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Biomedical subjects

H C Gooi

Publications and source records attributed to H C Gooi.

At least 19 recordsLinked to original sources
PubMed2007

Low gammaglobulin subclass 2 levels in paediatric cystic fibrosis patients followed over a 2-year period.

The aim of this study was to relate serum immunoglobulin G2 subclass levels in a large paediatric population with cystic fibrosis, to clinical status and antibody levels to Haemophilus influenzae type b and Streptococcus pneumoniae and to observe any changes over a 2-year period. IgG subclasses were measured in 131 patients. Results were compared with levels from age-related normal population data. The following clinical data were collected at baseline and 2 years later; genotype: height, weight, and BMI z-scores: FEV1 (as percent predicted): Shwachman-Kulczcyki and Northern chest X-ray scores: Pseudomonas aeruginosa status. Antibody levels to H. influenzae type b and S. pneumoniae measured at baseline were related to IgG2 level. There was a reduction in the prevalence of low levels of IgG2 from 29% to 10% over the 2-year period. Low levels of IgG2 were not associated with any decline in clinical well-being. Low levels of IgG2 alone were associated with low antibody levels to S. pneumoniae. Low levels of IgG2 and low levels of antibody to H. influenzae and S. pneumoniae were not associated with any decline in clinical well-being. Children with high levels of IgG2 had worse lung function, worse Shwachman-Kulczcyki and Northern chest X-ray scores and higher levels of P. aeruginosa infection. Children with low IgG2 levels were not worse clinically compared to those with normal or high IgG2 levels. High IgG2 levels were associated with a worse clinical status.

Adolescent↗
PubMed2006

The measurement of whole blood pre-treatment cyclosporine A: metabolite ratios predicts the onset of renal dysfunction in recipients of allogeneic stem cell transplantation.

BACKGROUND: In the context of post-transplant immunosuppression, cyclosporine A (CSA) is dose adjusted in accordance with whole blood drug monitoring. While currently available immunoassay systems primarily target the parent drug, cross-reactivity results in the detection of the major circulating CSA metabolites, though their contribution to both immunosuppression and toxicity remain unclear. This study examines the relationship of CSA metabolites to hepatic and renal dysfunction and the incidence of graft-versus-host disease (GvHD) through parallel assaying of parent drug and drug/metabolites expressed as a metabolite ratio (Cp:mR). METHOD: Sequential pre-treatment (trough) whole blood samples (n=527) were collected from 31 allo-stem cell transplantation (SCT) recipients. Both parent drug and drug/metabolite levels were determined using the Abbott fluorescence polarization immunoassay. RESULTS: The average mean Cp:mR was significantly higher in patients with hepatic (P=0.004) and renal dysfunction (P=0.004) than in those without. Significantly higher Cp:mR were also found in patients with grades II-IV GvHD (P=0.001) than were observed in patients who did not experience significant GvHD. When measured prospectively, an increasing Cp:mR predated the rise in serum creatinine concentration by a median of two weeks. CONCLUSIONS: This study demonstrates a clinically useful CSA metabolite ratio that shows association with hepatic and renal dysfunction and with GvHD. The measure can be used to predict those patients on CSA therapy who are likely to develop renal dysfunction.

Adolescent↗
PubMed2005

Immunoglobulin and IgG subclass levels in a regional pediatric cystic fibrosis clinic.

