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Biomedical subjects

P L Yap

Publications and source records attributed to P L Yap.

At least 19 recordsLinked to original sources
PubMed2001

Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission.

Genetic variation at the human leukocyte antigen (HLA) loci has been shown to be an important risk factor for progression to HIV disease, but its significance in infection is less well understood. We have investigated its role in HIV transmission in a cohort of individuals at risk for heterosexual infection. Analysis of over 80 individuals revealed that that the degree of concordance at HLA A, B, and DR loci differs significantly between transmitting and nontransmitting couples at risk for heterosexual HIV transmission (p <.02), suggesting that allogeneic immune responses may confer a degree of protection against HIV infection. Analysis of the frequencies of specific alleles at the A, B, and DR loci revealed a significantly higher frequency of HLA DR5 among exposed uninfected individuals, relative to population controls.

Alleles↗
PubMed2001

Acute phase responses following minimal access and conventional thoracic surgery.

OBJECTIVES: Major thoracic surgery is associated with trauma-related immunological changes. These may impair anti-tumour immunity. We hypothesize that the reduced operative trauma associated with a video-assisted thoracic surgery (VATS) approach may decrease acute phase responses and, consequently, lead to better preservation of immune function. This prospective randomized study compared the effects of conventional open thoracic surgery and VATS on acute phase responses in patients undergoing pulmonary lobectomy. METHODS: Acute phase indicators were analyzed in patients undergoing lobectomy for suspected bronchogenic carcinoma. Surgery was prospectively randomized to pulmonary lobectomy by VATS or limited postero-lateral thoracotomy. Blood was taken pre-operatively and at 4, 24, 48, 72, 120 and 168 h post-operatively for analysis of C-reactive protein (CRP; 41 patients: open, n=22; VATS, n=19) interleukin (IL)-6, tumour necrosis factor (TNF) receptors (TNF-sR55, TNF-sR75) and P-selectin (24 patients: open, n=12; VATS, n=12). Samples taken at 48 and 168 h were also analyzed for phagocyte reactive oxygen species (ROS) production (25 patients: open, n=16; VATS, n=19). RESULTS: Surgery increased acute phase responses. VATS was associated with lower CRP and IL-6 levels. In the open surgery group, significant increases in ROS in neutrophils (up to 36% greater than before surgery, n=12, P<0.02-0.05) were detected at 2 days after surgery, but in the VATS group, the increase after surgery (of up to 17%, n=18) did not reach significance. Similarly, monocyte ROS increases of up to 25% in the mean ROS in the open surgery group and of up to 17% in the VATS group were detected on days 2 and 7 after surgery. CONCLUSIONS: VATS pulmonary lobectomy is associated with reduced peri-operative changes in acute phase responses. This finding may have implications for peri-operative tumour immuno-surveillance in lung cancer patients.

Acute-Phase Reaction↗
PubMed2000

Lymphocyte responses following open and minimally invasive thoracic surgery.

BACKGROUND: Immunosuppression associated with surgery may predispose to increased tumour growth or recurrence. Lymphocytes are central components of the immune network, signalling specific and non-specific responses in tumour immunosurveillance. This study was therefore designed to compare the effects of minimally invasive and conventional approaches to major thoracic surgery on lymphocyte populations and oxidative activity. PATIENTS AND METHODS: The effects of conventional and minimally invasive video-assisted thoracic surgery (VATS) on the numbers and types of circulating lymphocytes and on lymphocyte oxidation were compared in a prospective randomized study of 41 patients undergoing lobectomy for peripheral bronchogenic carcinoma. Blood taken pre-operatively and on days 2 and 7 post-operatively was analysed for T (CD4, CD8), B (CD19) and natural killer (NK) (CD56, CD16) cell counts and for lymphocyte oxidative activity. Leucocyte numbers were compared with pre-surgical values and oxidative rate with healthy donor controls. RESULTS: Lymphocyte counts fell after surgery; VATS was associated with less effect on circulating T (CD4) cells at 2 days and on NK lymphocytes at 7 days post-surgery. Lymphocyte oxidation was less suppressed in the VATS group 2 days after surgery. In general, post-surgical changes in key cells of cellular immunity were smaller in the VATS group, and recovery to normal levels was more rapid. CONCLUSION: The degree of invasiveness of thoracic surgery may influence the extent of immunosuppression in patients undergoing pulmonary lobectomy for pulmonary neoplasm.

