The complex enterprise of modelling prenatal exposure to cigarettes: what is ‘enough’?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement.
Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.     

The effect of light intensity on double bond conversion and flexural strength of a model, unfilled dental resin.

OBJECTIVE: Two visible light sources (tungsten-quartz-halogen and xenon-arc plasma) with vastly different intensities (200 and 1800 mW/cm(2)) but similar spectral outputs, were used to examine the effects of light intensity on conversion and flexural strength of a model dental resin formulation (75/25wt% bis-GMA/TEGDMA). METHODS: The exact same polymer samples were used to correlate double bond conversion (measured with near-IR spectroscopy) to flexural strength, both immediately after light exposure and after storage. RESULTS: In general, polymers which were irradiated with the high light intensity source exhibited greater double bond conversion. However, increasing the light intensity also increased the maximum temperature reached during polymerization. Therefore, the greater double bond conversion was caused by a combination of both photo and thermal effects. Regardless of the light intensity, a single linear relationship existed between conversion and final flexural strength (measured 4 days after cure) over the conversion range analyzed (50-80%). However, deviations from linearity were noted in several samples that were tested immediately after exposure. SIGNIFICANCE: These findings illustrate that light intensity does not affect the final flexural strength of a dental resin as long as the final conversions are similar.     

Thoracic trauma in children: an indicator of increased mortality

This study was undertaken to assess the significance of thoracic trauma as a marker of morbidity and mortality in children. During a 34-month period, 2,086 children younger than 15 years old were consecutively admitted to a Level I pediatric trauma center with blunt or penetrating trauma. For each child we prospectively recorded Trauma Score (TS), Injury Severity Score, (ISS), medical, and etiologic data. One hundred four children (4.4%) presented with thoracic trauma. The most common mechanisms of injury were pedestrian injury (36%), motor vehicle crashes (32%), and armed assault (12%). The most common injuries were pulmonary contusion (48%), pneumothorax, hemothorax, or pneumohemothorax (39%), and rib fractures (32%). Multisystem injury was present in 82% of the children. The mean TS and ISS were 11 and 27, respectively, significantly worse than scores for children without thoracic injury (15 and 7; P less than .0001). Seventy-one percent of the children were admitted to the intensive care unit, where they stayed an average of 6 days; 20% required surgery. The mortality rate was 26%. Injuries to the heart or great vessels had the highest mortality rate (75%), followed by hemothorax (53%), lung laceration (43%), and rib fracture (42%). Mortality for children with isolated chest injury was 5%, compared with rates of 20% for abdominal and chest trauma, 35% for head and chest trauma, and 39% for trauma to the head, chest, and abdomen. Less than 5% of the admissions to a pediatric trauma center incurred thoracic injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of isoelectric point on biodistribution and inflammation imaging with indium-111-labelled IgG

Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge on the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its iso electric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats withEscherichia coli thigh infections. The biodistribution was significantly affected by pl. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3–2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.     

Acetyl-Carnitine and Alzheimer''s Disease

In a double-blind, randomized, controlled clinical trial, progression of Alzheimer's disease was significantly reduced in patients who received acetyl-carnitine (2 g/day) for one year.     

Levels of prostate specific antigen that predict skeletal spread in prostate cancer.

The ability of serum prostate specific antigen (PSA) and serum acid phosphatase (SAP) to identify skeletal spread was evaluated in untreated patients with prostatic cancer. Twenty patients with scintigraphic evidence of metastatic disease in bone (M1) at diagnosis were compared with 50 untreated patients in whom scans were repeatedly negative during long-term surveillance. Using the present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise discriminant analysis demonstrated that SAP was able to stage patients correctly (bone scan positive or negative) with 81% predictive accuracy at an optimum cut-off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are highly indicative of spread to the skeleton, even in the absence of radiological or scintigraphic evidence of metastases.     

Inter-rater reliability of the International Cooperative Ataxia Rating Scale (ICARS).

We assessed the inter-rater reliability of the 100-point International Cooperative Ataxia Rating Scale (ICARS). Three neurologists independently rated videotaped ICARS examinations of 22 subjects with genetically determined ataxias (spinocerebellar ataxia [SCA] Type 1 in 11; SCA Type 2 in 1; Friedreich's ataxia in 10) and 4 controls. Scores on live ICARS assessment had ranged from 0 to 7 for controls and 11 to 74 for ataxic subjects (clinically very mildly affected to wheelchair-bound). Inter-rater correlation was very high for the total score (Kendall's omega 0.994, 95% confidence interval, 0.988-0.997), and high to very high for each component subscore (0.791 for speech to 0.994 for posture/gait). All correlations were significant at P < 0.00001. The ICARS exhibits very high inter-rater reliability even without prior observer standardisation and is sensitive to a range of ataxia severities from very mild to severe.