Management of acute otitis media in an era of increasing antibiotic resistance

Development of resistance to available antimicrobial agents has been identified in every decade since the introduction of the sulfonamides in the 1930s. Current concerns for management of acute otitis media (AOM) are multi-drug resistant Streptococcus pneumoniae and beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis. In the USA, amoxicillin remains the drug for choice for AOM. Increasing the current dose to 80 mg/kg/day in two doses provides increased concentrations of drug in serum and middle ear fluid and captures additional resistant strains of S. pneumoniae. For children who fail initial therapy with amoxicillin an expert panel convened by the Centers for Disease Control and Prevention suggested amoxicillin-clavulanate, cefuroxime axetil or intramuscular ceftriaxone. To protect the therapeutic advantage of antimicrobial agents used for AOM, it is important to promote judicious use of antimicrobial agents and avoid uses if it is likely that viral infections are the likely cause of the disease, to implement programs for parent education and to increase the accuracy of diagnosis of AOM. Conjugate polysaccharide pneumococcal vaccines are currently in clinical trial; early results indicate protective levels of antibody can be achieved with a three dosage schedule beginning at 2 months of age. Finally, alternative medicine remedies may be of value for some infectious diseases including AOM; garlic extract is bactericidal for the major bacterial pathogens of AOM but is heat- and acid-labile and loose activity when cooked or taken by mouth.     

High-resolution computed tomography of the chest in children with cystic fibrosis: support for use as an outcome surrogate

Background. Outcome surrogates are indicators that reflect, rather than directly measure, patient benefit. In order to provide useful results, however, outcome surrogates must be carefully chosen and must meet specific criteria. Objective. To support development of high-resolution computed tomography (HRCT) as an outcome surrogate in cystic fibrosis (CF) by demonstrating the ability of HRCT to show short-term improvement in the appearance of the lungs in children with CF. Materials and methods. HRCT was performed at admission and after discharge on 8 children during 15 admissions for acute pulmonary exacerbation of CF. Three radiologists scored each study separately, then compared admission and discharge pairs. Results. HRCT scores improved in 13/15 admissions. Mean score decreased from 25 to 22. The decrease was significant (P = 0.014). Comparison of admission and discharge scans showed improvement in peribronchial thickening (P = 0.007), mucous plugging (P = 0.002), and overall appearance (P = 0.025). Conclusion. HRCT has the potential to be a useful outcome surrogate in CF. A necessary attribute of an outcome surrogate is that it improves rapidly with effective therapy. Despite widespread belief among radiologists and pulmonologists that HRCT meets this criterion, no previous report has demonstrated this ability in children. These findings support further development of HRCT as an outcome surrogate in children with CF. Received: 8 February 1999 Accepted: 27 May 1999     

Management and prognosis of primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma

We retrospectively analyzed 143 women treated in 28 departments from 1980 to 1995, to study the impact of prognostic factors in primary carcinoma of the fallopian tube. Further aims of the study were to evaluate the treatment of fallopian tube carcinoma in Austria. Staging of disease was done according to the modified FIGO system, and grading according to the criteria suggested by Hu et al. The mean age of the patients was 62.5 years. Sixty (42%) tumors were found to be in stage I, 28 (19%) in stage II, 38 (27%) in stage III, and 17 (12%) in stage IV. Radical resection was achieved in 102 (71%) patients. In 122 (85%) women surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperatively patients underwent adjuvant therapy consisting of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all stages of disease was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV. FIGO stage, histologic grading and residual tumor showed an independent prognostic impact in multivariate analysis.     

Differential dosing of prostate and seminal vesicles using dynamic multileaf collimation

Purpose: We have investigated the potential of applying different doses to the prostate (PTV2) and prostate/seminal vesicles (PTV1) using multileaf collimation (MLC) for intensity modulated radiation therapy (IMRT). Current dose-escalation studies call for treatment of the PTV1 to 54 Gy in 27 fractions followed by 20 Gy minimum to the PTV2. A daily minimum PTV dose of 2 Gy using a 7-field technique (4 obliques, opposed laterals, and an ant-post field) is delivered. This requires monitor unit calculations, paper and electronic chart entry, and quality assurance for a total of 14 fields. The goal of MLC IMRT is to improve efficiency and deliver superior dose distributions. Acceptance testing and commissioning of the dynamic MLC (DMLC) option on a dual-energy accelerator was accomplished. Most of the testing was performed using segmental MLC (SMLC) IMRT with stop-and-shoot sequences built within the dynamic mode of the DMLC.

Methods and Materials: The MLC IMRT fields were forward planned using a three-dimensional treatment planning system. The 14 fields were condensed to 7 SMLC IMRT fields with two segments each. In this process, steps were created by moving the leaves to the reduced field positions. No dose (<0.01%) was delivered during this motion. The monitor units were proportioned according to the planned treatment weights. Film and ionization chamber dosimetry were used to analyze leaf positional accuracy and speed, output, and depth-dose characteristics. A geometric phantom was used for absolute and relative measurements. We obtained a volumetric computerized tomography (CT) scan of the phantom, performed 3D planning, and then delivered a single treatment fraction.

Results: The acceptance testing and commissioning demonstrated that the leaves move to programmed positions accurately and in a timely manner. We did find an 1 mm offset of the set leaf position and radiation edge (50%) due to the curved-end nature and calibration limitations. The 7-field SMLC IMRT treatment duplicated the 14-field static plan dose distribution with variations no greater than 1.5%.

Conclusions: The MLC IMRT approach will improve efficiency because the number of electronic and chart entries has decreased by a factor of 2. Portal images are able to capture the initial and final MLC segments. The question of differential daily dose to the prostate and seminal vesicles remains.     

Epstein-Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen

EBNA-3 (also called EBNA-3A) is one of the EBV encoded nuclear antigens that are necessary for B-cell transformation. EBNA-3 is known to target RBPs, nuclear proteins that also interacts with EBNA-2, EBNA-4 and EBNA-6. In order to identify additional EBNA-3 targets, an EBV-transformed human lymphocyte cDNA library was screened in the yeast two-hybrid system with N-terminus truncated EBNA-3 that cannot interact with RBP-Jkappa. A clone, encoding Xap-2 protein, a cellular partner of Hepatitis B virus X-antigen was isolated. This protein is also known as the p38 subunit of the aryl hydrocarbon receptor complex (ARA9). The specific binding to EBNA-3 was confirmed by showing that the GST-Xap-2 precipitated EBNA-3 from CV1 cells that were infected with recombinant vaccinia virus expressing EBNA-3. Deletion of the C-terminus of Xap-2 eliminated the binding. Fusion with green fluorescent protein showed that Xap-2 is preferentially cytoplasmic but translocates to the nucleus upon expression of EBNA-3.