Parental punitive discipline, negative life events and gene-environment interplay in the development of externalizing behavior.

BACKGROUND: To investigate the extent to which three putative 'environmental' risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior. METHOD: The sample consisted of 2647 participants, aged 12-19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively. RESULT: Genetic influences overlapped for externalizing behavior and each 'environmental' risk, indicating gene-environment correlation. When controlling for the gene-environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior. CONCLUSION: The magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene-environment correlation.

Relationship between antisocial behaviour, attention-deficit hyperactivity disorder and maternal prenatal smoking.

BACKGROUND: There is substantial evidence that maternal smoking during pregnancy is associated with both antisocial behaviour and symptoms of attention-deficit hyperactivity disorder (ADHD) in offspring. However, it is not clear whether maternal smoking during pregnancy is independently associated with antisocial behaviour or whether the association arises because antisocial behaviour and ADHD covary. AIMS: To examine the relationship between maternal smoking during pregnancy, antisocial behaviour and ADHD in offspring. METHOD: Questionnaires concerning behaviour and environmental factors were sent to twins from the CaStANET study and data analysed using a number of bivariate structural equation models. RESULTS: Maternal prenatal smoking contributed small but significant amounts to the variance of ADHD and of antisocial behaviour. The best fitting bivariate model was one in which maternal prenatal smoking had a specific influence on each phenotype, independent of the effect on the other phenotype. CONCLUSIONS: Both antisocial behaviour and ADHD symptoms in offspring are independently influenced by maternal prenatal smoking during pregnancy.

Tolerance of the normal canine brain to epithermal neutron irradiation in the presence of p-boronophenylalanine.

Twelve normal dogs underwent brain irradiation in a mixed-radiation, mainly epithermal neutron field at the Brookhaven Medical Research Reactor following intravenous infusion of 950 mg of 10B-enriched BPA/kg as its fructose complex. The 5 x 10 cm irradiation aperture was centered over the left hemisphere. For a subgroup of dogs reported previously, we now present more detailed analyses including dose-volume relationships, longer follow-ups, MRIs, and histopathological observations. Peak doses (delivered to 1 cm3 of brain at the depth of maximum thermal neutron flux) ranged from 7.6 Gy (photon-equivalent dose: 11.8 Gy-Eq) to 11.6 Gy (17.5 Gy-Eq). The average dose to the brain ranged from 3.0 Gy (4.5 Gy-Eq) to 8.1 Gy (11.9 Gy-Eq) and to the left hemisphere, 6.6 Gy (10.1 Gy-Eq) to 10.0 Gy (15.0 Gy-Eq). Maximum tolerated 'threshold' doses were 6.7 Gy (9.8 Gy-Eq) to the whole brain and 8.2 Gy (12.3 Gy-Eq) to one hemisphere. The threshold peak brain dose was 9.5 Gy (14.3 Gy-Eq). At doses below threshold, some dogs developed subclinical MRI changes. Above threshold, all dogs developed dose-dependent MRI changes, neurological deficits, and focal brain necrosis.

Causes of excessive bitewing exposure: results of a survey regarding radiographic equipment in New York.

OBJECTIVE: The purpose of this study was to identify the causes of excessive exposure in those dental practices that were found to use exceptionably high levels of radiation in bitewing radiography. STUDY DESIGN: Using the parameters of the Dental Exposure Normalization Technique survey, certified radiation equipment safety officers conducted on-site inspections of 186 intraoral x-ray machines in 77 dental facilities. RESULTS: In 23 facilities, the safety officers identified 43 units (23.1%) that delivered entrance exposures greater than 10% in excess of the upper limit of recommended exposures. For each of 27 (63%) of these units, the cause of the elevated exposure was clearly identifiable. CONCLUSIONS: The factors contributing to increased exposure, listed from most frequent to least frequent, were as follows: improper processing, kilovoltage miscalibration, use of D-speed techniques with E-speed film, use of newly installed units with default timer settings that were too high, exposure timer failure, and insufficient half-value layer. Only 18% of the facilities surveyed reported using E-speed film.

