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Biomedical subjects

R Ameratunga

Publications and source records attributed to R Ameratunga.

14 recordsLinked to original sources
PubMed2004

Increased risk of adverse events when changing intravenous immunoglobulin preparations.

Intravenous immunoglobulin (IVIG) therapy has represented a major advance in the treatment of patients with primary immune deficiency disorders. In September 2000 a new IVIG formulation, Intragam P, was introduced into clinical use. Intragam P is prepared by delipidation of pooled plasma followed by an ion exchange chromatography step to eliminate immunoglobulin aggregates. It is then pasteurized for 10 h at 60 degrees C for viral inactivation before storage at pH 4.25 in 10% maltose. We report initial clinical experience with this new preparation. The details of adverse reactions of patients who received the new preparation were gathered shortly after it became apparent there was a change in IVIG formulation. Seven of 49 patients receiving Intragam P spontaneously reported adverse effects, which were temporally related to infusions. Subsequently, all seven patients have been able to tolerate the product with prophylactic use of antihistamines and paracetamol. This case series indicates that long-term tolerance of an older IVIG product does not necessarily equate to tolerance to a newer product, even if technically superior. Caution should be exercised when changing IVIG products, as they are not biologically equivalent.

Adult↗
PubMed2000

The kinetics of CD154 (CD40L) expression in peripheral blood mononuclear cells of healthy subjects in liver allograft recipients and X-linked hyper-IgM syndrome.

UNLABELLED: The costimulatory pathways play a key role in T cell activation during allograft rejection (AR). Inhibition of the T cell costimulatory molecule CD154 (CD40 ligand) has been effective in producing long-term allograft survival in rodents and non-human primates. The role of the CD40-CD154 pathway in human orthotopic liver transplantation (OLT) has not been examined. AIM: To describe the patterns of CD154, CD69 and CD152 (CTLA4) expression in OLT recipients and to determine their temporal relationship to AR. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 OLT allograft recipients just prior to and for seven consecutive days postoperatively. Gene and protein expression of CD154, CD69 and CD154 were examined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FC), respectively. RESULTS: FC failed to demonstrate an up-regulation of CD154 and CD152 protein expression during the first postoperative week. Intracellular FC did not increase the sensitivity. There was an increased level of CD3+ CD8+ T cells expressing CD69 at the time of rejection compared to that on day 0. RT-PCR demonstrated a sporadic expression of CD154 and CD69 mRNA, with no correlation to episodes of acute cellular rejection. In vitro stimulation of PBMCs revealed an impaired up-regulation of CD154 in patients receiving conventional immunosuppression compared to healthy controls. The assays were validated using positive and negative controls, including a family with X-linked hyper-IgM syndrome. CONCLUSION: We found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Immunosuppression resulted in impaired responses to ex vivo stimulation. Lymphocyte costimulatory pathways play a critical role in mediating acute allograft rejection. However, we found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Furthermore, stimulation in vitro resulted in less up-regulation of CD154 than for healthy controls.

Abatacept↗
PubMed2000

The simultaneous presentation of sarcoidosis and common variable immune deficiency.

Sarcoidosis and common variable immune deficiency can rarely present simultaneously in the same individual. We describe a child who presented with both disorders. The diagnosis of sarcoidosis was delayed because of the atypical appearances of the liver biopsy. She failed to respond to intravenous immunoglobulin but improved once cyclosporin and corticosteroids were added to her treatment regimen. It is important that the co-existence of both disorders is recognised so that treatment with a combination of intravenous immunoglobulin and immunosuppression can be in instituted to treat both the immune deficiency as well as the granulomatous disorder. As illustrated here, patients may fail to respond if either modality is used alone.

Child, Preschool↗
PubMed1998

Molecular analysis of the third component of canine complement (C3) and identification of the mutation responsible for hereditary canine C3 deficiency.

Genetically determined deficiency of the third component of complement (C3) in the dog is characterized by a predisposition to recurrent bacterial infections and to type 1 membranoproliferative glomerulonephritis. The current studies were undertaken to characterize the cDNA for wild-type canine C3 and identify the molecular basis for hereditary canine C3 deficiency. Amplification, cloning, and sequence analysis indicated that canine C3 is highly conserved in comparison with human, mouse, and guinea pig C3. Southern blot analysis failed to show any gross deletions or rearrangements of DNA from C3-deficient animals. Northern blot analysis indicated that the livers of these animals contain markedly reduced quantities of a normal length C3 mRNA. The full-length 5.1-kb canine C3 cDNA was amplified in overlapping PCR fragments. Sequence analysis of these fragments has shown a deletion of a cytosine at position 2136 (codon 712), leading to a frameshift that generates a stop codon 11 amino acids downstream. The deletion has been confirmed in genomic DNA, and its inheritance has been demonstrated by allele-specific oligonucleotide hybridization.

