Primary Atomic Frequency Standards at NIST.

The development of atomic frequency standards at NIST is discussed and three of the key frequency-standard technologies of the current era are described. For each of these technologies, the most recent NIST implementation of the particular type of standard is described in greater detail. The best relative standard uncertainty achieved to date for a NIST frequency standard is 1.5×10(-15). The uncertainties of the most recent NIST standards are displayed relative to the uncertainties of atomic frequency standards of several other countries.

13C NMR study of how the oxyanion pKa values of subtilisin and chymotrypsin tetrahedral adducts are affected by different amino acid residues binding in enzyme subsites S1-S4.

A range of substrate-derived chloromethane inhibitors have been synthesized which have one to four amino acid residues. These have been used to inhibit both subtilisin and chymotrypsin. Using 13C NMR, we have shown that all except one of these inhibitors forms a tetrahedral adduct with chymotrypsin, subtilisin, and trypsin. From the pH-dependent changes in the chemical shift of the hemiketal carbon of the tetrahedral adduct, we are able to determine the oxyanion pKa in the different inhibitor derivatives. Our results suggest that in both the subtilisin and chymotrypsin chloromethane derivatives the oxyanion pKa is largely determined by the type of amino acid residue occupying the S1, subsite while binding in the S2-S4 subsites only has minor effects on oxyanion pKa values. Using free energy relationships, we determine that the different R groups of the amino acid residues binding in the S1 subsite only have minor effects on the oxyanion pKa values. We propose that the lower polarity of the chymotrypsin active site relative to that of the subtilisin active site explains why the oxyanion pKa is higher and more sensitive to the type of chloromethane inhibitor used in the chymotrypsin derivatives than in the subtilisin derivatives.

MR imaging in children with dermatomyositis: musculoskeletal findings and correlation with clinical and laboratory findings.

OBJECTIVE: The purpose of this study was to describe the musculoskeletal MR findings in childhood dermatomyositis and to correlate MR findings with indicators of disease activity such as muscle strength and serum levels of muscle enzymes. SUBJECTS AND METHODS: This prospective study included 24 children: 19 children with dermatomyositis and five control subjects. The diagnosis of dermatomyositis was established by clinical findings and serum levels of muscle enzymes in all patients, electromyography in six patients, and biopsy in four patients. At the time of the initial MR evaluation, patients were classified on the basis of clinical findings as having active (n = 15) or inactive (n = 4) disease. A total of 44 MR evaluations of patients with dermatomyositis were included in the study: 19 initial MR examinations and 12 examinations repeated after 4-6 months of therapy in patients with active disease. An additional 13 examinations were performed on five patients. Conventional T1-weighted (SE 600/20) and T2-weighted (SE 2500/80) spin-echo and fat-suppressed MR images were obtained. The T2-weighted images (TE = 80) were used for comparison. In addition to the visual assessment, ratios between the signal intensity of muscles (gluteus, adductors, quadriceps, and hamstrings) and the signal intensity of subcutaneous fat in the same tomographic section were calculated. RESULTS: All patients with clinically active disease (n = 15) had abnormal findings on MR studies, whereas those with inactive disease (n = 4) had normal MR findings. Signal-intensity ratios of patients with active disease were greater than those in control subjects, whereas the ratios in patients with inactive disease were not different from those in control subjects. After 4-6 months of therapy, the average signal-intensity ratios of treated patients with repeated MR evaluations (n = 12) differed from ratios obtained before therapy in the same patients, but were not different from the ratios in control subjects. Other MR findings observed were perimuscular edema, enhancement of the chemical-shift artifact, and inflammatory changes of subcutaneous fat. Fat-suppressed imaging enhanced visualization of abnormalities. Markedly abnormal signal intensities of muscle were associated with marked elevations of serum levels of muscle enzymes; however, abnormal MR findings were visualized with normal serum levels of muscle enzymes. CONCLUSION: Findings of active childhood dermatomyositis on T2-weighted MR images include increased signal intensity in affected muscle, perimuscular edema, enhanced chemical-shift artifact, and increased signal intensity in subcutaneous fat. After therapy, signal intensity of muscle returns to normal. These MR findings are enhanced on fat-suppressed images.(ABSTRACT TRUNCATED AT 400 WORDS)

Managing diversity in hospitals.

Hospital work force diversity, although potentially a source of creativity and improved problem solving, is often a source of political strife and the mistreatment of people based on their identification with one or another of the diverse groups that are employed in hospitals. Factors linked to these phenomena are discussed and are the basis for suggestions about how administrators can deal with the organizational pathologies that are often associated with unmanaged work force diversity.

