Reproducibility and predictive values of routine blood pressure measurements in children. Comparison with adult values and implications for screening children for elevated blood pressure

A study of the variability of blood pressure was conducted among a total of 780 Massachusetts children, 335 children in East Boston and 445 children in Brookline, ages 8-18 years. All children had their blood pressure measured with a standard mercury sphygmomanometer in a school setting on four visits one week apart with three measurements per visit. In East Boston, repeat measurements were made for the same children for four consecutive years. A nested random effects model was used to estimate between- and within-visit variance components. For children aged 8-12 years, these were, respectively, 33.1, 12.0 in boys and 31.2, 11.1 in girls for systolic blood pressure and 57.7, 21.3 in boys and 56.6, 22.6 in girls for systolic muffling blood pressure (Korotkoff phase 4). For children aged 13-18 years of age, they were, respectively, 41.1, 11.8 in boys and 35.2, 12.2 in girls for blood pressure and 40.6, 15.5 in boys and 36.1, 11.4 in girls for diastolic blood pressure (Korotkoff phase 5). Within-person variability for systolic pressure was comparable to previously published data for 434 white adults ages 30-49 years not on antihypertensive medications; however, within-person variability for diastolic pressure was considerably higher in the children, accounting for over 75% of total variability among 8-12-year-old children, compared with 27% for adults. No meaningful effects of age, sex, or blood pressure level on variability of systolic pressure were found. However, age and level of blood pressure each had a large and independent inverse association with variability of diastolic pressure; variance components for younger children (ages 8-12 years) and children with low diastolic pressure (less than 60 mmHg) were approximately twice as large as for older children (ages 13-18 years) and children with diastolic pressure greater than or equal to 60 mmHg, respectively. Finally, predictive value estimates of blood pressure are provided for particular age-sex groups to enable one to efficiently identify children whose true mean level of blood pressure exceeds the 90th percentile for their age-sex group with minimum misclassification. Because of the substantial variability of diastolic pressure in young children, resulting in relatively low predictive value estimates, systolic pressure (either alone or in combination with diastolic pressure) may be more useful as the primary tool for screening children under age 13 years for high blood pressure.     

Potential role of paramyxoviruses in multiple sclerosis

At the present time, the cause of multiple sclerosis (MS) remains unknown, although it seem likely that one or more infectious agents triggers the disease, perhaps through an autoimmune mechanism. In this article, evidence linking the paramyxoviruses, canine distemper, and measles to MS is reviewed.     

Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development.

Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.     

Identifying Myelopathy Caused by Thoracic Syringomyelia: A Case Report

Myelopathy is a form of neurological disease caused by compression of the spinal cord. Upper and lower quarter screens are commonly used in identifying myelopathy, although most of the screen components demonstrate poor or unstudied diagnostic value. The purpose of this case report is to describe the diagnostic process in detecting syringomyelia, an intramedullary lesion that may cause myelopathy. The patient was a 47-year-old female with a thoracic syrinx that was discovered by spinal magnetic resonance imaging (MRI) following a complicated and delayed clinical diagnostic course. Following surgical intervention and a two-week inpatient rehabilitation stay, the patient was discharged using a rolling walker for ambulation and was performing most transfers with modified independence. A complicating pattern of signs and symptoms combined with a diagnostic process guided by poorly studied screen components demonstrates the diagnostic dilemma associated with identifying the cause of myelopathy within the thoracic spine. This also indicates the need for further investigation of individual and clustered components of the neurological screen to improve the ability to identify patients in need of complete imaging studies in a more timely fashion.     

Leucine excess and niacin status in rats

Young rats were fed a niacin-deficient diet with and without 15 g/kg supplementary L-leucine. Both groups grew slowly for 5 wk and showed no difference in the severity of their condition. Nor did their 14CO2 production differ after intraperitoneal dosing with [methylene-14C]tryptophan. In a 2 X 3 X 3 multifactorial trial with a niacin-free basal diet, the effects of 15 g/kg supplementary leucine were compared with isonitrogenous glycine supplements. Half of the diets were also marginally deficient in pyridoxine and resulted in slower growth, but no interactive effect with leucine. The leucine supplement depressed excretion of N1-methylnicotinamide only in the groups receiving supplementary tryptophan. It was also associated with a depression in the level of nicotinamide nucleotides in the rats' livers that was not eliminated by addition of either 25 mg/kg nicotinic acid or 1 g/kg L-tryptophan. The existence of pellagra in Hyderabad, India, has been hypothesized to result from excessive leucine in the diet rather than from a deficiency of niacin/tryptophan. Neither our results with rats nor those of others appear to provide support for this hypothesis.     