Aged↗
PubMed1999

Variation of hepatitis C virus following serial transmission: multiple mechanisms of diversification of the hypervariable region and evidence for convergent genome evolution.

We have studied the evolution of hepatitis C virus (HCV) from a common source following serial transmission from contaminated batches of anti-D immunoglobulin. Six secondary recipients were each infected with virus from identifiable primary recipients of HCV-contaminated anti-D immunoglobulin. Phylogenetic analysis of virus E1/E2 gene sequences [including the hypervariable region (HVR)] and part of NS5B confirmed their common origin, but failed to reproduce the known epidemiological relationships between pairs of viruses, probably because of the frequent occurrence of convergent substitutions at both synonymous and nonsynonymous sites. There was no evidence that the rate at which the HCV genome evolves is affected by transmission events. Three different mechanisms appear to have been involved in generating variation of the hypervariable region; nucleotide substitution, insertion/deletion of nucleotide triplets at the E1/E2 boundary and insertion of a duplicated segment replacing almost the entire HVR. These observations have important implications for the phylogenetic analysis of HCV sequences from epidemiologically linked isolates.

Adolescent↗
PubMed1999

A second outbreak of hepatitis C virus infection from anti-D immunoglobulin in Ireland.

OBJECTIVE: To investigate the infectivity for hepatitis C virus (HCV) of intravenous anti-D immunoglobulin batches manufactured in Ireland between 1991 and 1994. METHODS: Women who had received anti-D manufactured between 1991 and 1994 were screened for serological markers of HCV infection and for the presence of HCV RNA by RT-PCR amplification and virus genotyping. RESULTS: 44 women exposed to anti-D manufactured between 1991 and 1994 were polymerase chain reaction positive for HCV RNA, 19 of whom were infected with genotype 3a virus shown by phylogenetic analysis of the NS5B gene to be closely related to that from the single implicated donor. CONCLUSIONS: Anti-D manufactured in 1991-1994 transmitted infection of HCV genotype 3a. The prevalence of HCV-specific antibody in anti-D recipients was relatively low (0.59%), consistent with the low level of virus RNA in these anti-D batches.

Disease Outbreaks↗
PubMed1998

Detection of a novel DNA virus (TTV) in blood donors and blood products.

BACKGROUND: A newly discovered DNA virus, transfusion-transmitted virus (TTV), has been implicated as a cause of post-transfusion hepatitis. We investigated the frequency of TTV viraemia in UK blood donors, and the extent to which TTV contaminates blood products such as factor VIII and IX clotting factors. We also investigated the possible aetiological role of TTV in cryptogenic fulminant hepatic failure (FHF). METHODS: We extracted DNA from plasma of blood donors and patients with FHF, and from blood products (factor VIII and IX clotting-factor concentrates, immunoglobulin preparations). We detected TTV by PCR using primers from a conserved region in the TTV genome. FINDINGS: TTV viraemia was detected in 19 (1.9%) of 1000 non-remunerated regular blood donors. Infection occurred more frequently in older donors (mean age 53 years), compared with the age prolife of donors infected with hepatitis C virus and other parenterally-transmitted viruses. TTV contamination was found in ten (56%) of 18 batches of factor VIII and IX concentrate manufactured from such non-remunerated donors, and in seven (44%) of 16 batches of commercially available products. Whereas solvent or detergent treatment had little effect on the detection of TTV in factor VIII and IX by PCR, this virucidal step seemed to inactivate TTV infectivity. TTV infection was detected in four (19%) of 21 patients with FHF; in three cases, infection was detected at the onset of disease and could thus not be excluded from its aetiology. INTERPRETATION: TTV viraemia is frequent in the blood-donor population, and transmission of TTV through transfusion of blood components may have occurred extensively. Clinical assessment of infected donors and recipients of blood and blood products, and assessment of TTV's aetiological role in hepatic and extra-hepatic disease, are urgently needed.

Adult↗
PubMed1998

Effect of blood transfusion on survival after esophagogastrectomy for carcinoma.

