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Investigators have reported that certain metabolic disorders (fatty acid oxidation (FAO) disorders and organic acidemias) contribute to unexpected early childhood deaths. We estimated the contribution of these metabolic disorders to a population-based sample of unexpected early childhood deaths. The study population included children less than 3 years of age who died during 1996-2001 and whose deaths were investigated by the Virginia Office of the Chief Medical Examiner (ME). Dried post-mortem blood on filter paper was sent to a reference laboratory for metabolic screening by tandem mass spectrometry. When molecular DNA analysis was available to identify known gene mutations, positive screens were confirmed. If molecular DNA analysis for a suspected disorder was not available, tandem mass spectrometry was performed on newborn blood spots when available. If DNA analysis was not available and newborn blood spots could not be obtained, an independent expert biochemical geneticist confirmed the post-mortem interpretation. We obtained screening results for 793 (88%) of 904 children examined. Eight children had a positive screen for FAO disorders or organic acidemias. One child would not have benefited from identification in the newborn period. However, seven children's outcomes might have been improved had they been identified during the newborn period and effectively treated. Post-mortem metabolic screening may identify a cause of death for about 1% of children who die unexpectedly before 3 years of age, allowing for identification and treatment of affected siblings. Identifying and treating affected children during the newborn period may offer an opportunity to reduce early childhood mortality.

Multiplexed assays using fluorescent microspheres is an exciting technique that has been gaining popularity among researchers, particularly those in the public health field. Part of its popularity is due to its flexibility, as both immunoassays and oligonucleotide hybridization assays can be developed on this platform. This report summarizes a workshop held by the Centers for Disease Control and Prevention that discussed issues surrounding these assays and the Luminex 100 xMAP instrument. Topics included instrumentation, assay design, sample matrix and volume, quality control, and development of commercial applications.

Terminology in any field is a complex mix of established conventions, accepted usages, disputed terms, and occasional misnomers. The terminology that has evolved for quantitative fluorescence cytometry (QFCM) is especially multifarious, in part because QFCM encompasses a range from subjective visual assessments to objective photon counts. Thus, while descriptive terms such as “dim” and “bright” are still quite useful, quantitative terms such as “binding capacity” should be used with collective understanding of their exact meanings. This article reviews current usage and proposes definitions that, with refinement from suppliers and users of QFCM technology, can provide the required clarity. Cytometry 33:97–105, 1998. Published 1998 Wiley-Liss, Inc.1

In the last decade, iodine deficiency disorders (IDD) have become recognized as the most common preventable cause of mental retardation worldwide. Iodine deficiency interferes severely with prenatal and postnatal growth and neurologic development of individuals. It has condemned tens of millions of children to cretinism—characterized by mental and growth retardation, rigid spastic motor disorders, deaf mutism, and severe hypothyroidism—and hundreds of millions of children to milder degrees of mental and physical impairments. Accompanying effects include increased rates of congenital anomalies, fetal wastage, infant mortality, goiter, and hypothyroidism in children and adults. Endemic cretinism has been classically divided into two types: a chronic neurological disorder and a condition with myxedema and severe hypothyroidism. Recent studies have shown considerable overlap in the findings of these two types, which are now thought to have a common etiology differing primarily by the timing and severity of the pre- and postnatal deficiency of iodine and maternal thyroxine. The severity of iodine deficiency and hypothyroidism in the mother during early and midgestation is related to the severity of the neural damage in the fetus. The most logical intervention for a community or population is the introduction of iodine prophylaxis. Although salt iodization is technically straightforward, community leadership is essential to any effort. The mobilization of global efforts through WHO, UNICEF, Program Against Micronutrient Malnutrition (PAMM), and International Council for Control of Iodine Deficiency Disorders (ICCIDD) since 1990 has led to goals to eliminate new cases of IDD by the year 2000. Most countries at great risk for IDD have met or are close to meeting the middecade goal of having iodized salt for 90% of households. This provisional success indicates that the goal of eliminating new IDD cases by the year 2000 may be achieved.

To determine the precision of cellular fluorescence intensity (FI) measurements derived from labeled microbead standards, FI results were compared from 43 different flow cytometers in 34 laboratories. All laboratories analyzed prepared aliquots of fluoresceinated calf thymocyte nuclei (Fluorotrol), human lymphocytes stained with fluoresceinated anti-CD4 antibody, and fluoresceinated microbeads used as both internal and external standards. Measurements were conducted by most laboratories on the third and fourth days after sample preparation. Results for percent of events within the gates and the histograms returned by participants indicated that the samples had remained stable and that gated populations had been properly identified. All standard curves showed strong linearity, and the pooled results from all standards produced a best-fit curve that was in close agreement with the assigned values. Nonetheless, results for cellular FI were highly variable, with CVs of 20-34%. Agreement within lab/instrument was much better, with CVs ranging from 3.0 to 9.9%. The overall variability was not obviously attributable to differences in the types of cytometer, nor could it be explained by attributes of the standard curves or any other single variable examined. However, the application of a corrective factor based on FI results for Fluorotrol allowed a two-fold improvement in the precision of FI measurements on CD4-stained lymphocytes, with an overall CV of 11%. Uncharacterized differences in the operating conditions of flow cytometers can influence cellular FI measurements, but consistent results can be obtained if a stained cellular calibrator is analyzed in addition to the proper microbead standards.