Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.

OBJECTIVE: To describe a multigenerational kindred with a frontotemporal dementia clinical syndrome (FTDS), extensive subcortical gliosis pathology, and autosomal dominant genetics. METHODS: Clinical, imaging, and pathologic evaluations of multiple family members. RESULTS: Symptom onset commonly occurred in the fifth or sixth decade, although some kindred members did not develop obvious symptoms until their eighth decade. White matter changes were prominent on both MRI and CT imaging. Results from six brain autopsy evaluations showed consistent but varying degrees of pathology that, while unique, share some histologic similarities with leukodystrophies. These brains were notably devoid of both tau- and ubiquitin-containing inclusions. CONCLUSIONS: Subcortical gliosis in this kindred arises from mutation of a novel gene or else represents a unique frontotemporal dementia clinical syndrome variant caused by mutation of an already known gene. Clinical relevance and research implications are discussed.

Identification of organically associated trace elements in wood and coal by inductively coupled plasma mass spectrometry.

1-Methyl-2-pyrrolidinone (NMP) was used to extract samples of wood (forest residue) and coal; the extracts were analysed by inductively coupled plasma mass spectrometry (ICP-MS) using two different sample preparation methods, in order to identify trace elements associated with the organic part of the samples. A sample of fly ash was similarly extracted and analysed in order to assess the behaviour of the mineral matter contained within the wood and coal samples. 32% of the biomass was extracted at the higher temperature and 12% at room temperature while only 12% of the coal was extracted at the higher temperature and 3% at room temperature. Less than 2% of the ash dissolved at the higher temperature. Size exclusion chromatograms of the extracts indicated the presence of significant amounts of large molecular mass materials (>1000 mu) in the biomass and coal extracts but not in the ash extract. Trace element analyses were carried out using ICP-MS on the acid digests prepared by 'wet ashing' and microwave extraction. Sixteen elements (As, Ba, Be, Cd, Co, Cr, Cu, Ga, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) were quantified, in the samples before extraction, in the extracts and in the residues. Concentrations of trace elements in the original biomass sample were lower than in the coal sample while the concentrations in the ash sample were the highest. The major trace elements in the NMP extracts were Ba, Cu, Mn and Zn from the forest residue; Ba, Cu, Mn, Pb and Zn from the coal; Cu and Zn from the ash. These elements are believed to be associated with the organic extracts from the forest residue and coal, and also from the ash. Be and Sb were not quantified in the extracts because they were present at too low concentrations; up to 40% of Mn was extracted from the biomass sample at 202 degrees C, while Se was totally extracted from the ash sample. For the forest residue, approximately 7% (at room temperature) and 45% (at 202 degrees C) of the total trace elements studied were in the extract; for the coal, approximately 8% (at room temperature) and 23% (at 202 degrees C) were in the extract. For the ash, only 1.4% of the trace elements were extracted at 202 degrees C, comprising 25% of Cd but less than 1% of Pb.

Sources of funding for schools.

Public school finance mechanisms differ from state to state, and they are often extremely complex. Most commonly, the federal government contributes about 7% of the total school budget, and the remainder is split fairly evenly between local contributions (primarily raised through local property taxes) and state contributions (primarily raised through state income taxes and sales taxes). The average amount of money provided per pupil varies greatly from one state to another. The method of distributing the state contribution to school districts is equally complex, often involving some combination of basic funding (which guarantees a minimum level of general purpose support per student), power equalization (which guarantees that a certain level of local taxation will yield a given level of per-pupil funding), local option (higher levels of taxation approved in some school districts, not equalized by the state), and categorical funding (supplemental state and federal funds, earmarked for specific needs such as special education or compensatory services to schools with a concentration of poverty, or to meet state-dictated priorities, such as reducing class size or purchasing state-approved textbooks). This complexity often leads to significant variation from district to district in the percentage of funding received from federal, state, and local sources and wide disparities in the level of support for the educational program. Typically, wealthier districts provide more of their funding from local taxes, while lower-income districts are more heavily dependent on state and federal sources.

Development and validation of sensitive method for determination of serum cotinine in smokers and nonsmokers by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.

We describe a sensitive and specific method for measuring cotinine in serum by HPLC coupled to an atmospheric pressure chemical ionization tandem mass spectrometer. This method can analyze 100 samples/day on a routine basis, and its limit of detection of 50 ng/L makes it applicable to the analysis of samples from nonsmokers potentially exposed to environmental tobacco smoke. Analytical accuracy has been demonstrated from the analysis of NIST cotinine standards and from comparative analyses by both the current method and gas chromatography/high-resolution mass spectrometry. Precision has been examined through the repetitive analysis of a series of bench and blind QC materials. This method has been applied to the analysis of cotinine in serum samples collected as part of the Third National Health and Nutrition Examination Survey (NHANES III).

