Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Incontinentia pigmenti: MR demonstration of brain changes.

PURPOSETo describe the MR findings in eight girls and women with incontinentia pigmenti, from two families. Four had skin lesions and neurologic disease, and four had only skin lesions.METHODSEight patients had physical examination, family history, electroencephalogram and MR examination of the brain. MR was repeated in the two cases with more severe changes several years after the first study.RESULTSMR revealed brain changes only in the four patients who had neurologic disease associated with the cutaneous lesions of incontinentia pigmenti. Abnormalities were located in the cerebral hemisphere contralateral to the most affected side of the body. In two cases, the MR changes were subjacent to the scalp areas where the most severe cutaneous lesions were located in the neonatal period. Hypoplasia of the corpus callosum, probably secondary to atrophy of one or both cerebral hemispheres, and abnormal signal and atrophy of the lateral regions of one of the cerebellar hemispheres also were found in all four cases. Although the changes were seen in both the T1- and T2-weighted images, they were most evident in the latter. The four patients in the fourth stage who had only cutaneous lesions without neurologic problems did not reveal any MR abnormalities.CONCLUSIONSThis study demonstrates MR signal changes and focal atrophy of the cerebrum, cerebellum, and corpus callosum in patients with incontinentia pigmenti and neurologic disorders. The MR images appear normal in patients with incontinentia pigmenti who have no neurologic abnormalities.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.