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Biomedical subjects

J A Barbara

Publications and source records attributed to J A Barbara.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prevention of transfusion-transmitted cytomegalovirus infection.

Cytomegalovirus (CMV) is a double-stranded DNA virus which can be transmitted by blood transfusion. Its seroprevalence in adults ranges from 40% to 100% depending on geographical and socioeconomic conditions. Seropositive individuals have latent CMV infection with viral DNA present in peripheral blood leucocytes. CMV can be associated with considerable morbidity and mortality in susceptible individuals, e.g. CMV-seronegative bone marrow allograft patients. Evidence, from a number of reports, suggests that provision of leucodepleted blood components may be as effective as the use of components from CMV-seronegative donors in preventing CMV infection and disease. This is relevant in the UK because Blood Transfusion Services are implementing universal leucodepletion of cellular blood components to minimize the theoretical risk of transmission of new variant Creutzfeldt-Jakob disease. This review examines data on the biology of CMV, discusses options for testing and summarizes the impact of CMV-seronegative and leucodepleted blood components on transfusion-transmitted CMV.

Antibodies, Viral↗
PubMed1999

Robotic selective sampling and total automation for anti-CMV screening.

The provision of anti-cytomegalovirus (CMV)-negative blood products causes the blood banking community considerable logistical problems. This is due firstly to the fact that only a select group of patients require anti-CMV-negative units, namely the immunocompromised. Secondly, the prevalence of CMV antibody in the blood donor population is high and, thirdly, the demand for anti-CMV-negative blood components continues to increase. To address this problem, a system of robotic selective sampling and total assay automation for anti-CMV screening has been developed. An in-house computer program generates a worklist from the donation database of samples requiring screening to meet clinical demand. Algorithms incorporated in the program ensure that the minimum number of samples possible are selected for provision of anti-CMV-negative products. This 'intelligent' selection of samples substantially reduces reagent cost. Robotic pipetting from the electronically derived worklist, masterplate to test plate robotic transfer and use of an automated assay processor maintains specific sample identification throughout. Results are read mechanically and transmitted directly to the main computer system. Robotic selective sampling and total assay automation produces an efficient, secure, auditable and completely traceable system for the provision of anti-CMV-negative units. The system produced a substantial reduction in labour costs with a 40% reduction in reagent usage. This system can be readily adapted for screening other markers on a selective basis.

Antibodies, Viral↗
PubMed1999

Induction of tolerance to alloantigen.

The study of transplantation tolerance has been a major area of immunological research since the pioneering work by Medawar and colleagues. It has been classically defined as the absence of an immune response to a specific antigen in the setting of an otherwise normal immune system. The induction of tolerance to alloantigen in the transplantation setting would not only allow better graft survival but would also obviate the need for immunosuppressive therapy. The induction of tolerance is considered by many to be the "holy grail" of organ transplantation but, despite many years of experimental investigation, reliable induction of allograft tolerance has not been achieved in humans. There exists four fundamental mechanisms of T cell tolerance that may be operational in the transplantation setting: deletion, functional anergy, ignorance and regulation/suppression. Several strategies to induce tolerance in transplantation have been employed, but most of these tolerogenic strategies have been investigated in rodents and it remains to be determined whether they can be transferred into large outbred animal models or clinical transplantation.

Animals↗
PubMed1998

Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5.

OBJECTIVE: To estimate the rate of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England and to describe the probable routes of infection in these donors. DESIGN: Retrospective survey of blood donors becoming positive for hepatitis C antibody and of the results of donation testing. SETTING: The 14 blood centres in England. SUBJECTS: All repeat donors giving blood between January 1993 and December 1995. MAIN OUTCOME MEASURES: Number of donors developing hepatitis C between donations during the three years of testing for hepatitis C antibody at English blood centres and the rate of seroconversion among repeat blood donors. Probable routes of infection. RESULTS: 14 donors during 1993-5 fulfilled the case definition for seroconversion to positivity for hepatitis C antibody. The estimated seroconversion rate for infection with hepatitis C in repeat donors was 0.26 per 100 000 person years (95% confidence interval 0.15 to 0.43). Counselling after diagnosis found that four of these donors had risk factors specified in the criteria excluding people from giving blood but these factors had not come to light before donation. Another of the donors who seroconverted had a risk factor that has since been included in the exclusion criteria. Heterosexual intercourse was considered to be the most likely route of infection for five of the 14 donors. CONCLUSIONS: The rate of seroconversion for positivity to hepatitis C antibody in repeat blood donors in England was extremely low. During 1993-5 fewer than 1 in 450 000 donations were estimated to have come from repeat donors who had become positive for hepatitis C antibody since the previous donation.

Adolescent↗
PubMed1998

Prevention of infections transmissible by blood derivatives.

