Consensus guidelines into the management of epilepsy in adults with an intellectual disability.

BACKGROUND: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. RESULTS: A Delphi process identified a list of priority areas for the development of evidence-based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group. CONCLUSION: There is a dearth of high-quality evidence from well-constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability.

Comparison of an immuno-turbidometric method (STalia D-DI) with an established enzyme linked fluorescent assay (VIDAS) D-dimer for the exclusion of venous thromboembolism.

The use of d-dimer tests for the exclusion of venous thromboembolism is an important advance in clinical practice and also has economic benefits. The Stalia D-Di (Diagnostica Stago, Asnieres, France) is a semi automated system for the quantification of d-dimer using an immuno-turbidometric method incorporating a suspension of latex microparticles coated with two different monoclonal antibodies specifically targeted against human d-dimer fragments. Results are available rapidly in <10 min compared with 35 min for the established VIDAS D-dimer automated enzyme-linked immunosorbent assay (ELISA, BioMerieux, Basingstoke, UK). During November and December 2005, 100 consecutive patients attending the outpatient deep venous thrombosis (DVT) clinic were tested using the VIDAS D-dimer as part of the routine DVT investigation. Using the same samples, D-dimer estimation was also performed on the STalia D-Di for comparison. Across a wide range of data (Vidas 83-5656) and (STali <200->4000), there was good agreement between the two methods. Using cutoff's of 500 microg/l fibrinogen equivalent units (Keeling et al., 1999), 42% (42/100) patients were negative (<500) and 46% (46/100) were positive (>500) on both systems. Six per cent (6/100) were positive on the Vidas but negative on the STalia and another 6% (6/100) were positive on the STalia but negative on the Vidas. In conclusion, 88% (88/100) of patients showed agreement and in the other 12% (12/100), one had a DVT as identified by Compression ultrasonography (CUS). In this study, there were seven patients with a DVT as identified by CUS and they all scored as 'likely' on a pretest clinical probability score and so negative D-dimer would not be used clinically to rule out the disease. The Vidas is a well established instrument for D-dimer measurement in outpatient DVT clinics, and in this small study the STalia compares very well and therefore would fit into an outpatient setting for D-dimer measurement. But ideally a larger study would be required before implementing new methodology in a clinical setting.

Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes.

Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.

Non-pharmacological interventions for epilepsy in people with intellectual disabilities.

BACKGROUND: Approximately 30% of epilepsy patients remain refractory to drug treatment and continue to experience seizures whilst taking one or more antiepileptic drugs. There are a number of non-pharmacological interventions available to refractory patients which may be used in conjunction with or as an alternative to antiepileptic medication. In view of the fact that seizures in intellectually disabled people are often complex and refractory to pharmacological interventions it is evident that good quality randomised controlled trials (RCTs) assessing the efficacy of alternatives or adjuncts to pharmacological interventions are needed in this population. OBJECTIVES: The aim of our study was to assess the data available from randomised controlled trials of non-pharmacological interventions in patients with epilepsy and intellectual disabilities. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006), MEDLINE OVID (1966 to October 2006) and PsychInfo OVID (1806 to October 2006). SELECTION CRITERIA: Randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria and extracted data. MAIN RESULTS: No RCTs were found for this study population. AUTHORS' CONCLUSIONS: This review has highlighted the need for well-designed randomised controlled trials to assess the effect of non-pharmacological interventions on seizure and behavioural outcomes in an intellectually disabled epilepsy population.

Pharmacological interventions for epilepsy in people with intellectual disabilities.

