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Biomedical subjects

J A Barbara

Publications and source records attributed to J A Barbara.

At least 19 recordsLinked to original sources
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

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↗
PubMed1996

Yersinia enterocolitica transmission from a red cell unit 34 days old.

In 1993 the North London Blood Transfusion Centre received its first report of Yersinia enterocolitica transmission from a unit of red cells supplied to a local hospital. The recipient was a 23-year-old male who was neutropenic following a third cycle of chemotherapy for treatment of acute myeloblastic leukaemia (FAB type M6) and received a 34-day-old red cell unit. During transfusion the patient developed septicaemia and endotoxin-mediated shock. The transfusion was stopped immediately and broad spectrum antibiotics administered immediately on suspicion of bacteraemia from the transfused unit. This prompt action undoubtedly prevented a fatal outcome. Y. enterocolitica was isolated from the blood bag. Antibody was also detected in the bag and in a sample taken from the donor 39 days post-donation. Antibody to serotype 03 was identified, the commonest serotype reported in transfusion-transmitted Y. enterocolitica. The donor reported no gastrointestinal upset or illness prior to donation. This transfusion reaction might not have occurred had the red cells been transfused earlier in their storage period, but would not have been prevented by the exclusion of donors with a history of gastrointestinal illness as the donor was asymptomatic. Nor would it have been prevented by inspecting the blood for a change in colour, as no such change was observed. Y. enterocolitica is a significant problem in transfusion medicine and transmission is generally associated with a high mortality rate. Hospitals should be urged to investigate bacteriologically all appropriate transfusion reactions so that the true extent of the problem in the United Kingdom can be assessed.

Adult↗
PubMed1996

Safety and efficacy of hepatitis C virus antibody screening of blood donors with two sequential screening assays.

BACKGROUND: Reactive samples in hepatitis C virus (HCV) antibody screening of blood donors are currently referred for a confirmatory assay. This scheme is not optimally efficient and is expensive because of the lack of specificity and cost of confirmatory tests, as well as the need to discard false-positive donations. As in some human immunodeficiency virus antibody-confirmatory schemes, the safety and efficacy of confirming anti-HCV with two sequential screening assays were evaluated. STUDY DESIGN AND METHODS: Three combinations of two anti-HCV screening assays were used to test 75,874 blood donors. Results were compared with the routine testing scheme and HCV RNA detection in any enzyme immunoassay-repeatably reactive samples. RESULTS: The use of an alternative screening assay for repeat testing decreased the proportion of enzyme immunoassay-positive donors from 0.28 to 0.05 percent. All samples that were "confirmed" as positive by the standard combination of immunoassays and all HCV RNA-positive samples were detected by the sequential screening assays. No samples that had discordant results on primary and secondary screening assays were confirmed by recombinant immunoblot assay or were found to contain detectable HCV RNA. CONCLUSION: The combination of screening assays for anti-HCV confirmation was as safe as, cheaper than, and nearly as efficient as the standard testing scheme.

Blood Donors↗
PubMed1995

Confidential unit exclusion: the North London Blood Transfusion Centre's experience.

A 'Confidential AIDS Questionnaire' has been used at North London Blood Transfusion Centre (NLBTC) donor sessions since July, 1985. The aim of the questionnaire is to encourage self-exclusion by those donors whose behaviour puts them at risk of HIV infection. In a situation where such individuals cannot avoid donating they can indicate, in confidence, that their blood should not be used for transfusion. Since the introduction of this procedure, an average of 10 donors per month, who admitted relevant risk behaviour, have been permanently excluded and a number of prospective donors have excluded themselves when faced with the questionnaire. We have found the questionnaire to be well accepted by donors. It is a useful adjunct to routine donor selection and microbiological testing of donations in our efforts to minimize transfusion-transmitted infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A multicentre assessment of the specificity of ten anti-HBc screening tests.

Samples from 1828 donations were screened for anti-HBc at seven sites in the UK using kits supplied by 10 manufacturers. Only 10 (0.55%) donations were considered to have true anti-HBc reactivity and these were detected by all 10 kits. Additional markers of HBV infection were found in nine of these 10 donations. Additional reactives were found by all kits, the number ranging from 1 to 43. In the four more specific kits, the 10 true reactives were clearly distinguished from the 'false reactives' by the strength of the reaction. It is concluded that the reliance on a single ELISA test for anti-HBc diagnosis is unwise. The use of a second test known to be more specific than the screening ELISA is recommended.

Blood Donors↗
PubMed1994

Dissociation of TNF-alpha cytotoxic and proinflammatory activities by p55 receptor- and p75 receptor-selective TNF-alpha mutants.

Human tumour necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine capable of killing mammalian tumour cells in vitro and in vivo, and of enhancing the proinflammatory activity of leucocytes and endothelium, the latter effects limiting its usage as an antitumour agent in humans. Using TNF-alpha mutants with a selective capacity to bind to the TNF p55 receptor (TNFR55) or to the p75 receptor (TNFR75) we show here that these two major activities of TNF-alpha can be dissociated. The TNFR55-selective mutants (R32W, E146K and R32W-S86T) which bind poorly to TNFR75 displayed similar potency to wild-type TNF in causing cytotoxicity of a human laryngeal carcinoma-derived cell line (HEp-2) and cytostasis in a human leukaemic cell line (U937). However, these TNFR55-selective mutants exhibited lower proinflammatory activity than wild-type TNF. Specifically, TNF-alpha's priming of human neutrophils for superoxide production and antibody-dependent cell-mediated cytotoxicity, platelet-activating factor synthesis and adhesion to endothelium were reduced by up to 170-fold. Activation of human endothelial cell functions represented by human umbilical venular endothelial cell (HUVEC) adhesiveness for neutrophils, E-selectin expression, neutrophil transmigration and IL-8 secretion were also reduced by up to 280-fold. On the other hand, D143F, a TNFR75-selective mutant tested either alone or in combination with TNFR55-selective mutants, did not stimulate these activities despite being able to cause cytokine production in TNFR75-transfected PC60 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1994

A study of anti-hepatitis C positive blood donors: the first year of screening.

In the U.K., blood donations have been routinely screened for anti-HCV since September 1991. In order to get the most epidemiological benefit from these extensive screening data, the histories obtained at counselling from donors confirmed to be anti-HCV positive, 'indeterminate' and falsely positive have been analysed in detail. In addition, the associations with potential risk factors have been investigated by comparing these groups of donors with a control group of 771 routine donors bled on one day during the study, at North London Blood Transfusion Centre. This paper documents the prevalence and demography of HCV infection in asymptomatic blood donors, to assess various possible sources of infection and the association between liver function test results and alcohol consumption in donors. One in 1400 previously untested donors was confirmed positive for anti-HCV. Age (the group 30-49 years being highest), tattooing and intravenous drug use in both sexes, ear-piercing in males and blood transfusion in females were all significantly associated with an increased risk of HCV infection. Intravenous drug use proved to be the factor most strongly associated with risk. Liver function tests (alanine aminotransferase) were elevated in a significant number of donors confirmed to be anti-HCV positive but no clear correlation between alanine aminotransferase level and either time since infection or alcohol consumption was found. Alcohol consumption was significantly higher in donors confirmed to be anti-HCV positive and was particularly marked in those admitting to previous intravenous drug use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