A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood

Use of preemptive analgesia in Neonatal Intensive Care Units is recommended for severe and/or invasive procedures. However, the potential long-term consequences of such analgesia, which may be prolonged, are only beginning to be studied. In this pilot study, a subset of subjects previously enrolled in the Neurological Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial was assessed at early childhood. These ex-preterm infants (born at 23-32 weeks of gestational age) required intubation within 72 h postpartum and were randomized to receive either preemptive morphine analgesia (maximum of 14 days) or placebo within 8 h post-intubation. At 5-7 years of age, neuropsychological outcomes, morphometrics, adaptive behavior, parent-rated behavior, motivation, and short-term memory were measured. Although overall IQ and academic achievement did not differ between the morphine treated (n = 14) and placebo (n = 5) groups, preemptive morphine analgesia was associated with distinct differences in other outcome variables. Head circumference of morphine treated children was approximately 7% smaller (Cohen's d: 2.83, effect size large) and body weight was approximately 4% less (Cohen's d: 0.81, effect size large); however, height did not differ. In the short-term memory task (delayed matching to sample), morphine treated children exhibited significantly longer choice response latencies than placebo children (3.86 ± 0.33 and 2.71 ± 0.24 s, respectively) (p < 0.03) and completed approximately 27% less of the task than placebo children (Cohen's d: 0.96, effect size large). Parents described morphine treated children as having more social problems, an effect specific to creating and maintaining friendships (Cohen's d: − 0.83, effect size large). Despite the small sample size and the preliminary nature of this study, these results are strongly suggestive of long-lasting effects of preemptive morphine analgesia. A larger investigation with more comprehensive assessments of some of these key features will enable a more complete understanding of the relationship between preemptive morphine treatment and long-term neurocognitive, behavioral, and adaptive outcomes.     

The distinct roles of spirituality and religiosity in physical and mental health after collective trauma: a national longitudinal study of responses to the 9/11 attacks

Researchers have identified health implications of religiosity and spirituality but have rarely addressed differences between these dimensions. The associations of religiosity and spirituality with physical and mental health were examined in a national sample (N = 890) after the September 11, 2001 terrorist attacks (9/11). Health information was collected before 9/11 and health, religiosity, and spirituality were assessed longitudinally during six waves of data collection over the next 3 years. Religiosity (i.e., participation in religious social structures) predicted higher positive affect (β = .12), fewer cognitive intrusions (β = −.07), and lower odds of new onset mental (incidence rate ratio [IRR] = .88) and musculoskeletal (IRR = .94) ailments. Spirituality (i.e., subjective commitment to spiritual or religious beliefs) predicted higher positive affect (β = .09), lower odds of new onset infectious ailments (IRR = 0.83), more intrusions (β = .10) and a more rapid decline in intrusions over time (β = −.10). Religiosity and spirituality independently predict health after a collective trauma, controlling for pre-event health status; they are not interchangeable indices of religion.     

Feasibility of cetuximab given with a simplified schedule every 2 weeks in advanced colorectal cancer: a multicenter, retrospective analysis

Cetuximab was approved using a weekly schedule, alone or in combination with chemotherapy (CT). However, many CT regimens in metastatic colorectal cancer (CRC) are delivered every 2 weeks (q2wks). Preliminary data suggested that a simplified schedule using cetuximab q2wks, 500 mg/m2 would be equivalent to the standard weekly administration. Medical data of all patients with advanced CRC who received cetuximab q2wks were retrospectively collected and checked for consistency by an independent monitor in 4 European centers. Ninety-one patients were treated between 2005 and 2007 when the K-RAS mutational status of tumors was not determined routinely. They received a median of 4 (0-5) previous drugs, including previous weekly cetuximab in 38.5% of patients. Cetuximab q2wks was associated with an irinotecan-based regimen in 85.7% of patients. The median number of cetuximab administrations was 6 (1-23). Skin toxicity was observed in 68.2% of evaluable patients (grade 3 in 15%). Only one grade 1 allergy was reported. In the 84 patients beyond first-line therapy, response rate was 29.3%. The median progression-free survival was 3.0 months (range 2.2-3.8), and median overall survival was 9.0 months (range 6.2-11.8). Cetuximab q2wks appears safe and effective in heavily pretreated patients and convenient in combination with q2wks CT schedules.     

