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Biomedical subjects

D Ciavarella

Publications and source records attributed to D Ciavarella.

52 records · Page 3Linked to original sources

Hematopoietic stem cell processing and storage.

The techniques to collect, process, and store HSC in anticipation of transplantation are now widely available. Important unresolved issues revolve around the as yet imperfect identification and classification of totipotential progenitors. However, much progress has been and will continue to be made despite this limitation. Research priorities of present and future stem cell processing laboratories should include: 1. Optimization of liquid (nonfrozen) storage techniques. This will permit more complex cell-specific manipulations, such as T-lymphocyte subset selection, isolation of CD34+ populations, treatment in vitro with growth factors, gene transfer experiments, and long-range transport of HSC, to be performed while preserving HSC integrity. 2. A better understanding of the regulation and kinetics of peripheral blood and umbilical cord HSC, to allow optimum collection procedures that do not require marrow harvesting. 3. An intensive study into the optimum conditions of collection, processing, and storage of megakaryocytic progenitors to decrease the long platelet-transfusion dependency of the myeloablated patient. 4. A search for a simple in vitro correlate of engraftment potential of a stem cell preparation. This will greatly improve the quality control functions of the laboratory as well as contribute to better patient selection for transplantation.

Animals↗

Marrow storage techniques: a clinical comparison of refrigeration versus cryopreservation.

Fifty-three patients were evaluated for a comparison of the efficacy, safety, and cost efficiency of bone marrow (BM) transplanted after either refrigeration or cryopreservation. Thirty-eight patients had BM stored at 4 degrees C for an average of 3 days and 15 patients had cryopreserved BM stored for an average of 56 days. The average number of cells harvested was 3.8 x 10(8)/kg. The time to WBC recovery greater than 1 x 10(9)/l was 17 days refrigerated and 23 days for cryopreserved BM. The time to platelet recovery greater than 20 x 10(9)/l was 24 days for refrigeration storage and 51 days for cryopreserved BM. Four of 38 patients with refrigerated vs. 4/15 patients with cryopreserved BM experienced delayed engraftment (p less than 0.05). Refrigeration storage requires no special equipment, is cheaper than and presents a safe and viable alternative to cryopreserved BM in reconstituting hemopoiesis following high-dose chemo-radiotherapy.

Adolescent↗

High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease.

Twenty three patients with Hodgkin's disease were treated with BCNU (carmustine), etoposide, and cyclophosphamide at doses of 450-600 mg/m2, 1500-2000 mg/m2, and 120 mg/kg respectively. Bone marrow refrigerated at 4 degrees C for 2-5 days or cryopreserved at -80 degrees C was used to reconstitute bone marrow function. The median age was 28 (range 16-48), and the median Karnofsky performance status was 70. Nineteen patients had progressive disease while on chemotherapy. The median number of prior regimens was three (1-7), and the median number of prior chemotherapy drugs was 10 (range 4-12). Ten patients had received at least two of the drugs used in this study and four had had all three. Indicator lesions included lung (10), peripheral lymph nodes (9), retroperitoneal nodes (8), liver (3), and chest wall masses (2). Ten patients achieved a complete remission (43.5%; 95% confidence limits 23-64%), and five patients had a partial remission (21.7%; 95% confidence limits 5-39%). The median duration of complete remission was 6 months (range 2-13+ months). Responses were shorter in duration for patients with primary refractory disease. Liver function abnormalities were noted in nine (39%) cases. Post transplant, the recovery time was 18 days (range 11-43) for WBC and 24 days (11-77) for platelets. Two patients died of septic episodes while neutropenic. The median number of RBC units used was seven (range 1-45). Ten patients had evidence of pulmonary dysfunction. In seven patients there was symptomatic improvement with steroid therapy, but three patients who were not treated with steroids died as a result of interstitial pneumonia. Future programs should consider bone marrow transplantation in patients with Hodgkin's disease earlier in the course of disease, at the time of minimal residual disease, and employ newer, potentially less toxic drugs.

Adolescent↗

Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba column) immunoadsorption.

Both antibodies and circulating immune complexes (CIC), which bind to platelets and induce the destruction and clearance of platelets by the reticuloendothelial system, are found in patients with human immunodeficiency virus (HIV) and immune thrombocytopenic purpura (ITP). IgG and CIC were removed from patients' plasma by extracorporeal immunoadsorption using protein A-silica columns (PROSORBA columns). Of the 36 HIV-positive ITP patients treated, 29 received more than one treatment and were evaluated for response. Sixteen patients showed more than a 50% increase in their platelet counts. Platelet-associated IgG (PAIgG) and/or platelet-directed IgG and CIC were elevated in all patients. After four to eight treatments, 16 of 29 patients showed a 170% to 430% increase in platelet counts. A decrease in CIC and PAIgG was noted in responding patients. The median duration of response to date was 8 to 12 months. This treatment was associated with immune modulation and the development of an anti-F (ab')2 antibody response. The antibody functions by complexing with both platelet-binding IgG and CIC, neutralizing their binding capacity for platelets and enhancing their clearance from the circulation. Nine patients with mitomycin-C-induced hemolytic uremic syndrome (HUS) were also treated with PROSORBA columns. Pretreatment platelet counts were markedly reduced while a definite increase in platelet counts was observed upon completion of therapy. There was a decrease of hemolysis and stabilization of renal function in three patients. PROSORBA column treatment has demonstrated marked activity against both HIV-ITP and HUS, and has successfully freed patients from the bleeding diathesis associated with these syndromes.

Acquired Immunodeficiency Syndrome↗

Acquired toxoplasmic retinochoroiditis after platelet transfusions.