Agents that are transmissible by blood or its derivatives typically have long incubation periods, may often be asymptomatic for several years and can set up carrier or latent persistent infections. Examples are hepatitis B virus (HBV), hepatitis C virus (HCV), the human immunodeficiency viruses (HIV 1 and 2) and cytomegalovirus. The prevention of transfusion-transmitted infection (TTI) is based on the exclusion of potential blood donors who are not fit and well, the education of donors to exclude themselves if they are at risk of contracting TTIs, the laboratory screening of all blood donations for evidence of infection with a range of potential TTIs, physical removal of white cells in those cases where the agent is cell associated, viral inactivation procedures for pooled plasma derivatives, detection of viral genomes in plasma pools and the avoidance of unnecessary transfusions.

Bacterial Infections↗
PubMed1998

Fatal Clostridium perfringens sepsis from a pooled platelet transfusion.

A male patient with acute myeloid leukaemia received a pooled platelet preparation prepared by Optipress system on the last day of its shelf life. The patient collapsed after two-thirds of the contents had been transfused. Clostridium perfringens was isolated from the platelet bag within 18 h of the acute event. Metronidazole, gentamicin and Clostridium antiserum were then administered in addition to the broad spectrum antibiotics started previously. However, the patient died 4 days after the platelets were transfused. The cause of death was given as cardiovascular shock, entirely compatible with an overwhelming bacteraemic and septic episode. A coroner's verdict of accidental death due to transfusion of a contaminated unit of platelets was recorded. On subsequent investigation Cl. perfringens type A serotype PS68,PS80 (identical to that found in the platelet bag) was cultured from the venepuncture site of the arm of one of the donors who contributed towards the platelet pool. The donor had two young children and frequently changed nappies. Faecal contamination of the venepuncture site was the suspected source for the transmission of Cl. perfringens, an organism commonly found in the soil and intestinal tract of humans. This case dramatically highlights the consequences of transfusing a bacterially contaminated unit. It is vital that such incidents are investigated and reported so that the extent of transfusion-associated bacterial transmission can be monitored and preventative measures taken if possible.

Acute Disease↗
PubMed1998

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↗
PubMed1997

Regulation of neutrophil apoptosis by tumor necrosis factor-alpha: requirement for TNFR55 and TNFR75 for induction of apoptosis in vitro.

Granulocyte apoptosis is an important mechanism underlying the removal of redundant neutrophils from an inflammatory focus. The ability of many proinflammatory agents to impede this event suggests that such agents act not only in a priming or secretagogue capacity but also increase neutrophil longevity by delaying apoptosis. We have examined whether this hypothesis holds true for all neutrophil priming agents, in particular tumor necrosis factor-alpha (TNF-alpha), which has been variably reported to either induce, delay, or have no effect on neutrophil apoptosis. After 20 hours coincubation TNF-alpha inhibited neutrophil apoptosis; however, more detailed analysis demonstrated its ability to promote apoptosis in a subpopulation of cells at earlier (2 to 8 hours) times. Formyl-Met-Leu-Phe, platelet-activating factor, inositol hexakisphosphate, lipopolysaccharide, leukotriene B4, and granulocyte-macrophage colony-stimulating factor all inhibited apoptosis at 6 and 20 hours. The early proapoptotic effect of TNF-alpha was concentration-dependent (EC50 2.8 ng/mL), abolished by TNF-alpha neutralizing antibody, and was not associated with any change in cell viability or recovery. Of relevance to the inflamed site, the ability of TNF-alpha to accelerate apoptosis was lost if neutrophils were primed with 1 micromol/L PAF or aged for 6 hours before TNF-alpha addition. The TNFR55-selective TNF-alpha mutants (E146K, R32W-S86T) induced neutrophil apoptosis but with a potency 14-fold lower than wild-type TNF-alpha. Although the TNFR75-selective mutant (D143F) did not induce apoptosis, blocking antibodies to both receptor subtypes abolished TNF-alpha-stimulated apoptosis. Hence, TNF-alpha has the unique ability to induce apoptosis in human neutrophils via a mechanism where TNFR75 facilitates the dominant TNFR55 death effect. This may be an important mechanism controlling neutrophil longevity and clearance in vivo.

Antibodies, Monoclonal↗
PubMed1997

Does anti-HBc reactivity reflect 'lifestyle' risk in north London blood donors?