The aim of this study was to report serum immunoglobulin (Ig) and IgG subclass levels in a large pediatric population with cystic fibrosis, and relate these to measures of disease severity. Total immunoglobulin levels were measured in 154 patients, and IgG subclass levels were measured in 136 patients and compared to age-related normal population data and to levels reported in previously published studies of children with cystic fibrosis. Clinical data were also collected: genotype; height, weight, and BMI standard deviation scores; FEV(1) (as percent predicted); Shwachmann-Kulczycki (S-K) and Northern chest X-ray scores; and Pseudomonas aeruginosa infection status. The clinical well-being of patients with hypo- or hyper-gammaglobulinemia was compared with age- and sex-matched control patients who had normal levels of gammaglobulin. IgG subclass levels were measured, and the results were compared with previous studies. Eleven patients had hypergammaglobulinemia (7.8% compared with 0-69% in the published literature). Patients with hypergammaglobulinemia had lower FEV(1) percent-predicted values, and worse S-K and Northern chest X-ray scores than controls. Three patients had hypogammaglobulinemia (1.9% compared with 0-10.8% in the published literature). There was no difference in any clinical parameter between controls and those with hypogammaglobulinemia. Nineteen patients (14%) had low levels of IgG1, and 40 patients (29%) had low levels of IgG2. The low percentage of patients with abnormally high immunoglobulin levels probably reflects the improved respiratory status of today's children with CF. The low percentage of those with low IgG probably reflects better nutritional status. The finding of worse lung function and clinical scores in patients with hypergammaglobulinemia agrees with the published literature. The high percentage of patients with low IgG2 was unexpected and was not previously reported. The clinical significance of this in patients with CF is unknown.

Adolescent↗
PubMed2004

Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection.

AIMS: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation. METHODS: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590. RESULTS: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection. After stratification for human leucocyte antigen (HLA) matching, it was found that kidneys from donors positive for the TNFA-A allele had a significantly increased incidence of acute rejection in HLA-DR mismatched transplants. CONCLUSIONS: This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.

Acute Disease↗
PubMed2001

Does the shared epitope genotype influence either the susceptibility to or the phenotype of corneal melting?

PURPOSE: To investigate the role of the shared epitope alleles in determining susceptibility to and the phenotype of corneal melting in patients with rheumatoid arthritis (RA). METHODS: The HLA class 1 and 2 genotype was determined for 17 patients with rheumatoid-associated comeal melting by the phototyping method. HLA-DR4 subtyping was performed by PCR sequence-based typing. The frequency of all the shared epitope alleles and, in particular, of the higher-risk *0401 and *0404 alleles, was compared with healthy controls and unrelated RA patients, with and without extra-articular manifestations. A comparison was also made between the shared epitope genotype of the corneal melt patients and local, ocular disease characteristics. RESULTS: Thirteen (76%) patients with corneal melt possessed at least one shared epitope allele and 5 (29%) possessed two alleles. The dominant alleles were variants of the DR4 family, notably the *0401, *0404 and *0408 alleles. Both the allele frequency and a double dose of shared epitope alleles were more common in the three RA patient groups than in the healthy, control group (p < 0.005). Although the frequency of the higher-risk alleles was similar in the three RA patient group, a trend existed for a double dose of higher-risk alleles to be more common in the patients with either corneal melt or other extra-articular manifestations (p > 0.2). No association was found between the number or type of shared epitope alleles and any of the ocular disease characteristics studied. CONCLUSIONS: The results of this study suggest that the shared epitope alleles do not influence the ocular disease phenotype of corneal melt in RA patients. Shared epitope determination of RA patients may help to identify those susceptible to either corneal melt or other extra-articular disease. RA patients with a double dose of higher-risk alleles may have an increased risk of corneal melt.

Alleles↗
PubMed2001

The carriage of pro-inflammatory cytokine gene polymorphisms in recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects 2-4% of couples, and remains largely unexplained. Recent studies have examined the role of cytokines in the maintenance of normal pregnancy, which is linked with an increased expression of Th2 cytokines. Overexpression of Th1 cytokines is associated with RPL. Knowing that functional polymorphisms exist for certain cytokines, it has therefore been suggested that women with RPL may have a genetic predisposition to overexpress Th1 cytokines. METHOD OF STUDY: The genes for interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) carry functional gene polymorphisms. In both cases these are biallelic polymorphisms that can be detected by polymerase chain reaction followed by restriction fragment length polymorphism. The aim of this pilot study was to assess whether carriage of the rarer alleles (TNF*2 and IL-1B*2) could act as independent risk factors in recurrent miscarriage. RESULTS: We found an increased incidence in the carriage of TNF*2, more pronounced in those women with two or more miscarriages. Carriage of the IL-1B*2 either alone or in association with TNF*2 was not associated with recurrent miscarriage. CONCLUSION: There may be a role for these cytokine gene polymorphisms in RPL.

Abortion, Habitual↗
PubMed2000

Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups.

OBJECTIVE: To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA). METHODS: This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls). RESULTS: The FcgammaRIIIA-158V/F polymorphism was associated with RA in both ethnic groups (P = 0.028 for UK Caucasians, P = 0.050 for North Indians and Pakistanis, and P = 0.003 for both groups combined). FcgammaRIIIA-158VF and -158W individuals had an increased risk of developing RA in both populations (UK Caucasians odds ratio [OR] 1.6, P = 0.050; North Indians and Pakistanis OR 1.9, P = 0.023; and combined groups OR 1.7, P = 0.003). In the UK Caucasian group, the highest risk was for nodular RA, a more severe disease subset, associated with homozygosity for the FcgammaRIIIA-158V allele (OR 4.4, P = 0.004). There was also evidence for an interaction between the RA-associated HLA-DRB1 allele and the presence of at least 1 FcgammaRIIIA-158V allele in predicting susceptibility to RA (OR 5.5, P = 0.000). CONCLUSION: We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.

Alleles↗
PubMed2000

Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.

The major cause of mortality in patients with cystic fibrosis (CF) is lung disease. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in the airways is a potential treatment. Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in modest, transient gene expression. It seems likely that repeated administration of the gene transfer vector will be required for long-term gene expression. We have undertaken a double-blinded study in which multiple doses of a DNA/liposome formulation were delivered to the nasal epithelium of CF patients. Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes, whilst two subjects received placebo. Each subject received three doses, administered 4 weeks apart. There was no evidence of inflammation, toxicity or an immune response towards the DNA/liposomes or the expressed CFTR. Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated nasal potential difference (PD) measurements. On average, six of the treated subjects were positive for CFTR gene transfer after each dose. All subjects positive for CFTR function were also positive for plasmid DNA, plasmid-derived mRNA and CFTR protein. The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered without apparent loss of efficacy.

Adolescent↗
PubMed2000

No strong association between alleles of tumour necrosis factor alpha and interleukin-1 receptor antagonist and corneal melting associated with systemic vasculitis.

AIMS: To investigate polymorphism within the tumour necrosis factor alpha (TNF-alpha) promoter region and within the interleukin-1 receptor antagonist (IL-1Ra) gene in a group of patients with vasculitis associated corneal melting. METHODS: The polymorphic regions at position -308 on the TNF-alpha promoter region and in intron 2 of the IL-1Ra gene were amplified by the polymerase chain reaction (PCR). The resultant products were separated by electrophoresis on agarose gels and visualised by ethidium bromide staining. Genotype and allele frequencies for the 20 patients were compared with healthy controls from the same geographical area. RESULTS: The allele frequencies in the patient and control groups respectively for the TNF-alpha and IL-1Ra sites studied were as follows: TNF1, 82.5% and 80.2%; TNF2, 17.5% and 19.8%; IL-1Ra*1, 82. 5% and 78.3%; IL-1Ra*2, 15% and 20%; IL-1Ra*3 2.5% and 1.5%. Although there was a trend for the IL1Ra*2 allele to be more common in the control group, no allele was found to have a statistically significantly association with the patient group: TNF1 p = 0.89; TNF2 p = 0.89; IL-1Ra*1 p = 0.65; IL-1Ra*2 p = 0.68; IL-1Ra*3 p= 0. 50. CONCLUSIONS: The results suggest that the polymorphic alleles of TNF-alpha and IL-1Ra studied play little or no part in the susceptibility to corneal melting among these patients with systemic vasculitis.

Alleles↗
PubMed1997

The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid arthritis.

