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Biomedical subjects

E J Nelson

Publications and source records attributed to E J Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Improved post-transfusion quality of density separated AS-3 red cells after extended storage.

A centrifugal method of red cell density separation was utilized for unit processing in these studies to determine the quality of the lighter fraction (neocytes) after storage for up to 42 d and to evaluate whether the heavier fraction (gerocytes) deteriorated more rapidly than neocytes during storage. Each unit was passed through a Leukotrap filter to remove white cells prior to density separation. Red cell recovery and survival were evaluated using double label technetium-99m with either chromium-51 or nonradioisotopic chromium which permitted concurrent paired analysis. In vivo neocyte red cell recovery, as tested on the same 11 donors on days 1, 7 and 42 of storage, was effectively unchanged. Recovery and survival half-life (that is, the number of days after transfusion at which half of the cells infused remain in the circulation) of 42 d stored gerocytes were significantly lower than similarly stored neocytes (75.5 +/- 7.2% and 20.1 +/- 6.5 d for gerocytes versus 84.4 +/- 4.9% and 39.0 +/- 9.0 d for neocytes). One-day stored neocytes showed a 16.5% increase in red cell availability over the combined average for 42 d stored neocytes and gerocytes. Statistically, while there were significantly higher ATP, 2,3-DPG, and lactate levels pre-storage by paired t-test for neocytes compared to gerocytes, by day 42 there were no significant differences detected between the two red cell fractions by any of the in vitro variables measured. These studies suggest that this simple separation technique for leucocyte-poor red cell units provides a neocyte population with improved viability and the potential for increased transfusion intervals in chronically transfused patients.

Blood Component Transfusion↗
PubMed1992

Characterization of multidrug-resistant pituitary tumor cells.

These studies were designed to investigate the role of P-glycoprotein in an endocrine cell line. Drug-resistant pituitary cells were obtained by growing GH4C1 cells in the presence of increasing concentrations of colchicine. Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells. Verapamil at 10 microM increased the sensitivity of GH4C1/RC.4 cells to colchicine, puromycin, and actinomycin D, almost completely reversing the drug resistance. Flow cytometry and fluorescence microscopy were used to demonstrate that GH4C1/RC.4 cells retained less rhodamine 123 than GH4C1 cells, and that the rate of efflux of rhodamine 123 was much faster for GH4C1/RC.4 cells. Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein. We used drug-resistant pituitary cells to assess the possible role of P-glycoprotein in uptake and efflux of several hormones. At equilibrium, GH4C1 and GH4C1/RC.4 cells bound similar amounts of [125I]L-triiodothyronine and [125I]L-thyroxine, and verapamil did not alter either equilibrium binding or thyroid hormone efflux kinetics. Multidrug-resistant GH4C1/RC.4 cells retained less [3H]hydrocortisone than parental GH4C1 cells at equilibrium, and verapamil increased the equilibrium concentration of [3H]hydrocortisone 3.6-fold. The effect of verapamil was due to its ability to reverse multidrug resistance, since two other chemosensitizers, quinidine and vinblastine, increased [3H]hydrocortisone retention as effectively as verapamil but another calcium channel blocker, nifedipine, had no effect. The drug-resistant GH4C1/RC.4 line synthesized more GH (290%) and much less PRL (5%) than the parent. Hydrocortisone stimulated GH synthesis and inhibited PRL similarly in GH4C1 and GH4C1/RC.4 cells. The results show that the GH4C1/RC.4 line is multidrug-resistant and overexpresses the 170-kilodalton P-glycoprotein and suggest that the P-glycoprotein pump contributes to hydrocortisone kinetics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Randomized comparison of routine vs highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies.

