Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Laparoscopic vs open subtotal colectomy for benign and malignant disease

AIM: The present meta-analysis aims to compare short-term and long-term outcomes in patients undergoing laparoscopic or open subtotal colectomy for benign and malignant disease. METHODS: A literature search of Medline, Ovid, Embase and Cochrane databases was performed to identify studies published between 1992 and 2005, comparing laparoscopic (LSC) and open (OSC) subtotal colectomy. A random effect meta-analytical technique was used and sensitivity analysis performed on studies published since the beginning of 2000, higher quality papers, those reporting on more than 40 patients, and those studies reporting on adult cases or acute colitis. RESULTS: A total of eight studies satisfied the criteria for inclusion. These included outcomes on 336 patients, 143 (42.6%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 5% (range 0-11.8%). Operative time was significantly longer in the laparoscopic group by 86.2 min (P < 0.001) and throughout subgroup analysis, although it was only in patients with acute colitis that this finding was without significant heterogeneity. Operative blood loss was less in the laparoscopic group by 57.5 millilitres in high quality and studies published since 2000, and 65.3 millilitres in those reporting on more than 40 patients. There was no significant difference in early or long-term complications between the groups. A statistically significant reduction in length of postoperative stay was observed in the laparoscopic groups by 2.9 days (P < 0.001). CONCLUSION: Laparoscopic subtotal colectomy was associated with longer operating times but a reduced length of stay compared to open surgery. Although short-term outcomes were equivalent in both groups, the suggested benefits in terms of reduced long-term obstructive complications were not supported by this meta-analysis.     

Repeated measurements of mite and pet allergen levels in house dust over a time period of 8 years

BACKGROUND: Studies of the association between indoor allergen exposure and the development of allergic diseases have often measured allergen exposure at one point in time. OBJECTIVE: We investigated the variability of house dust mite (Der p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years. METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the child's mattress, the parents' mattress and the living room floor was collected at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno assay. RESULTS: Mite allergen concentrations for the child's mattress, the parents' mattress and the living room floor were moderately correlated between time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on the child's mattress, the within-home variance was close to or smaller than the between-home variance in most cases. For Fel d 1, the within-home variance was almost always smaller than the between-home variance. Results were similar for allergen levels expressed per gram of dust and allergen levels expressed per square metre of the sampled surface. Variance ratios were smaller when samples were taken at shorter time intervals than at longer time intervals. CONCLUSION: Over a period of 4 years, mite and cat allergens measured in house dust are sufficiently stable to use single measurements with confidence in epidemiological studies. The within-home variance was larger when samples were taken 8 years apart so that over such long periods, repetition of sampling is recommended.     

Synovial sarcoma of the mandible

The term synovial sarcoma was first proposed for the histologically well defined entity by Knox in 1936. The name was proposed due to the fact that at least the cases reported in the early part showed some resemblance of the tumour to normal synovial tissue histologically. Thereafter, tumours have been diagnosed from areas without synovial tissue. The diagnosis of monophasic tumours can be difficult and immunostains appear to be a good diagnostic tool in those cases. The occurrence in the mandible is extremely rare. This is a case of synovial sarcoma arising in the condyle involving most of the ramus. The tumour was diagnosed as synovial sarcoma with predominant spindle cell component by correlation of histopathology with immunostains (cytokeratin, epithelial membrane antigen, actin and desmin). The patient has been treated with surgery and radiotherapy.