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J McCullough

Publications and source records attributed to J McCullough.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro collection and posttransfusion engraftment characteristics of MNCs obtained by using a new separator for autologous PBPC transplantation.

BACKGROUND: A clinical study was performed to evaluate the peripheral blood progenitor cell (PBPC) collection, transfusion, and engraftment characteristics associated with use of a blood cell separator (Amicus, Baxter Healthcare). STUDY DESIGN AND METHODS: Oncology patients (n = 31) scheduled for an autologous PBPC transplant following myeloablative therapy were studied. PBPCs were mobilized by a variety of chemotherapeutic regimens and the use of G-CSF. As no prior studies evaluated whether PBPCs collected on the Amicus separator would be viable after transfusion, to ensure patient safety, PBPCs were first collected on another cell separator (CS-3000 Plus, Baxter) and stored as backup. The day after the CS-3000 Plus collections were completed, PBPC collections intended for transfusion were performed using the Amicus instrument. For each transplant, >2.5 x 10(6) CD34+ PBPCs per kg of body weight were transfused. RESULTS: Clinical data collected on the donors immediately before and after PBPC collection with the Amicus device were comparable to donor data similarly obtained for the CS-3000 Plus collections. While the number of CD34+ cells and the RBC volume in the collected products were equivalent for the two devices, the platelet content of the Amicus collections was significantly lower than that of the CS-3000 Plus collections (4.35 x 10(10) platelets/bag vs. 6.61 x 10(10) platelets/bag, p<0.05). Collection efficiencies for CD34+ cells were 64 +/- 23 percent for the Amicus device and 43 +/- 14 percent for the CS-3000 Plus device (p<0.05). The mean time to engraftment for cells collected via the Amicus device was 8.7 +/- 0.7 days for >500 PMNs per microL and 9.7 +/- 1.5 days to attain a platelet count of >20,000 per microL-equivalent to data in the literature. No CS-3000 Plus backup cells were transfused and no serious adverse events attributable to the Amicus device were encountered. CONCLUSIONS: The mean Amicus CD34+ cell collection efficiency was better (p<0.05) than that of the CS-3000 Plus collection. Short-term engraftment was durable. The PBPCs collected with the Amicus separator are safe and effective for use for autologous transplant patients requiring PBPC rescue from high-dose myeloablative chemotherapy.

Adolescent↗
PubMed1999

Neuropsychologic outcome after deep hypothermic circulatory arrest in adults.

INTRODUCTION: Pediatric patients undergoing prolonged periods of deep hypothermic circulatory arrest have been found to experience long-term deficits in cognitive function. However, there is limited information of this type in adult patients who are undergoing deep hypothermic circulatory arrest for thoracic aortic repairs. METHODS: One hundred forty-nine patients undergoing elective cardiac or thoracic aortic operations were evaluated preoperatively; 106 patients were evaluated early in the postoperative period (EARLY), and 77 patients were evaluated late in the postoperative period (LATE) with a battery of neuropsychologic tests. Seventy-three patients had routine cardiac operations without deep hypothermic circulatory arrest, and 76 patients with deep hypothermic circulatory arrest were divided into 2 subgroups: those with 1 to 24 minutes of deep hypothermic circulatory arrest (n = 36 patients) and those with 25 minutes or more of deep hypothermic circulatory arrest (n = 40 patients). The neuropsychologic test battery consisted of 8 tests encompassing 5 domains: attention, processing speed, memory, executive function, and fine motor function. Data were normalized to baseline values, and changes from baseline were analyzed by analysis of covariance, multivariate logistic regression, and survival functions. RESULTS: In all domains, poor performance or inability to be tested EARLY were significant predictors of poor performance LATE (odds ratio, 5.27; P <.01). Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were significant predictors of poor performance LATE for the memory and fine motor domains. Deep hypothermic circulatory arrest of 25 minutes or more (odds ratio, 4. 0; P =.02) was a determinant of prolonged hospital stay (>21 days). CONCLUSION: Deep hypothermic circulatory arrest of 25 minutes or more and advanced age were associated with memory and fine motor deficits and with prolonged hospital stay.