We present a rare well-documented case of acquired toxoplasmic retinochoroiditis transmitted by platelet transfusion. A 52-year-old woman developed severe thrombocytopenia shortly after receiving a sulfamethoxazole-containing antibiotic. This episode was treated with platelet transfusions and a three-day course of corticosteroids. Thirteen days later, she developed an acute febrile illness typical of the typhus-like form of toxoplasmosis. Fifty-six days later, while still taking corticosteroids for recurrent immune thrombocytopenia, she developed an acute macular retinochoroiditis OD. Serology showed recently acquired toxoplasmosis. Epidemiologic investigation revealed no possible source for the toxoplasmosis other than the platelet transfusion.

Adrenal Cortex Hormones↗

Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient.

Clotting factor activities and coagulation screening tests in 36 massively transfused patients were measured after every 12 units of blood and whenever diffuse microvascular bleeding (MVB) developed. Moderate deficiencies in clotting factors were common, but they were not associated with MVB. MVB was associated with severe abnormalities of coagulation, i.e. a fibrinogen level less than 0.5 g/l or clotting factor levels less than 20%. The quantitative relationship between the prothrombin (PT) and partial thromboplastin (PTT) times and underlying clotting factor levels was explored by multiple linear regression. Clotting factor levels accounted for only 65-85% of the variability in these tests. However, clotting factor activities less than 20% were reliably reflected by marked prolongations of the PT and PTT (values greater than 1.8 times control). Our data suggest that commonly used replacement formulas are not likely to prevent MVB, since consumption of platelets and/or clotting factors, rather than simple dilution, is a major cause of the deficiencies leading to MVB. Modified whole blood alone was sufficient replacement therapy for most patients. Guidelines for transfusion of supplemental components during massive transfusion are given.

Blood Coagulation Factors↗

Preparation for blood group-incompatible bone marrow transplantation: comparison of two techniques.

Two similar techniques of red cell depletion of blood group-incompatible marrow prior to bone marrow transplantation were compared in 8 patients. The first method involved a single sedimentation step and removed a mean of 91% of marrow red cells and 33% of marrow nucleated cells. The second method involved multiple sedimentation steps and removed a mean of 96% of red cells and 29% of nucleated cells. Both methods can be recommended to a transfusion service newly involved in a bone marrow transplantation program.

Blood Group Incompatibility↗

Partial plasma exchange in patients with AIDS and Kaposi's sarcoma. Plasmapheresis in AIDS.

Intensive plasma exchange was performed in seven male homosexual patients with AIDS and Kaposi's sarcoma. Serial 1.2 plasma volume exchange procedures were performed three times a week for six weeks. In five of the patients, plasma replacement included gamma globulin in the form of plasma (two patients), or an IV IgG preparation (three patients). No changes in the mean number of helper-inducer or suppressor-cytotoxic cells were noted during the treatment period or the weeks following completion of the last procedure. The mean mitogenic response of the patients' lymphocytes to PHA increased by 32.4% during the course of the plasmapheresis procedures (p less than .05), but returned to baseline over the eight weeks following treatment. Mitogenic responsiveness to PWM did not significantly increase during the course of treatment. No regression of Kaposi's sarcoma lesions was found in any of the patients treated.

Acquired Immunodeficiency Syndrome↗

Prophylactic platelet administration during massive transfusion. A prospective, randomized, double-blind clinical study.

Prior studies at Harborview Medical Center have suggested that dilutional thrombocytopenia is a major etiology of microvascular, nonmechanical bleeding (MVB). We undertook a prospective randomized double-blind clinical study to compare the prophylactic effects of 6 units of platelet concentrates (PLT) versus 2 units of fresh frozen plasma (FFP) administered with every 12 units of modified whole blood in patients undergoing massive transfusion (12 or more units in 12 hours). After exclusions, three of 17 patients who received PLT and three of 16 patients who received FFP developed MVB, an incidence no different from our previous findings. Regression lines of platelet counts during transfusion were no different between groups, and both groups had higher platelet counts than predicted from a standard washout equation. Only one patient had evidence of dilutional thrombocytopenia as a cause for MVB. Prophylactic platelet administration is not warranted as a routine measure to prevent MVB.

Adult↗

Coagulation factor activity in platelet concentrates stored up to 7 days: an in vitro and in vivo study.

The in vitro and in vivo recovery of coagulation factor activity in platelet concentrates stored up to 172 h was studied. In vitro studies revealed that fibrinogen and antithrombin III levels do not change with storage. Factors II, V, VII, VIII, IX, X and XI all showed statistically significant falls from baseline over the 172 h storage period. However, most factor activities remained above 70%, with the major exception of factors V and VIII. These factors fell to less than 30% activity over the storage period, consistent with their known lability during whole blood storage. In vivo studies after platelet concentrate infusion in patients with concurrent thrombocytopenia and coagulation deficiencies revealed that the measured in vitro activity was recoverable in vivo. We conclude that platelet concentrates stored for 172 h are an adequate source of clotting factors. However, like stored whole blood, they may not provide therapeutic doses of factors V and VIII.

Antithrombin III↗

Transient agranulocytosis associated with non-A, non-B hepatitis.

A 44-yr-old woman with non-A, non-B hepatitis developed agranulocytosis and absence of marrow granulocyte precursor cells with only mild involvement of other blood elements. The agranulocytosis was complicated by gram-negative septicemia, successfully treated with antibiotic therapy. Marrow recovery followed 2 wk of supportive therapy. Before reversal of the agranulocytosis, a future bone marrow transplant was a consideration, making the use of therapeutic granulocyte transfusions, with their ability to sensitize the recipient, potentially harmful. Experience in this case indicates that agranulocytosis associated with non-A, non-B hepatitis may be reversible, and supports the use of supportive care including appropriate antibiotics, and if necessary, granulocyte transfusions, pending marrow recovery.

Adult↗

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Diagnosis↗