OBJECTIVE: To compare routine versus highly selective use of Doppler ultrasound and biophysical scoring in higher risk pregnancy. DESIGN: A pragmatic randomized trial. SETTING: St James's University Hospital, Leeds. SUBJECTS: 500 pregnant women at high risk of intrauterine growth retardation or still birth. INTERVENTIONS: Regular monitoring with biophysical profile assessment and Doppler velocity waveform recording in umbilical and uteroplacental arteries. Results immediately available to clinicians. MAIN OUTCOME MEASURES: Gestational age at delivery, obstetric intervention rates and short-term neonatal morbidity. RESULTS: Risk factors were distributed very evenly between the 250 patients in the study and control groups respectively. A total of 902 biophysical profile and Doppler assessments were done in the 250 study group patients and only in 12 patients in the control group. In the study group, absent end-diastolic flow was found in only 2.7% of all 902 measurements. A persistently abnormal biophysical score was always associated with absence of end-diastolic flow. The mean gestational age at induction of labour was statistically and clinically similar in the two groups and there was no overall statistically significant difference in intervention rates between the two groups. There was a statistically significant lower frequency of depressed 5-min Apgar scores in the study group. Serious neonatal morbidity was also statistically significantly more common in the control group than in the study group. CONCLUSIONS: The use of Doppler ultrasound in higher risk pregnancies does not lead to an increase in iatrogenic preterm delivery. The total rate of positive tests on Doppler ultrasound is very low and persistently abnormal biophysical scores are unlikely to be found in patients where umbilical end-diastolic blood flow is present. Surrogate measures for fetal damage seem to be improved when clinicians have access to Doppler ultrasound assessments.

Adult↗
PubMed1989

Beneficial effect of brief pre-transfusion incubation of platelets at 37 degrees C.

The effects of brief warming of stored platelet concentrates were assessed in 15 children undergoing transfusion for stable thrombocytopenia due to chemotherapy (n = 13) or aplastic anaemia. Half of a pool of platelet concentrates stored at 22 degrees C was incubated at 37 degrees C for 1 hour and the other half at room temperature. Each patient received one bag of warmed and one of unwarmed cells transfused in random order 2 h apart. Platelet warming improved transfusion efficacy, as assessed on the basis of corrected platelet count increments (CCIs) and platelet morphology. Compared with unwarmed bags, warmed bags had a higher morphology score (p = 0.0001) and a higher CCI (adjusted for the transfusion order) at 1 h (n = 11; p = 0.014) and at 2 h (n = 15, p = 0.006) post transfusion. Thus, with platelets stored at room temperature bags warmed before transfusion to 37 degrees C for 1 h provide a larger number of circulating platelets after transfusion than do unwarmed bags.

Adolescent↗
PubMed1977

The surgeon, genetics, and cancer control: the Cancer Family Syndrome.

A family manifesting the Cancer Family Syndrome has been evaluated extensively from the medical and genetic standpoint. Findings of excess occurrence of carcinoma of the colon and endometrium, multiple primary cancer, early age of onset, and autosomal dominant mode of genetic transmission mandate a program of increased surveillance and cancer education. Prophylactic surgical implications are provided for certain of these enormously high cancer risk patients.

Adult↗
PubMedDate not supplied

Extension of platelet concentrate storage.

Extension of the storage time of platelet concentrates in a satellite bag which is part of a new blood bag system was studied by reinfusing autologous 51Cr-labeled platelets into normal volunteers, and measuring postinfusion platelet counts and bleeding times in patients requiring platelet transfusions. This satellite bag, made of polyvinylchloride plasticized with a new agent, was found to protect platelet concentrates against fall of pH better than other containers studied. This protection was felt to be due to the greater gas permeability of the new plastic. Mean in vivo recovery and half-life (greater than 31% and 3.3 days, respectively) of autologous reinfused platelets were satisfactory following 5 days of storage. Following 7 days of storage, mean recovery was 41 percent and half-life was 2.8 days. Peripheral platelet count increments in patients following platelet transfusions with concentrates stored 4 to 7 days in the new plastic were comparable to increments following transfusion of platelets stored 2 to 3 days in the other plastics studied. Bleeding times shortened in three of four patients receiving platelet concentrates stored from 4 to 6 days in the new plastic. Platelet concentrates stored in the new bag at 20 to 24 degrees C with flat-bed or elliptical agitation could be transfused for up to 5 days following phlebotomy with acceptable clinical results. The new plastic container is promising for storage of platelet concentrates for up to 7 days. Due to the higher pH of 50-ml platelet concentrates stored in bags made with the new plastic, the concentrates were superior at any storage interval to those stored in bags made of the other plastics studied.

Blood Coagulation Tests↗
PubMedDate not supplied

In vitro function and in vivo viability of stored platelet concentrates. Effect of a secondary plasticizer component of PVC storage bags.

