PubMed Health⌕ Search

Biomedical subjects

C Prowse

Publications and source records attributed to C Prowse.

At least 19 recordsLinked to original sources

Interruption of agitation of platelet concentrates: effects on in vitro parameters.

BACKGROUND AND OBJECTIVES: When platelet concentrates (PCs) are shipped from one centre to another, they may remain unagitated for a considerable period of time. It was therefore our aim to study the effects of interruption of agitation on the in vitro parameters of PCs stored in platelet additive solutions. MATERIALS AND METHODS: In this multicentre study, PCs were prepared either by apheresis or from pooled buffy coats, paired to minimize donor-dependent differences, and aliquoted into 3 units with a 'low concentration' (approximately 1 x 10(9) platelets/ml; groups A, B and C) and 3 units with a 'high concentration' (approximately 2 x 10(9) platelets/ml; groups D, E and F). The final composition of the storage medium was 30% plasma and 70% additive solution in all PCs. Either PASIIIM or Composol was used as the additive solution. Agitation was interrupted for 2 days (between days 3 and 5, groups A and D), or for 4 days (between days 1 and 5, groups B and E), and continuous agitation served as the reference (groups C and F). A number of in vitro parameters were used for testing on days 1, 5 and 7. RESULTS: On day 7, reference units C and F in PASIIIM had significantly higher pH values than the study units in PASIIIM, but all retained a pH of > 6.5 at 37 degrees C. Hypotonic shock response (HSR) results were significantly lower in the high concentration/4-day interruption group (E) than in the other groups. The low-concentration groups in PASIIIM, with agitation interrupted for either 2 days (group A) or 4 days (group B), did not have HSR values significantly different from the respective references. Study groups A, B, D and E in Composol, a solution lacking phosphate, had a pH of approximately 6.5 on day 7, which was significantly lower than that of the references and of the corresponding units in PASIIIM. The pH values were > 7.0 in reference groups C and F in Composol, not significantly different from those in PASIIIM. HSR values were also significantly lower in the Composol study groups. On the other hand, the reference Composol groups showed results similar to units in PASIIIM. CONCLUSIONS: PCs in PASIIIM additive solution with a platelet concentration of approximately 1 x 10(9)/ml can sustain 4 days without agitation. Phosphate may be of importance in maintaining good in vitro characteristics during interruption of agitation.

Blood Platelets↗

In-vitro evaluation of the PALL Leukotrap Affinity Prion Reduction Filter as a secondary device following primary leucoreduction.

BACKGROUND AND OBJECTIVES: A filter (PRF1) designed to remove abnormal prion proteins from red-cell units has been developed. The purpose of this study was to evaluate the quality of red cells produced using this device. MATERIALS AND METHODS: Leucocyte-depleted red-cell units (CPD, CPD-A1 and CPD/SAGM) processed according to standard UK practices were filtered using PRF1. Filtered and control units were stored and sampled on day 1, day 7 and on the date of expiry and were tested using standard measures of red-cell quality. RESULTS: Filtered units were found to have significantly higher percentage haemolysis levels, lower haemoglobin levels and a smaller volume compared with controls. All results, however, were well within the permitted 0.8% haemolysis level at the end of storage and all units met the UK guidelines for haemoglobin and volume. The other test parameters measured showed no significant differences between the test and control units. CONCLUSIONS: The PRF1 filter was found to be easy to use and resulted in red-cell units that met all relevant UK and European Guidelines.

Erythrocyte Transfusion↗

Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium.

BACKGROUND AND OBJECTIVES: In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS-III) was found to have a significant influence on platelet metabolism (using apheresis-derived, as well as buffy-coat-derived platelets) when compared with standard PAS-III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS-III containing 20% plasma was comparable to storage in standard PAS-III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted. MATERIALS AND METHODS: Platelets from 30 pools of approximately 20 buffy coat (BC) units each and 24 pooled apheresis platelet units were aliquoted for storage in plasma (reference) or synthetic medium using either a specific additive solution (PAS-III) containing 30% plasma or a modification of PAS-III containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM) and either 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days during which in vitro testing was carried out for biochemical, haematological and functional parameters. RESULTS: Storage of platelets in PAS-IIIM resulted in a reduction in the rate of glycolysis and better retention of pH and hypotonic shock response reactivity. Storage in PAS-IIIM containing 20% plasma appeared to result in the retention of in vitro properties, similar to those observed during storage in standard PAS-III containing 30% plasma. CONCLUSIONS: The results of this study confirm the preliminary results. Similar results were seen with platelets prepared by BC and apheresis methods, despite differences in equipment, the preparation technique and in the final platelet contents achieved in the platelet units. Storage of platelets in PAS-IIIM should be considered to improve platelet function and allow plasma reduction to 20%.

