An 83 year old man had an acute attack of gout. He treated himself with colchicine drops (2 mg in two days) and received diclofenac because of continuous pain. Concurrently he had muscle weakness in his limbs. Four days later he became immobile and was transferred to hospital with flaccid tetraparesis (British Medical Research Council grade II-III). He had no signs of infection, hepatic or renal impairments, or stroke. Laboratory values were normal except a brief increase of creatine kinase to 1288.2 IU/l. Repeated nerve conduction studies did not show any relevant pathology, including normal terminal latencies and F wave latencies. Electromyography subsequently showed signs of lower motor neurone lesion. Muscle biopsy showed one isolated vacuole that could not be related to a colchicine induced myoneuropathy. Analysis of cerebrospinal fluid was unremarkable and indicated only a slight disturbance in the blood-cerebrospinal fluid barrier (protein 548 mg/l). An atypical Guillain-Barré syndrome was clinically diagnosed.He was also taking 120 mg/day of slow release verapamil continuously for tachyarrhythmia, a sick sinus syndrome of the heart basically controlled by a pace maker, furosemide, acetylsalicylic acid, ambroxol, and theophylline. A tetraparesis due to neuromyopathy induced by colchicines was diagnosed because of concentration-time curves in serum and cerebrospinal fluid.The diagnosis was revised to neuromyopathy induced by colchicine when excessive colchicine concentrations in serum as well as in cerebrospinal fluid were determined retrospectively using a radioimmunoassay.1 Although the serum concentration decreased slightly it remained constant in the cerebrospinal fluid in the following days (figure). The calculated half life in serum was increased eightfold compared with a dose and age matched reference population (272 hours v 34 hours).1 The colchicine cerebrospinal fluid to serum ratio of about 50% was much higher than normal (less than 10%). At the follow-up on day 40, he had recovered incompletely but colchicine was not detectable in serum.Typical features of colchicine induced myoneuropathy such as high cumulative doses, long term treatment, or renal insufficiency 2 were not found in our case. Verapamil is an inhibitor of CYP3A and a potent inhibitor (with norverapamil threefold stronger) of the P-glycoprotein transporter acting as a blood-brain barrier drug efflux pump.3 An increase of colchicine uptake was seen in a rat's brain as well as in a rat's plasma by verapamil up to 4.5-fold and 1.65-fold, respectively. These results indicate a dominant responsibility of the P-glycoprotein inhibition for the colchicine accumulation in cerebrospinal fluid. 4 Colchicine is a substrate for CYP3A4 in the liver. Its inhibition might be responsible for increased colchicine serum concentrations.Colchicine related tetraparesis is most likely due to a pharmacokinetic interaction in the human brain with verapamil and norverapamil.
Justification of radiological requests, standardization of procedures and optimization of protection measures are key principles in the protection of individuals exposed to ionizing radiation for diagnostic purposes. Nowhere is this more pertinent than in the imaging of children and, following the recent introduction of the Ionising Radiation (Medical Exposure) Regulations, there is now a regulatory requirement for diagnostic radiology departments to demonstrate compliance with these principles. A study was undertaken to compare all aspects of paediatric radiological practice at two specialist and two non-specialist centres. An initial study involved analysis of nearly 3000 patient doses. The second phase of the project involved assessment of referral criteria, radiographic technique and approximately 100 radiographs at each centre by two consultant paediatric radiologists. While all radiographs were found to be diagnostically acceptable, major differences in technique were evident, reflecting the disparity in experience between staff at the specialist and non-specialist centres. The large number of sub-optimum films encountered at the latter suggests that there is a need for specific training of less experienced radiographic and clinical staff.
A dosimetric survey of 14 routine X-ray examinations in children was carried out between 1993 and 1995. Two children's hospitals and four general hospitals took part in the survey which involved the calculation and measurement of nearly 3000 doses. Entrance surface doses (ESD) were calculated from exposure factors for radiographic procedures, and dose-area products (DAP) were recorded for both radiographic and fluoroscopic procedures. Doses were in good agreement with earlier studies, but for some procedures were significantly lower than those reported from other European countries. The main dose influencing factors for radiographic procedures were found to be the speed of the film-screen system and the use of an antiscatter grid. For the main head/trunk examinations, specialist centres often delivered higher doses to the younger children as a result of widespread use of a grid. In fluoroscopy, where the main dose influencing factors were the use of a grid and the dose rate dependence of the image intensifier, the children's hospitals consistently delivered significantly lower doses. Both ESDs and DAPs were found to increase with patient age for the main head/trunk examinations, although in some cases (AP/PA chest) this relationship was weak. The dependence of dose on age necessitates the subdivision of the paediatric sample into a number of age categories. It is suggested that all authors use the same age groupings.
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