Previous studies have shown that CL-2399 (Cutter) and PL-130 (Fenwal) polyvinyl chloride (PVC) plastic bags are unsatisfactory for storage of platelet concentrates (PC) at 22 degrees C. In an effort to explain the effects of plastic bags, the chemical make-up of CL-2399 and PL-130 PVC films was determined and compared with that of P1-146 (Fenwal) PVC, which is satisfactory for PC storage at 22 degrees C. The only significant difference between the three materials was the incorporation of tetrahydrofurfuryl oleate (THFO) as a secondary plasticizer in CL-2399 and PL-130. The response of platelets to aggregating agents, uptake of serotonin, recovery from hyptonic stress, and serotonin release during storage following storage in a modified CL-2399 plastic prepared without THFO and designated CL-3000 (Cutter) was equivalent to PL-146 and far superior to CL-2399. In vivo studies in two laboratories of platelets stored in CL-3000 bags showed satisfactory recovery (56 +/- 4.2% and 46.7 +/- 2.7%) and survival (6.4 +/- 0.4 days and 7.4 +/- 0.6 days). From these studies we conclude that the THFO secondary plasticizer component of PL-130 and CL-2399 is the cause of the poor platelet viability of platelets stored in these plastic bags. The mechanism of impairment is not known. The causative agent(s) may be degradation products of THFO (formed during manufacture of the PVC film) that are leached from the plastic into PC during storage.

Blood Platelets↗
PubMedDate not supplied

Preservation of red cell antigens during storage of blood with different anticoagulants.

A major concern when storing blood is that the antigens of the red cells will lose some of their reactivity in vitro. As part of a study of blood stored in newer anticoagulants, we tested the persistence of the ABO, Rh, Lewis, and P antigens. Blood was stored for 21 to 35 days in several anticoagulant-preservative systems, such as citrate-phosphate-dextrose and several additive solutions, while using bags of polyvinyl chloride plasticized with di(2-ethyl hexyl) phthalate or tri (2-ethyl hexyl) trimellitate. No significant loss of antigenicity occurred in the ABO and Rh systems, but antigens in the Lewis and P systems lost some reactivity during storage.

Anticoagulants↗
PubMedDate not supplied

Extension of platelet concentrate storage to 7 days in second-generation bags.

Platelet concentrates stored for 7 days in 50 ml of plasma in both thin film and enlarged variations of the standard 5-day CLX plastic bags were evaluated for pH maintenance and in vivo viability by two laboratories working independently. 51Cr-labeled platelets were reinfused into normal volunteers at the end of storage and recovery and half-life calculated. The pH was maintained well; less than 10 percent of units fell below 6.0 at 7 days. Mean 7-day recovery for both laboratories was 43.6 +/- 11.6 percent in the thin-film bag and 45.4 +/- 8.52 percent in the enlarged bag, compared with 43.6 +/- 8.8 percent at 5 days in the 5-day plastic licensed bag. After 7 days storage the half-life was 3.6 +/- 0.9 days in the thin-film bag and 3.7 +/- 0.6 days in the enlarged bag, compared with 3.6 +/- 0.5 days in the previously licensed CLX plastic bag after 5 days. Thus, platelet viability was maintained well at 7 days of storage in both of the container variations that allowed increased gas exchange.

Blood Platelets↗
PubMedDate not supplied

Effects of AS-3 nutrient-additive solution on 42 and 49 days of storage of red cells.

Storage of red blood cells in a nutrient-additive solution, AS-3 (Nutricel, Cutter Biological, Berkeley, CA), was evaluated after 42 and 49 days of storage by in vitro measurements of hemolysis, adenosine triphosphate (ATP) levels, glucose levels and other constituents, and in vivo study of 24-hour survival of autologous, reinfused red cells labeled with 51Cr with and without 125I human serum albumin. Two laboratories conducted the studies independently. After 42 days of storage, hemolysis was within an acceptable range (0.72 +/- 0.4% and 1 +/- 0.2%), ATP decreased to 61 percent and 56 percent in the two laboratories, and 24-hour survivals were 85.1 +/- 8.3 percent for single-label cells in one laboratory and 82.8 +/- 10 percent (single-label cells) and 84.1 +/- 13.1 percent (double-label cells) in the second laboratory. Thus, results for single- and double-label cells were similar. After 49 days of storage, ATP fell to 45 and 46 percent in the two laboratories. Twenty-four-hour recovery fell to 69.4 +/- 7.4 percent with single-label cells and to 68.2 +/- 6.7 percent with double-label cells in one laboratory. In the other laboratory, a paired study comparing AS-3 with the already approved AS-1 solution (Adsol; Fenwal Laboratories, Deerfield, IL) showed nearly identical 24-hour survivals of 71.9 +/- 8.8 percent in Nutricel and 71.8 +/- 6.5 percent in Adsol. These studies demonstrate the excellent viability of the new solution after 42 days of study. At 49 days of study, viability decreased significantly and was comparable in the two nutrient-additive solutions studied. The value of paired comparison study is demonstrated by the latter results.

Blood Preservation↗
PubMedDate not supplied

Five-week red cell storage with preservation of 2,3 DPG.

The 2,3 diphosphoglycerate (2,3 DPG) content of red cells stored in current anticoagulant-preservative products decreases rapidly after the first few days of storage, and by 3 weeks the red cells are essentially depleted of 2,3 DPG. Because ascorbic acid and ascorbate-2-phosphate (A-2-P) are effective in maintaining erythrocyte 2,3 DPG during liquid preservation, ascorbate was stabilized through autoclaving and subsequent storage by adding it as the trisodium salt of A-2-P to a phosphate-adenine-saline solution at a pH of 8.5 to 9.0. Red cell concentrates prepared from blood drawn into citrate-phosphate-double-dextrose were supplemented with the A-2-P additive solution (AS-4) and studied in vitro and in vivo. Mean 2,3 DPG values for 22 units were 147.6, 113.5, and 82.3 percent of initial value after storage for 3, 4, and 5 weeks, respectively. Maintenance of 2,3 DPG was at the expense of adenosine triphosphate (ATP), which fell to as low as 22.2 percent of initial value after 5 weeks. Despite the low ATP values, the 24 hour 51Cr-labeled red cell recoveries averaged 80.8 and 74.1 percent after 4 and 5 weeks of storage, respectively. The AS-4 system provides a red cell product with acceptable viability and improved oxygen off-loading function.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Ascorbate-2-phosphate in red cell preservation. Clinical trials and active components.

A red cell additive solution (AS-005) containing ascorbate-2-phosphate (AsP) to maintain 2,3-diphosphoglycerate, plus adenine, phosphate, and mannitol to retain viability and reduce hemolysis, was evaluated by human clinical trials. A crossover design was used with another additive solution (Nutricel AS-3, Cutter Laboratories) serving as the control for each donor. Each additive solution was evaluated at 35 and 42 days of storage. There was no significant difference between the red cell viability of the two storage solutions at either time period. Split-bag, AS-005 in vitro studies at two temperatures (2.5 and 5.5 degrees C), both within the range of 1 to 6 degrees C approved by the American Association of Blood Banks and the Food and Drug Administration, resulted in dramatically different in vitro parameters, including a threefold difference in 2,3-diphosphoglycerate (2,3-DPG), a fivefold difference in glucose, and significant differences in pH and adenosine triphosphate. High-pressure liquid chromatography data confirmed the preliminary report that 1 to 2 percent (wt/wt) oxalate was present in preparations of AsP. In vitro storage data confirmed that oxalate is the active component of AsP that preserves 2,3-DPG during storage.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Posttransfusion survival of red cells frozen for 8 weeks after 42-day liquid storage in AS-3.

Current standards recommend that red cells (RBCs) should be frozen within 6 days of donation. There are situations, however, in which it is desirable to freeze RBCs that are older than 6 days, such as for the salvage of rare or autologous units. To determine the therapeutic efficacy of RBCs frozen after prolonged liquid storage, standard units were drawn from nine normal donors and stored at 4 degrees C for 42 days in a nutrient-additive solution, AS-3. 51CrRBC survival assays were performed (24-hour survival: 78.2 +/- 12.4%; n = 8) and the units were frozen at -80 degrees C in glycerol for 8 weeks. After deglycerolization, the mean RBC recovery was 81.0 +/- 4.1 percent and the mean 24-hour 51Cr survival was 78.0 +/- 9.1 percent. The index of therapeutic effectiveness (ITE) was determined by multiplying the postdeglycerolization 24-hour 51Cr survival by the mean RBC recovery (63.3 +/- 9.2). ITE values greater than 60 percent (75% 51Cr survival x 80% RBC recovery) were considered acceptable. Mean adenosine triphosphate levels declined from an initial 3.81 +/- 0.56 micromol per g of hemoglobin to 2.33 +/- 0.55 micromol per g after frozen storage. These findings show that an acceptable percentage of RBCs survives frozen storage after maximum liquid storage (mean ITE greater than 60%). If necessary, RBCs stored in AS-3 can be frozen at any time before 42 days.

2,3-Diphosphoglycerate↗