Screening for risk of persistent posttraumatic stress in injured children and their parents

Context  Injury, a leading health threat to children, is also a common cause of posttraumatic stress disorder (PTSD) in childhood. Most injured children with PTSD are not diagnosed or treated. Objective  To develop a stand-alone screening tool for use by clinicians during acute trauma care to identify injured children and their parents who are at risk of significant, persistent posttraumatic stress symptoms. Design  The Screening Tool for Early Predictors of PTSD (STEPP) was derived from a 50-item risk factor survey administered within 1 month of injury as part of a prospective cohort study of posttraumatic stress in injured children and their parents. Symptoms of PTSD were assessed at least 3 months after injury. Setting  Urban, pediatric level I trauma center. Participants  A sample of 269 children aged 8 to 17 years admitted for treatment of traffic-related injuries between July 1999 and October 2001, and one parent per child, completed a risk factor survey assessing potential predictors of PTSD outcome. One hundred seventy-one families (63%) completed a follow-up assessment. Main Outcome Measures  The Clinician-Administered PTSD Scale for Children and Adolescents and the PTSD Checklist served as criterion standards for child and parent outcomes, respectively. Positive cases were defined as those meeting criteria for at least subsyndromal PTSD with continuing impairment ("persistent traumatic stress"). Results  The STEPP contains 4 dichotomous questions asked of the child, 4 asked of one parent, and 4 items obtained easily from the emergency medical record. STEPP sensitivity in predicting posttraumatic stress was 0.88 for children and 0.96 for parents, with negative predictive values of 0.95 for children and 0.99 for parents. The odds ratio for prediction of persistent traumatic stress was 6.5 (95% confidence interval [CI], 1.8-22.8) in children and 26.6 (95% CI, 3.5-202.1) in parents. Conclusions  The STEPP represents a new method to guide clinicians in making evidence-based decisions for the allocation of scarce mental health resources for traumatic stress. Its brevity and simple scoring rule suggest that it can be easily administered in the acute care setting.      

Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

The cytokine interleukin-1 (IL-1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL-1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL-1 are involved in hippocampal-dependent memory and long-term potentiation (LTP). To examine this hypothesis, we studied IL-1 receptor type I knockout (IL-1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL-1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild-type controls. Furthermore, IL-1rKO exhibited diminished contextual fear conditioning. In contrast, IL-1rKO mice were similar to control animals in hippocampal-independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory-cued fear conditioning was normal. Electrophysiologically, anesthetized IL-1rKO mice exhibited enhanced paired-pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired-pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL-1rKO mice compared with WT controls. These results suggest that IL-1 contributes to the regulation of memory processes as well as short- and long-term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation.     

Exercise, methacholine, and adenosine 5'-monophosphate challenges in children with asthma: relation to severity of the disease

Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5'-monophosphate (AMP) challenges in 135 children and young adults (mean age +/- SD, 12.4+/-3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment. The sensitivity of MCH challenge in detecting bronchial hyperreactivity (at or below 8 mg/mL) was 98%, that of AMP challenge (at or below 200 mg/mL) 95.5%, and that of exercise (more than 8.2% fall in FEV(1)) was 65%. There was a significant difference between mild asthmatic children (85 patients, intermittent asthma, step 1 of NIH guidelines) and moderate asthmatics (50 patients, steps 2 and 3 of guidelines) in relation to the logarithmic mean provocation concentration to elicit a 20% fall in FEV(1) (PC(20)) to MCH (0.49 mg/mL vs. 0.15 mg/mL, P<0.00001), that to AMP (7.67 mg/mL vs. 3.60 mg/mL, P = 0.001), and in relation to the mean percent fall in FEV(1) after exercise (13.9% vs. 22.0%, P = 0.001). Sensitivity and specificity curves between the two severity groups of asthma were constructed, and the intersection point of the two curves for each type of challenge was determined. When mild asthmatics were compared to moderate asthmatics, the intersection points for MCH, AMP, and exercise were 66%, 63%, and 61%, respectively. Logistic regression analysis and receiver operating characteristic (ROC) curves of the three challenges for the two severity groups of asthma showed that methacholine was a better discriminating challenge between the severity groups than the other two challenges. We conclude that the sensitivities of AMP and MCH challenges in the detection of bronchial hyperreactivity in children and young adults with asthma are very similar and higher than that of exercise. There is a significant difference between mild and moderate asthmatics within the three bronchial challenges, with MCH discriminating better than AMP or exercise between groups.     

Increased glucose improves recovery of neuronal function after cerebral hypoxia in vitro

The rat hippocampal slice preparation was used to evaluate the effect of increasing glucose levels in the perfusion medium on the recovery of synaptic function after a standardized hypoxic insult. Slices exposed to low glucose (5 mM) did not recover from a standard hypoxic insult (10 min of 95% N₂/5% CO₂ atmosphere). Following the same insult, 39% of the control (10 mM glucose) slices recovered their synaptic function, while 93% of the slices provided with high glucose level (20 mM) exhibited recovery of synaptic function. Thus, a dose-dependent effect of glucose on recovery of neuronal function following an intermediate period (10 min) of oxygen deprivation was found. The high-glucose-treated slices could tolerate a severe hypoxic insult of 15 min or even 20 min from which 94% and 81% of them recovered, respectively. Only 21% of the control (10 mM glucose) slices recovered their synaptic activity following 15 min of hypoxia, and none survived 20 min of that insult.The adverse effects of hyperglycemia reported in vivo were not seen in our study. This may be due to the sustained perfusion of the brain slice preparation, which could limit accumulation of lactic acid during hypoxia. However, treatment of slices with lactic acid prior to and during the hypoxic insult did not worsen the outcome. Alternatively, glucose may protect against the damaging effects of oxygen free radicals formed during reoxygenation. Nevertheless, the antihypoxic effect of glucose appears to be a metabolic one, since l-glucose (the non-metabolic analog of d-glucose) was innocuous in this respect.     

Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines

We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected with Candida albicans by inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) production in the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-kappaB translocation in lung epithelium and macrophages in MXF-treated mice. In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.e., IL-8, TNF-alpha, and IL-1beta) by activated human peripheral blood monocytes and THP-1 cells and analyzed the effects of the drug on the major signal transduction pathways associated with inflammation: NF-kappaB and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase (JNK). The levels of IL-8, TNF-alpha, and IL-1beta secretion rose 20- and 6.7-fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells, respectively. MXF (5 to 20 microg/ml) significantly inhibited cytokine production by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively. In THP-1 cells, the level of NF-kappaB nuclear translocation increased fourfold following stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited (38%) by 10 microg of MXF per ml. We then assayed the degradation of inhibitor (I)-kappaB by Western blotting. LPS-PMA induced degradation of I-kappaB by 73%, while addition of MXF (5 microg/ml) inhibited I-kappaB degradation by 49%. Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10 microg/ml). We conclude that MXF suppresses the secretion of proinflammatory cytokines in human monocytes and THP-1 cells and that it exerts its anti-inflammatory effects in THP-1 cells by inhibiting NF-kappaB, ERK, and JNK activation. Its anti-inflammatory properties should be further assessed in clinical settings.     

Effects of colonoscopy on intracranial pressure: observation in a large animal model

BACKGROUND AND STUDY AIMS: Increased intra-abdominal pressure has been associated with increased intracranial pressure. Bowel insufflation during colonoscopy may increase the intra-abdominal pressure. It was hypothesized that colonoscopy may be associated with intracranial pressure elevation subsequent to an elevation in intra-abdominal pressure. MATERIALS AND METHODS: Colonoscopy was carried out in seven anesthetized pigs, and the colonoscope was advanced up to 60 cm from the anal verge. Insufflation was used to allow safe advancement of the colonoscope and to allow visualization of the colon, in the same way as in the procedure performed in humans. Intra-abdominal pressure was measured by determining the hydrostatic pressure in the urinary bladder. A subarachnoid screw was used to monitor intracranial pressure. The mean arterial blood pressure and intra-abdominal venous pressure were directly monitored via the femoral vessel access; all parameters were recorded before and during colonoscopy. RESULTS: A statistically significant elevation in intracranial pressure was demonstrated during colonoscopy. The average increase in intracranial pressure was 3.1 mm Hg. The intra-abdominal pressure and intra-abdominal venous pressure were also significantly elevated during the procedure. CONCLUSIONS: Colonoscopy may increase intracranial pressure due to an increase in intra-abdominal pressure. This may have clinical implications when colonoscopy is conducted in patients with brain pathology associated with high intracranial pressure.     

Hepatic and cardiac iron overload among patients with end‐stage liver disease referred for liver transplantation

O’Glasser AY, Scott DL, Corless CL, Zaman A, Sasaki A, Gopal DV, Rayhill SC, Orloff SL, Ham JM, Rabkin JM, Flora K, Davies CH, Broberg CS, Schwartz JM. Hepatic and cardiac iron overload among patients with end‐stage liver disease referred for liver transplantation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01136.x.
© 2009 John Wiley & Sons A/S. Abstract: Background: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post‐mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. Aims: To assess the results of testing for iron overload in liver transplant candidates at our institution. Methods: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ≥50% and ferritin ≥250 ng/mL underwent liver biopsy graded for iron. Patients with 3–4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. Results: Eight hundred and fifty‐six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty‐seven patients (34%) had transferrin saturation ≥50% and ferritin ≥250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty‐three patients underwent liver biopsy. Twenty‐six patients (17%) had 3–4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. Conclusions: Non‐HFE‐related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation.     

Measurement of circulating cell-free DNA levels by a new simple fluorescent test in patients with primary colorectal cancer

Elevated circulating cell-free DNA (CFD) levels were found in patients with cancer. The standard CFD assays are work-intensive and expensive. The aim was to evaluate in patients with cancer a new simple CFD assay. In mice inoculated with cancer cells, CFD levels correlated with tumor size. Compared with healthy subjects, 38 patients with colorectal cancer (CRC) had higher preoperative CFD levels (798 ± 409 vs 308 ± 256 ng/mL; P < .0001). Compared with patients free of disease at 1 year, CFD levels were elevated in patients who remained with disease or died (DD). CFD correlated with DD (P = .033), and a combined index of carcinoembryonic antigen × CFD exhibited a better correlation to DD than did pathologic staging (P = .0027 vs P = .0065). For patients with CRC, CFD levels were prognostic of death and disease. A large prospective study will need to be performed to truly evaluate the efficacy of this method for early detection, follow-up, and evaluation of patient response to treatment.