BACKGROUND: The development of epilepsy in a person with intellectual disabilities is a common occurrence. In view of the fact that seizures in intellectually disabled people are often complex and refractory to treatment and that antiepileptic medication may have a profound effect upon behaviour in this patient group, it is evident that good quality randomised controlled trials are needed in this population. OBJECTIVES: The aim of our study was to assess the data available from randomised controlled trials of antiepileptic drug interventions in people with epilepsy and intellectual disabilities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4), MEDLINE OVID (1966 to October 2006), PsychInfo OVID (1806 to October 2006) and EMBASE OVID (1980 to April 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs) of pharmacological interventions for people with epilepsy and a learning disability. RCTs where inadequate methods of allocation concealment had been used were also included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Outcome measures included the following.(1) Retention on treatment.(2) Seizure freedom.(3) Reduction in seizure frequency.(4) Seizure severity scales.(5) Global rating scales.(6) Behavioural outcomes.(7) Cognitive outcomes.(8) Adverse effects.(9) Quality of life. MAIN RESULTS: Data were heterogenous and a descriptive analysis is presented. This review confirms that in the majority of cases where antiepileptic drugs (AEDs) were trialled in this population, moderate reduction in seizure frequency and occasional seizure freedom were obtained. In general it seems reasonable to say that AEDs proven effective in the general epilepsy population are also effective in refractory epilepsy in people with intellectual disability. It is not possible to comment on relative efficacy between medications making clinical choice decisions difficult. Clinical decision is also likely to be guided by concern over side effects. The quality of the studies does not aid clinicians greatly to this respect. In general it seems that in trial settings patients continue on treatment, in the majority of cases, and placebo groups often experience less in the way of side effects. Where side effects are experienced they appear similar to those seen in non-intellectual disability studies. One area of key concern is that of behavioural exacerbation. The majority of studies are unhelpful due to lack of or non-reliable measures in this area. However, where measured, little obvious impact on behaviour is seen in terms of behaviour disorder. AUTHORS' CONCLUSIONS: In summary this review broadly supports the use of AEDs to reduce seizure frequency in people with refractory epilepsy and intellectual disability. The evidence suggests that side effects are similar to those in the general population and that behavioural side effects leading to discontinuation are rare but that other effects are under researched.

Synthesis of phospholipids by human peritoneal mesothelial cells.

OBJECTIVE: To assess the capacity of cultured human peritoneal mesothelial cells to synthesize choline-containing phospholipids. The study compares the phospholipids secreted from cultured cells with those which we, and others, have identified in the dialysate of patients treated by continuous ambulatory peritoneal dialysis (CAPD). PATIENTS: CAPD effluent was collected from 8 patients who had been receiving CAPD treatment for at least 11 months and who had normal ultrafiltration. CELL CULTURES: Using human omental tissue, homogeneous cultures of mesothelial cells were established. METHODS: Synthesis of phospholipids by mesothelial cells was assessed following incubation with [methyl-14C] choline chloride--a precursor capable of being incorporated into phosphatidylcholine (PtdCho) and sphingomyelin. Lipids from CAPD effluent, cultured cells, and cell medium were extracted in chloroform/methanol. Phospholipids were separated and identified by thin layer chromatography. Synthesis and secretion of PtdCho and other choline-containing lipids by the mesothelial cells were determined by beta scintillation counting of the appropriate bands, while the fatty acid composition of the phospholipids was ascertained by gas liquid chromatography. RESULTS: Synthesis and secretion of PtdCho by mesothelial cells were observed during a 96-hour period. When maintained in medium replete with essential fatty acids, the fatty acid composition of the PtdCho synthesized by cultured mesothelial cells closely resembled that isolated from the peritoneal cavity. CONCLUSION: The demonstration of phospholipid secretion from mesothelial cells, with a fatty acid composition similar to the phospholipids isolated from peritoneal dialysate, lends added support to the hypothesis that the mesothelial cells are the source of the peritoneal phospholipids. As such they offer a useful experimental system in which to study peritoneal phospholipid synthesis.

Intraperitoneal phosphatidylcholine levels in patients on continuous ambulatory peritoneal dialysis do not correlate with adequacy of ultrafiltration.

