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Biomedical subjects

R M Warwick

Publications and source records attributed to R M Warwick.

At least 19 recordsLinked to original sources

Donor exclusion in the National Blood Service Tissue Services living bone donor programme.

National Blood Service (NBS) Tissue Services (TS) operates living donor and deceased donor tissue banking programmes. The living bone donor programme operates in collaboration with 91 orthopaedic departments across the country and collects bone donations, in the form of surgically removed femoral heads (FHs), from over 5,000 patients per annum undergoing total hip replacement. Bone donated via the living programme constitutes approximately 55% of the total bone donated to NBS. Non-NBS tissue banks, primarily in hospital orthopaedic departments, also bank donated bone for the UK. A survey of information received from 16 collaborating orthopaedic centres, between April 2003 and August 2004, identified 709 excluded donors. The total number of donations banked from these sites was 1,538. Donations can be excluded before collection if there are contraindications noted in a potential donor's medical history before their operation. Donors may also be excluded after collection of the FH, for instance because of reactive microbiology tests for blood borne viruses, or if the donation storage conditions or related documentation have not met stringent quality requirements. In this survey, bone or joint conditions were the major reasons for excluding potential donors before donation (154 of 709 exclusions, 22%), followed by a current or a past history of malignancy (139 of 709 exclusions, 20%). Local staffing and operational difficulties sometimes resulted in potential donors being missed, or specific reasons for exclusion not being reported (117 exclusions). These out numbered exclusions due to patient refusal (80 exclusions). A small number (< 5) appear to have been excluded erroneously. There was considerable local variation in the reasons given for exclusion and certainly under-reporting. A survey of donations discarded after collection in the same period highlighted that 43% were donor related; 110 of 370 did not provide a follow-up blood sample. More than 30% were due to delays in forwarding blood samples to the microbiological laboratory for testing, resulting in deterioration of the sample quality. Training to ensure that standards are complied with and a firm evidence base for exclusion criteria, applied uniformly, will help focus donor identification efforts on individuals meeting rational criteria so that fewer potential donations are lost.

Bone Banks↗

Ecological consequences of dredged material disposal in the marine environment: a holistic assessment of activities around the England and Wales coastline.

This study provides a holistic perspective on the ecological effects of dredged material disposal, both intertidally and subtidally. A number of numerical techniques (univariate, distributional, multivariate and meta-analysis) were used to assess impacts at 18 different disposal sites. The analyses revealed that ecological effects associated with dredged material disposal were dependent on the numerical techniques used, and that impacts were disposal-site specific. Disposal-site communities were generally faunistically impoverished to varying degrees, and impacts following intertidal placement were comparable to those of subtidal placement. We conclude that any assessment of the consequences of dredged material disposal to the coastal environment must take account of site-specific variation in prevailing hydrographic regimes and in ecological status, along with information on the disposal activity itself (mode, timing, quantity, frequency and type of material). As would be expected, variability in the latter presents a significant challenge in attempts to generalise about environmental and ecological impacts.

Animals↗

Freeliving marine nematodes as a pollution indicator of the Bohai Sea.

A hierarchical diversity index--taxonomic distinctness index delta+, which was first defined by Warwick and Clark in 1998, was employed to evaluate the pollution status of the Bohai Sea with freeliving marine nematodes. The result showed that the Bohai Bay and other coastal sampling sites might be affected by oil and gas production and other anthropogenic influences. In other words, anthropogenic disturbance was affecting this component of the benthos in these locations. And most offshore sampling sites in the middle of the Bohai Sea were clear and unpolluted.

Animals↗

Evidence for the effects of metal contamination on the intertidal macrobenthic assemblages of the Fal Estuary.

The intertidal invertebrate macrofauna of five creeks in the Fal estuarine system, Cornwall, UK, is compared with data from 40 locations in six other estuaries in south-west Britain. Multivariate analysis shows that the community composition in the Fal is distinct from all the other estuaries. The differences are principally due to the absence of two crustacean species, Corophium voluntator and Cyathura carinata, and the high abundance of small opportunistic annelid species. The Fal Estuary is heavily contaminated with heavy metals as a result of mining in the catchment, and the faunistic features are commensurate with what is known of the relative sensitivities of marine invertebrate taxa to pollution.