Amino Acid Sequence↗
PubMed1997

Defective antigen-induced lymphocyte proliferation in the X-linked hyper-IgM syndrome.

We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.

Antigens↗
PubMed1996

Molecular pathology of the X-linked hyper-immunoglobulin M syndrome: detection of wild-type transcripts in a patient with a complex splicing defect of the CD40 ligand.

The X-linked hyper-immunoglobulin M syndrome (XHIM) is a primary immune deficiency disorder characterized by an inability to produce immunoglobulin isotypes other than immunoglobulin M (IgM) and IgD. Recently, a B-cell surface antigen (CD40) and its conjugate T-cell counterstructure (CD40 ligand) were shown to mediate immunoglobulin isotype switching in the presence of cytokines such as interleukin 4. Most patients with XHIM have been shown to have mutations of the extracellular domain of the CD40 ligand. Here we describe a novel point mutation of an intronic splice acceptor site which results in a complex splicing defect of the CD40 ligand in a patient with XHIM. In addition to two species of deleted transcripts, wild-type transcripts were also detected in this individual. The demonstration of wild-type CD40 ligand transcripts may be an explanation for previous observations suggesting that some XHIM patients are able to undergo immunoglobulin isotype switching in vivo.

Adolescent↗
PubMed1996

Repertoire of transcribed peripheral blood T-cell receptor beta chain variable-region genes in acute rheumatic fever.

Patients with severe group A streptococcal infections have abnormalities in the Vbeta repertoire of peripheral blood T cells that are consistent with superantigen stimulation by cytoplasmic membrane proteins. The purpose of this study was to determine whether similar changes in Vbeta repertoire could be found for patients with acute rheumatic fever (ARF). The mean Vbeta repertoire of peripheral blood T cells in nine hospitalized ARF patients was similar to that of 34 controls and did not change during 6 months of follow-up in 6 of the ARF subjects. We were unable to detect changes in the Vbeta repertoire of peripheral blood T cells from patients with ARF that could be attributed to the influence of a superantigen.

Acute Disease↗
PubMed1994

A survey of wasp sting injuries in urban Auckland from December to April in 1991/2 and 1992/3.

AIM: To determine the numbers and the seasonal variations in patients seeking medical consultation for wasp sting injuries in urban Auckland. METHOD: A monthly record of the number of people seeking treatment for wasp stings was kept by 50 general practitioners from 18 medical centres and accident and emergency departments from three hospitals in urban Auckland. RESULTS: From December to April, 47 people in 1991/2 and 49 in 1992/3 received treatment for wasp sting injuries from the family practitioners surveyed. In addition, 27 people and 35 people received treatment at the three accident and emergency clinics over the same time period in 1991/2 and 1992/3 respectively. Paper wasps were found to be responsible for the majority of the sting injuries reported. CONCLUSION: Our data indicates that wasp stings have a significant impact on the health of the Auckland population and indicates the urgent need for more detailed studies in other parts of New Zealand.

Animals↗
PubMed1993

The regulation of IgG4. 1. An immunoassay to detect bee venom specific IgG4 subclass levels.

Serum IgG consists of 4 subclasses designated IgG1-4. IgG subclasses have differing structures and different functions. The levels of antigen specific immunoglobulin in each of the subclasses is difficult to quantitate accurately but may be of significant diagnostic and therapeutic value. IgG4 constitutes approximately 4% of total IgG level in the serum. We describe an immunoassay which is highly sensitive and specific for IgG4 directed against bee venom. The assay can be performed in a routine diagnostic laboratory enhancing its value as a clinical tool. It is potentially useful in identifying patients who fail to respond to standard immunotherapy with bee venom. This immunoassay format can also be adapted to other antigens.

Allergens↗
PubMed1988

The alveolar carbon monoxide uptake fraction: a simple, alternative measure of carbon monoxide transfer.

The measurement and interpretation of "diffusing capacity" by either single-breath or steady-state methods are complicated by both technical and conceptual difficulties. The CO uptake fraction is less complex but, as originally described, it is unacceptably sensitive to dead-space ventilation. A modification (the "alveolar CO uptake fraction", UA) largely removes this factor. We have measured UA in thirteen healthy subjects and 100 patients with a variety of pulmonary disorders. It is reproducible and appears sensitive to clinical abnormality. Its technical and interpretative simplicity suggest its use as an alternative to other measures of CO transfer.

Carbon Monoxide↗