Impact of serum on clearance predictions obtained from suspensions and primary cultures of rat hepatocytes.

The objective of the present study was to compare two configurations of the hepatocyte model namely suspensions (SH) and conventional primary cultures (CPC) for their ability to predict the hepatic clearance in vivo in the rat and, to investigate the impact of serum on the prediction accuracy. The metabolic competences of several cytochrome P450 isoenzymes were investigated both in CPC and SH in the presence or absence of serum. Under the same conditions, the in vitro intrinsic clearance of six test compounds metabolised by a variety of phase I and phase II enzymes (antipyrine, RO-X, mibefradil, midazolam, naloxone and oxazepam) were derived from Vmax/Km scaled up to the corresponding in vivo hepatic metabolic clearance. CYP activities were shown to be stable in both CPC and SH for up to 6 h of incubation, except for the CYP 3A1 activity that decreased in CPC even in the presence of serum. Moreover, the clearances predicted from SH in the presence of serum were closer to the in vivo values than those obtained from CPC. SH represent a convenient model to assess the hepatic metabolism of xenobiotics, the presence of serum in the incubation medium significantly improved in several instances the quality of the predictions.     

Prospective, double-blind, randomized trial of equimolar mixture of nitrous oxide/oxygen to prevent pain induced by insertion of venous access ports in cancer patients

BACKGROUND: To assess the efficacy of equimolar mixture of nitrous oxide/oxygen (EMNO) to prevent pain induced by venous access ports (VAPs) implantation in cancer patients. PATIENTS AND METHODS: In a randomized, double-blind study on an adult population not knowing the effects of EMNO, cancer patients were randomly assigned to breath via a facial mask, EMNO or a placebo mixture comprising 50% oxygen and 50% nitrogen. The primary end-point was the patients' assessment of the severity of pain evaluated using a visual analog scale (VAS, 0 to 100) and the proportion of patients suffering pain in each group. The secondary criteria were side effects, tolerability of EMNO, and the level of satisfaction of both the patients and the medical team. RESULTS: Eighty-three adults (42 in the EMNO group and 41 in the placebo group) were included. VAPs were implanted in the jugular vein in 95% of patients. In the placebo group, 78% of the patients declared that they found VAP implantation painful vs. 34% in the EMNO group (p=0.001). The severity of the pain was reduced by 50% in the EMNO group in comparison with placebo (p=0.0125). Although the median time to perform implantation was strictly identical in both groups (20 min), the estimated duration of surgery seemed longer to patients in the control group. Patient and investigator satisfaction indexes were >90% in both groups. CONCLUSION: EMNO provides an effective solution for the prevention of pain during placement of VAPs.     

Age-specific analysis of normal cytokine levels in healthy infants.

While pathophysiology of elevated cytokines is well delineated, reference values for children are unknown, although they may vary physiologically with age and differ from those of adults. Between June and November 2001, interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-alpha) concentrations from blood samples of 79 healthy children in six different age groups (group I: 0-3 months; group II: 4-12 months; group III: 13-24 months; group IV: 25-36 months; group V: 37-48 months; group VI: 49-60 months) were measured with ELISA. TNF-alpha was within 2.2-3.5 pg/ml in all groups with a trend toward higher values in groups II and III (p = ns). IL-6 was significantly lower in group III than in groups IV (p = 0.0165) and VI (p = 0.0147). IL-10 was within 3.3-5.5 pg/ml in all groups (p = ns). In regression analysis no correlation between age and cytokine concentrations was found. Although not statistically significant, IL-6 was lower and TNF-alpha higher than the adult reference values provided by the kit manufacturer. Although reference cytokine levels seem not age-related during early infancy, IL-6 is significantly lower during the second year of life than later. In infants aged 5 years or younger, reference levels of IL-6 should be chosen lower, and those of TNF-alpha higher, than the adult reference values.     

Source monitoring deficits in hallucinating compared to non-hallucinating patients with schizophrenia.

In two source memory tests, hallucinating patients with schizophrenia (N=30), compared to non-hallucinating (N=31), are impaired in recognizing internal self-generated items and misattribute them to an external event. They are not impaired in recognizing events from two internal sources. Results support a selective source-monitoring deficit in the occurrence of auditory hallucinations.     

Routine use of mupirocin at the peritoneal catheter exit site and mupirocin resistance: still low after 7 years.

OBJECTIVE: The purpose of this study (the third in a series of similar studies) is to evaluate the prevalence of Staphylococcus aureus (SA), methicillin-resistant SA (MRSA) and mupirocin-resistant SA (MuRSA) carriers in a peritoneal dialysis centre where patients have been instructed to use prophylactic mupirocin ointment at the catheter exit site over the last 7 years. METHODS: Swabs were taken from catheter exit site, nares, axillae and groin in 147 chronic peritoneal dialysis out-patients between November 2003 and January 2004. Axillae/groin and nasal samples were pooled and cultured in the same medium, whereas exit site swabs were cultured separately. All SA isolated were tested for methicillin and mupirocin resistance using oxacillin screening plates and E-test strips. RESULTS: Sixteen of 147 patients (10.9%) were found to be SA carriers: of these 13 (8.8%) had a positive nasal/axillae/groin culture; two (1.4%) had both nasal/axillae/groin- and exit site-positive culture; and one (0.7%) had only exit site-positive culture. In these 16 SA carriers, we found mupirocin-resistant strains (MuRSA) in four patients (25%) and MRSA in two patients (12.5%). Among the four MuRSA carriers, one had both nasal/axillae/groin- and exit site-positive culture and three had only nasal/axillae/groin-positive culture. Three high-level resistance and one low-level resistance MuRSA carriers were isolated. One MuRSA strain was also methicillin resistant. All MRSA strains were sensitive to vancomycin and rifampicin. CONCLUSION: After 7 years' routine use of prophylactic mupirocin ointment at the catheter exit site in non-selected chronic peritoneal dialysis patients, MuRSA was found in 25% of SA strains isolated or in 2.7% of the patients. Compared with our previous study, 3 years earlier, there is no significant increase in the MuRSA prevalence in peritoneal dialysis patients who routinely apply mupirocin ointment at the catheter exit site.