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Biomedical subjects

T H Price

Publications and source records attributed to T H Price.

At least 37 records · Page 2Linked to original sources
PubMed1996

The effect of recombinant human erythropoietin on the efficacy of autologous blood donation in patients with low hematocrits: a multicenter, randomized, double-blind, controlled trial.

BACKGROUND: This randomized controlled study was undertaken to determine the effect of recombinant human erythropoietin (rHuEPO) on erythropoiesis, autologous blood collection, and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits. STUDY DESIGN AND METHODS: Patients (n = 204) with low baseline hematocrits ( < or = 39%), scheduled for orthopedic surgery within 25 to 35 days, were seen every 3 to 4 days for 21 days. At each visit, 450 mL of blood was collected if the hematocrit was > or = 33 percent, and rHuEPO (600 U/kg) or placebo was administered intravenously. RESULTS: One hundred seventy-three patients were evaluable. The number of autologous units collected from the rHuEPO and control groups, respectively, was 4.5 +/- 1.0 and 3.0 +/- 1.1 (p < 0.001), and marrow production of red cells increased by 668 +/- 222 and 353 +/- 155 mL over and above baseline production (p < 0.05). Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients (p = 0.09). Excluding 8 patients who received > 6 units, 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood (p = 0.015). Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO (p = 0.025). CONCLUSION: The use of rHuEPO stimulates erythropoiesis, permits the storage of more autologous blood, and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery. Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy.

Adult↗
PubMed1995

Blood center perspective of granulocyte transfusions: future applications.

The role of the blood bank in provision of an optimal granulocyte concentrate is discussed. The importance of the granulocyte dose is emphasized, and recent developments permitting the collection of larger numbers of cells are reviewed. In particular, the administration of granulocyte colony-stimulating factor to normal donors has been reported to result in dramatically increased neutrophil yields. Recent data has also suggested that increased efficiencies of collection can be realized by the use of hetastarch as the red cell sedimenting agent.

Blood Banks↗
PubMed1995

The endogenous erythropoietin response and the erythropoietic response to blood loss anemia: the effects of age and gender.

The endogenous erythropoietin (EPO) response and the erythropoietic response to anemia in the elderly, as compared with that in younger subjects, is controversial. We therefore studied autologous blood donors undergoing aggressive phlebotomy to determine the effect of age and gender on the EPO response to blood loss anemia, along with the erythropoietic response to endogenous EPO and to exogenous recombinant human EPO therapy. Seventy-one patients underwent phlebotomy, up to 6 units over 3 weeks, and received either placebo (n = 18), EPO 150 U/kg (n = 16), EPO 300 U/kg (n = 18), or EPO 600 U/kg (n = 19) at each of the six visits. Linear regression analysis of the hemoglobin/log EPO relationship for 18 placebo patients revealed no differences in the endogenous EPO response to phlebotomy, as determined by the slopes and intercepts, for males versus females or as a function of age. We found no differences in endogenous EPO-stimulated red blood cell (RBC) volume expansion for males and females (7.06 +/- 2.4 and 7.22 +/- 2.2 ml/kg, respectively, p = 0.88) or as a function of age (estimated rate of change = -0.58 +/- 0.33 ml/kg for every 10 years of life, p = 0.10). Similarly, we found no differences in RBC response to EPO for males versus females (1.4 +/- 0.3 ml/kg vs 1.5 +/- 0.3 ml/kg per 1000 U/kg EPO, respectively, p = 0.80) or as a function of age (estimated rate of change = 0.051 +/- 0.15 ml/kg per 1000 U/kg EPO for every 10 years of life, p = 0.74).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effects of in vivo recombinant methionyl human granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers.

Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24-fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.

Adult↗
PubMed1994

In vivo neutrophil and lymphocyte function studies in a patient with leukocyte adhesion deficiency type II.

We investigated in vivo neutrophil and lymphocyte function in a patient who lacks Sialyl-Lewis-X, a ligand for the selectin family of leukocyte adhesion molecules (leukocyte adhesion deficiency II, LAD II). As assessed by skin chamber and skin window techniques, in vivo chemotaxis of neutrophils was markedly impaired (less than 6% of normal values). A marginal pool was present as determined by an increase in circulating neutrophils after epinephrine injection and calculated recovery of infused radiolabeled autologous neutrophils. Kinetic studies showed a reduced half-life of 3.2 hours (normal 7 hours) and markedly increased turnover rate (cells/kg/d) of approximately eight times the normal value. A normal antibody response to the T-cell-dependent antigen bacteriophage phi X174 showed that T/B-cell interaction is not affected in LAD II. These findings provide direct evidence that the selectin family and its ligands play an important role in neutrophil function.