Animals↗

The banking of arterial allografts in the United kingdom. A technical and clinical review.

The standard graft materials for reconstructive vascular surgery are autologous vessels and synthetic prostheses. However, the clinical results are unsatisfactory when the diameter of the required graft is less than 6 mm and attention has therefore been directed to the possibility of using vascular allografts when autologous conduits are not available. In this review, we consider the evidence that cryopreserved allogeneic vessels might meet this need. Other factors being equal, the literature suggests that arteries will give superior performance to veins when grafted into the arterial circulation. Conventional cryopreservation techniques have been developed and these can provide structurally intact and functional small elastic arteries in animal experiments. We conclude that cryopreservation per se produces only modest injury which may well be recoverable following grafting. However, both experimental and clinical studies suggest that immunological injury is a greater problem. Nevertheless, the general indication is that appropriate risk-benefit analysis in individual cases will justify the clinical use of cryopreserved allograft vessels. Immunosuppression with careful immunological monitoring may be justified in the more desperate clinical situations. Finally we conclude that the existing tissue bank network in the United Kingdom is well placed to provide surgeons with such tissue.

Journal Article↗

A UK survey of virological testing of cadaver tissue donors. Microbiology Working Group of the NIBSC steering group on Tissue/Cell Banking and Engineering.

OBJECTIVES: To analyse information about virological testing of cadaveric tissue donors, including the kits used and the rates of test reactivity. MATERIALS AND METHODS: Retrospective data were collected using a standardised questionnaire sent to 16 tissue banks in the UK. The rates of repeat reactive screen tests and confirmed positive results for the markers HBsAg, anti-HCV, anti-HIV were analysed in 1,833 cadaver tissue donors tested at 12 tissue banks over one year up to March 1998. RESULTS: There was a wide range of kits in use for virological screen testing of cadaver donors. The rates of repeat reactivity in the screen tests varied from 0 to 42%. CONCLUSION: The findings have implications for policies based on discard of tissues from donors with repeat reactive results, and raise important safety issues with regards to cadaveric virological testing, as the test systems in use have not been validated for cadaver blood samples.

Cadaver↗

Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloimmune anemia.

BACKGROUND: In alloimmune anemia of the newborn, the level of hemolysis caused by the presence of antibodies to antigens of the Kell blood-group system is less than that caused by antibodies to the D antigen of the Rh blood-group system, and the numbers of reticulocytes and normoblasts in the baby's circulation are inappropriately low for the degree of anemia. These findings suggest that sensitization to Kell antigens results in suppression of fetal erythropoiesis as well as hemolysis. METHODS: We compared the growth in vitro of Kell-positive and Kell-negative hematopoietic progenitor cells from cord blood in the presence of human monoclonal anti-Kell antibodies and anti-D antibodies and serum from women with anti-Kell antibodies. RESULTS: The growth of Kell-positive erythroid progenitor cells (erythroid burst-forming units and colony-forming units) from cord blood was markedly inhibited by monoclonal IgG and IgM anti-Kell antibodies in a dose-dependent fashion (range of concentrations, 0.2 to 20 percent), but monoclonal anti-D antibodies had no effect. The growth of these types of cells from Kell-negative cord blood was not affected by either type of antibody. Neither monoclonal anti-Kell antibodies nor monoclonal anti-D antibodies inhibited the growth of granulocyte or megakaryocyte progenitor cells from cord blood. Serum from 22 women with anti-Kell antibodies inhibited the growth of Kell-positive erythroid burst-forming units and colony-forming units but not of Kell-negative erythroid burst-forming units and colony-forming units (P<0.001 for the difference between groups). The maternal anti-Kell antibodies had no inhibitory effects on granulocyte-macrophage or mega-karyocyte progenitor cells from cord blood. CONCLUSIONS: Anti-Kell antibodies specifically inhibit the growth of Kell-positive erythroid burst-forming units and colony-forming units, a finding that supports the hypothesis that these antibodies cause fetal anemia by suppressing erythropoiesis at the progenitor-cell level.

Anemia, Hemolytic, Autoimmune↗

Safety aspects of cord blood banking.