Age Factors↗
PubMed1999

Collection of two peripheral blood stem cell concentrates from healthy donors.

When peripheral blood stem cell (PBSC) concentrates are used for allogeneic transplants, two or more apheresis procedures must often be performed. To determine how many cells could be collected from healthy people by two back-to-back apheresis procedures and what effect these collections would have on donors, we gave 19 healthy people 5 micrograms kg-1 day-1 and 21 people 10 micrograms kg-1 day-1 of granulocyte colony stimulating factor, filgrastim, for 5 days. We then collected two PBSC concentrates, one on day 5 and one on day 6. A third group of six people was given filgrastim 10 micrograms kg-1 day-1 for 5 days but had no PBSC concentrates collected. PBSC concentrate cell counts and donor cell counts, symptoms, and blood chemistries were assessed for up to 1 year. On day 5, three times more CD34+ cells were collected from donors given 10 micrograms kg-1 day-1 than those given 5 micrograms kg-1 day-1 (P = 0.009) but on day 6 the quantity of cells collected was the same (P = 0.23). The total number of CD34+ cells collected was two times greater in donors given the higher dose of filgrastim (median = 579 x 10(6); range = 174-1639 x 10(6) compared to 237 x 10(6); 103-1670 x 10(6); P = 0.061). Platelet counts fell after each PBSC concentrate collection, but there were no differences between the two groups of donors in platelet counts measured immediately after each collection. The platelet counts also fell in people who did not donate PBSC concentrates. The lowest counts in all three groups of people also occurred on day 10. In PBSC donors given 10 micrograms kg-1 day-1 of filgrastim the absolute neutrophil count (ANC) fell below premobilization counts on day 14. In donors given 5 micrograms kg-1 day-1 the ANC fell below premobilization counts on days 21, 28 and 49, CD34+ cell counts were significantly lower than premobilization counts on days 14 and 28 in donors given 10 micrograms kg-1 day-1 of filgrastim and on day 14 in those given 5 micrograms kg-1 day-1. No decrease in neutrophil or CD34+ cell counts occurred after filgrastim was given in the people who did not donate PBSC concentrates. The incidence of symptoms was similar in both groups of PBSC concentrate donors, except that those given 10 micrograms kg-1 day-1 were more than twice as likely to experience myalgias as those receiving the lower dose (P = 0.029). Several blood chemistries changed. Levels of alkaline phosphatase, LDH, SGPT, SGOT, uric acid and sodium increased. Levels of bilirubin, total protein, potassium, calcium and chloride decreased. In conclusion, twice as many CD34+ cells were collected from donors given 10 micrograms kg-1 day-1 of filgrastim. Platelet, neutrophil and CD34+ cell counts fell after the PBSC concentrate collections. The fall in platelet counts was due to both the collection and the administration of filgrastim. The falls in neutrophil and CD34+ cell counts were due to the loss of haematopoietic progenitor cells in the PBSC concentrates. Allogeneic PBSC concentrate donors should be given 10 micrograms kg-1 day-1 of filgrastim, and if possible only one component should be collected in order to avoid thrombocytopenia.

Adult↗
PubMed1999

Improved progenitor assay standardization using peripheral blood progenitor cells from a donor treated with granulocyte-colony-stimulating factor.

