A technique for performing antegrade selective cerebral perfusion without interruption of forward flow or cannula relocation for pediatric aortic arch reconstruction

New technology and advances in extracorporeal bypass circuitry and surgical techniques have drastically improved outcomes in infants with congenital heart defects. Hypothermia with circulatory arrest has fallen out of favor in many institutions over the last decade in part from data implicating even short circulatory arrest times to long-term neurologic sequelae. Implementing continuous cerebral perfusion techniques for aortic arch reconstruction is desirable in ameliorating neurologic complications because long-term survival of complex defects can be more routinely achieved. Many centers have implemented alternative means of alleviating cerebral ischemic periods by incorporating selective antegrade or retrograde cerebral perfusion techniques. The incidence of post-operative neurologic events is low when alternative cerebral perfusion techniques are used. Many techniques used to perform continuous cerebral perfusion involve brief periods of circulatory arrest, usually for perfusion cannula repositioning. Herein we describe a technique for performing continuous antegrade cerebral perfusion without a need to interrupt forward flow.     

Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection

Palivizumab (Synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV). RSV is the leading cause of hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced RSV-related hospitalizations by 55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically significant congenital heart disease (HSCHD). Reductions were statistically significant versus placebo in infants with BPD/CLD, with all degrees of prematurity, and with acyanotic/other heart disease. Palivizumab was generally well tolerated, with < or =1.9% of recipients discontinuing treatment for tolerability reasons. In placebo-controlled trials, the most common potentially drug-related adverse events were fever, nervousness, injection-site reactions, and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials. Very few serious potentially drug-related adverse events occurred in clinical trials; four occurred in 2 of 285 patients in one open-label trial. No significant anti-palivizumab antibodies developed during palivizumab use. Palivizumab trough serum concentrations were below the recommended 40 microg/mL in about 33% and up to 14% of children prior to their second and third palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per hospitalization averted was generally lowest in the highest-risk infants. Drug cost was generally the most influential factor in sensitivity analyses. In conclusion, prophylaxis with palivizumab significantly reduces the incidence of RSV-related hospitalization relative to placebo and is generally well tolerated in high-risk infants aged <2 years, including those with prematurity and BPD/CLD or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab is approved for use in these patients. Other high-risk infants in whom palivizumab has not been formally assessed, such as those with immunodeficiency, cystic fibrosis, or location-specific risk factors (including extended hospital stays) might potentially benefit from palivizumab. The use of palivizumab in these other high-risk populations is likely to be determined as much by pharmacoeconomic considerations as by efficacy outcomes.     

RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics

The candidate tumor suppressor gene RASSF1A is inactivated in many types of adult and childhood cancers. However, the mechanisms by which RASSF1A exerts its tumor suppressive functions have yet to be elucidated. To this end, we performed a yeast two-hybrid screen to identify novel RASSF1A-interacting proteins in a human brain cDNA library. Seventy percent of interacting clones had homology to microtubule-associated proteins, including MAP1B and VCY2IP1/C19ORF5. RASSF1A association with MAP1B and VCY2IP1/C19ORF5 was subsequently confirmed in mammalian cell lines. This suggested that RASSF1A may exert its tumor-suppressive functions through interaction with the microtubules. We demonstrate that RASSF1A associates with the microtubules, causing them to exist as hyperstabilized circular bundles. We found that two naturally occurring tumor-associated missense substitutions in the RASSF1A coding region, C65R and R257Q, perturb the association of RASSF1A with the microtubules. The C65R and R257Q in addition to VCY2IP1/C19ORF5 showed reduced ability to induce microtubule acetylation and were unable to protect the microtubules against the depolymerizing action of nocodazole. In addition, wild-type RASSF1A but not the C65R or the R257Q is able to block DNA synthesis. Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells.     

Recent trends in the epidemiology of sexually transmitted infections in the European Union

Sexually transmitted infections (STIs) are a major public health problem in Europe. We review recent trends in the epidemiology of the major acute STIs in the European Union and Norway, their key determinants, and opportunities for enhancing STI prevention interventions in the region.     

Atypical teratoid/rhabdoid tumor of the central nervous system in children: an atypical series and review

Primary atypical teratoid/rhabdoid tumor (AT/RhT) of the central nervous system is a recently described, highly malignant neoplasm in infants and young children. This tumor is an unusual combination of mixed cellular elements, similar but not typical of teratomas, and rhabdoid cells. This tumor is most common in the posterior fossa in children less than 2 years, and is radiologically similar to medulloblastoma. No pathognomonic imaging features are present. The two tumors can be separated on histologic, molecular, and cytogenetic grounds. Separation of these two tumor types is crucial because the prognosis for AT/RhT is grim even with current multimodality treatment. We present four consecutive cases of AT/RhT, three in locations other than the cerebellum, seen at our institution in a 14-month period, indicating that this tumor may be more common than previously thought.     

A strategy for improving nurse retention and recruitment levels

A nursing shortage in one trust prompted a full investigation into the retention and recruitment of nurses. Workload, staffing levels, skill mix and working conditions were all problem areas for staff. The project highlighted the need to support the development of strong nurse leadership within each of the trust's directorates and to create more educational opportunities for staff.     

Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents

The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine ((131)I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents. NIS expression was determined by two blinded examiners and graded as absent = 0, minimal = 1, moderate = 2, intense = 3, and very intense = 4. NIS was detected in 35% (eight of 23) of PTC, 44% (four of 9) of FTC, 25% (two of eight) of benign tumors, and 100% (four of four) of autoimmune lesions. The intensity of NIS expression was similar in PTC (0.61 +/- 0.24), FTC (0.56 +/- 0.24), and benign tumors (0.50 +/- 0.33) but was more intense in autoimmune lesions (3.0 +/- 0.7, p < 0.005). Distant metastases were found only among PTC with undetectable NIS (two of 15, 13%), and recurrence developed exclusively from PTC and FTC with undetectable NIS (four of 20, 20% versus zero of 12, p = 0.043). The dose of iodine 131 required to achieve remission in the five patients with PTC who had undetectable NIS (213.3 +/- 53 mCi) was greater than that required by patients with similar age and extent of disease for whom NIS expression is unknown (109 +/- 22 mCi, p = 0.06). We conclude that NIS expression is associated with a lower risk of recurrence for PTC and FTC of children and adolescents.     

Waiting times during the management of head and neck tumours

The waiting times incurred during the management of 75 consecutive head and neck oncology patients attending for post-treatment follow-up were reviewed. Data were gleaned from general practitioner (GP) referral letters, patient case-notes as well as radiology and histology reports. The mean time for GP referral to ENT was 5.1 weeks. From ENT to endoscopy was 3.1 weeks, to histology 3.5 weeks, to computed tomography (CT) scan 5.6 weeks, to magnetic resonance scan (MR) 4.1 weeks, to primary radiotherapy 10.3 weeks and to surgery 5.5 weeks. The mean symptom duration prior to referral was 4.9 months. Our results compare unfavourably with the standards recommended by the BAO-HNS. Local modifiations may improve matters, but significant increases in funding, manpower and equipment are required to achieve the stipulated standards. Moreover, criteria for referral have to be re-emphasized and patient education has to be addressed as these appear to contribute the longest delay in the diagnosis of head and neck tumours.