia developing in a more primitive pluripotent stem cell.

Antigens, CD↗
PubMed1991

Increase in circulating colony-forming units-granulocyte-macrophage during large-volume leukapheresis: evaluation of a new cell separator.

Peripheral blood stem cell (PBSC) collection was evaluated in two groups of normal donors who underwent large-volume leukapheresis on a blood cell separator. In Group A (n = 10), a 3-hour leukapheresis was performed. An average of 11.8 L of blood was processed with a mean flow rate of 66 mL per minute and a collection rate of 3 mL per minute. The PBSC product contained a mean 1.4 x 10(10) mononuclear cells (MNCs) (lymphocytes and monocytes), 1.27 x 10(6) colony-forming units-granulocyte-macrophage (CFUs-GM), and an average hematocrit of 4 percent (0.04). Postapheresis blood counts showed significant reductions in MNCs (19%) and platelets (45%) (p less than 0.005). Twenty-four hours later, the MNCs had returned to preapheresis levels. The platelet count returned to baseline only after 7 days. Circulating CFUs-GM remained stable for 3 days after apheresis but were increased twofold by Day 7 after apheresis (p = 0.025). Varying the product hematocrit from 1 percent (0.01) to 13.3 percent (0.13) did not change the number of CFUs-GM collected per MNC. In Group B (n = 4), an average of 18.5 L of blood was processed with a mean flow rate of 94 mL per minute and a collection rate of 3 mL per minute. The PBSC product was collected as four sequential samples and assayed for MNCs and CFUs-GM. Total MNCs averaged 1.7 x 10(10) (an increase of 21% relative to Group A) and CFUs-GM averaged 3.08 x 10(6) (an increase of 143%). Mean MNCs did not vary significantly among the four samples. However, CFUs-GM collected per minute (relative to the first sample) did show 1.26-fold (p = 0.001), 1.86-fold (p = 0.011), and 2.52-fold (p = 0.04) increases in the second, third, and fourth samples. These data suggest that MNCs and committed progenitor cells are recruited during large-volume leukapheresis. Moreover, there is a twofold increase in circulating CFUs-GM 1 week after apheresis.

Adult↗
PubMed1990

Autoimmune hemolytic anemia in Kawasaki disease: a case report.

A 3-year-old boy presented with the fever, conjunctivitis, rash, and lymphadenopathy diagnostic of Kawasaki disease. Treatment with antibiotics, aspirin, and intravenous immunoglobulin was instituted. The hematocrit decreased from 35 percent on admission to 11 percent by hospital Day 10, and the white cell count had increased from 13.7 to 42 x 10(3) per microL, and the patient had a leukoerythroblastic blood smear. The direct antiglobulin test demonstrated IgG but not complement on the red cell (RBC) surface. An acid eluate reacted (titer of 4) with all panel cells in the antiglobulin phase. Intravenous immunoglobulin from the same lot used for treatment did not contain antibody that reacted with the patient's group O RBCs or a panel of group O RBCs, but did contain IgG anti-A and -B (titer of 4). The patient received a transfusion and was given methylprednisone. The direct antiglobulin test and acid eluate were negative 4 days later. The patient had an uneventful recovery. The distinction between antibody-mediated hemolytic anemia and autoimmune hemolytic anemia is important in the treatment of this disease.

Anemia, Hemolytic, Autoimmune↗
PubMed1990

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↗