ABSTRACT
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.
Subject(s)
Cyclosporine/blood , Fluorescence Polarization Immunoassay/methods , Kidney Diseases/blood , Stem Cell Transplantation , Adolescent , Adult , Child , Child, Preschool , Cyclosporine/metabolism , Cyclosporine/therapeutic use , Drug Monitoring/methods , Female , Graft vs Host Disease/blood , Graft vs Host Disease/diagnosis , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/therapeutic use , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Liver Diseases/blood , Liver Diseases/diagnosis , Liver Diseases/physiopathology , Male , Middle Aged , Reproducibility of ResultsABSTRACT
A highly sensitive and specific immunoradiometric assay, based upon a monoclonal antibody, was used to measure interferon-alpha (IFN-alpha) in the cerebrospinal fluid (CSF) of patients with central nervous system infections and in controls with non-infectious neurological disorders. IFN-alpha was detected in all 21 patients with viral meningitis but in only one of four patients with non-viral aseptic meningitis. It was also present in the CSF of three of four patients with herpes encephalitis and five of seven patients with acute bacterial meningitis. By contrast, IFN-alpha was present in the CSF in low concentrations in only five (7%) of 71 neurological controls. This rapid test is positive in viral meningitis and may help in distinguishing viral infection from other causes of aseptic meningitis. It is usually negative in non-infective disorders but will not distinguish between viral and bacterial infections.
Subject(s)
Encephalitis/diagnosis , Interferon Type I/cerebrospinal fluid , Meningism/diagnosis , Meningitis, Viral/diagnosis , Meningitis/diagnosis , Adolescent , Adult , Bacterial Infections/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Male , Meningitis, Aseptic/diagnosis , Middle Aged , Predictive Value of Tests , RadioimmunoassayABSTRACT
Interferon gamma (IFN-gamma) was measured in the CSF of neurological patients using a highly specific and sensitive immunoradiometric assay. It was detected in 52% of patients presenting as suspected meningitis or encephalitis and in 83% with proven viral meningitis. In contrast IFN-gamma was detected in only 26% of patients who did not have an acute infection at the time of presentation. Only 15% of patients with multiple sclerosis had detectable CSF IFN-gamma. The presence of IFN-gamma in CSF in response to acute viral infections of the central nervous system may be of importance in relation to the pathophysiology of immunologically mediated neurological disorders.
Subject(s)
Interferon-gamma/cerebrospinal fluid , Nervous System Diseases/cerebrospinal fluid , Encephalitis/cerebrospinal fluid , Humans , Meningitis/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Neuromuscular Diseases/cerebrospinal fluid , Polyradiculoneuropathy/cerebrospinal fluid , RadioimmunoassayABSTRACT
It has been suggested that patients with cystic fibrosis have abnormal immune responses to foods. We have measured IgE antibodies to inhalants and foods (by RAST) in 105 patients with cystic fibrosis aged between 8 months and 28 years. Serum IgE was elevated (greater than 180 kU/l) in 21 patients. In 43, IgE antibodies were detected in serum. The majority of positive results were with house-dust mite, grass pollen or Aspergillus. Only four of the patients had a positive RAST to a food--one to milk, one to wheat and two to egg. On the basis of high serum IgE or positive RAST results, 44.8 per cent of the patients were atopic and the frequency of atopy was age-related, being higher in patients aged 4 years or more. However, the presence of food antibodies was unrelated to age. This study confirms the high prevalence of atopy in patients with cystic fibrosis but unequivocally demonstrates that the presence of IgE antibodies to foods in their serum is rare.
