RESUMO
A patient was prescribed a new treatment, 40 mg furosemide. Her pharmacist mistakenly dispensed 40 mg gliclazide instead. After 3 weeks of treatment, the patient was found in a coma, was hospitalised and died after a week. Hair sample was collected during post-mortem examination and tested for gliclazide on three 2 cm sections, starting at the root end. Hair strands were decontaminated, segmented and incubated in the presence of diazepam-d5, and a solid-liquid extraction has been performed. Finally, toxicological analyses were performed by UFLC Shimadzu Prominence - MS/MS Sciex 6500 QTRAP. Gliclazide was found on the proximal (238 pg/mg), median (77 pg/mg) and distal (69 pg/mg) segments. The concentration in the proximal segment was largely higher than in the other two, which demonstrates repeated intake of gliclazide by the patient during at least the last 2 months before death. The lower concentrations in the medial and distal segments, as well as a part of the concentration in the proximal segment, may be linked to external hair contamination. These could be due to either radial sweat diffusion, possibly occurring in the last week hospitalisation of the patient, or to biological fluids contamination during post-mortem examination. This case illustrates the opportunity to confirm slow and fatal chronic poisoning by gliclazide using hair analysis and shows the benefit of hair testing for the investigation of medical or dispensing errors.
RESUMO
OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF-R), and c-erb B-2 were determined immunohistochemically in formalin-fixed paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The prognostic significance of these growth factors and their receptors as well as of tumor stage and malignancy grade was examined with respect to survival and tumor recurrence by following up the fate of the patients after nephrectomy (mean follow-up time 5.2 years). RESULTS: The members of the EGF family and their receptors studied were expressed to a variable degree in all RCCs investigated. However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007) and malignancy grade (p < 0.007) but none of the growth factors or receptors studied (p > 0.05, respectively) exhibited prognostic significance with respect to both survival and disease-free period. On the contrary, there was a significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p = 0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03). The coexpression of the factors studied also showed no prognostic relevance. CONCLUSION: The expression of these members of the EGF family seems not to bear evaluable prognostic information for clinical use in the case of RCC.