BACKGROUND: Progenitor assays are the principal method for evaluating hematopoietic cell function. The magnitude of assay variability and the assay steps contributing to variability were determined, and modifications intended to increase assay consistency were evaluated. STUDY DESIGN AND METHODS: Assays were performed using a serum-free progenitor assay medium with cells plated at 5.0 x 10(4) and 1.0 x 10(5) cells per plate. A peripheral blood progenitor cell component collected from a normal donor after administration of granulocyte-colony-stimulating factor was divided into identical aliquots. Each experiment involved at least 5 technologists, each performing assays in duplicate on five aliquots, with each person scoring all assay plates. Three sample preparation methods were tested: 1) ficoll mononuclear cell enrichment and sample dilution, 2) sample dilution without ficoll separation, and 3) sample dilution without ficoll separation, with cell counts performed before and after each dilution step, dilution volumes calculated on the basis of each cell count, automated electronic pipettors used in dilution steps, and colony frequency calculated on the basis of cell counts from the final specimen. RESULTS: Global variability for colony-forming units-granulocyte-macrophage, represented by the percentage of CV for all specimens and all technologists, was 89.6 percent at 5.0 x 10(4) cells per plate and 81.3 percent at 1.0 x 10(5), when ficoll separation was used. Subjective differences in scoring plates did not account for most of the variability observed, as results for any individual plate read by multiple technologists had a mean CV of 15.6 percent and 19.7 percent at the two plating concentrations. Method 3 resulted in the greatest improvement, reducing CV to 24.4 percent at 5.0 x 10(4) cells per plate and to 24.2 percent at 1.0 x 10(5) cells per plate. Similar results were obtained for erythroid-burst-forming units. CONCLUSIONS: Baseline assay results were extremely inconsistent. Interindividual differences in colony interpretation did not contribute significantly to assay variability, although sample preparation and plating did. Improved control over cell concentration decreased assay variability by 70 to 73 percent.

Blood Donors↗
PubMed1999

Effects of granulocyte-colony-stimulating factor on potential normal granulocyte donors.

BACKGROUND: The use of granulocyte-colony-stimulating factor (G-CSF) to increase the granulocyte count and the yield from leukapheresis in normal donors is leading to renewed interest in granulocyte transfusion. Therefore, it is important to understand the side effects of G-CSF. STUDY DESIGN AND METHODS: We studied the effect of G-CSF on peripheral blood counts and recorded the side effects experienced 24 hours after an injection of G-CSF in normal subjects donating peripheral blood progenitor cells for research. RESULTS: Following administration of G-CSF to 261 donors, the neutrophil count increased to 20.6 to 24.5 x 10(9) per microL depending on the dose of G-CSF. This represented a 6.2 to 7.4-fold increase over the neutrophil count before G-CSF administration. Of all donors, 69 percent experienced one or more side effects. The most common effects were: muscle and bone pain, headache, fatigue, and nausea. There was a relationship between the dose of G-CSF and the likelihood of experiencing a side effect. Most side effects were mild, but about 75 percent of donors took analgesics because of them. CONCLUSIONS: In a granulocyte donation program involving G-CSF stimulation, about two-thirds of donors would experience one or more side effects, but these would usually be mild and well tolerated.

Adolescent↗
PubMed1999

Retroviral transduction and expansion of peripheral blood lymphocytes for the treatment of mucopolysaccharidosis type II, Hunter's syndrome.

BACKGROUND: Gene therapy using autologous peripheral blood lymphocytes (PBLs) has been used to produce adenosine deaminase with which to treat patients with severe combined immunodeficiency. Patients with mucopolysaccharidosis type II (MPS II) lack iduronate-2-sulfatase (IDS), and serial PBL gene therapy may benefit these patients. STUDY DESIGN AND METHODS: The purpose of these studies was to develop a method to transduce PBLs from a patient with MPS II by using a retroviral vector, LS2N, containing the IDS gene. PBLs were collected by apheresis and cryopreserved in aliquots for the performance of multiple transductions and expansions. The PBLs were expanded in number and then transduced in a hollow-fiber bioreactor (HFBR). Additional culture allowed for further expansion. RESULTS: Fresh PBLs (6.2 x 10(7)) from a patient with MPS II were transduced with L2SN and expanded in an HFBR with an extracapillary space of 11 mL. After 10 days of culture, 4.1 x 10(9) cells were harvested. Cryopreserved MPS II PBLs could not be reliably expanded if they were placed in the HFBR immediately after being thawed; however, cells were successfully transduced and expanded in the HFBR if they were first cultured in a bag. To increase the cell yield, PBLs were expanded in a 60-mL HFBR after transduction and expansion in an 11-mL HFBR. In four separate experiments, 2 x 10(8) cryopreserved PBL were cultured for 3 days in a bag and transferred to an 11-mL HFBR, where they were transduced daily with L2SN for 3 days and then expanded for 4 additional days. Cells were then transferred into a 60-mL HFBR and expanded for an additional 7 days. In the four experiments, 5.5 x 10(9), 7.4 x 10(9), 1.12 x 10(9), and 19.4 x 1(9) cells were produced. The vector was detected in the harvested cells, but the proportion of cells transduced was less than 2.5 percent, the lowest standard used in the assay. In two of the experiments, cells harvested from the HFBR were used in a gene therapy clinical trial. CONCLUSION: Autologous cryopreserved PBLs can be transduced and expanded to produce >1 x 10(10) cells. This procedure is being used for a Phase I/II clinical trial of lymphocyte gene therapy.