The safety of cord blood for transplantation depends upon a considered approach to donor selection, testing and processing of donations. It should be undertaken within a total quality system and good manufacturing practice facilities. Protocols should be developed based upon risk assessment and cost efficiency. In this context the retesting of donors for HIV is considered and the risk of a serological window period HIV transmission by cord blood illustrated to be minimal compared to the risks of transplant procedures or of not having a donor.

Blood Banks↗

Safe tissue grafts.

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Bacterial Infections↗

Skin storage.

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Cryopreservation↗

Role of the blood transfusion service in tissue banking.

Tissue transplantation and banking are rapidly growing services throughout the world reflecting the widening availability of transplantable cadaver tissue and the mounting clinical indications particularly in orthopaedic, plastic and cardiovascular surgery. In the US tissue banking is more established, yet continues to show a rapid growth profile. In the UK it is currently organised in a variety of different ways and by a number of different organisations. The risks of disease transmission by tissue transplantation are similar to those for blood transfusion and the majority of tissues are grafted during procedures that are not life saving. The danger of disease transmission has resulted in the introduction of legislation in the US which allows the FDA to inspect tissue banks and to recall and destroy tissues. In the UK, there is currently no regulation or inspection of tissue banks to demonstrate that donor selection, tissue processing and tracking are conducted to acceptable standards. Blood transfusion services in the UK, US, New Zealand, Australia and possibly other countries have extended their roles to include organ and tissue donation to varying degrees, with the collection, processing and distribution of bone and tendon allografts most commonly undertaken. They have readily available special capabilities and experience with an established infrastructure, compliant with Good Manufacturing Practice, placing them in an ideal position to provide this service safely and cost-effectively.

Blood Transfusion↗

Accuracy of prenatal determination of RhD type status by polymerase chain reaction with amniotic cells.

OBJECTIVE: Our purpose was to determine the accuracy of RhD typing by use of amniocytes obtained at amniocentesis in RhD-negative women. STUDY DESIGN: One hundred thirty-five RhD-negative women undergoing amniocentesis for management of suspected alloimmunization (n = 95) or routine second-trimester cytogenetic indications (n = 40) were studied. Amniocytes were then used as template to amplify specific portions of the Rh D and Rh CcEe genes by polymerase chain reaction. The fetal RhD type was confirmed by serologic techniques either after fetal blood sampling or cord blood samples at birth. RESULTS: Thirty-six fetuses were serologically typed as RhD negative and all 36 were typed RhD negative by polymerase chain reaction. Ninety-eight fetuses were serologically typed as RhD positive; of these, 96 were correctly typed as RhD positive and two were incorrectly typed as RhD negative, with an overall error rate of 1.4%. Both of the errors occurred in a single batch of six samples tested at the same time. In one of these cases the fetus had mild Rh alloimmune disease and required exchange transfusion at birth. In the second case the fetus had severe hydrops fetalis and died in utero at 28 weeks. Deoxyribonucleic acid isolated from fetal blood was tested with the same polymerase chain reaction technique after delivery, and in both cases the fetus was correctly typed as RhD positive. Deoxyribonucleic acid amplification repeatedly failed in one case. CONCLUSION: Prenatal fetal RhD typing by polymerase chain reaction with amniotic fluid cells is accurate and reliable. In sensitized pregnancies it allows early management of Rh disease and avoids invasive procedures in RhD-negative fetuses. In nonsensitized pregnancies it avoids the use of anti-RhD immunoglobulin after invasive procedures or during pregnancy. To eliminate the possibility of genetic and laboratory sources of errors, we suggest using different sets of primers at two different loci (e.g., exon 4 to 5 and exon 10).

Amniocentesis↗

Needle modifications for invasive fetal procedures.

