ERT is now available for other lysosomal storage disorders (LSDs) but none of these highly expensive treatments has had the same efficacy. This review explores why these newer treatments have failed to live up to expectations and how future products might be made more effective.
Recent
findings
In Gaucher, the target cells for ERT are macrophages, which are efficiently accessed by intravenously Cyclosporin A chemical structure injected recombinant enzyme. The target tissues in other LSDs receive much lower doses of enzyme and intravenous ERT does not enter the brain at all. Uptake of recombinant enzyme is via the mannose-6-phosphate receptor (M6PR). Recent work has looked at improving the efficiency of enzyme delivery to tissues by altering both the ligand on the infused enzyme and the expression of the M6PR on cells. For delivery to the central nervous system, intrathecal routes of administration have been explored.
Summary
Work in tissue culture and in animal models has shown increased efficiency of enzyme delivery and clinical trials of second-generation products and novel delivery systems are now underway.”
“A best evidence topic was written according to a structured protocol. The question addressed was whether routine chest radiography is indicated following chest drain removal
in patients undergoing cardiothoracic surgery. A total 5-Fluoracil solubility dmso of 356 papers were found using the reported searches; of which, 6 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are selleck products tabulated. Reported measures were mean duration of drains left in situ,
timing of drain removal, pathology detected on chest radiographs (CXRs), interventions following imaging and clinical assessment, complications in patients not undergoing routine CXRs and the cost saving of omitting routine CXRs. One large cohort study reported the detection of pathology in 79% of clinically indicated CXRs in comparison to 40% of routine CXRs (P=0.005). Ninety-five per cent of the non-routine CXR cohort remained asymptomatic and required no intervention. One large observational study reported the detection of new pneumothoraces in 9.3% of patients, 70.3% of which were barely perceptible. Intervention following CXR was required in 0.25% and only one medium-sized pneumothorax would have been potentially missed without CXR. Another large observational study reported intervention following CXR in 1.9% and the presence of relevant clinical signs and symptoms to be a significant predictor of major intervention (P<0.01). A smaller observational study reported no pathology detected or intervention following CXR in 98% and the cost saving of omitting a single CXR at 10 000 per annum. Another small observational study reported only 7% of CXRs to be clinically indicated with a false-positive rate of 100%, and a false-negative rate of 7% in CXRs not clinically indicated.