BACKGROUND AND OBJECTIVES: To determine whether antibody to hepatitis B core (anti-HBc) reactivity, as a marker of hepatitis B virus infection, reflects a 'lifestyle' risk in donors in North London, we have obtained detailed histories from donors with various manifestations of HBV infection. MATERIALS AND METHODS: Interviews based on a standardised questionnaire were conducted with 70 donors confirmed to be anti-HBc reactive. RESULTS: Comparison with controls (known to be anti-HBc-negative) and donors reactive for anti-hepatitis-C virus showed that current donor strategies are effective; in our area, reactivity for anti-HBc is not associated with a lifestyle risk for those donors who are unreactive in current mandatory screening tests. CONCLUSIONS: Blood from donors positive for both anti-HBc and anti-HBs should be considered suitable for transfusion purposes. This is consistent with the practice of accepting blood from naturally immune donors for preparation of hepatitis B immunoglobulin.

Antibodies, Viral↗
PubMed1997

Evaluation of a malaria antibody ELISA and its value in reducing potential wastage of red cell donations from blood donors exposed to malaria, with a note on a case of transfusion-transmitted malaria.

BACKGROUND AND OBJECTIVES: Blood donations are often wasted for lack of a satisfactory procedure to evaluate donors potentially exposed to malaria. MATERIALS AND METHODS: We evaluated a commercial ELISA for the detection of antibodies to malaria and compared it with an immunofluorescent antibody test (IFAT). RESULTS: When 5,311 sera from routine non-exposed donors were tested, 24 (0.45%) were positive by the ELISA, using a Plasmodium falciparum antigen. Seventeen were subjected to confirmatory testing but none were positive by IFAT. Of 1,000 donors potentially exposed in endemic areas 15 (1.5%) were repeatably reactive by ELISA. 10 of these were tested by IFAT and 2 were positive. When 150 patients attending the Hospital for Tropical Diseases in London with acute malaria were tested, 73% of those infected with P. falciparum were repeatably reactive for malarial antibodies by ELISA and 56% with Plasmodium vivax. Of 88 stored clinical sera tested by both IFAT and ELISA 56 were positive by IFAT and of these 52 (93 degrees/0) were positive by ELISA. CONCLUSION: The ELISA is sufficiently sensitive and specific to screen at-risk donors. Its use could safely retrieve 40,000 red cell units currently discarded each year in Great Britain.

Animals↗
PubMed1997

Quinine-induced hemolytic uremic syndrome.

Although quinine use is very common, hemolytic uremic syndrome (HUS) following exposure to quinine is only a recently reported phenomenon, with the first description published in 1991. Previous reports have concentrated on the nature of the hematological process and in particular characterization of the quinine-induced antibodies involved. We present a case of HUS with a clear temporal and immunological relationship to quinine which demonstrates the pathognomonic renal features of HUS. An indirect antiglobulin test with the patient's serum agglutinated red blood cells only in the presence of quinine. Renal biopsy features included glomerular and arteriolar endothelial swelling, capillary loop thrombi, mesangiolysis, segmental sclerosis and segmental ischemia. Early empiric treatment with plasma exchange and corticosteroids was instituted and this resulted in recovery of renal function to normal.

Biopsy↗
PubMed1996

Tumour necrosis factor-alpha (TNF-alpha): the good, the bad and potentially very effective.

When the tumour necrosis factor-alpha (TNF-alpha) gene was cloned the protein became available for use in clinical trials as an antineoplastic agent. However, side effects have severely limited its application in cancer treatment. Studies on the species specificity of TNF have indicated that the p75 TNF receptor (TNFR75) may play an important role in the generation of these side effects in humans. Using human TNF mutants with selective receptor-binding properties it has been demonstrated in neutrophils and endothelium that TNFR75 is involved in the mediation of the proinflammatory activity of TNF by facilitating the p55 TNF receptor (TNFR55). However, only TNFR55 appears to be involved in mediating TNF cytotoxicity. Therefore the potential exists for the successful reintroduction of TNF-alpha, in the form of TNFR55-selective mutants, into the clinical arena with the promise of reduced side effects.

Animals↗
PubMed1996

Reducing risks in blood transfusion: process and outcome.

The last decade has seen substantial improvements in the provision of safe "infection-free' blood for patients in many countries. This has resulted from the combined effects of better donor education, selection, testing and exclusion processes. The residual risk of infection with HBsAg attributable to laboratory error is less than 0.1/ 100,000 (1/750,000). The risk for HIV remains to be quantified but may approach this figure. With such low risks it will be difficult to provide statistical evidence that further improvements in the process of selection, testing or exclusion will have an impact on reducing risk from either agent. Over the same time, less progress has been made reducing risk to the recipient attributable to problems in the clinical supply process, i.e. getting the right blood, to the right person, at the right place, at the right time. Uniform definitions of terminology defining blood donation characteristics, together with the sharing of performance data are essential if we are to make national and international comparison of the risks that patients face when they receive a transfusion. Equally, the use of agreed definitions, and the sharing of data on the clinical outcomes of transfusion can provide the key to better prescribing based on evidence of actual risks and benefits.

Blood Banks↗