OBJECTIVE: To investigate the effect of needle size and siliconization on fetal blood sampling, transfusion, and electrocardiography. METHODS: Standard needles were modified by increasing the internal (but not the external) diameter and either siliconization of the bore or external Teflon coating. The siliconized needles were subjected to a series of flow experiments with either blood or saline at various driving pressures, and assessed in clinical use during fetal transfusion and fetal blood sampling. The Teflon-coated needles were used for fetal transfusion to try and facilitate the fetal electrocardiogram (ECG). RESULTS: Under conditions simulating fetal transfusion, the siliconized needle allowed a 93% increase in flow rate compared to the standard needle (P < .05). Samples obtained after fetal transfusion with the siliconized needles were free of clots, whereas 50% of the post-transfusion samples with the standard needle had clots present. Similarly, samples taken for fetal platelet count were free of platelet clumping and clots with siliconized needles, but not with standard needles. Fetal ECG recordings were recorded successfully when Teflon-coated needles were used to access the fetal circulation via the intrahepatic vein. CONCLUSIONS: Modifications to standard needles improved blood flow and reduced the activation of coagulation during both fetal intravascular transfusion and platelet count measurement. Direct fetal ECG recording was facilitated by Teflon coating the external surface of the needle, insulating the fetal signal from maternal electrical signals.

Blood Transfusion, Intrauterine↗

Transfusion-associated graft-versus-host disease and its prevention.

Transfusion-associated graft-versus-host disease is a rare but usually fatal complication of transfusion of cellular blood components, caused by multiorgan engraftment and proliferation of donor T lymphocytes. The classical features of skin rash, diarrhoea and hepatitis, along with striking bone-marrow failure, are seen 1-2 weeks after transfusion. Although early reports described the condition only in immunosuppressed individuals, sharing of an HLA haplotype between donor and an immunocompetent recipient can also result in transfusion-associated graft-versus-host disease. The condition is entirely preventable by gamma irradiation of cellular blood components to 25 Gy, although this results in some reduction of red-cell viability and increased loss of red-cell potassium. The major indications for irradiated blood components include bone marrow/stem cell auto- or allografting, Hodgkin's disease, intrauterine transfusions, and transfusions from relatives or HLA-selected platelet donors.

Blood Donors↗

Clinical utility of fetal RhD typing in alloimmunized pregnancies by means of polymerase chain reaction on amniocytes or chorionic villi.

OBJECTIVE: Our purpose was to describe the clinical utility of a deoxyribonucleic acid amplification method for determining fetal RhD status in alloimmunized pregnancies STUDY DESIGN: Six RhD-negative women with alloimmunized pregnancies and heterozygous partners underwent amniocentesis (n = 5) or chorionic villus sampling (n = 1). Fetal RhD type was determined by polymerase chain reaction and results disclosed to the attending physicians. RESULTS: Knowledge of the fetal RhD status avoided further invasive procedures in two pregnancies and facilitated the timing or performance of intrauterine transfusions in the remainder. CONCLUSIONS: In alloimmunized pregnancies the ability to RhD-type the fetus in amniotic fluid avoids the risks of fetomaternal hemorrhage and increased sensitization associated with fetal blood sampling or chorionic biopsy. This allows more rational pregnancy management, avoiding invasive procedures in the presence of an RhD-negative fetus, or planning therapeutic interventions or offering termination of pregnancy in the presence of an RhD-positive fetus.

Amniotic Fluid↗

In vitro culture of colony forming unit-megakaryocyte (CFU-MK) in fetal alloimmune thrombocytopenia.

Perinatal alloimmune thrombocytopenia (PAITP) causes intracranial haemorrhage in the fetus and neonate. However, the severity of the thrombocytopenia correlates poorly with maternal anti-platelet antibody titres. To test the hypothesis that reduced platelet production contributes to fetal thrombocytopenia in PAITP, maternal sera from three HPA-1a-negative mothers whose pregnancies were complicated by anti-HPA-1a (two severe cases, one mild case) were added to colony forming unit-megakaryocyte (CFU-MK) cultures from HPA-1a positive and negative individuals. Sera from the two severely affected pregnancies containing anti-HPA-1a caused 66-100% inhibition of HPA-1a-positive fetal and neonatal CFU-MK, whereas CFU-MK from two HPA-1a-negative mothers were not inhibited by the anti-HPA-1a-containing sera. Maternal serum from the case of mild PAITP caused only mild inhibition of HPA-1a-positive cord and adult CFU-MK and did not inhibit HPA-1a-positive fetal CFU-MK. Taken together, these findings suggest that reduced megakaryocyte production contributes to fetal thrombocytopenia due to maternal anti-HPA-1a antibodies and also that the degree of CFU-MK inhibition correlates with severity of fetal thrombocytopenia.

Adult↗