Prediction of neutropenia-related effects of a new combination therapy with the anticancer drugs BI 2536 (a Plk1 inhibitor) and pemetrexed.

This study investigated the feasibility of predicting the neutropenia-related effects of a therapy that combines the investigational drug BI 2536 (inhibitor of Polo-like kinase 1) and pemetrexed, an approved anticancer drug. Predictions were arrived at using the pharmacokinetic/pharmacodynamic (PK/PD) parameters of each of the drugs obtained from monotherapy studies and assuming that the neutropenic effect is additive when the drugs are administered as a combination therapy. Subsequently, a PK/PD model was developed to determine whether this assumption of additive effect was reasonable in relation to these two drugs. All analyses and simulations were performed using the population approach in NONMEM, version VI.

Treatment during primary HIV infection does not lower viral set point but improves CD4 lymphocytes in an observational cohort.

OBJECTIVE: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes. METHODS: Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/ microl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses. RESULTS: 156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p<0.001) and median CD4 lymphocyte (449/ microl vs. 613/ microl; p<0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/ microl vs. -86/ microl (p = 0.01). Median time until CD4 lymphocytes decreased to <350/ microl (including all patients with CD4 lymphocytes <500/ microl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p<0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences. CONCLUSIONS: Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes <350/ microl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes <500/ microl during seroconversion.

Switch from a ZDV/3TC-based regimen to a completely once daily (QD) regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT).

OBJECTIVES: To assess the efficacy and safety of a treatment switch from a twice-daily (BID) regimen containing zidovudine (ZDV) and lamivudine (3TC) plus a third agent to a once daily (QD) regimen containing the fixed-dose combination of tenofovir DF/emtri?citabine (TDF/FTC, Truvada) plus a divergent third QD agent in HIV-1 infected patients. METHODS: Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA <50 copies/ml and CD4+ T-cell count >50 cells/microl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. RESULTS: During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs). At week 48, plasma HIV-1 RNA was <50 copies/ml in 40 patients (78.4%). No patient experienced virological failure (defined as HIV-1 RNA > or =50 copies/ml at two consecutive post-baseline measurements) during the study. Immunologic control was maintained, with no significant changes in CD4+ or CD8+ T-cell counts. A statistically significant improvement from baseline in haemoglobin level was observed at week 48 (median change 0.8 g/dl; p<0.001). There was also a statistically significant decrease in total cholesterol concentration at week 48 (-26.0 mg/dl; p = 0.001) in a subset of patients (n = 22) entering the study with elevated total cholesterol. Treatment was well tolerated and no treatment-related grade 3 or 4 AEs were seen. - CONCLUSIONS: Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

Molecular and electronic structure in NaCl electrolytes of varying concentration: identification of spectral fingerprints.

Near edge x-ray absorption spectra at the Na K edge in aqueous NaCl electrolytes are presented as a function of concentration. The spectra are modeled by electronic structure calculations. We find and identify the orbital origin of two spectral fingerprints with sensitivity to the Na+-H2O distance and the Na+-Cl- distance in the electrolyte. Interionic interaction is found to be crucial for the description of the electrolytes at high concentrations.

Melanoma of the iris: conservative or radical therapy?

A case of melanoma of the iris is reported. A simple enucleation of the eye was performed. The patient is alive 24 years after the operation.

Penetrating wound of the orbit: a 31-year follow-up.

The case is described of a man who at the age of 17 suffered accidental penetration of his right orbit by a rod and spring from a machine gun. Operation was successful, and follow-up 31 years later showed normal vision at 20/20 in both eyes.