In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.     

Pharmacokinetics and Inflammatory Fluid Penetration of Clinafloxacin

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 μg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 μg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.     

ABNORMAL CORNEAS MEASURED BY A NEW PHOTOGRAMMETRIC TECHNIQUE

The limitations of keratometry and photokeratoscopy are briefly discussed. A new photogrammetric technique of measuring corneal topography is described. Contours and cross-sections of abnormal corneas are presented to illustrate the scope and application of the new technique.     

Vitamin D replacement in Asians with diabetes may increase insulin resistance.

We report three cases of vitamin D replacement in British Asians with vitamin D deficiency and non-insulin-dependent diabetes mellitus. In all cases, replacement resulted in an increase in insulin resistance and a deterioration of glycaemic control.     

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.     

Fornix transection impairs conditional visuomotor learning in tasks involving nonspatially differentiated responses.

Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response.     

Rapid molecular cytogenetic analysis of X-chromosomal microdeletions: Fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency

Diagnosis of X-chromosomal microdeletions has relied upon the traditional methods of Southern blotting and DNA amplification, with carrier identification requiring timeconsuming and unreliable dosage calculations. In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. CGKD deletions involve the genes for glycerol kinase, Duchenne muscular dystrophy, and/or adrenal hypoplasia congenita. We report an improved method for diagnosis of deletions in individuals with CGKD and for identification of female carriers within their families, using fluorescence in situ hybridization (FISH) with a cosmid marker (cosmid 35) within the glycerol kinase gene. When used in combination with an Xq control probe, affected males demonstrate a single signal from the control probe, while female carriers demonstrate a normal chromosome with two signals, as well as a deleted chromosome with a single signal from the control probe. FISH analysis for CGKD provides the advantages of speed and accuracy for evaluation of submicroscopic X-chromosomal deletions, particularly in identification of female carriers. In addition to improving carrier evaluation, FISH will make prenatal diagnosis of CGKD more readily available. © 1995 Wiley-Liss, Inc.