Blood Component Removal↗

The release of prion protein from platelets during storage of apheresis platelets.

BACKGROUND: Recent studies using a time-resolved fluoroimmunoassay method (dissociation-enhanced lanthanide fluoroimmunoassay) showed that platelets and plasma are the main reservoir of the normal isoform of cell-associated prion protein (PrPc) in human blood. The aims of the present study were to monitor PrPc levels in various fractions of apheresis platelets during storage by using the DELFIA method and to assess the association of this release with alpha-granule protein ss-thrombo-globulin and cytoplasmic LDH. STUDY DESIGN AND METHODS: Units of apheresis platelets (n = 6) were obtained from volunteer donors by the use of a cell separator and stored up to 10 days. Samples (7-9 mL) were aseptically collected from each unit on storage Days 1, 2, 3, 4, 5, 8, and 10. Platelet-poor plasma and apheresis platelets were prepared and the former split into two fractions, one centrifuged at 40,000 x g for 2 hours at 4 degrees C to remove microparticles. The spun microparticles, apheresis platelets and platelet samples, platelet-poor plasma, and high-spun plasma fractions were stored in a frozen state until they were tested. RESULTS: The results showed that the mean overall levels of PrPc throughout storage remained within 15 percent of Day 1 levels. In contrast, the mean cellular levels in platelets significantly decreased to 46 percent of Day 1 levels by Day 10 of storage (p<0.01), while the corresponding levels in plasma significantly rose as much as 329 percent (p<0.01). Moreover, although microparticle-bound PrPc was released during storage, it was increasingly superseded by soluble protein. PrPc and ss-thrombo-globulin release exhibited very similar patterns (p<0.01). In contrast, LDH showed a significant increase in high-spun plasma only toward the end of the storage period (p<0.01). CONCLUSION: These results indicate that PrPc is released from platelets during the storage of apheresis platelets and that this release is probably due mainly to platelet activation and alpha-granule release in the first few days of storage. Moreover, the released PrPc is increasingly composed of soluble proteins, as the storage period exceeds 5 days.

Blood Platelets↗

Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components.

BACKGROUND AND OBJECTIVES: To quantify the cellular isoform of prion protein (PrP(c)) in human blood using a new time-resolved dissociation-enhanced fluoroimmunoassay (DELFIA). MATERIALS AND METHODS: The DELFIA was optimised for human blood samples and applied to isolated cell and plasma fractions from blood donations. The physicochemical properties of PrP(c) were analysed. RESULTS: 26. 5% of blood PrP(c) was associated with the platelet fraction, 0.8% with polymorphonuclear leucocytes, 2.4% with mononuclear leucocytes, 1.8% with red cells and 68.5% with plasma (mean values from 4 processed donations). CONCLUSION: The majority of blood PrP(c) is found in the platelet and plasma compartments.

Antigens↗

Analysis of peptides derived from Pro Atrial Natriuretic Peptide that circulate in man and increase in heart disease.

The present investigation was designed to determine the levels and circulating forms of peptides derived from Pro Atrial Natriuretic Peptide (ProANP) and to assess their usefulness as markers for severity of heart disease. A sensitive and specific "two-site" immunoradiometric assay (IRMA) for the measurement of C-terminal ProANP 99-126 (alpha ANP) and two radioimmunoassays (RIAs) for the measurement of N-terminal ProANP 31-67 and ProANP 79-98 were developed. Immunoassays were validated by measurement of circulating peptide concentrations in 15 normal volunteers and 44 patients with varying degrees of heart disease. Mean concentrations of immunoreactive (ir) alpha ANP, ProANP 79-98 and ProANP 31-67 in normal volunteers (n = 15) were 8.5 +/- 1.1, 143 +/- 16 and 587 +/- 83 pmoles/l, respectively, increasing in patients with mild heart disease (NYHA I to II; n = 22) to 17.1 +/- 2.1, 691 +/- 197 and 2160 +/- 540 pmoles/l with greatest increases being observed in patients with severe heart disease (NYHA III to IV; n = 22) of 103 +/- 23, 4550 +/- 590 and 10,600 +/- 1350 pmoles/l, respectively. RP-HPLC of pooled plasma revealed peaks corresponding to alpha ANP, beta ANP, ProANP 1-126, ProANP 1-98, ProANP 31-67 and ProANP 79-98, all apparently increased in heart disease. In conclusion, using a series of immunoassays, we observed the graded increase of alpha ANP, irProANP 31-67 and irProANP 79-98 with increasing severity of heart disease. All peptides proved useful markers, but only ProANP 79-98 levels were able to distinguish patients with mild heart disease (NYHA I) from normals. Finally, RP-HPLC analysis indicated that ProANPs 31-67 and 79-98 circulate as distinct entities, in addition to ProANP 1-98.

