A longitudinal PKPD model based on in vitro data successfully predicted a previous in vivo study of meropenem. The type and magnitude of the PK/PD index were sensitive to the experimental design, the MIC and the PK. Therefore, it may be preferable to perform simulations for dose selection based on an integrated PK-PKPD model rather than using a fixed PK/PD index target.

The results of conventional surgery for lithium-associated HPT are poor. The surgical approach should be adjusted for the multiglandular disease that is usually the cause of HPT in patients on chronic lithium therapy.

We investigated the short-term (1 hour-3 days) effects of a 45 minute run on calcium, parathyroid hormone, the carboxyterminal propeptide of type I procollagen (PICP), and the immunoactive carboxyterminal telopeptide of type I collagen in serum (ICTP) in young females. Fourteen healthy young women, aged 25.2 +/- 0.6 years (mean +/- SEM) with regular menstruations, participated. The test was outdoor jogging for 45 minutes at an intensity of 50% of VO2 max. Blood samples were collected 15 minutes before the test and 1, 24, and 72 hours after the test. The measured values were adjusted for changes in plasma volume. A significant decrease of ionized calcium was observed at 1 hour (P < 0.001) and 72 hours (P < 0.05) and a significant increase of parathyroid hormone (PTH) was noted 24 (P < 0.01) and 72 hours (P < 0.05) after the test. A significant decrease of PICP at 1 hour (P < 0.05) was followed by an increase after 24 (P < 0.01) and 72 hours (P < 0.001) and a significant increase in ICTP was noted at 24 and 72 hours (P < 0.05). A strong positive correlation was found between serum levels of PICP and ICTP (r = 0. 55-0.84; P < 0.05) throughout the experiment. In conclusion, young females showed biochemical signs of increased bone collagen turnover and altered homeostasis of calcium and PTH after a single bout of moderate endurance exercise.

In this study we describe, to our knowledge, the first experiment using the microdialysis technique for studying the release of prostaglandin E 2 (PGE 2 ) in the proximal tibia metaphysis secondary to mechanical loading. Nine healthy females, six in the loading group and three controls, mean age 34 Ϯ 2 (years Ϯ SEM), participated. A standard microdialysis catheter was inserted into the tibia metaphyseal bone under local anesthesia. Samplings were done every 15 min under a 2-h equilibration period. Thereafter, heel-drops (one impact per second) with as hard impact of the heels into the floor as possible, were done for 5 min by the subjects in the loading group. The control group performed no exercise. Sampling continued after this for another 2-h period.Basal levels of PGE 2 in the proximal tibial metaphysis were determined to a mean of 45 Ϯ 10 pg/ml (mean Ϯ SEM, n ϭ 6). The major finding was a 2.5-3.5-fold increase in the release of PGE 2 after mechanical loading. The increase was statistically significant ( P Ͻ 0.05 compared with basal levels) 1 h after the mechanical loading and persisted for the rest of the experimental period. No major alterations were observed in the control group. In conclusion, our data demonstrate that in situ microdialysis is a useful method for studying the PGE 2 production in human bone. Furthermore, a rapid and significant increase in PGE 2 levels was noticed in response to dynamic mechanical loading.

Background We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. Methods This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. Results Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]). Conclusions Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. Clinical Trials Registration NCT01732250