Atrioventricular conduction in children of women with systemic lupus erythematosus.

The neonatal lupus syndrome consists of transient cutaneous lupus lesions or permanent congenital complete heart block (or hepatic fibrosis), or both, in infants born to mothers with systemic lupus erythematosus (SLE). The frequency of conduction abnormalities was examined in 86 offspring of 53 women affected by SLE. Electrocardiograms from the offspring demonstrated normal sinus rhythm in 84 of 86 offspring. The PR interval was normal for age (< 95th percentile) in 82 offspring and normal for heart rate in 81. Three children had a PR interval > 95th percentile (i.e., first-degree heart block) for both age and heart rate. The PR interval of the other 6 subjects with first-degree heart block for age or heart rate (> or = 95th percentile) was < or = 0.18 second. In contrast, using a rank assignment of PR intervals in relation to heart rate and age derived from published standards, grouped data indicated that heart rate adjusted for age was greater and PR interval adjusted for heart rate longer in offspring of mothers who had the onset of SLE before or during pregnancy than in the normal population; this observation did not hold for offspring whose mothers developed SLE after the pregnancy. These findings indicate that offspring of mothers with SLE, even in the absence of an abnormal electrocardiogram, may have experienced a maternal internal environment that produces subclinical changes in atrioventricular conduction. However, newborns with a normal pulse rate are unlikely to have significant abnormalities in atrioventricular conduction and do not need screening electrocardiograms at birth.

Fat-suppressed MR imaging of myositis.

A hybrid fat-suppression sequence in magnetic resonance (MR) imaging was used to evaluate inflammatory muscle disorders in seven children: five patients with dermatomyositis, one patient with vasculitis, and one patient with viral myositis. Fat-suppressed multisection axial images obtained with the same repetition and echo times as those used to obtain standard spin-echo (SE) images enabled direct comparison of images, with little variation of T1 and T2 weighting. In six patients, the contrast on images obtained with T2 fat suppression was 15%-20% greater than contrast on conventional T2-weighted SE images. In all seven patients, the subjective judgment was that T2-weighted fat-suppression sequences improved visualization of muscle abnormalities. It is concluded that T2 fat suppression is useful in evaluation of inflammatory muscle disorders in children because it increases contrast and eliminates fat as a cause of muscle abnormality.

Serial magnetic resonance imaging in juvenile dermatomyositis.

Magnetic resonance imaging (MRI) was used to follow the course of juvenile dermatomyositis from the onset of disease through resolution of a primary relapse. The signal intensity of the T2-weighted image of involved muscles was elevated during periods of disease activity, and returned to approximately normal levels with effective suppression of disease activity. T1-weighted images of involved muscles remained approximately normal despite disease activity.

Carpo-metacarpal growth disturbance and the assessment of carpal narrowing in children with juvenile rheumatoid arthritis.

Second metacarpal length (M2), radio-metacarpal length (RM), and intermetacarpal width (W) were measured on 96 radiographs in 52 children with polyarticular juvenile rheumatoid arthritis (JRA), and compared with body height and skeletal maturation in order to: (1) differentiate between processes resulting in retardation of bone growth and those producing delay in skeletal maturation; (2) assess the severity and progression over time of such retardation; and (3) assess the impact of retardation of the second metacarpal on the assessment of carpal narrowing in children with JRA. All measurements were converted into z scores (the units of standard deviation above or below the normal mean for each measurement) based on published norms. Retardation of M2 (mean z scores -0.91) began earlier and was more severe compared with retardation of height (mean z score -0.25). This disproportion widened with increasing duration of disease. That this primarily represents a disturbance in M2 growth rather than a secondary effect due to altered maturation is suggested by the bone ages being normal (mean z score 0.14) and the absence of premature closure of the metacarpal physes. Z scores for RM/W (mean -3.53) were at least 1 Z more negative than for corresponding measurements of RM/M2 (mean -2.41) in 47 (90.4%) children and the mean difference between the z scores for RM/W was -1.12. This discrepancy between RM/W and RM/M2 was eliminated by correcting for the reduction in M2.

Distal interphalangeal joint abnormalities in children with polyarticular juvenile rheumatoid arthritis.

Involvement of the distal interphalangeal (DIP) joints was noted radiographically in 24 (43.6%) of 55 patients with polyarticular juvenile rheumatoid arthritis. DIP changes were apparent later in the course of the disease and were less severe than in other affected joints. Soft tissue swelling and joint space narrowing were the most frequent abnormalities in the DIP joints. Erosive changes and angular deformities were uncommon. There was no significant correlation between DIP joint involvement and sex, age at presentation, involvement of the hands and wrists at presentation, or positivity of either rheumatoid factor or antinuclear antibody. There was a strong correlation between the presence of extraarticular signs and symptoms and involvement of the DIP joints; however, this may reflect the greater severity of the disease in these patients generally.