Antibody Formation↗
PubMed1994

A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, and efficacy.

BACKGROUND: Previous clinical trials have shown that the use of recombinant human erythropoietin (EPO) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation. However, the role of EPO therapy in nonanemic patients remains undefined. To identify this role, a randomized, controlled, multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent (0.39). STUDY DESIGN AND METHODS: EPO (150, 300, or 600 units/kg) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period. Sixteen (14%) of 116 patients were unable to complete the treatment protocol because of adverse events (n = 11) or for personal reasons (n = 5); 2 patients (1 EPO and 1 placebo) experienced serious adverse events. RESULTS: In 91 evaluable patients, additional red cell production during the study period was 440 +/- 176, 621 +/- 215, 644 +/- 196, and 856 +/- 206 mL (mean +/- SD), respectively, for patients receiving placebo and EPO at 150, 300, and 600 units/kg (p < 0.05 for all EPO groups compared to placebo). However, the percentages of patients in each group who received allogeneic blood did not differ: 2 (9%) of 23 placebo patients and 6 (9%) of 68 EPO patients. CONCLUSION: It is concluded that, while EPO therapy increased preoperative red cell production, no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation.

Adolescent↗
PubMed1994

Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy.

Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150 U/kg, n = 16, 300 U/kg, n = 18, or 600 U/kg, n = 19) or placebo (n = 18). Using data from the three preoperative study visits, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO-treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patient's postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia.

Adult↗
PubMed1994

Aging and marrow neutrophil reserves.

OBJECTIVES: Measurement of blood neutrophil (PMN) counts after the administration of hydrocortisone, granulocyte colony-stimulating factor (G-CSF) and epinephrine. DESIGN: Prospective study, with subjects serving as their own controls before and after administration of hydrocortisone, G-CSF, and epinephrine. SETTING: The G-CSF and hydrocortisone studies were conducted at the Clinical Research Center, University of Washington, and the epinephrine study was conducted at the Seattle VA Medical Center. PARTICIPANTS: Healthy volunteers of both sexes (ages 20 to 30 years and 70 to 80 years) were recruited from the community. The subjects had no acute or chronic medical problems and were on no prescription medications. MAIN OUTCOME MEASURES: Change in the blood PMN count after administration of hydrocortisone (25 and 200 mg intravenously), G-CSF (30 and 300 micrograms subcutaneously), or epinephrine (10, 25, and 50 ng/kg/min intravenously). RESULTS: Baseline PMN counts were similar for all comparison groups. The peak PMN response (maximum count-baseline count) to hydrocortisone was significantly less in the older subjects (P < 0.01) at both doses. The peak PMN responses were 4588 +/- 418/mm3 (25 mg) and 6906 +/- 1121/mm3 (200 mg) in the young and 1886 +/- 399/mm3 (25 mg) and 2387 +/- 372/mm3 (200 mg) in the elderly subjects. The peak PMN response following G-CSF was not different (P > 0.05) in the two groups at both the dosages: 6696 +/- 736/mm3 (30 micrograms) and 9801 +/- 893/mm3 (300 micrograms) in the young and 6340 +/- 833/mm3 (30 micrograms) and 9733 +/- 956/mm3 (300 micrograms) in the elderly. There was no age-related change in the response to epinephrine. CONCLUSIONS: Aging has no effect on baseline PMN counts, bone marrow PMN reserves as measured with G-CSF, and blood PMN pools as measured with epinephrine. However the ability to mobilize these PMNs from the marrow into blood, as measured by the hydrocortisone response, is significantly reduced in the elderly.

Adult↗
PubMed1993

The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis.

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG-CSF in normal granulocyte donors are warranted.

Adult↗
PubMed1992

Preoperative red cell production in patients undergoing aggressive autologous blood phlebotomy with and without erythropoietin therapy.

Previous studies have demonstrated that autologous blood donors have a suboptimal endogenous erythropoietin response to the mild anemia induced by blood donation. Recent studies in baboons subjected to aggressive phlebotomy have shown an acceleration of erythropoiesis that may be beneficial perioperatively. To address the issue of accelerated erythropoiesis in autologous blood donors, red cell production during an aggressive preoperative autologous blood donation program was analyzed. The volume of red cells increased 568 mL (27% over baseline) and 911 mL (47% over baseline) for 23 placebo and 21 erythropoietin-treated patients, respectively, by hospital admission (9 days after last drug administration and 26 days after beginning therapy). The mean rate of additional red cell production was 22 mL per day in the placebo group and 34 mL per day in the erythropoietin group (p less than 0.001), which represents a twofold and a 2.5-fold increase over basal erythropoiesis, respectively. The major difference in red cell production in the placebo and erythropoietin groups occurred early in the collection period. It can be concluded that an aggressive autologous blood phlebotomy program results in clinically important increased erythropoiesis at the time of surgery. In patients unsuited for aggressive autologous phlebotomy, a more modest autologous blood procurement program, coupled with the administration of recombinant erythropoietin, may be a preferable approach.

Blood Transfusion, Autologous↗
PubMed1991

Iron-restricted erythropoiesis as a limitation to autologous blood donation in the erythropoietin-stimulated bone marrow.

Recombinant human erythropoietin has been demonstrated to significantly increase autologous blood procurement. To determine the importance of dietary or prescribed iron absorption, we analyzed iron-restricted erythropoiesis in this setting. No differences were found when premenopausal placebo and erythropoietin treatment groups were compared for hematocrit changes, number of units donated, percentage of phlebotomies deferred, and total blood volume procured. Seven of 10 women who had not reached menopause donated more blood iron than the apparent amount of total mobilizable iron available, demonstrating that dietary or prescribed iron had to be absorbed to donate the amount of blood iron stored. Thus oral iron absorption can potentially be a limitation to erythropoiesis in the presence of erythropoiesis therapy in women who have not reached menopause. In contrast, none of 16 women who had reached menopause and only two of 21 men required oral absorption of dietary or prescribed iron for the amount of blood iron donated. We conclude that although oral iron supplementation may not be necessary in men and in women who have reached menopause, alternatives to oral ferrous salt supplementation could be tested to determine whether such alternatives would improve the response to erythropoiesis in premenopausal women.

Adult↗
PubMed1989

Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy.

To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before surgery, we conducted a randomized, controlled trial of erythropoietin in 47 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin (600 units per kilogram of body weight) or placebo intravenously twice a week for 21 days, during which time up to 6 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 34 percent. All patients received iron sulfate (325 mg orally three times daily). The mean number of units collected per patient (+/- SE) was 5.4 +/- 0.2 for the erythropoietin group and 4.1 +/- 0.2 for the placebo group. The mean red-cell volume donated by the patients who received erythropoietin was 41 percent greater than that donated by the patients who received placebo (961 vs. 683 ml, P less than 0.05). Only 1 of the 23 patients treated with erythropoietin was unable to donate greater than or equal to 4 units (4 percent) as compared with 7 of the 24 patients who received placebo (29 percent). No adverse effects were attributed to erythropoietin. We conclude that recombinant human erythropoietin increases the ability of patients about to undergo elective surgery to donate autologous blood.

Adult↗
PubMed1989

Treatment of cyclic neutropenia with granulocyte colony-stimulating factor.

Six patients with cyclic neutropenia were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months. All had a history of recurrent aphthous stomatitis, pharyngitis, lymphadenopathy, fever, and numerous infections during periods of neutropenia. Serial blood-cell counts, findings on bone marrow examination, and signs and symptoms were evaluated before and during the daily administration of G-CSF (3 to 10 micrograms per kilogram of body weight per day), either intravenously or subcutaneously. The kinetics of labeled autologous blood neutrophils and the migration of neutrophils to skin chambers were also measured. Recombinant human G-CSF increased the mean (+/- SEM) neutrophil counts from 717 +/- 171 per microliter to 9814 +/- 2198 per microliter (P = 0.009). In five of the six patients, the cycling of blood-cell counts continued, but the length of the period decreased from 21 to 14 days. The number of days of severe neutropenia was reduced (P = 0.002). Neutrophil turnover increased almost four-fold (P = 0.005), whereas neutrophil migration to a skin chamber was normal. G-CSF therapy reduced the frequency of oropharyngeal inflammation, fever, and infections in these patients. During the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans.

Adolescent↗
PubMed1987

In vivo inhibition of neutrophil function in the rabbit using monoclonal antibody to CD18.

