Acute opioid overdose in pediatric patients.

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

Invasive Yersiniosis in a Pediatric Patient With ß-Thalassemia Major: Acute Decompensation After Rapid Blood Transfusion.

Yersinia enterocolitica infection, or yersiniosis, is a common cause of gastroenteritis in developing nations, but the disease is less common in the developed world. Yersiniosis typically presents as a self-limited gastroenteritis in an immunocompetent patient and rarely progresses to the more fulminant disseminated form. Certain patient populations are at greater risk of disseminated disease, and providers caring for these patients should have heightened suspicion for invasive disease. Patients dependent on serial transfusion therapy, such as those with inherited hemoglobinopathies, often have chronically elevated serum iron levels. These patients are at increased risk of fulminant yersiniosis due to the bacteria's siderophilic nature. Yersinia infection can be devastating in these patients, and early intervention with empiric antibiotics combined with targeted resuscitation can be essential in their care. The following case illustrates the utility for heightened surveillance, early intervention, and guided resuscitation in the management of this at-risk population.

Exchange Autotransfusion for Rapid Correction of Hyperkalemia During Liver Transplantation: A Case Report.

A 46-year-old woman with alcoholic cirrhosis and hepatorenal syndrome requiring hemodialysis presented with hyperkalemia (5.5 mEq/L) immediately before liver transplantation. For correction of hyperkalemia, an exchange transfusion began by removing her blood into an autotransfusion system to wash out noncellular components while maintaining normovolemia. Additionally, she received washed homologous red blood cells, insulin, and glucose to minimize or reduce the degree of hyperkalemia. Serum potassium level decreased to 4.0 mEq/L within 3 hours and was 5.0 mEq/L 30 seconds after reperfusion of the grafted liver. Postreperfusion syndrome was not observed. In summary, exchange transfusion was used successfully for rapid correction of hyperkalemia, showing the value of its application in liver transplantation.

Redox Regulation of Pro-IL-1ß Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice.

AIMS: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. RESULTS: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/-) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of NOX2. The levels of interleukin-1ß (IL-1ß) and IL-6 in inflamed joints were higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1ß were equally effective in suppressing arthritis in wild-type mice, while IL-1ß blockade was more effective than TNFα blockade in Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1ß to its active form and this activity was suppressed by ROS. INNOVATION: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. CONCLUSION: Our results suggest that ROS act as a negative feedback to constrain IL-1ß-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.

Best practice updates for pediatric/adolescent weight loss surgery.

The objective of this study is to update evidence-based best practice guidelines for pediatric/adolescent weight loss surgery (WLS). We performed a systematic search of English-language literature on WLS and pediatric, adolescent, gastric bypass, laparoscopic gastric banding, and extreme obesity published between April 2004 and May 2007 in PubMed, MEDLINE, and the Cochrane Library. Keywords were used to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. In light of evidence on the natural history of obesity and on outcomes of WLS in adolescents, guidelines for surgical treatment of obesity in this age group need to be updated. We recommend modification of selection criteria to include adolescents with BMI >or= 35 and specific obesity-related comorbidities for which there is clear evidence of important short-term morbidity (i.e., type 2 diabetes, severe steatohepatitis, pseudotumor cerebri, and moderate-to-severe obstructive sleep apnea). In addition, WLS should be considered for adolescents with extreme obesity (BMI >or= 40) and other comorbidities associated with long-term risks. We identified >1,085 papers; 186 of the most relevant were reviewed in detail. Regular updates of evidence-based recommendations for best practices in pediatric/adolescent WLS are required to address advances in technology and the growing evidence base in pediatric WLS. Key considerations in patient safety include carefully designed criteria for patient selection, multidisciplinary evaluation, choice of appropriate procedure, thorough screening and management of comorbidities, optimization of long-term compliance, and age-appropriate fully informed consent.

High resolution hard x-ray microscope on a second generation synchrotron source.

A full-field, transmission x-ray microscope (TXM) operating in the energy range of 7-11 keV has been installed at the U7A beamline at the National Synchrotron Radiation Laboratory, a second generation synchrotron source operating at 0.8 GeV. Although the photon flux at sample position in the operating energy range is significantly low due to its relatively large emittance, the TXM can get high quality x-ray images with a spatial resolution down to 50 nm with acceptable exposure time. This TXM operates in either absorption or Zernike phase contrast mode with similar resolution. This TXM is a powerful analytical tool for a wide range of scientific areas, especially studies on nanoscale phenomena and structural imaging in biology, materials science, and environmental science. We present here the property of the x-ray source, beamline design, and the operation and key optical components of the x-ray TXM. Plans to improve the throughput of the TXM will be discussed.

Best practice guidelines in pediatric/adolescent weight loss surgery.

OBJECTIVE: To establish evidence-based guidelines for best practices in pediatric/adolescent weight loss surgery (WLS). RESEARCH METHODS AND PROCEDURES: We carried out a systematic search of English-language literature in MEDLINE on WLS performed on children and adolescents. Key words were used to narrow the field for a selective review of abstracts. Data were extracted, and evidence categories were assigned according to a grading system based on established evidence-based models. Eight pertinent case series, published between 1980 and 2004, were identified and reviewed. These data were supplemented with expert opinions and literature on WLS in adults. RESULTS: Recommendations focused on patient safety, reduction of medical errors, systems improvements, credentialing, and future research. We developed evidence-based criteria for eligibility, assessment, treatment, and follow-up; recommended surgical procedures based on the best available evidence; and established minimum guideline requirements for data collection. DISCUSSION: Lack of adequate data and gaps in knowledge were cited as important reasons for caution. Physiological status, comprehensive screening of patients and their families, and required education and counseling were identified as key factors in assessing eligibility for surgery. Data collection and peer review were also identified as important issues in the delivery of best practice care.

A simple method for the production of recombinant proteins from mammalian cells.

Expression of recombinant proteins in mammalian cells is useful for obtaining products with normal post-translational modifications. We describe a simple and economical method for the production of milligram levels of proteins in murine fibroblasts. Retroviral or LIPOFECTAMINE (Gibco Laboratories) transduction was employed to generate stable murine-fibroblast producer cells. Confluent cultures of stable fibroblast clones were maintained for up to 1 month in 0.5% serum. Culture medium was collected every 2-3 days and polyhistidine-tagged proteins were purified by ammonium sulphate precipitation and Ni(2+)-nitrilotriacetic acid affinity chromatography. Highly pure, active, glycosylated recombinant proteins, including human beta-glucuronidase, mouse beta-glucuronidase, aminopeptidase N (CD13) and a single-chain antibody-enzyme fusion protein, were obtained with yields of 3-6 mg/l of culture medium. Fc-tagged proteins were also produced and purified in a single step by Protein A affinity chromatography with yields of 6-12 mg/l. The techniques described here allow simple and economical production of recombinant mammalian proteins with post-translational modifications.