Cells, Cultured↗
PubMed1999

Changes in serum osteocalcin and bone-specific alkaline phosphatase are associated with bone pain in donors receiving granulocyte-colony-stimulating factor for peripheral blood stem and progenitor cell collection.

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used to increase the number of CD34+ peripheral blood stem and progenitor cells collected by apheresis for use in autologous or allogeneic progenitor cell transplantation. The most frequent side effect of G-CSF treatment is bone pain, which occurs in over 80 percent of healthy progenitor cell donors. STUDY DESIGN AND METHODS: The possible mechanism of bone pain was investigated by measuring serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), acid phosphatase (ACP), and tartrate-resistant acid phosphatase (TRAP) in seven healthy progenitor cell donors treated with human recombinant G-CSF administered subcutaneously for 5 consecutive days. RESULTS: All seven patients experienced bone pain during the treatment period. Serum levels of OC, BAP, ACP, and TRAP were measured in blood samples drawn on Days 0, 4, 5, 6, and 14. Levels of BAP were increased (p<0.05) over baseline on Days 4, 5, and 6, while those of OC decreased on Days 4, 5, and 6 (p<0.05). No significant changes occurred in ACP or TRAP levels. OC and BAP are considered markers of bone formation (osteoblast activity), and they correlate in many patients with metabolic bone disorders. The pattern of increased BAP and decreased OC has been reported in patients with osteolytic bone metastases. CONCLUSION: G-CSF treatment in healthy stem and progenitor cell donors may affect osteoblastic activity, and this activity may be associated with bone pain.

Alkaline Phosphatase↗
PubMed1998

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose.

Emerging issues in stimulating apheresis platelet donors with platelet growth factors, the relative costs of apheresis and random donor platelet concentrates, optimal platelet transfusion dose, and leucoreduction of platelet products have caused renewed debate regarding apheresis products vs. random, pooled concentrates. The future role of apheresis products in platelet transfusion therapy will in large part be determined by costs, which are increasingly recognized to be influenced by donor platelet count, apheresis yield, and platelet transfusion dose.

Blood Donors↗
PubMed1998

Expression of neutrophil antigens after 10 days of granulocyte-colony-stimulating factor.

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is becoming the standard agent for mobilizing granulocytes. Most granulocyte donors are given a single dose of G-CSF, but in some cases they are given G-CSF for several days, and multiple granulocyte concentrates are collected. The administration of a single dose of G-CSF induces several changes in the expression of neutrophil antigens, but the effects of multiple daily doses of G-CSF are not known. STUDY DESIGN AND METHODS: Seven healthy people received 5 microg per kg of G-CSF for 10 days. Their expression of several neutrophil antigens before, during, and after the administration of G-CSF was analyzed through the use of flow cytometry. RESULTS: The expression of L-selectin (CD62L), Fcgamma receptor (FcgammaR) III (FcgammaRIII, CD16), and the leukocyte function antigen (CD11a) decreased throughout the course of G-CSF administration, while the expression of FgammaR I (FcgammaRI, CD64) and lipopolysaccharide-binding protein receptor (CD14) increased. The expression of FcgammaR II (FcgammaRII, CD32) also increased, but not until the fourth day of G-CSF administration. The expression of amino peptidase N (CD13), C3bi receptor (CD11b), and the neutrophil beta2 integrin unit (CD18) did not change during the administration of G-CSF, but that of both CD13 and CD18 increased 3 days after the last dose. The expression of neutrophil-specific antigen NB1 initially increased, returned to pre-G-CSF levels after 4 days, and then increased again after 10 days of G-CSF administration. CONCLUSION: Changes in the expression of several neutrophil antigens occurred throughout a 10-day course of G-CSF Most of the changes occurred after one dose, but additional changes occurred later in the 10-day course and after its completion. These changes may affect the function of G-CSF-mobilized granulocytes.