Magnetic resonance imaging appearance of the muscles in childhood dermatomyositis.

Documentation of muscle involvement in a child thought to have dermatomyositis may require the performance of invasive procedures such as electromyography and/or muscle biopsy. We describe four patients with dermatomyositis in whom magnetic resonance imaging (MRI) demonstrated the muscle involvement. The involved muscles had increased signal intensity on the T2-weighted images (SE 2500/80) and normal appearance on the T1-weighted images (SE 600/20). The involvement of the muscles was not uniform. There was good correlation between the distribution of muscle involvement by MRI and functional testing. Follow-up MRI scans in patients with favorable outcome demonstrated that the affected muscles had returned to normal signal intensity. Although the MRI findings are not specific, in the proper clinical context they may be helpful in establishing the diagnosis of dermatomyositis. MRI may also be used in establishing an appropriate muscle biopsy site. In addition, MRI may be used for monitoring the progress of the disease.

Children with juvenile rheumatoid arthritis at school. Functional problems, participation in physical education. The implementation of Public Law 94-142.

Parents of 135 children with juvenile rheumatoid arthritis (JRA) completed a mailed questionnaire about problems at school. Writing was the most frequently reported difficulty, with hand involvement causing more problems than decreased mobility. Compared to children with pauciarticular JRA, those with polyarticular or systemic JRA were significantly more likely to miss school, experience problems, participate less in physical education, have an Individualized Educational Plan (IEP) developed, and receive related services. Only 39 parents had heard of PL 94-142, and only 21 of those could define the federal law. Twenty children had an IEP within the previous two years. Possible deficiencies in the implementation of PL 94-142 were discovered. This study demonstrates that the treatment of children with JRA should include efforts to: 1) identify and remediate potential performance limitations before they become problematic at school; 2) communicate this information to parents and school personnel; 3) and improve parents' awareness and understanding of PL 94-142.

Factor VIII related antigen and childhood rheumatic diseases.

Factor VIII related antigen (FVIIIRAg) levels were measured in the plasma of 63 children with rheumatic diseases and 20 controls. High levels were found in patients with systemic juvenile arthritis, systemic lupus erythematosus, dermatomyositis and systemic forms of vasculitis. The amount of circulating FVIIIRAg seemed to be independent of values for erythrocyte sedimentation rate, C-reactive protein and fibrinogen, implying that it was not just another acute phase reactant. Rather, a high level of circulating FVIIIRAg most likely reflects the presence of vascular endothelial injury, and this test may be useful in monitoring disease activity in children with rheumatic diseases in which vasculitis is present.

The NIST Automated Computer Time Service.

The NIST Automated Computer Time Service (ACTS) is a telephone time service designed to provide computers with telephone access to time generated by the National Institute of Standards and Technology at accuracies approaching 1 ms. Features of the service include automated estimation by the transmitter of the telephone-line delay, advanced alert for changes to and from daylight saving time, and advanced notice of insertion of leap seconds. The ASCII-character time code operates with most standard modems and computer systems. The system can be used to set computer clocks and simple hardware can also be developed to set non-computer clock systems.

Juvenile dermatomyositis: histological findings and pathogenetic hypothesis for the associated skin changes.

Skin biopsies from patients with scleroderma and juvenile dermatomyositis (DM) share many histologic features. Characteristics common to both diseases are particularly evident in the dermal microvasculature and include endothelial swelling and concentric thickening of the vascular basement membrane. Biopsies performed on 3 patients with the severe vasculitic form of juvenile DM showed these changes as well as dropout of vessels and linear deposition of collagen. The latter findings, seen late in the course of the disease, are indistinguishable from those of advanced scleroderma. A hypothesis is presented which attempts to relate these histological findings to a common underlying pathophysiologic mechanism.

HLA-DR and MT associations with the clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis.

Significant HLA-DR and MT associations were observed with certain clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis (PO-JRA). An increase in the MTI frequency was found in 56 children with PO-JRA in comparison to 95 normal controls. This association was limited to children with a younger age of onset (less than 6 years) and a persistent pauciarticular course. An increase in HLA-DRW8 and a decrease in DR4 were associated with a younger age of onset and antinuclear antibody (ANA) seropositivity. In addition, an increased frequency of DR5 was seen in ANA positive children. All of these HLA-DR and MT associations were independent of coassociating Ia specificities.