Idiosyncratic reactions are the most common cause of abnormal liver function tests in patients with cystic fibrosis.

BACKGROUND: Beta-lactam antibiotic-related liver enzyme derangement can limit treatment options for infective exacerbations in cystic fibrosis (CF) bronchiectasis. AIM: To identify risk factors for elevated liver function tests (LFT) in CF patients receiving parenteral antibiotics. METHODS: All patients attending The Prince Charles Hospital (TPCH) Adult CF Centre in 2012 were identified using the CF Research Database and CF Data Registry. Biochemistry and haematology panels between 1 January 2012 and 31 December 2012 for each patient were retrieved from Queensland Health Pathology and private pathology providers. Patients with LFT more than three times the upper limit of normal were identified. For each laboratory test, concurrently administered antibiotic(s) were analysed from TPCH pharmacy dispensing system for patients who received intravenous (IV) antibiotic treatment. RESULTS: Abnormal liver enzymes were evident in significantly more patients receiving IV antibiotics than patients who did not (43% vs 18%, P < 0.001). Pre-existing CF-related liver disease and total IV antibiotic treatment days were not associated with abnormal LFT. Higher C-reactive protein and peripheral eosinophil counts were not more common in patients with abnormal LFT. Male sex, poorer lung function and lower leucocyte counts were associated with abnormal LFT; however, these variables only explained 4.2% of the variance in the multivariable logistic model. CONCLUSION: Elevated LFT are common during IV antibiotic treatment in CF. Although specific antibiotic exposure may contribute to abnormal LFT in a minority of cases, our study demonstrates that antibiotic-induced liver injury is largely idiosyncratic and unpredictable.

Stage I seminoma in a 15-year-old boy.

Seminomas are very rare tumours in children and adolescents. We describe a case of seminoma in a 15-year-old boy who was managed with orchidectomy but no adjuvant therapy. He remains relapse-free 8 years after surgery as determined by clinical, radiological and serological surveillance. This study emphasizes the uncertainty over the need for adjuvant treatment in the management of seminoma in the adolescent patient, in particular in prepubescent children.

Discrimination of complex histopathological tumour profiles by experienced and inexperienced observers.

One of the tasks that pathologists routinely perform in diagnosis is the assessment of complexity of shape or texture of microscopic images. Because some of these complex patterns can be approximated in terms of fractal structures, it is important to understand how fractal structures are perceived by pathologists, and whether pathologists use specific perceptual strategies to quantify such patterns. Knowledge about this could be advantageous for either producing specific training programmes to increase complexity discrimination or to utilise more unbiased and quantitative imaging methodologies in histopathology. We have previously demonstrated that non-expert observers with high abilities in simultaneous information processing were best at the task of discriminating the fractal dimension of self-similar computer-generated curves. Here we compare the performance of experienced and inexperienced observers in a similar task of discriminating epithelial profiles. The results suggest that there are no differences between experienced and inexperienced observers in this task of complex profile discrimination.

Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone.

OBJECTIVES: (1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children. METHODS: In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis. RESULTS: Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively. CONCLUSIONS: The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables.

Luminescence, electron paramagnetic resonance, and optical properties of lunar material.

Dust samples have been found to luminesce weakly under proton excitation, but not under ultraviolet. Damage, recovery, and heating effects have been investigated. Chips of breccia show luminescence, from white inclusions only, under ultraviolet and protons. Some rock chips show general luminescence, mainly from plagioclase. No natural or excited thermoluminescence has been found for dust or chips. The electron paramagnetic resonance spectrum shows the same broad Fe(3+) dipole resonance for dust and for some chips; other chips show no response. The polarization characteristics of dust are found to be identical to those of the Sea of Tranquillity, independently of proton damage. Chips show characteristics unlike any part of the lunar surface.