Adult↗

Human parvovirus B19 and blood products.

BACKGROUND AND OBJECTIVES: Human B19 parvovirus (B19), identified in 1975, was only recognised as the causative agent of fifth disease in 1983. The incidence of viraemia is low, around 1 in 1,000, but is sufficient to ensure that most plasma pools for fractionation contain some virus. While infection usually occurs in childhood and is benign, chronic infection sometimes occurs and may be of concern in certain patient groups. MATERIALS AND METHODS: This review is based on a meeting held in March 1995, and addresses recent concerns regarding the potential transmission of B19 infection by pooled plasma products. RESULTS: Recent data on the pathophysiology and assay of this virus are summarised along with possible approaches to donor screening, product screening, and virus removal. Only five cases of symptomatic infection have been reported in persons with haemophilia, but no technology for virus removal is established, and infection may be of concern in pregnant women, and in patients with enhanced red cell turnover or who are immunosuppressed, including those infected with human immunodeficiency virus, but only rarely in immunocompetent patients. CONCLUSIONS: For the future, well-validated assays relevant to virus infectivity are required if blood donations, plasma pools, or plasma products are to be screened, and an in-process virus inactivation step for B19 would be highly desirable. In the interim, non-plasma or recombinant products or a selective transfusion policy might be used in patient groups in which B19 infection is of particular concern. Further clinical data on the prognosis and impact of B19 infection are needed to justify both such policies and the future adoption of new technologies designed to reduce any excess B19 infectivity arising from transfused products.

Female↗

A new incision for placement of cochlear implants.

A straight, vertical post-aural incision for the 'Cochlear' multichannel cochlear implant has been evaluated in 52 patients (20 adults and 32 children). Nineteen of the children were under three years of age and five of these were under two years of age. The 7 cm long incision is placed approximately 3 mm behind the post-auricular crease and runs from the tip of the mastoid to a point 3 cm above the superior attachment of the pinna. The incision heals within several days. Because the incision is straight interruption of the blood supply to the flaps raised is the least possible. This also minimizes the possibility of scalp necrosis and implant extrusion. The likelihood of infection is reduced by the small size of the incision, minimal soft tissue dissection and small amount of dead space. Rapid healing has occurred in all cases despite infection in one.

Adult↗

In vivo models of thrombogenic potential: usefulness and limitations.

The thrombogenicity of prothrombin complex concentrates (PCCs) has been known as a risk factor since their first clinical use about 30 years ago. The development of in vivo models to define the thrombogenic components in PCCs was instrumental in providing a logical basis for selecting in vitro assays to screen for the distribution of such components during the manufacture of PCCs, and to minimize their appearance in the final product. Even so, these thrombogenic components are not completely removed, as shown in our canine nonstasis model of thrombogenicity: PCCs were still found to elicit a thrombogenic response, shown by increased fibrinopeptide A, fibrin(ogen) degradation products, activated partial thromboplastin time, and decreased fibrinogen and platelet counts when clinically relevant doses were used. The new generation of high-purity factor IX (HP-FIX) concentrates differs from PCCs because these products contain only negligible amounts of clotting factors other than factor IX, lower amounts of activated clotting factors, and, in products we have assayed, no coagulant-active phospholipids. When we infused a number of HP-FIX products in the canine nonstasis model, no thrombogenic response was observed at doses considerably greater than PCC doses that did elicit a response. Likewise, HP-FIX products were much less thrombogenic than PCCs when tested in small-animal stasis and nonstasis thrombogenicity models. Small-animal models are also useful for evaluating the role of factor IXa as a potential thrombogenic contaminant of concentrates and ensuring minimal amounts in the final product. The limitations associated with extrapolating in vivo model data will be shown to be minimal if ongoing clinical studies continue to demonstrate the low thrombogenic potential of HP-FIX concentrates in humans.

Animals↗