Infectious, genetic factors, and autoimmunity have been considered as potential causes of sarcoidosis (SA). Pathological similarities between SA and tuberculosis (TB) suggest M. tuberculosis ...antigen(s) as causative agent(s). Our published comparative analysis of the human leukocyte antigens (HLA) system in patients with SA or TB in the same ethnic group revealed that some antigens were connected with high risk of developing of SA or TB, but other were comparable in both patient populations. Is it possible that the predominating occurrence of HLA antigens characteristic for TB may cause tuberculosis in patients with SA? To answer this question we evaluated the HLA class I and II alleles frequency by PCR amplification with sequence-specific primers in three women with histopathologically proven pulmonary SA, who developed bacteriologically confirmed TB on a corticosteroids (CS) therapy. Analysis of HLA in every case separately revealed a trend for higher occurrence of both alleles predisposing and protecting from TB than SA, in comparison with healthy individuals in our previously mentioned HLA genotyping study. Overall, the number of alleles predisposing to TB was statistically greater than the number of alleles connected with a high risk of developing SA. Also, the frequency of protecting alleles was statistically higher for TB than for SA. Therefore, SA in these patients developed at first, and the presence of additional environmental factors, e.g., age, CS might decrease an immune response and provoked TB. There is a possibility that the occurrence of HLA antigen more associated with high risk of developing TB than SA causes the development of tuberculosis in our patients with sarcoidosis.
Abstract
Background
Azathioprine (AZA) is an immunosuppressive drug, which is metabolised in the liver and kidneys into 6-thioguanine- the form responsible for the therapeutic effect. Despite its ...anti-inflammatory, antibacterial and immunomodulating properties, azathioprine has also dose-related side effects, such as bone marrow suppression, liver damage and pancreatitis. The purpose of this study was to assess the usefulness of monitoring the concentration of azathioprine metabolites: 6-tioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in the group of paediatric patients with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).
Methods
The clinical data of 46 paediatric patients (24 girls) with IBD and AIH, aged 8–17 years, hospitalised in the Department of Gastroenterology, who had undergone a blood examination for AZA metabolites concentration, were analysed.
Results
Initial mean dose of azathioprine was 1.23 mg/kg/day in IBD and 1.16 mg/kg/day in AIH. In 30% of patients, the concentrations of 6-TG and 6-MMP were within the normal range. Forty-eight per cent of patients required a dose change due to: elevated 6-TG concentration (32.6%) or underdosage (15.4%). After modification the mean dose was 1.16 mg/kg/day in IBD and 0.85 mg/kg/day in AIH. In 10.7 % of patients, the concentrations of 6-TG and 6 MMP were below the proper range, in the same percentage of patients metabolites were undetectable.
Conclusion
In a significant number of cases monitoring the concentration of AZA metabolites indicated the necessity to reduce the dose of AZA allowing to achieve the therapeutic optimum and prevent serious side effects. Receiving undetectable concentration of metabolites is a sign of non-compliance. The final doses of AZA were found to be lower than the recommended doses. Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels is a good strategy that can be used to optimise IBD and AIH therapeutics.
The intra- and inter-observer variability in delineation of the parotids on the
kilo-voltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) were
examined to establish their ...impact on the dose calculation during adaptive head and neck
helical tomotherapy (HT). Three observers delineated left and right parotids for ten
randomly selected patients with oropharynx cancer treated on HT. The pre-treatment kVCT
and the MVCT from the first fraction of irradiation were selected to delineation. The
delineation procedure was repeated three times by each observer. The parotids were
delineated according to the institutional protocol. The analyses included intra-observer
reproducibility and inter-structure, -observer and -modality variability of the volume and
dose. The differences between the left and right parotid outlines were not statistically
significant (p > 0.3). The reproducibility of the delineation was
confirmed for each observer on the kVCT (p > 0.2) and on the MVCT
(p > 0.1). The inter-observer variability of the outlines was
significant (p < 0.001) as well as the inter-modality variability
(p < 0.006). The parotids delineated on the MVCT were 10% smaller
than on the kVCT. The inter-observer variability of the parotids delineation did not
affect the average dose (p = 0.096 on the kVCT and p =
0.176 on the MVCT). The dose calculated on the MVCT was higher by 3.3% than dose from the
kVCT (p = 0.009). Usage of the institutional protocols for the parotids
delineation reduces intra-observer variability and increases reproducibility of the
outlines. These protocols do not eliminate delineation differences between the observers,
but these differences are not clinically significant and do not affect average doses in
the parotids. The volumes of the parotids delineated on the MVCT are smaller than on the
kVCT, which affects the differences in the calculated doses.
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