Polycationic peptides as prophylactic agents against methicillin-susceptible or methicillin-resistant Staphylococcus epidermidis vascular graft infection

Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses, followed by topical inoculation with 2 x 10(7) CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.     

Measurement of eye length and eye shape by optical low coherence reflectometry

BACKGROUND: The precise and rapid measurement of eye length and eye shape are essential for investigating eye growth regulation and myopia. For this purpose, we developed an optical low coherence reflectometer and obtained preliminary measurements in volunteers. METHODS: The instrument includes a rotating glass cube to produce longitudinal scans at a velocity of 0.42 m/s and a repetition rate of approximately 13 scans/s. Heterodyne detection of light reflected from the anterior cornea and the posterior retina permits to measure axial eye length and eye shape (off-axis eye length). Each measurement consists of five consecutive scans. Reproducibility and precision were determined in one volunteer by measuring axial eye length five consecutive times, each time repositioning the eye. Eye shapes were determined in right eyes of four volunteers by measuring eye length every 3.3 degrees from 10 degrees nasally to 10 degrees temporally. RESULTS: Axial eye length measured repeatedly in one volunteer did not differ between or within the measurements (one-factor ANOVA). The average standard deviation was 11 microns. Eye shapes a) varied substantially among subjects and b) differed considerably from the corresponding shapes of spherical model eyes with identical axial eye lengths. CONCLUSION: The newly developed reflectometer permits the precise and rapid measurement of eye length and eye shape. Such measurements, especially in children, may provide important information about mechanisms of eye growth regulation and the development of myopia.     

Topiramate therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs

The authors assessed the effect of concomitant antiepileptic therapy on steady-state plasma concentrations of the new antiepileptic drug (AED) topiramate and the potential relation between topiramate plasma levels and side effects in a cohort of 116 patients with epilepsy. On the basis of concomitant AEDs, patients were divided into two subgroups, otherwise comparable for age and weight-adjusted daily dose of topiramate. Group A (n = 73) received topiramate plus AED inducers of cytochrome P450 (CYP) metabolism, such as carbamazepine, phenobarbital, and phenytoin. Group B (n = 43) received topiramate plus AEDs without inducing properties of CYP metabolism (namely valproic acid and lamotrigine). Weight-normalized topiramate clearance values, calculated as dosing rate/steady-state plasma drug concentration, were about 1.5-fold in patients receiving AED inducers compared with patients receiving AED noninducers. Topiramate plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 25 to 800 mg/d, although, at a given daily dose, a large interpatient variability was observed in matched plasma drug concentrations within each group of patients. Thirty-nine patients (34%) reported side effects associated with topiramate, mostly central nervous system effects. No consistent relation was observed between topiramate plasma concentrations and adverse effects, either in the cohort of patients as a whole or within each subgroup. From a clinical point of view, patients receiving concurrent treatment with enzyme-inducing AEDs can show twofold lower topiramate plasma concentrations compared with patients receiving valproic acid or lamotrigine, and appropriate topiramate dosage adjustments may be required when concomitant AED inducers are either added or withdrawn. Due to the observed variability in topiramate metabolic variables and the complex spectrum of possible pharmacokinetic and pharmacodynamic interactions with the most commonly coprescribed AEDs, monitoring of plasma topiramate concentrations may help the physician in the pharmacokinetic optimization of the drug dosage schedule in individual patients.     

Plasma long-chain polyunsaturated fatty acids and neurodevelopment through the first 12 months of life in phenylketonuria

The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid (LCPUFA) status at diagnosis of phenylketonuria (PKU) and neurodevelopment through the first 12 months of life, and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status. Twenty infants with PKU were prospectively examined through the first year of life. Plasma fatty acids were measured in infants at diagnosis. Plasma phenylalanine levels were determined monthly. Main outcome measures were the Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 5 and 12 months of age, and the visual function at 12 months, evaluated by P100 wave latencies with visual evoked potentials. A higher PDI score was associated with higher plasma arachidonic acid at diagnosis (adjusted correlation coefficient of PDI at 5 months, r=0.38, p=0.05). P100 wave latency at 15 minutes of arc (15') was associated with the early plasma arachidonic acid (adjusted r=-0.56, p=0.02) and phenylalanine levels at 12 months (adjusted r=0.22, p=0.05). No association was found between MDI score and any essential fatty acids. Breastfed infants exhibited higher plasma arachidonic acid (mean difference, delta, =3.4%; 95% confidence interval [CI]=1.2-5.6%) and shorter P100 wave latency at 15' (delta=-21 ms, 95%CI=-30 to -12) than bottlefed infants. Within the population of this study, a weak positive association has been found between plasma LCPUFAs at diagnosis (higher in breastfed infants) and neurodevelopmental indices through the first year of life.     

Oral cancers and the need for secondary prevention programs

Each year, 250,000 people all over the world develop oral cancer, while 130,000 die for this condition. In Italy, these figures are 6000 and 3000, respectively. The 53% average survival rate in five years is one of the lowest, although it increases to 72-86% if oral cancer is diagnosed at the TNM stage I. However, in more than half the cases this condition is diagnosed at more severe stages. This situation can improve significantly because the oral cavity can be easily checked and the cancer is often predictable by precancerous lesions. Since alcohol and tobacco are responsible for 75% of cases, primary prevention basically relies on their control. Secondary prevention, aimed at the early detection of this condition, is based on the examination of oral mucosae and can be performed by dentists, dental hygienists or the patients themselves. The first step to take is to foster information among the subjects at risk, namely people over 40. The authors suggest that educational programs should be held by health professionals so as to teach patients how to perform selfexamination and address to hospitals in case of suspected cancerous lesions.