Disposition, metabolism, and excretion of U-71038, a novel renin inhibitor peptide, in the rat

The in vivo fate of U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi [CHOHCH2] Val-Ile-(aminomethyl)pyridine), a potent renin inhibitor, was investigated in rats by single iv administration of tritium-labeled drug at a dose level of 5 mg/kg. The plasma concentrations of drug-related radioactivity diminished very rapidly during the first hour after dosing, with the initial concentrations measured at 2 min falling by more than 95% during the first 30 min. Estimates of the approximate half-life of this earliest phase of the plasma concentration-time curve gave an average value of 4 min. The residual amount of radioactivity after 30 min was cleared from the plasma more slowly, with trace levels still detected 48 hr after dosing. The radioactivity was recovered chiefly (91% of the dose) in feces, indicating biliary clearance as the primary route of elimination from systemic circulation. Urinary recoveries averaged 4% of the dose. Radio-HPLC profiling of plasma, urine, and bile extracts detected only a single radioactive drug-related component in these samples. Preparative HPLC was used to isolate this component from bile; mass spectral comparison to U-71038 confirmed its identity as the unchanged drug. Therefore, U-71038 does not undergo significant systemic metabolism in this species and is eliminated in bile and urine in intact form. Distribution of drug-related radioactivity was very rapid to most of the organs and tissues that were sampled, with the exception of very limited penetration into the central nervous system. Highest tissue levels of tritium were generally found in organs associated with elimination (liver, intestine, kidney) and in thyroid.     

Assessment of 18F gaseous releases during the production of 18F-fluorodeoxyglucose

Fluorodeoxyglucose labeled with 18F (18F-FDG) is the most commonly used radiopharmaceutical in positron emission tomography (PET). Fluorine-18-labeled FDG is used as a diagnostic tool in PET studies to monitor the physiology of the brain, diagnose heart function and disease, and to image cancerous tumors. At the University of California, Los Angeles (UCLA), three cyclotrons produce [18F]-fluoride ion using 18O-enriched water targets. Fluorine-18, which has a half-life of 109.8 min, is produced using an 18O(p.n.)18F reaction and is chemically processed to yield 18F-FDG. This study presents data which demonstrate that during the radiochemical processes involved in the production of 18F-FDG, gaseous effluent containing 18F is released. Forty cyclotron production runs with average end of cyclotron bombardment activities of 15.9 +/- 1.88 GBq (430 +/- 50.8 mCi) and end of radiochemical synthesis activities of 5.40 +/- 1.27 GBq (146 +/- 34.3 mCi) yield 18F gaseous effluent releases ranging from 0 to 2560 MBq (0 to 69.2 mCi) with a mean of 437 MBq (11.8 mCi). Temporal correlation of the 18F gaseous releases during 18F-FDG radiochemical production has tied the 18F release to the addition of the glucose precursor (mannotriflate) and ethyl ether in the radiochemical processing. The results are presented in terms of activities released and dilution factors required from the release stack point to maintain controlled (occupational) and uncontrolled (public) area limits in accordance with the recommendations of the International Commission on Radiological Protection and the regulatory requirements of the federal government.     

Assessment of the role of nonheme-iron availability in iron balance

To assess the nutritional relevance of absorption studies that use extrinsically labeled single meals, we developed a method for measuring nonheme-iron absorption from the diet and compared the results with absorption from single meals. When subjects consumed their usual diet, there was good agreement between dietary absorption (6.4%) and representative single meals fed in the laboratory (6.1%). Nonheme-iron availability, as estimated by a model that incorporated the effect of both enhancers and inhibitors, correlated significantly with absorption from single meals but not with dietary absorption. When the diet was modified to promote iron absorption maximally, dietary absorption increased only slightly (8.0%) and remained significantly lower than it was from single meals (13.5%). With an inhibitory diet, the decrease in absorption from single meals was similarly exaggerated. These results indicate that in the context of a varied Western diet, nonheme-iron bioavailability is less important than absorption studies with single meals would suggest.