Single-and dual-energy CT with monochromatic synchrotron x-rays.

We explored the potential for clinical research of computed tomography (CT) with monochromatic x-rays using the preclinical multiple energy computed tomography (MECT) system at the National Synchrotron Light Source. MECT has a fixed, horizontal fan beam with a subject apparatus rotating about a vertical axis; it will be used for imaging the human head and neck. Two CdWO4-photodiode array detectors with different spatial resolutions were used. A 10.5 cm diameter acrylic phantom was imaged with MECT at 43 keV and with a conventional CT (CCT) at 80 kVp: spatial resolution approximately equal to 6.5 line pairs (lp)/cm for both; slice height, 2.6 mm for MECT against 3.0 mm for CCT; surface dose, 3.1 cGy for MECT against 2.0 cGy for CCT. The resultant image noise was 1.5 HU for MECT against 3 HU for CCT. Computer simulations of the same images with more precisely matched spatial resolution, slice height and dose indicated an image-noise ratio of 1.4:1.0 for CCT against MECT. A 13.5 cm diameter acrylic phantom imaged with MECT at approximately 0.1 keV above the iodine K edge and with CCT showed, for a 240 micrograms I ml-1 solution, an image contrast of 26 HU for MECT and 13 and 9 HU for the 80 and 100 kVp CCT, respectively. The corresponding numbers from computer simulation of the same images were 26, 12, and 9 HU, respectively. MECT's potential for use in clinical research is discussed.

In vivo MR imaging and spectroscopy using hyperpolarized 129Xe.

Hyperpolarized 129Xe has been used to obtain gas phase images of mouse lung in vivo, showing distinct ventilation variation as a function of the breathing cycle. Spectra of 129Xe in the thorax show complex structure in both the gas phase (-4 to 3 ppm) and tissue-dissolved (190-205 ppm) regions. The alveolar gas peak shows correlated intensity and frequency oscillations, both attributable to changes in lung volume during breathing. The two major dissolved peaks near 195-200 ppm are attributed to lung parenchyma and to blood; they reach maximum intensity in 5-10 s and decay with an apparent T1 of 30 s. Another peak at 190 ppm takes 20-30 s to reach maximum; this must represent other well-vascularized tissue (e.g., heart and other muscles) in the thorax. The maximum integrated area of the tissue components reaches 30-80% of the maximum alveolar gas area, indicating that imaging at tissue frequencies can be achieved.

Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex.

PURPOSE: Intraperitoneal (IP) injection of the solubilized fructose complex of L-p-boronophenylalanine (BPA-F) produced higher boron concentrations in a rat brain tumor model than was possible using intragastric (IG) administration of L-p-boronophenylalanine (BPA). The effectiveness of IP BPA-F was compared to IG BPA in boron neutron capture therapy irradiations of the 9L rat brain tumor model. METHODS AND MATERIALS: The time course of boron accumulation in tumor and normal tissues was determined in male F344 rats bearing either SC or intracerebral 9L gliosarcomas following a single IP injection of BPA-F. On day 14 after inoculation of intracranial tumors, rats were irradiated with single doses of either: 250 kVp X rays; the thermal neutron beam of the Brookhaven Medical Research Reactor following IG administration of BPA; or thermal neutrons following IP injection of BPA-F. Magnetic resonance imaging was used to visualize the tumor scars and to assess damage to the normal brain in long-term survivors. RESULTS: 4 h after IP injection of 1200 mg/kg of BPA-F the boron concentrations in tumor, blood, and normal brain were 89.6 +/- 7.6, 27.7 +/- 2.8 and 17.5 +/- 1.5 micrograms 10B/g, respectively. Two IG doses of BPA (750 mg/kg each, 3 h apart) produced 39 +/- 5, 12 +/- 1 and 10 +/- 1 micrograms 10B/g in tumor, blood and brain, respectively at 5 h after the second dose. Three groups of rats were treated with thermal neutrons: one following IG BPA and two groups following IP BPA-F. The total physical absorbed doses to the tumor in the three BNCT groups were 15.5 Gy (IG BPA, n = 12), 17.0 Gy (IP BPA-F, n = 8), and 31.5 Gy (IP BPA-F, n = 8), respectively. The median survival of the untreated controls was 22 days. The median survival of the rats treated with 22.5 Gy of 250 kVp X rays (n = 23) was 35 days with 20% long-term survivors. Fifty percent of the rats in the IG BPA + thermal neutrons group survived over 1 year. All rats in both groups that received IP BPA-F + thermal neutrons have survived over 8 months. Magnetic resonance imaging of the brains of the long-term boron neutron capture therapy survivors showed a scar at the site of tumor implantation in all animals. In the IP BPA-F high-dose group one rat showed evidence of edema and one rat showed a fluid-filled cyst replacing the tumor. CONCLUSION: The use of IP BPA-F has significantly improved long-term survival compared to IG BPA. The high percentage of long-term tumor control (100%, n = 16) in the intracerebral rat 9L gliosarcoma brain tumor model, together with little or no damage to the surrounding normal brain in the majority of surviving animals, demonstrate the substantial therapeutic gain produced by boron neutron capture therapy.

Small animal MRI at 0.35 Tesla: growth and morphology of intra-organ murine tumors.

A whole-body small animal radiofrequency coil was designed and built for use with a 0.35 Tesla clinical magnetic resonance imager. The primary motivation for this work was to evaluate the effectiveness of this system for small animal magnetic resonance imaging of tumor-bearing mice. This noninvasive technique is shown to provide high resolution whole-body images of mice, to be capable of detecting intra-organ tumors, and to be useful for evaluating tumor size and growth. Its potential for monitoring response to experimental therapeutic regimens is also noted. Two tumor models were examined--colon adenocarcinoma MCA-38 and human ASPC-1 pancreatic adenocarcinoma.

Effects of radiotherapy on mandibular reconstruction plates.

The radiation dose in the vicinity of metal mandibular implants was measured using lithium fluoride (TLD-100) thermoluminescent dosimeters. Dosimeters were positioned in contact with Vitallium and stainless steel (AO) reconstruction plates. Simple transmission was measured with a solid state detector removed from the implant at a depth of 2.5 cm in a polystyrene phantom. The measurements were made for a 6 mV photon beam from a linear accelerator. At points in front of, but in contact with the metal implants, the dose was greater by 23 percent for Vitallium and 17 percent for stainless steel than that with no implant. At contact behind the implant, the dose was reduced considerably: 14 percent for Vitallium and 13 percent for stainless steel. At remote points behind the implant, the dose was reduced due to attenuation.

Isointense model for the evaluation of tumor-specific MRI contrast agents.

An isointense model has been developed to evaluate the applicability of putative tumor-specific MRI contrast agents. Data for tissue relaxation measurements in the presence of Mn(III)TPPS4 are used to illustrate the model. The concentration of contrast agent in tumor tissue required for a tumor/normal tissue signal difference-to-noise ratio of 5 (delta SNR = 5) is determined for a T1 weighted pulse sequence and several hypothetical tumor/normal tissue pairs. The impact of various contrast agent characteristics including initial tumor/normal tissue relaxation values, differential uptake of contrast agent, and in vivo relaxivity are considered. Isointense tumor/normal tissue with longer initial relaxation times are shown to be more affected by the presence of contrast agent. In addition those with initially longer relaxation times have less rigorous requirements for tumor specificity. Typically, a normal tissue/tumor uptake ratio of 1:2 increases the concentration required for delta SNR = 5 by a factor of two compared to that of exclusive uptake in tumor. For the T1 weighted pulse sequence employed, the concentration required for delta SNR = 5 is shown to be linear with the inverse of in vivo relaxivity for the hypothetical tissues considered. The isointense model is also extended to predict the field dependence of tumor-specific contrast enhancement by Mn(III)TPPS4.

Proton relaxation enhancement by manganese(III)TPPS4 in a model tumor system.

Managanese(III)tetraphenylporphine sulfonate [Mn(III)TPPS4] has been investigated as a tumor specific paramagnetic contrast agent for magnetic resonance imaging (MRI) of L1210 solid tumors in mice. Mn(III)TPPS4 was found to clear rapidly from the blood and concentrate in the kidneys, tumor and liver. Although relatively high ratios of tumor to normal tissues could be obtained (e.g., greater than 90 for tumor/muscle), the kidneys were found to have the highest concentration of the metalloporphyrin at all doses and time periods tested. A significant decrease in the longitudinal relaxation time was measured for excised tissues (kidney, tumor, liver, muscle) from mice that were treated with Mn(III)TPPS4. A linear correlation was observed between the longitudinal relaxation rate determined for L1210 tumor and the corresponding concentration of Mn(III)TPPS4 found at various injected doses and time intervals between the injection and analysis. A small animal radiofrequency receiver coil designed for use with a 0.15-T clinical imager was employed to evaluate the ability of Mn(III)TPPS4 to selectively increase the signal intensity of the implanted L1210 tumor. The images show a conspicuous enhancement in the contrast between the tumor and adjacent tissue upon treatment with this agent. The results indicate that Mn(III)TPPS4 is a useful prototype paramagnetic metalloporphyrin MRI contrast agent with a significant affinity for the L1210 tumor.

Activated charcoal filter counting for radioiodine effluent concentration determination in protein iodinations.

Regulatory agencies have recently placed emphasis upon quantification of 125I released to the environment during protein iodinations at radioiodination facilities. This necessitates air sampling in order to determine the concentration of 125I in the effluent. Air sample trapping mechanisms generally employed are activated charcoal filters. Difficulty arises in quantifying the activity of 125I trapped because of the attenuation of the 125I decay photons by the charcoal. Evaluation of the activity incident upon commercially available filters using a scintillation detector and large detector source separation is considered here. It is demonstrated that the activity in the filter may be treated as an exponential distribution within an attentuating matrix. This treatment essentially adds a constant correction factor to the counting efficiency of a given geometry for a filter-affluent flow rate combination. Finally, it is shown that an approximation assuming a uniform distribution of activity produces a large error in correction factor to the counting efficiency for the filters examined.

Protein radioiodination in a radioassay laboratory: evaluation of commercial Na125I reagents and related biohazards.

Three commercial Na125I solutions (Amersham, New England Nuclear, and Union Carbide) have been examined with respect to multiple parameters affecting their use in the radioiodination of three representative peptides (insulin, growth hormone, and gastrin): % of radioiodine incorporation in protein; immunoreactivity and non-specific binding properties of the radiolabeled proteins; pH, volatility, and radionuclidic purity of radioiodine solutions; and vial construction with respect to multidose use. All three commercial Na125I produced radioiodinated proteins of good quality for use in radioligand assays. The radioiodines differed with respect to the amount of iodine released during initial vial opening as a consequence of different pH levels: 15 nCi/mCi (pH 12.5) to 1.0 microCi/mCi (pH 7.5). Two of the three products were shipped in vials with poor construction with respect to multidose use. Selection of a radioiodine was therefore reduced to the secondary considerations of iodine volatility and vial construction. The volatilized radioiodine observed during the spill of millicuries quantities of unbuffered pH 7.5 Na125I was 14 microcuries per millicurie within the first 30 minutes. One thickness of rubber gloves reduced potential skin contamination from an accidental spill to insignificant levels: 20-30 picocuries per microcurie. Common good housekeeping procedures: i.e. rubber gloves, laboratory coat and a fume hood were found to be sufficient protection to eliminate most radioiodine volatility and contamination hazards associated with protein radiolabeling procedures.