Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

INTERFERONS IN ONCOLOGY

SUMMARY The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.     

Are NHS primary care performance indicator scores acceptable as markers of general practitioner quality?

BACKGROUND: In 2002 the Department of Health published a list of 20 indicators to judge the performance of the 302 primary care organisations (PCOs) in England during 2001-2002. General practitioners (GPs) have expressed doubts about the relevance, applicability and evidence base of these indicators for actual practice. AIMS: To fashion NHS performance indicators to be acceptable and relevant to practicing GPs. DESIGN OF STUDY: A Delphi technique followed by simple mathematical modelling. METHODS: We asked a group of 24 senior GP educators to place the Department of Health performance indicators in rank order as markers of quality in general practice. We found just seven indicators comprised 73% of the markers chosen and all seven were chosen by over three-quarters of the responders. Using a simple 'sign test' system, we then calculated a composite points score for all 302 PCOs. RESULTS: We found that there were almost twice as many PCOs at the upper and lower ends of performance and fewer in the middle than we predicted theoretically. The results suggest that pan-PCO or practice factors account for the low performance scores of 16 of 35 PCOs with extremely poor performance and for the high scores of 17 of the 36 PCOs with extremely high performance. CONCLUSION: We have developed a method that shows how numerous Department of Health performance indicators can be merged into a single composite performance score. We show that this composite performance score is easy to derive, simple to interpret, is acceptable to GPs, and has face validity.     

Inter-ethnic differences in postoperative pethidine requirements.

A preliminary study of 24 hours' postoperative analgesia using a patient-controlled analgesia technique was undertaken in eight European and fourteen Asian adult patients. All patients had upper abdominal surgery and received weight-related doses of pethidine postoperatively via a Cardiff Palliator. Both groups had a similar degree of analgesia as assessed by visual analogue score but the Asian patients were more sedated in the postoperative period. The Asian patients made 24% fewer demands for analgesia and had a smaller mean (SD) pethidine consumption, 7.62 (2.04) mg.kg-1, compared with the European patients, 9.97 (2.14) mg.kg-1, (P less than 0.05) during the first 24 hours. Further research is necessary to determine whether the smaller requirement for analgesia in Asian patients is a result of pharmacokinetic or pharmacodynamic differences.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.