A qualitative and quantitative study was undertaken to determine the lipid composition of dialysate effluent from patients maintained on continuous ambulatory peritoneal dialysis (CAPD). Effluent, after a 4-h, 2.27% dextrose dwell, was collected on ice, centrifuged and extracted for lipids with chloroform and methanol. Lipids were separated and identified by thin layer chromatography, and the constituent fatty acids were quantitated by gas liquid chromatography. Effluents from 10 patients were assayed at the commencement of CAPD treatment and again after 6 months of therapy. There was a significant fall in phosphatidylcholine and phospholipid concentrations (P < 0.007) with time, whereas the fatty acid compositions of these lipids remained constant. Dialysate phosphatidylcholine and phospholipid concentrations were not significantly different between seven patients with poor ultrafiltration and eight patients who had normal fluid removal. This study demonstrates that there is no relationship between dialysate phospholipid levels and the adequacy of filtration, although it corroborates previous reports of an inverse correlation between time on CAPD and dialysate lipid concentrations. These results do not support a rationale for ip phosphatidylcholine administration in patients with poor ultrafiltration.

Plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin during total hip replacement after intravenous bolus injection of magnapen.

1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection every 6 h for up to 72 h until removal of the wound drains. 2. The plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin were measured by a differential small plate microbiological assay method using Sarcina lutea and a penicillinase producing Staph. aureus Russell as the test organisms. 3. The mean +/- s.e. mean concentrations of ampicillin after this regimen were 4222.2 +/- 285.0 microgram/ml (plasma), 65.6 +/- 1.3 microgram (g (hip capsule), 19.1 +/- 3.8 microgram/g (cancellous bone), and 211.1 +/- 65.6 microgram/g (ground up bone) respectively. 4. The mean +/- s.e. mean flucloxacillin concentrations after this regime were 137.2 +/- 28.4 microgram/ml (plasma), 61.8 +/- 15.0 microgram/g (hip capsule), 47.1 +/- 9.5 microgram/g (cancellous bone) and 139.4 +/- 21.8 microgram/g (ground up bone) respectively. 5. An intravenous bolus injection of Magnepen (4.0 g), given immediately before induction of general anaesthesia, provides concentrations of ampicillin and flucloxacillin in plasma, hip capsule, cancellous and ground up bone, and drain fluid that exceed the MICs of these antibiotics against Staph. aureus and E. coli. 6. The plasma, hip capsule, cancellous and ground up bone concentrations of ampicillin after this dose of Magnapen do not, however, exceed the MICs of the Gram negative anaerobes that sometimes cause postoperative wound infections in these patients.

Plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin during total hip replacement.

1 Lincomycin (600 mg) was given 6 h preoperatively by intramuscular injection, as an intravenous infusion over 30 min and for 72 h postoperatively in twelve patients having total hip replacement. 2 The plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin were almost always above the M.I.C. of lincomycin against penicillinase producing Staphylococcus aureus. 3 There was a good correlation between the estimated concentrations of lincomycin in bone by the grinding and agitation methods of analysis. 4 Two patients developed pseudomembranous colitis after parenteral lincomycin.

Ascending lumbar venography in the diagnosis of lumbar disc lesions.

Fifty-five patients suffering from low back pain with or without sciatica were submitted to ascending lumbar venography. Six patients had anatomical variations which prevented adequate catheterization and 6 had equivocal radiographic appearances, which we could not assess. Fourteen patients had normal venograms but in 29 an abnormality was demonstrated. These 43 patients were then submitted to radiculography and, where appropriate, surgery. The 14 patients with normal venograms also had normal radiculograms; while the 29 with abnormal venograms had an abnormality confirmed on radiculography and/or surgery. However, in 10 of the patients the lesion was found to be one disc space lower than that demonstrated on venography; Side-effects were very few, and the procedure can be used on out-patients. This technique would appear to be a useful addition to the radiological investigation of the spine.

Colitis and diarrhoea: a problem with antibiotic therapy.

During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis.