Antibiotics are administered to cystic fibrosis patients for chronic endobronchial infection complicated by frequent exacerbations. Agents active against Staphylococcus aureus, Pseudomonas aeruginosa or both are administered. Serum antibiotic concentrations were measured in cystic fibrosis patients in an effort to optimise antibiotic dose and frequency. This led to the observation that cystic fibrosis subjects had (in general) a larger Vd and increased total body clearance of beta-lactams and aminoglycosides than non-cystic fibrosis subjects. The larger Vd is mainly due to the increased amount of lean body mass per kg bodyweight, although increased tissue binding may also account for part of this. The increased total body clearance of beta-lactams appears to be due to increased renal elimination, particularly tubular secretion. Decreased tubular reabsorption and increased non-renal clearance contribute to the increased total body clearance of metabolised beta-lactams and aminoglycosides. However, the lack of concomitant controls in many studies make these generalisations tentative. The result of the apparent cystic fibrosis-specific differences is lower peak serum antibiotic concentrations, a smaller AUC, and a shorter elimination half-life than non-cystic fibrosis subjects. Since sputum (and bronchial mucosal) concentration is dependent on the peak serum concentration (and AUC), cystic fibrosis subjects require larger doses of most antibiotics more frequently. Newer quinolones may be an exception. Studies comparing the efficacy and safety of larger and more frequent antibiotic doses to conventional therapy are not available. Although it appears logical to mimic serum antibiotic concentrations found in non-cystic fibrosis subjects, the lack of information on the ideal sputum concentration versus time curve should temper our enthusiasm for cystic fibrosis-specific dosage regimens.

Structural Maintenance of Chromosome (SMC) protein complexes are the key organizers of the spatiotemporal structure of chromosomes. The condensin SMC complex, which compacts DNA during mitosis, was recently shown to be a molecular motor that extrudes large loops of DNA.The mechanism of this unique motor, which takes large steps along DNA at low ATP consumption, remains elusive however. Here, we use Atomic Force Microscopy (AFM) to visualize the structure of yeast condensin and condensin-DNA complexes. Condensin is foundto exhibit mainly open 'O' shapes and collapsed 'B' shapes, and it cycles dynamically between these two states over time. Condensin binds double-stranded DNA via a HEAT subunit and, surprisingly, also via the hinge domain. On extruded DNA loops, we observe a single condensin complex at the loop stem, where the neck size of the DNA loop correlates with the width of the condensin complex. Our results suggest that condensin extrudes DNA by a fast cyclic switching of its conformation between O and B shapes, consistent with a scrunching model.

Selected clinical and laboratory parameters were studied respectively in patients with meningitis caused by enterococci and viridans streptococci in an academic children's hospital. During a nine-year period (1981-1989), enterococci or viridans streptococci were isolated from the cerobrospinal fluid (CSF) of 48 patients. In nine of these 48 patients, enterococci or viridans streptococci were the causative agents of meningitis. These nine children constituted 2.0% of 450 patients with bacterial meningitis in this period. All nine children suffered from underlying diseases; neurosurgical procedures were performed in six of these patients, of whom four had ventricular drains. A head trauma preceded the development of meningitis in another patient. Drainage of the lacrimal duct was associated with the development of meningitis in another patients. One child concurrently suffered from severe gastroenteritis. CSF leukocyte count and CSF protein levels were moderately elevated, whereas CSF glucose levels were either slightly decreased or within the normal range. Meningitis due to enterococci or viridans streptococci is seen predominantly in children under the age of one year. Predisposing factors, including neurosurgical procedures, head trauma and severe gastroenteritis, are usually present in these patients. The prognosis for recovery is generally good.