Cis-diamminedichloroplatinum (DDP) was used as the initial treatment in a pilot study of 17 patients with biopsy-proven transitional cell carcinoma of the bladder. No patient had received any previous radiotherapy or chemotherapy. The clinical stages of the tumours were T2 (2 patients), T3 (13) and T4 (2). Before treatment the tumours were assessed by cystoscopy, biopsy, examination under anaesthesia (EUA), computed axial tomography (CT scan) and ultrasound. DDP was given at a dose of 100 mg/m2 intravenously with hydration using mannitol and saline. Each patient received three treatments at 3-weekly intervals. Twelve days after the third treatment, response was assessed by cystoscopy, biopsy, EUA, CT scan and ultrasound. Eleven of the 17 patients had a partial response. Survival was significantly increased in responders compared with non-responders. Seven patients had a low creatine clearance following treatment, 5 had audiograms showing evidence of ototoxicity and 2 developed leucopenia during treatment. This study confirmed the activity of DDP in bladder cancer and showed that it was active in producing a response in the primary tumour in 11 of 17 patients.

BackgroundGTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family.MethodsWe present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed.ResultsWe have identified a novel missense variant, c.5A > G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes.Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype.ConclusionsWe propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD.

done from the top downwards. Although obvious air bubbles were eliminated, small bubbles in the interior of the dialyser could not be seen. Thus it seems probable that more gas (and hence conceivably residual ethylene oxide) remained within the dialyser with this technique.We immediately rectified our technique, and no new patients developed the syndrome subsequently. None the less, three patients continued to have symptoms whenever they used a new disposable dialyser. ConclusionAlthough we have no absolute proof, we suggest that the following sequence of events may have occurred. Incorrect priming of the dialysers resulted in small amounts of ethylene oxide or some other easily removed substance remaining in small gas bubbles in the dialyser. This gradually sensitised some patients, who subsequently reacted to trace amounts in blood returning from incorrectly primed dialysers but were not affected by dialysers sterilised with formalin. Three patients became so sensitive that they continued to react to the even smaller amounts of ethylene oxide inevitably diffusing out of a dialyser despite proper preparation. An allergic reaction to ethylene oxide bound to albumin has been described previously.7This explanation is not, however, entirely satisfactory. We do not understand why these attacks appeared in an epidemic fashion in 1981, when there had been no obvious change in the technique of priming dialysers over the previous five years. The reactions were not attributable to faults in the manufacture or sterilisation of the dialysers since the products of four different firms were involved simultaneously.We are grateful to Extracorporeal Ltd for the time, trouble, and expense expended by them in attempts to solve our problem. We continue to use their flat plate dialysers with confidence.ADDENDUM-Since we submitted this paper a further patient who had not previously reacted to dialysis developed sneezing, wheezing, watery eyes, and urticaria within a minute of connection to a disposable flat plate dialyser. The dialyser had been properly primed in hospital. This further case strengthens our belief that incorrect priming of dialysers was not the sole cause of this syndrome. Haemophilia and the kidney: assessment after 11-year follow-up M SMALL, P E ROSE, N McMILLAN, J J F BELCH, E B ROLFE, C D FORBES, J STUART Abstract Radiological and biochemical investigations of renal function were performed in 57 patients with haemophilia, 27 of whom had been previously investigated in 1969. Although one-third of patients had a renal radiographic abnormality, only two had abnormalities persisting since 1969 and attributable to renal bleeding. Isotope renography was a sensitive indicator of renal abnormality whereas a history of haematuria was a poor discriminator for patients with abnormal intravenous urograms or impaired creatinine clearance. Haematuria was not associated with progressive loss of renal function and its natural history in haemophilia is probably benign. References

Background The diagnosis of Alzheimer's disease (AD) remains at times difficult to make using available neuropsychological measures. Neuro-imaging is a relatively new form of detecting the changes associated with dementia. The present study investigated the role of magnetic resonance imaging (MRI) in diagnosing AD in adults with Down's syndrome (DS). Methods Subjects with DS and Alzheimer-type dementia were matched to non-demented controls with DS. Magnetic resonance imaging findings (i.e. volumetric and two-dimensional scans) were compared between the two groups in order to show a relationship between the changes of AD and structural MRI abnormalities. Results Specific structural abnormalities which are seen in non-intellectually disabled subjects with dementia are also found in individuals with both DS and AD. However, such findings cannot be used to diagnose clinical AD with good accuracy in adults with DS. A number of practical issues of patient compliance and over-sedation are demonstrated by the findings.

Primary presenile dementia slows the major positive component of the visual evoked potential to flash stimulation but does not affect the visual evoked potential to patterned stimulation. The progressive effect of Alzheimer's disease was followed in a 58 year old woman over three and a half years from the development of the earliest symptoms to complete mental incapacity. The pattern reversal visual evoked potential remained normal, but the flash visual evoked potential gradually slowed from 129 ms in 1981 to 153 ms in 1984. The severity of the abnormality of the flash visual evoked potential thus reflected the severity of the dementia. Electroencephalography, computed tomography, and psychometric tests indicated generalised cortical disease, but the results were not specific to dementia.