Transcutaneous bilirubinometry is a reliably conservative method of assessing neonatal jaundice

Objective: In order to reduce invasive testing in newborns prior to discharge, we tested the direction of the correlation between transcutaneous bilirubin (TcB) and total serum bilirubin (TSB), the likelihood of missing high TSBs with a raised threshold for confirmatory testing, and also calculated potential cost savings from fewer laboratory testing.

Methods: We performed a cross-sectional analysis of single paired TcB and TSB results measured at 36?±?2?h of life in neonates?≥37 weeks admitted only to the Level 1 nursery. TcB was measured using the BiliChek® meter.

Results: Of the 552 infants, 512 (92.8%) had TSB levels below TcB values. Correlation between TcB and TSB was 0.69. If TSB confirmation was to be performed at 11.7 mg/dL (medium risk threshold for phototherapy), the negative predictive value was 99.4%, with a potential cost savings of $6555.00 ($1500.00 per 100 patients). Of the 495 infants with TcB?<11.7?mg/dL, only 3 had TSB levels higher than 11.7?mg/dL, and none met phototherapy threshold for low risk infants.

Conclusions: TcB screening at our institution has a high negative predictive value, and can be used as a stand-alone test until values are close to phototherapy threshold, thus reducing invasive testing and cost.     

Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome

This study assessed social behavior in a mouse model of Fragile X syndrome (FXS), the Fmr1 (tm1Cgr) or Fmr1 "knockout" (KO) mouse. Both the KO and wild-type (WT) mice preferred to be near a novel conspecific than to be alone. However, during the initial interaction with a novel conspecific, (1) a greater proportion of the KO mice exhibited high levels of grooming; and (2) the average duration of nose contact with the stimulus mouse was significantly shorter for the KO mice, both indicative of increased arousal and/or anxiety. Both groups exhibited a robust novelty preference when the novel animal was a "preferred" mouse. However, when the novel mouse was a "nonpreferred" animal, both groups showed a diminished novelty preference but this effect was more pronounced for the WT mice. This blunted negative reaction of the KO mice to a nonpreferred animal may indicate that they were less proficient than controls in distinguishing between positive and negative social interactions. These findings provide support for the use of this animal model to study the autistic features of FXS and autism spectrum disorders.     

MotherNature: establishing a Canadian research network for natural health products (NHPs) during pregnancy and lactation

BACKGROUND: It has been estimated that between 7% and 55% of expectant mothers use herbal medicines or other types of natural health products (NHPs). Unfortunately, the safety and efficacy of NHPs during pregnancy and lactation is largely unknown. The Motherisk Program, at the Hospital for Sick Children, Toronto, Ontario, Canada, the is the major Canadian group to counsel and monitor outcomes of women using medications or NHPs, or of women exposed to chemicals, radiation or infection during pregnancy and lactation. OBJECTIVE: To create a network for research on NHPs during pregnancy and lactation by forming longstanding collaborations among Canadian medical and complementary and alternative medicine (CAM) practitioners and scientists. METHODOLOGY: MotherNature Network members participated in three 2-day workshops and three conference calls throughout the length of this study. Each member was responsible to lead discussions surrounding one theme and address the following: initiation; development; presentation; and synthesis of comments of all members on the designated theme. RESULTS: We prioritized areas in high need for future research and collaborative means to conduct such research. NHPs were prioritized for their importance for future study. Areas for the prospective collection of data on NHP use in pregnancy and lactation were identified. A research and business plan was developed for the long-term sustainability of the Network. CONCLUSIONS: The MotherNature Network is well-situated to create a new climate in Canada, where data are collected and interpreted on the effects and safety of NHPs during pregnancy and lactation.     

Dextran Mass Ratio Controls Particle Drying Dynamics in a Thermally Stable Dry Powder Vaccine for Pulmonary Delivery

Pharmaceutical Research - Thermally stable, spray dried vaccines targeting respiratory diseases are promising candidates for pulmonary delivery, requiring careful excipient formulation to...     

Risk factors for peripheral arterial disease in the tropics and its comparison with the western population

ObjectiveTo identify and compare the existence of similar and other risk factors in the perspective of an Indian population.MethodsIt was designed as a case control study and was conducted in the Department of General and Vascular Surgery Unit 2 of Christian Medical College, Vellore, India between the periods July 2003 to June 2005. 100 patients with an ABPI< 0.9 and 100 controls were studied.ResultsPeripheral arterial disease (PAD) was found to be commoner among males (87%). While atherosclerosis was the commonest aetiology (54%), the incidence of Thromboangiitis Obliterans was also not uncommon (38%). Smoking was the main risk factor in the Indian context (83%) as compared to hypercholesterolemia (60%) in the West. The patients with atherosclerotic PAD were middle-aged and had concomitant diabetes (50%) and hypertension (30%).ConclusionsPeripheral arterial disease occurs in a relatively younger age group in India as compared to their Western counterparts. Thromboangiitis Obliterans was found to be a significant aetiology for arterial occlusive disease, with smoking as the primary risk factor followed by diabetes, hypertension and hypercholesterolemia.     

Pharmacokinetic disposition and clinical outcomes in infants and children receiving intravenous busulfan for allogeneic hematopoietic stem cell transplantation.

We conducted a retrospective pharmacokinetic analysis of i.v. busulfan in children undergoing hematopoietic stem cell transplantation (HSCT) and describe its relation to transplantation outcomes. Forty-five children (median age, 3 yr) underwent HSCT at The Hospital for Sick Children from April 2003 through January 2006 and received i.v. busulfan every 6 h as part of their conditioning regimen. Initial busulfan doses were based on actual patient weight: <9 kg, 0.95 mg/kg per dose; 9-16 kg, 1.2 mg/kg per dose; 16-23 kg, 1.1 mg/kg per dose; 24-34 kg, 0.95 mg/kg per dose; >34 kg, 0.8 mg/kg per dose. Plasma busulfan concentrations were obtained after the first dose. The fourth and subsequent busulfan doses were adjusted to achieve an area under the concentration versus time curve (AUC) of 900-1500 microM.min. Development of hepatic venous occlusive disease (HVOD; modified Baltimore criteria) and engraftment (absolute neutrophil count >or=0.5 x 10(9)/L) were evaluated. Busulfan pharmacokinetic parameters were calculated using 1-compartment methods. Mean busulfan pharmacokinetic parameters were maximum concentration (C(max); 4.7 +/- 0.75 microM), volume of distribution at steady state (0.68 +/- 0.17 L/kg), elimination rate constant (0.0051 +/- 0.0010 min(-1)), total body clearance (3.5 +/- 1.23 mL/[min.kg]), and AUC (1271 +/- 280 microM.min). Mean volume of distribution at steady state was larger in children <1 yr of age (0.77 +/- 0.24 vs 0.64 +/- 0.11 L/kg; P = .040) and children <4 yr of age (0.73 +/- 0.18 vs 0.60 +/- 0.11 L/kg; P = .001) than in older children. Compared with older children, mean weight-adjusted total body clearance was higher in children <4 yr of age (3.8 +/- 1.40 versus 3.0 +/- 0.76 mL/[min.kg]). HVOD was diagnosed in 8 children (18%), including 4 children <1 yr of age. Children who developed HVOD achieved a lower C(max) than did those without HVOD (4.2 +/- 0.68 versus 4.8 +/- 0.73 microM; P = .035). Other than C(max), no association was observed between busulfan disposition and development of HVOD in children for whom i.v. busulfan doses were adjusted to achieve a target AUC. The influence of factors other than busulfan disposition on transplantation outcomes, such as genetic polymorphisms, should be evaluated.     

Impaired sustained attention and altered reactivity to errors in an animal model of prenatal cocaine exposure

Although correlations have been reported between maternal cocaine use and impaired attention in exposed children, interpretation of these findings is complicated by the many risk factors that differentiate cocaine-exposed children from SES-matched controls. For this reason, the present dose-response study (0, 0.5, 1.0, or 3.0 mg/kg cocaine HCl) was designed to explore the effect of prenatal cocaine exposure on visual attention in a rodent model, using an intravenous injection protocol that closely mimics the pharmacokinetic profile and physiological effects of human recreational cocaine use. In adulthood, animals were tested on an attention task in which the duration, location, and onset time of a brief visual cue varied randomly between trials. The 3.0 mg/kg exposed males committed significantly more omission errors than control males during the final 1/3 of each testing session, specifically on trials that followed an error, which implicates impaired sustained attention and increased reactivity to committing an error. During the final 1/3 of each testing session, the 0.5 and 1.0 mg/kg exposed females took longer to enter the testing alcove at trial onset, and failed to enter the alcove more frequently than control females. Because these effects were not seen in other tasks of similar duration and reinforcement density, these findings suggest an impairment of sustained attention. This inference is supported by the finding that the increase in omission errors in the final block of trials in each daily session (relative to earlier in the session) was significantly greater for the 1.0 mg/kg females than for controls, a trend also seen for the 0.5 mg/kg group. Unlike the cocaine-exposed males, who remain engaged in the task when attention is waning, the cocaine-exposed females appear to opt for another strategy; namely, refusing to participate when their ability to sustain attention is surpassed.