The variability of urinary cotinine levels in young children: implications for measuring ETS exposure.

This study examined the within-subject variability of urinary cotinine levels in young children (aged = 0.6-7.2 years) of smoking parents to determine the number of urine samples needed to provide accurate estimates of exposure to environmental tobacco smoke (ETS) for different time intervals. Secondary analyses were conducted of five independent studies (N = 376), in which multiple urinary cotinine measures had been collected over time periods up to 13 months. Over measurement periods of 4-15 days, the within-subject cotinine levels varied 3-5 times more than would be expected based on measurement error alone. Over 7-13 months, the within-subject variability was 10-20 times higher than would be expected based on the measurement error. Findings indicated that cotinine measures from single urine samples provided highly accurate estimates of only recent exposure (i.e., 2-3 days; rho = 0.99). To achieve similarly precise estimates of the mean cotinine level of an individual child over 4-15 days, up to nine urine samples may be necessary. Up to 12 urine samples may be required to achieve similarly precise estimates of ETS exposure over a 4- to 13-month period. Epidemiologic and clinical research on ETS exposure in children can benefit from multiple urine samples (a) to accurately measure average exposure at the level of the individual child, (b) to describe temporal patterns, (c) to detect incidences of peak exposure that would remain underrecognized if monitoring is limited to a single time point, and (d) to establish stable baseline levels and endpoints based on urine samples collected over clinically relevant time periods.     

Nonradioactive Northern blotting with biotinylated and digoxigenin-labeled RNA probes

The application of nonradioactive RNA probes for Northern blotting offers the advantage of a rapid turn-around time for results without the loss of sensitivity for target mRNA detection. However, a problem that has impeded the widespread use of nonradioactive RNA probes for use in Northern blotting is the difficulty in stripping these probes from nylon membranes after hybridization. In this report we describe two protocols for stripping digoxigenin (Dig)-labeled RNA probes from nylon membranes. One protocol utilizes a phosphate-buffered formamide stripping solution to remove nonchemically modified (regular) RNA probes while the other method utilizes strippable probes that were produced with a chemically modified nucleotide (CTP) and removed by a specific stripping solution. This latter method was developed by Ambion Inc. and is called Strip-EZ. We also describe a protocol for the detection of two separate rat mRNAs using both biotin and digoxigenin-labeled RNA probes that does not require stripping the membrane after hybridization. Finally, we describe the use of another new labeling technology, called Chem-Link, that quickly and conveniently labels RNA for use in Northern blotting.     

Microelectrochemistry on Surfaces with the Scanning Electrochemical Microscope (SECM)

The scanning electrochemical microscope (SECM) is one of the scanning probe techniques that have been developed following the introduction of the scanning tunneling microscope. The approaches that have been used to modify surfaces with lateral resolution using the SECM are presented and discussed. These approaches made it possible to drive a variety of microelectrochemical reactions on surfaces, as well as to study the mechanism of these processes due to the unique advantages that the SECM offers.     

All‐Hex Mesh Generation via Volumetric PolyCube Deformation

While hexahedral mesh elements are preferred by a variety of simulation techniques, constructing quality all‐hex meshes of general shapes remains a challenge. An attractive hex‐meshing approach, often referred to as sub‐mapping, uses a low distortion mapping between the input model and a PolyCube (a solid formed from a union of cubes), to transfer a regular hex grid from the PolyCube to the input model. Unfortunately, the construction of suitable PolyCubes and corresponding volumetric maps for arbitrary shapes remains an open problem. Our work introduces a new method for computing low‐distortion volumetric PolyCube deformations of general shapes and for subsequent all‐hex remeshing. For a given input model, our method simultaneously generates an appropriate PolyCube structure and mapping between the input model and the PolyCube. From these we automatically generate good quality all‐hex meshes of complex natural and man‐made shapes.     

Effect of pindolol on hormone secretion and body temperature: partial agonist effects

Pindolol has been shown to be a partial agonist at 5-HT1A receptors in preclinical studies. It has also been reported to inhibit the effects of other 5-HT1A partial agonists such as ipsapirone and buspirone on hormone secretion and body temperature in man, indicating its antagonist action at 5-HT1A receptors in man. To determine if pindolol has 5-HT1A agonist as well as antagonist effects in man, pindolol, 30 mg, p.o. and placebo, were given single blind in random order to 23 normal men with indwelling venous catheters and its effects on hormone secretion and body temperature noted. Pindolol significantly increased basal plasma cortisol concentrations, whereas it decreased plasma prolactin (PRL) concentrations and body temperature. The increase in plasma cortisol due to pindolol suggests a 5-HT1A agonist action and is consistent with a 5-HT1A partial agonist mechanism in man whereas the PRL effects are consistent with an antagonist action at 5-HT1A receptors. The effects of pindolol on plasma cortisol concentration and body temperature were significantly negatively correlated. Furthermore, these results indicate significant differences in the 5-HT1A-dependent regulation of PRL and the hypothalamo-pituitary-adrenal (HPA) axis and body temperature, and suggest that human basal PRL secretion is tonically stimulated by 5-HT1A mechanism whereas the HPA axis and body temperature are not. Since rodent studies suggest differences in 5-HT1A receptor sensitivity between males and females, the results reported here need to be replicated in females. These differences in the effect of pindolol are discussed in terms of receptor reserve theory.     

The importance of dietary control in metabolic studies of manic-depressive patients

Diet control of electrolyte intake appears to diminish day to day variation of urinary electrolyte output. Urine sodium concentration is more affected by diet control than potassium, possibly due to the greater variation in sodium ingestion on uncontrolled diets. The coefficient of variation of urinary sodium excretion on the controlled diet was not significantly greater than the variation in sodium ingestion. These experimental results suggest that controlled diets reduce random variation in sodium and potassium excretion and therefore enhance the possibility of observing illness-related biological changes.     

A study of injected dose for brain mapping on the ECAT HR+: activation maps for a parametric verbal working memory task

The success of the 15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (the N-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of 15O-water. At each activity level the volunteers were required to perform four different levels of the N-back task, a task in which a letter displayed on a monitor is matched with the letter displayed N letters previously. With increasing N, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of 15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of 15O-water around 15 mCi. For this particular choice of N-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose.