Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS).

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a progressive, multisystemic disease caused by a deficiency of iduronate-2-sulfatase. Patients with the severe form of the disease have cognitive impairment and typically die in the second decade of life. Patients with the less severe form do not experience significant cognitive involvement and may survive until the fifth or sixth decade of life. We studied the relationship of both severity of MPS II and the time period in which patients died with age at death in 129 patients for whom data were entered retrospectively into HOS (Hunter Outcome Survey), the only large-scale, multinational observational study of patients with MPS II. Median age at death was significantly lower in patients with cognitive involvement compared with those without cognitive involvement (11.7 versus 14.1 years; p = 0.024). These data indicate that cognitive involvement is indicative of more severe disease and lower life expectancy in patients with MPS II. Median age at death was significantly lower in patients who died in or before 1985 compared with those who died after 1985 (11.3 versus 14.1 years; p alpha 0.001). The difference in age at death between patients dying in or before, relative to after, the selected cut-off date of 1985 may reflect improvements in patient identification, care and management over the past two decades. Data from patients who died after 1985 could serve as a control in analyses of the effects of enzyme replacement therapy with idursulfase on mortality in patients with MPS II.

Echodense spinal subarachnoid space in neonates with progressive ventricular dilatation: a marker of noncommunicating hydrocephalus.

OBJECTIVE: Our purpose was to evaluate the frequency and clinical significance of echogenic debris in the spinal subarachnoid space of neonates at risk for progressive ventricular dilatation. SUBJECTS AND METHODS: Spinal sonography was performed on 15 neonates with severe intracranial hemorrhage (n = 10) or bacterial meningitis (n = 5). Spinal sonography also was performed on 16 control neonates. Images were analyzed for the presence and location of echogeric debris within the thoracolumbar subarachnoid space. Lumbar punctures were performed on all 31 neonates, and CSF was analyzed for cell count and protein content. Ten of 15 neonates required ventricular drainage procedures. RESULTS: Progressive ventricular dilatation occurred in 11 of 15 neonates with intracranial hemorrhage or meningitis. Echogenic debris was present in the thoracolumbar subarachnoid space on spinal sonography in every neonate with progressive ventricular dilatation compared with none of the 16 control neonates (p < .0001 by chi-square analysis). In addition, the 11 neonates with echogenic subarachnoid space had significantly higher protein and RBC contents in the lumbar CSF (p < .04). CONCLUSION: Echogenic subarachnoid space revealed by sonography is associated with progressive ventricular dilatation after severe intracranial hemorrhage or bacterial meningitis and is caused by high protein and RBC contents in the subarachnoid space. This finding may be helpful in identifying neonates who will not benefit from serial lumbar punctures for treatment of hydrocephalus.

Alterations in spinal fluid drainage in infants with hydrocephalus.

We describe two cases of hydrocephalus in which spinal sonography revealed underlying causes responsible for the failure of therapeutic lumbar punctures.

A collaborative exercise on cytogenetic dosimetry for simulated whole and partial body accidental irradiation.

An experiment sponsored by the International Atomic Energy Agency was undertaken to compare dose estimation by cytogenetic analysis on aliquots of samples of irradiated blood sent by air to participating laboratories. Accidental acute whole-body irradiations to 0.7 and 2.34 Gy and half-body irradiations to 3.5 Gy were simulated with X- and gamma-rays. For the partial irradiations the size of the irradiated fraction and its dose were estimated by the Qdr and contaminated Poisson techniques. Each laboratory's in vitro dose-response data were fitted to the quadratic model by the iteratively reweighted least squares method. Interlaboratory variations in dose-response curves, and in the aberration yields and dose estimates for the simulated accidents were noted. However, in general, most participants consistently obtained results acceptably close to the true values.

The present state and perspectives of micronucleus assay in radiation protection. A review.

The occurrence of micronuclei proved to be a sensitive biological indicator of clastogenic effects of many chemical and physical agents. The possibility of using the micronucleus technique in radiation protection as an alternative to the traditional chromosomal analysis has recently been followed with increasing interest. This review outlines the main biological and practical aspects of the micronucleus assay and discusses its potential to serve as a rapid and reliable measure of radiation overexposures and hypersensitivities.

Simultaneous detection of SCE and Q-bands on human chromosomes by a double-staining technique.

Human lymphocytes were cultured for two cell cycles in the presence of bromodeoxyuridine (BrdU), and the resulting metaphase chromosomes were first stained with quinacrine mustard (QM) and then, immediately afterwards, with Hoechst 33258, without any intermediate destaining. Both Q-banding patterns and sister chromatid differential staining were photographed subsequently on the same metaphase using two different filter blocks of the fluorescence microscope.