Kinetics of fiber solidification

Many synthetic or natural fibers are produced via the transformation of a liquid solution into a solid filament, which allows the wet processing of high molecular weight polymers, proteins, or inorganic particles. Synthetic wet-spun fibers are used in our everyday life from clothing to composite reinforcement applications. Spun fibers are also common in nature. Silk solidification results from the coagulation of protein solutions. The chemical phenomena involved in the formation of all these classes of fibers can be quite different but they all share the same fundamental transformation from a liquid to a solid state. The solidification process is critical because it governs the production rate and the strength that fibers can sustain to be drawn and wound. An approach is proposed in this work to investigate the kinetics of fiber solidification. This approach consists in circulating solidifying fibers in the extensional flow of a surrounding liquid. Such as polymers in extensional flows, the fibers break if resultant drag forces exceed the fiber tensile strength. The solidification kinetics of nanotube composite fibers serves as a validation example of this approach. The method could be extended to other systems and advance thereby the science and technology of fiber and textile materials. It is also a way to directly visualize the scission of chain-like systems in extensional flows.     

Does experience with laparoscopic colorectal surgery influence intraoperative outcomes?

Background  This study aimed to define the management and risk factors for intraoperative complications (IOC) and conversion in laparoscopic colorectal surgery, and to assess whether surgeon experience influences intraoperative outcomes. Methods  Consecutive patients undergoing laparoscopic colorectal procedures from 1991 to 2005 were analyzed from a longitudinal prospectively collected database. All patients referred to the four surgeons involved in this study were offered a minimally invasive approach. Patient characteristics, perioperative variables, and surgeon experience data were analyzed and compared. Results  A total of 991 consecutive laparoscopic colorectal procedures were studied. The majority of operations were performed for malignant disease (n = 526, 53%), and most frequently consisted of segmental colonic resections (n = 718, 72%). A total of 85 patients (8.6%) had an IOC. Patients experiencing an IOC had a significantly higher median body weight (75 versus 68 kg, p = 0.0047) and had a higher proportion of previous abdominal surgery (31% versus 20%, p = 0.029). Only 39% of patients suffering an IOC required conversion to open surgery. A total of 126 (13%) cases were converted to open surgery. On multivariable analysis, previous abdominal surgery [odds ratio (OR) 3.40, 95% confidence interval (CI) 1.39–8.35, p = 0.0076] was independently associated with having an IOC and a conversion to open within the same procedure. With increasing experience, individual surgeons were found to operate on heavier patients (p = 0.025), and on patients who had a higher rate of previous intra-abdominal surgery (p < 0.0001). Despite these risk factors, the early and late experience demonstrated no significant difference in terms of IOCs (p = 0.54) and conversion to open surgery (p = 0.40). Conclusions  The majority of IOCs can be managed laparoscopically. With increasing experience surgeons can perform laparoscopic colorectal surgery on a patient population with a greater proportion of previous abdominal surgery and a higher mean body weight without adversely affecting their rates of intraoperative complications or conversion. Oral presentation at the Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons, April 12th, 2008, Philadelphia, PA.     