Adult↗
PubMed1998

Mobilization and transduction of peripheral blood progenitor cells in patients with mucopolysaccharidosis I.

Mucopolysaccharidosis type I (MPS I) results from a deficiency of alpha-L-iduronidase enzyme (IDUA), an enzyme responsible for the catabolism of glycosaminoglycans. Genetically modified progenitor cells may permit a therapeutic effect similar to that obtained from allogeneic BMT without the associated risks. To that end, CD34+ peripheral blood hematopoietic progenitor cells from patients with MPS I were mobilized using G-CSF, collected by apheresis, and enriched using avidin-biotin separation techniques. These cells were cultured in a hollow fiber bioreactor and transduced with a retroviral vector (LP1CD) containing the cDNA for human IDUA and a murine dihydrofolate reductase (DHFR) enzyme. Approximately 4%-16% of the colonies expressed methotrexate drug resistance. Expression of the IDUA enzyme in the progenitor cells was initially high and declined after approximately 10 days of culture. These results indicate that PBPC from patients with MPS I can be mobilized, isolated, enriched, and transduced with a therapeutic gene.

Adult↗
PubMed1998

The potential impact of platelet growth factors in transfusion medicine.

The long-sought platelet growth factor, thrombopoietin, has been identified, the gene cloned, and the molecule is now available for clinical use. Thrombopoietin may be useful in transfusion medicine by: 1) reducing the demand for platelets by decreasing the severity and duration of thrombocytopenia, 2) reducing the time required for platelet donation, thus making more platelet donors available, 3) increasing the number of platelets that can be collected from existing platelet donors, 4) increasing the yield of peripheral blood stem cells through synergy with other hematopoietic growth factors, 5) expanding progenitor cells ex vivo through its effect on early progenitors, and 6) producing platelets in ex vivo culture systems.

Animals↗
PubMed1997

Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET).

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Adenocarcinoma↗
PubMed1997

Comparison of two blood cell separators in collecting peripheral blood stem cell components.

To ensure that a sufficient number of CD34+ cells are collected for an allogeneic blood progenitor cell transplant, the most effective blood cell separator should be used to collect peripheral blood stem cell (PBSC) components. We compared the effectiveness of two blood cell separators. We gave 29 healthy people 7.5 or 10 micrograms kg-1 of granulocyte colony stimulating factor (G-CSF) daily for 5 days and collected one PBSC component with either a Fenwal CS3000 (n = 15) or a Cobe Spectra (n = 14) blood cell separator. The volume of blood processed was the same for each machine (8.4 +/- 1.0 L; range = 4.9-9.4 L for the CS3000 and 8.9 +/- 1.0 L; range 6.7-10.9 L; P = 0.71). The components collected with the CS3000 contained more mononuclear cells (39.6 +/- 21.9 x 10(9) compared with 26.9 +/- 5.6 x 10(9), P = 0.02) and fewer neutrophils (1.38 +/- 1.88 x 10(9) compared with 5.53 +/- 8.71 x 10(9), P = 0.001). The total number of CD34+ cells collected with the two instruments was the same (470 +/- 353 x 10(6) for the CS3000 and 419 +/- 351 x 10(6) for the Spectra; P = 0.64) as was the number of CD34+ cells collected per litre of whole blood processed (55.9 +/- 42.0 x 10(6) L-1 compared with 45.9 +/- 37.9 x 10(6) L-1; P = 0.59). The mononuclear cell collection efficiency was greater for the CS3000 (82.4 +/- 54.9% compared with 53.3 +/- 14.1; P = 0.04) but the CD34+ cell collection efficiencies were the same (87.4 +/- 61.1% for the CS3000 compared with 56.3 +/- 23.5% for the Spectra; P = 0.07). In conclusion, both blood cell separators collected components which contained large numbers of CD34+ cells, but those collected with the CS3000 contained fewer neutrophils and the CS3000 was more efficient at collecting mononuclear cells.

Adult↗