The CD11b/CD18 membrane antigen complex has been shown to be essential for normal neutrophil function in vitro, and patients lacking this antigen exhibit severe neutrophil dysfunction. Murine monoclonal antibody 60.3 (Ab 60.3), directed toward CD18, is a potent inhibitor of human neutrophil function in vitro. To determine whether Ab 60.3 might similarly inhibit neutrophil function in vivo, we measured the effect of antibody administration on neutrophil localization to polyvinyl sponges placed s.c., in rabbits. Studies in 25 animals showed that infusion of Ab 60.3 at the time of sponge insertion resulted in dose-dependent inhibition of in vivo neutrophil migration with almost complete paralysis of neutrophil migration at higher antibody doses. These studies confirm the functional relevance of CD18, demonstrate that neutrophil function can be profoundly inhibited in vivo by Ab 60.3, and suggest that substances such as AB 60.3 may be clinically useful as potent anti-inflammatory agents.

Animals↗
PubMed1987

Predeposited autologous blood for elective surgery. A national multicenter study.

To determine the extent to which autologous blood that has been donated in advance ("predeposited") is used in patients undergoing elective surgery and to assess whether predonation decreases the use of homologous blood and the demand on the blood supply, we studied 4996 patients undergoing elective surgery at 18 tertiary care hospitals. Cross-matched blood was ordered for 1287 patients (26 percent), and of these, 590 (46 percent) were considered eligible for predepositing blood. Only 5 percent (32) of the eligible patients actually predeposited blood, indicating that predonation is not widely used. Of those who predeposited, only 13 percent (4 of 32) subsequently received homologous blood, as compared with 36 percent (199 of 558) of those who did not predeposit (P less than 0.01). Among the 199 patients who did not predeposit but required transfusion, we estimate that predonation could have avoided homologous transfusion in as many as 68 percent. If all eligible patients had predeposited autologous blood, they could have supplied as much as 72 percent of their own transfused red cells. The blood for as much as 10 percent of all red-cell transfusions could have been predonated by and transfused into the patients undergoing elective surgery. Greater use of predonation would not only reduce the demand on the blood supply by decreasing the need for homologous transfusion, but would probably also reduce the risk of hepatitis and other transfusion-associated illnesses.

Blood Banks↗
PubMed1986

Adult-onset cyclic neutropenia is associated with increased large granular lymphocytes.

Human cyclic neutropenia occurs in adults as well as children. Clinical illness is similar in the childhood and adult diseases, but distinctly different modes of onset suggest heterogeneity in its pathophysiology. We studied seven patients with cyclic neutropenia, three with disease acquired in adulthood, and four with the childhood-onset disorder. All three patients with adult-onset cyclic neutropenia had increased numbers of circulating large granular lymphocytes (LGL), whereas the four children with cyclic neutropenia had normal LGL counts. LGL from patients with adult-onset cyclic neutropenia expressed cell surface antigens HNK-1 (three of three patients) and IgG Fc receptors (two of three patients), although natural killer activity was low. Two of these patients were treated with alternate-day steroids, resulting in decreased LGL counts and abrogation of neutrophil cycling. We suggest that adult-onset cyclic neutropenia may be distinguished from the childhood-onset form of the disease by increased numbers of LGL. Furthermore, increased LGL may identify a subset of patients with cyclic neutropenia who respond to steroid therapy.

Agranulocytosis↗
PubMed1985

Collaborative study on the isolation of salmonella from artificially contaminated milk powder.

The suitability of artificially contaminated milk powder as a substrate for salmonella reference samples and its stability under different storage conditions were studied. The need for a reconstitution step in the standard isolation method for salmonellas from milk powders was also investigated. When milk powder was examined in this way with a reconstitution step, differences in laboratory methods and/or storage times had no significant effect on the results after storage at 4 degrees C. With powder stored at room temperature there was a systematic decrease in the number of samples positive as the storage time increased. It is concluded therefore that milk powder contaminated with salmonellas should be stored at 4 degrees C. Examination of such milk powder with a reconstitution step yielded better results than without it and this step is therefore necessary for improving the reproducibility of the method. No significant differences were encountered between the standard isolation method and that used in the authors' laboratories. The results of this study indicate that milk powder is suitable as basic material for reference samples and that a reconstitution step should be included in the standard salmonella isolation procedure.

Animals↗