Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.     

Concurrent medical and psychiatric disorders among schizophrenic and neurotic outpatients

The records of two groups of patients (358 schizophrenics and 69 neurotics), attending the community mental health center of the Johns Hopkins Hospital, were reviewed to assess the extent and severity of reported medical problems. Results indicate that 38% of the schizophrenics and 53% of the neurotics report medical problems, but schizophrenics present with serious medical problems more often than do the neurotics. The authors draw attention to the need for properly assessing the severity of these medial problems and for adequately coordinating psychiatric and medical care. Strategies to overcome these difficulties are suggested.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Ligamentary structure of the base of the nail

Summary The authors report the results of 115 dissections of the base of the distal phalanx of fingers and toes. In 85% of cases including hypoplastic supernumerary digits, there is a connective ligament-like structure. It is a dorsal expansion of the lateral ligament of the distal inter-phalangeal joint arising from the intermediate phalanx and ending in the matrix and the lunula. This ligament may have a role in biomechanical strains on the nail. It can explain some dystrophic nails associated with some malpositioned joints in fingers or toes.

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Structure ligamentaire de la base de l'ongle

Résumé Les auteurs rapportent les résultats de 115 dissections portant sur la base de la phalange distale des doigts ou des orteils. Ils retrouvent dans 85 % des cas, y compris sur des doigts hypoplasiques surnuméraires, une formation conjonctive de type ligamentaire. Il s'agit d'une expansion dorsale du ligament latéral de l'articulation interphalangienne distale, naissant de l'extrémité distale de la phalange intermédiaire et se terminant au sein de la matrice et sur la lunule. Ce ligament ostéomatriciel peut jouer un rôle dans la transmission des contraintes biomécaniques sur l'ongle et expliquer les dystrophies unguéales stéréotypées associées à certaines malpositions articulaires des doigts ou des orteils.