Analysis of benzoylecgonine in dried blood spots by liquid chromatography--atmospheric pressure chemical ionization tandem mass spectrometry.

Residual samples from blood spots (i.e., whole blood spotted onto filter paper) are a useful source for epidemiological screening studies involving newborns. However, the small volume of blood available from residual blood spots complicates the assay. A method for analyzing benzoylecgonine (BZE; the primary metabolite of cocaine) in blood spots, in which the blood spot is eluted with aqueous ammonium acetate-methanol containing N-methyl trideuterated-BZE as an internal standard, followed by high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry using multiple reaction monitoring, has been developed. This approach provides a rapid, direct, sensitive (limit of detection, approximately 2 ng/mL, based on a 12-microL sample size), and highly specific means of determining BZE concentrations in blood spots. We have applied this method for confirmatory analyses in a large epidemiological study of the prevalence of cocaine use during late pregnancy.

Multiple, large deletions in rat mitochondrial DNA: evidence for a major hot spot.

This study identified 33 different deletions in mitochondrial DNA from four aging Fischer-344 rat brains and from a cultured rat lymphoma cell line (Nb2 cells). The deletions were located in the longer arc between the heavy and light strand origins of replication. PCR products that spanned across the deleted regions were sequenced, and deletions ranging between 6548 bp and 9977 bp in length were identified. Short direct repeats of < or = 8 bp were present at the end points of all but one of the deletions. The remaining deletion contained, instead, a near-perfect direct repeat (9/10 bp) within two base pairs of its end points. In 24 of the deletions, a sequence equivalent to one member of the paired direct repeats was lost with the deleted segment. In the remaining nine, either more or less of the base pairs of a single repeat were lost. Twelve of the 33 different deletions terminated on one side at a common locus (major hot spot) of 5 bp in length, located at the 5' end of the tRNAThr gene. The opposite ends of these 12 deletions were at different sites. The hot spot was located in a region of the mtDNA with strong potential for secondary structure and was flanked by a pair of AT-rich sequences. The utilization of the hot spot as an end point for deletions appeared to be widespread in that it was represented in 1/3-1/2 of the deletions characterized in each of the five mtDNA sources examined. In addition, several minor hot spots, where one end of two or three different deletions coincided, were also identified.

Radioimmunoassay screening of dried blood spot materials for benzoylecgonine.

Residual samples of blood spots, which are routinely collected on almost all newborns in the United States, can be used to determine seroprevalence information on newborns and maternal exposures to various substances, including drugs of abuse. By modifying a commercial radioimmunoassay (RIA) kit for urinary samples, one can use blood spotted on filter paper as a matrix to quantitate the cocaine metabolite benzoylecgonine (BE). BE is stable for long periods of time in blood spots and we were able to quantitatively extract it with aqueous buffer. There were no matrix effects of the blood spot eluate on the RIA, and excess lipid in the blood did not alter measurement of BE. By using standards made up of BE in negative blood spot eluate and calibrators of blood that were spiked with BE and then spotted on filter paper to determine extraction efficiency, low levels of BE in blood could be measured. The limit of detection was 5 ng/mL, and the limit of quantitation was 10 ng/mL. Levels of BE in blood collected at autopsy in eluates of blood spots were measured, and they established excellent correlation (r2 = 0.93) with gas chromatography/mass spectrometry measurements. To test this technology, residual blood spots on 545 infants from three states were analyzed for BE.

Pediatric family care: an interdisciplinary team approach.

Providing adequate psychosocial support for hospitalized pediatric patients and their families is sometimes difficult. An interdisciplinary team can help caregivers to assess needs and develop strategies for working with difficult patients and families. This paper describes the development of a pediatric family care team that has been effective in one hospital, outlining the general steps followed in establishing the team. A review of practical considerations related to team membership, costs, and procedures is followed by a discussion of the problems encountered. A case study demonstrates how the team helped meet the psychosocial needs of one pediatric patient.

Monoclonal antibodies evaluated for use in a screening assay for conjugates of human serum albumin and pyridoxal 5'-phosphate.

This enzyme immunoassay (EIA) was developed to measure pyridoxal 5'-phosphate bound to albumin (PLP-HSA) in human serum. The monoclonal antibody titer was 1:2000 and a sequential saturation analysis curve, prepared with samples containing from 10 to 1000 nmol/L, showed a 50% inhibition of antibody at 50 nmol of the conjugate per liter. The lower limit of detection for PLP-HSA was 10 nmol/L, a sensitivity 1000-fold greater than that for any potential interferent. When serum samples gave negative results in the assay, we compared the antigenicity of the principal sites for PLP binding on HSA. It was apparent that the preferred physiological site was not antigenic; however, three additional sites for PLP binding on HSA elicited comparable antibody avidity. This EIA is potentially quite sensitive and specific for PLP-HSA, but considerable additional effort is required to convert serum PLP to an HSA-bound form detectable in the assay, which limits its application as a screening method.