Royal London Hospital

About: Royal London Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 4854 authors who have published 5081 publications receiving 168207 citations. The organization is also known as: London Infirmary & London Hospital.

Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies

Abstract: Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channel.

Recurrent erythema multiforme: clinical features and treatment in a large series of patients

Abstract: Recurrent erythema multiforme is an uncommon disorder. We have reviewed the clinical features and treatment of 65 patients with this condition. The mean number of attacks per year was six (range 2-24), and the mean duration of the disease was 9.5 years (range 2-36) reflecting its chronicity. The majority of patients had oral mucous membrane involvement (69%). In 46 patients (71%) the condition was precipitated by a preceding herpes simplex virus infection. Acyclovir was found to be the most useful first-line treatment, with 55% of patients deriving benefit from either continuous oral acyclovir or a patient-initiated 5-day oral course at the onset of herpes simplex virus infection. Of those failing to respond to acyclovir, a small proportion responded to dapsone. The most resistant patients (11) were treated with azathioprine, with complete disease suppression in all cases.

A model of gastric emptying using paracetamol absorption in intensive care patients

Abstract: Objectives: To describe the range and factors which may affect gastric emptying in the ICU patient. Design: Validation sample. Setting: The adult Intensive Care Unit (ICU) of a teaching hospital. Patients: Twenty-seven ICU patients, aged 18–65 years were studied within 3 days of their ICU admission. All patients had normal hepatic and renal chemistry and had no contraindications to enteral feeding. Measurements and main results: The area under the concentration curve from 0–60 min (AUC60) of a paracetamol absorption test was used as the measure of gastric emptying. The variables of the presence or absence of bowel sounds, volume of gastric aspirate ( > 50 ml or < 50 ml), an estimated risk of death (ROD), an APACHE II score calculated 24 h before the study, a pHi measurement, the use of dopamine (2.5–5 μg/kg , yes or no) and of opioids were included in a multiple regression analysis. Using Pearson correlation, AUC60 was positively correlated with the estimated ROD (r = 0.50, p < 0.05). There was a statistically significant difference in the mean AUC60 between those patients who did, and those who did not, receive dopamine (t = 3.06, p < 0.005). On multiple regression analysis the only variable which was significantly associated with AUC60 was estimated ROD, which accounted for 25 % of the variance in AUC60. Conclusion: The results suggest that there is a wide range in gastric emptying in critically ill patients. The results may be due to the case mix of the patients. The use of dopamine may adversely affect gastric emptying and requires further investigation in the ICU patient. Prediction of gastric emptying is difficult in these patients and further investigation is necessary in order to improve our understanding of this process.