Protective effects of 7-nitroindazole on ketamine-induced neurotoxicity in rat forebrain culture

Ketamine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, is used as a pediatric anesthetic for surgical procedures. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the dose and temporal response of ketamine using newborn rat forebrain cultures and also to determine if co-administration of 7-nitroindazole, a nitric oxide synthase (NOS) inhibitor, could protect or reverse ketamine-induced cell death. Neural cells collected from the rat forebrain were incubated for 24h with 1, 10 or 20 microM ketamine alone or with ketamine plus 1, 5, 10 or 20 microM 7-nitroindazole. Ketamine (10 microM) caused an increase in DNA fragmentation and elevated immunoreactivity to nitrotyrosine, a marked reduction in the expression of the neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and in mitochondrial metabolism, as well as an increased Bax/BCL-XL ratio. No significant effect was observed in the release of lactate dehydrogenase (LDH). Ketamine-induced neurotoxic effects were effectively blocked by 7-nitroindazole (10 microM). These data indicate a role for nitric oxide in the enhanced degeneration induced by ketamine in vitro and also suggest that blocking neuronal nitric oxide synthase (nNOS) may help reduce the risk of ketamine in pediatrics.     

Acute combined central and peripheral nervous system demyelination in children

Reports of acute combined central and peripheral nervous system acquired inflammatory demyelination are rare in children. This study aimed to (1) define the clinical features and prognoses of patients with this entity; and (2) compare these patients with children presenting isolated acute central or peripheral nervous system demyelination. A retrospective chart review of 523 children with central or peripheral nervous system demyelination hospitalized between 1993-2006 was undertaken. Among these, 93 fulfilled criteria (clinical features and positive magnetic resonance imaging or electromyography/nerve conduction studies) for either acute central (n = 37; 39.8%) or peripheral (n = 43; 46%) nervous system demyelination, or a combination of the two (n = 13; 14%). Significant differences between groups were evident for age (median, 10 versus 7 versus 11 years, respectively; P = 0.047), admission to pediatric intensive care unit (8% versus 30% versus 58%, respectively; P = 0.001), length of hospital stay (median, 8 versus 9 versus 29 days, respectively; P < 0.001), treatment with steroids (52% versus 7% versus 75%, respectively; P < 0.001) and immunoglobulins (11% versus 81% versus 75%, respectively; P < 0.001), and poor evolution (3% versus 12% versus 54%, respectively; P = 0.002). This entity in children is not rare, and has a poorer outcome than isolated central or peripheral nervous system demyelination. Assessment is needed for a better understanding of risk factors, etiologies, management, and prognosis.     

Prenatal activation of 5-HT2A receptor induces expression of 5-HT1B receptor in phrenic motoneurons and alters the organization of their premotor network in newborn mice

In newborn mice of the control [C3H/HeJ (C3H)] and monoamine oxidase A-deficient (Tg8) strains, in which levels of endogenous serotonin (5-HT) were drastically increased, we investigated how 5-HT system dysregulation affected the maturation of phrenic motoneurons (PhMns), which innervate the diaphragm. First, using immunocytochemistry and confocal microscopy, we observed a 5-HT(2A) receptor (5-HT(2A)-R) expression in PhMns of both C3H and Tg8 neonates at the somatic and dendritic levels, whereas 5-HT(1B) receptor (5-HT(1B)-R) expression was observed only in Tg8 PhMns at the somatic level. We investigated the interactions between 5-HT(2A)-R and 5-HT(1B)-R during maturation by treating pregnant C3H mice with a 5-HT(2A)-R agonist (2,5-dimethoxy-4-iodoamphetamine hydrochloride). This pharmacological overactivation of 5-HT(2A)-R induced a somatic expression of 5-HT(1B)-R in PhMns of their progeny. Conversely, treatment of pregnant Tg8 mice with a 5-HT(2A)-R antagonist (ketanserin) decreased the 5-HT(1B)-R density in PhMns of their progeny. Second, using retrograde transneuronal tracing with rabies virus injected into the diaphragm of Tg8 and C3H neonates, we studied the organization of the premotor network driving PhMns. The interneuronal network monosynaptically connected to PhMns was much more extensive in Tg8 than in C3H neonates. However, treatment of pregnant C3H mice with 2,5-dimethoxy-4-iodoamphetamine hydrochloride switched the premotoneuronal network of their progeny from a C3H- to a Tg8-like pattern. These results show that a prenatal 5-HT excess affects, via the overactivation of 5-HT(2A)-R, the expression of 5-HT(1B)-R in PhMns and the organization of their premotor network.