BACKGROUND: There is growing evidence that blood transfusion is associated with clinical factors that can lead to transfusion-induced immunosuppression. This effect can be beneficial or deleterious. METHODS: The effect of perioperative allogeneic blood transfusion on survival was studied retrospectively in 524 patients who were discharged from the hospital after esophagogastrectomy for carcinoma performed in a single unit over a 10-year period. RESULTS: The median operative blood loss for the series was 500 mL (range, 50 to 3,750 mL). Three hundred thirty-five patients (64%) received a perioperative allogeneic blood transfusion related to esophagogastrectomy, and 189 (36%) did not. The median perioperative blood transfusion administered was 900 mL (range, 300 to 12,950 mL). Perioperative allogeneic blood transfusion was associated with reduced survival for patients in stage III (p < 0.05) at 1 year, but no significant difference was found in this stage at 3 or 5 years after resection. Stage III disease accounted for 250 (48%) of the 524 patients discharged. CONCLUSIONS: Although perioperative allogeneic blood transfusion does not affect long-term survival after esophagogastrectomy for carcinoma, it does have a significant association with short-term survival in a group whose overall survival is often limited after resection. Attention should be directed toward minimizing operative blood loss and transfusing only for factors known to be clinically important, such as oxygen delivery and hemodynamics, not arbitrary hemoglobin levels.

Adenocarcinoma↗
PubMed1998

Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C.

This look-back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion-transmitted HCV infection acquired in the neonatal period. A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti-D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994-95; the past donations of five of the donors, who had received anti-D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994-95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined. Twenty-one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti-HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis. The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.

Adolescent↗
PubMed1998

Prevalence, incidence, and clinical characteristics of hepatitis G virus/GB virus C infection in Scottish blood donors.

The prevalence, incidence, clinical features, and natural history of hepatitis G virus (HGV) or GB virus C (GBV-C) were investigated in a non-remunerated blood donor population to determine its clinical significance and its impact on blood safety. Of 1020 regular blood donors, 23 (2.25%) were positive for plasma HGV/GBV-C RNA. Alanine aminotransferase levels were lower than in uninfected donors (median, 20 IU/mL; 32 IU/mL in controls; P=.015). Clinical examination produced no other evidence for hepatitis or for shared nonhepatic diseases. Fifteen of 17 donors excreted HGV/GBV-C in saliva (mean level, 8x103 copies of RNA/mL). Testing of previous donations indicated an incidence of 170-200 new infections with HGV/GBV-C per 100,000 donor-years. The absence of further clinicopathologic data and the limitations of current polymerase chain reaction-based methods for screening suggests that it is neither necessary nor practical to commence screening.

Adult↗
PubMed1998

Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort.

The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed.

Amino Acid Sequence↗
PubMed1997

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↗
PubMed1997

The origin of hepatitis C virus genotypes.

For many RNA viruses, relatively recent times of origin of extant viruses are implied by the high rate of substitution observed in longitudinal studies. However, extrapolation of short-term rates of substitution can give misleading estimates of times of divergence. We show here that the common ancestor of different types of hepatitis C virus (HCV) is older than previously thought. The rate of HCV sequence change was measured amongst a cohort of individuals infected following administration of anti-D immunoglobulin. Virus sequences were obtained in the E1 and NS5B genes and compared with each other and with sequences from an infective batch. Taking account of the bias towards synonymous transition substitutions, the time of divergence of variants of subtype 1b is estimated to have occurred 70-80 years ago. The numerous subtypes of HCV are proposed to derive from more than 300 years of endemic infection in certain geographical regions, with recent spread of some subtypes to other parts of the world. Estimation of the time of origin of the major HCV genotypes (types 1-6) is problematic, but our data and analogy with other viruses suggest that divergence occurred at least 500-2000 years ago.

Antibodies, Anti-Idiotypic↗
PubMed1997

Use of intravenous immunoglobulin to prevent or treat infections in persons with immune deficiency.

Intravenous immunoglobulin (IVIG) concentrates were originally developed as replacement therapy for individuals with primary deficiencies of the immune system. However, in various well-designed, controlled clinical trials, the ability of IVIG to prevent and possibly treat infections in patients with secondary immune deficiencies has also been considered. In this review, we briefly consider these different applications and suggest whether the data are sufficient to employ IVIG in these clinical settings.

Acquired Immunodeficiency Syndrome↗