The production of superoxide by the peripheral blood neutrophils of 19 patients with active rheumatoid arthritis was measured during treatment with sulphasalazine (SASP). The response to drug treatment was determined by change in plasma viscosity, CRP, early morning stiffness and articular index over a 10-point scale. Of the 19 patients studied, eight were considered to have responded well to SASP and seven to have responded poorly or not at all. Over the treatment period, plateau levels of superoxide production fell in seven of the eight responders (P = 0.028) compared with a non-significant fall in 3/7 of the non-responder groups. The initial rate of superoxide production also fell in the responder group, but this was not statistically significant. Initial values in both the responder and non-responder groups were comparable with those seen for normal controls. Analysis of drug levels showed all patients to be compliant with drug treatment; however, drug levels and neutrophil activity were not correlated. Studies of the effect of SASP and sulphapyridine on superoxide production in vitro showed no difference between good and poor responders. These results suggest that there is no inherent difference between good and poor responders regarding the susceptibility of their neutrophils to SASP. SASP's action on neutrophils, therefore, appears not to be its main mechanism of disease-modifying activity in RA.

Antirheumatic Agents↗
PubMed1996

An assessment of the comparative utility of functional and molecular level analyses in the investigation of patients with thrombophilia.

Aim-To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia.Methods-Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method.Results-Low APCR ratios do not necessarily predict possession of the Leiden mutation. Conversely, normal ratios do not exclude the mutation. Of 14 individuals with low APCR ratios, the Leiden mutation was absent in five. Of the remainder, three were heterozygous and six homozygous. Of nine heterozygote individuals, only three had low APCR ratios. All patients homozygous for the defect had low APCR ratios.Conclusions-These results lend further weight to the hypothesis that the APC resistant phenotype results from more than one genetic defect and indicate the value of combined functional and molecular investigations in all patients with thrombophilia.

Journal Article↗
PubMed1994

Bedside filtration of blood products in the prevention of HLA alloimmunization--a prospective randomized study. Alloimmunisation Study Group.

To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cells and platelets. Quality control of bedside filtration was explored by sequential sampling downstream of the filter, but this did not predict the total number of leucocytes transfused. After exclusions, 123 evaluable patients were assessed every two weeks until the end of therapy. HLA antibodies developed in 21 of 56 (37.5%) nonfilter (NF) and 15 of 67 (22%) filter (F) patients (risk ratio estimate, 0.60 [95% confidence interval, 0.34 to 1.05]; P = .07). Patients with acute myeloid leukemia (AML; n = 53) had higher alloimmunization rates in both arms of the study, with a greater effect of filtration (62.5% NF and 31.0% F; P = .025). Bedside filtration did not affect the overall incidence of febrile transfusion reactions (FTRs; 37% NF and 34% F; P = .71) or of platelet refractoriness assessed in 50 patients (30% NF and 26% F), despite an association between broad HLA reactivity and both FTRs and refractoriness. However, FTRs were also seen in 28 patients without HLA antibodies. Five alloimmunized refractory patients (2 F and 3 NF) required HLA-selected platelets. This report, the first prospective study of bedside filtration, has failed to show clear clinical benefit. Methodological limitations may account in part for this failure, notably the difficulties in accurately assessing the number of leucocytes transfused.

Adolescent↗
PubMed1993

Sequential study of bacterial antibody levels and faecal flora in rheumatoid arthritis patients taking sulphasalazine.

Faecal and serum samples were collected from 31 patients with active RA during treatment with DMARD sulphasalazine (SASP). These were examined for changes in faecal flora and antibodies to bacterial antigens respectively. Faecal counts of Clostridium perfrigens but not Escherichia coli or total aerobic or anaerobic counts fell significantly after 2 weeks of treatment, this decrease being maintained throughout the treatment period. There was, however, no relationship between changes in the faecal carriage of this micro-organism and response to drug treatment, as assessed using clinical and biochemical indicators of disease activity. Changes in antibody levels to antigen preparations of this organism were also unrelated to response to drug treatment. These results suggest that the anti-rheumatic properties of SASP are independent of its antibacterial effect on bacteria in the bowel and also that neither faecal carriage of, nor antibody responses to this bacterium are involved in disease pathogenesis. Antibody levels to an antigen preparation of Cl. perfringens were found to be significantly lower in those patients who respond well to SASP than those patients who show poor response; this may prove useful as a clinical marker for predicting those patients likely to respond to SASP therapy.

Adult↗