Rate-controlled rectal drug delivery in man with a hydrogel preparation

Cylindrical hydrogels of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent were prepared by radical polymerization at 70°C. After washing they were soaked in an aqueous drug solution of antipyrine or theophylline. The in vitro drug release experiments were performed in 100 ml isotonic glucose at 37°C. Rectal administration of a hydrogel preparation containing antipyrine was performed in two subjects for 72 h. With a theophylline-containing hydrogel preparation rectal drug administration was performed in six volunteers for 24 h. Plasma and saliva samples were taken regularly and the in vivo drug release was determined by means of a deconuolution procedure. In vitro 1.12g antipyrine had been released according to a matrix-type profile for 72 h, whereas it was calculated that this was 1.13 and 1.09 g in vivo in the two subjects. The release profile in vivo was very similar to that in vitro. The theophylline hydrogel preparation released in vitro a total of 288 ± 6 mg of drug in 24 h and in vivo this amount was calculated to be 288 ± 11 mg (mean ± s.d.). Near-constant plasma theophylline concentrations were obtained after administering the hydrogel preparation. In all six subjects the cumulative drug profile was in almost perfect agreement with that observed in vitro. Hydrogels offer interesting perspectives as rate-controlled rectal drug delivery systems because of the predictable release profile in vivo on the basis of observations in a simple in vitro model

Theory for incongruent crystallization: application to a ZBLAN glass

Equations which describe incongruent nucleation and subsequent crystal growth are derived. A ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) glass was used to test the validity of these equations. Nucleation rate measurements were fitted to theory and some growth rate measurements were in reasonable agreement with theor. predictions. Both nucleation theory and crystal growth theory were used for computer simulations of the crystn. behavior during heat treatments. Some heat treatments were performed in a DSC app. to verify the theories. The exptl. results were in good agreement with the numerical data. Using these theor. results it is possible to est. fiber scattering losses due to crystn. Depending on drawing temp., estd. losses can vary from 0.014 (310 Deg) to >=25 decibel/km (320 Deg). [on SciFinder (R)

Communicatie en strategie van de Afghaanse Taliban vanuit het perspectief van het leiderschap

As a result of a more limited military presence of the Netherlands in Afghanistan the Dutch information position regarding the Taliban has decreased as well. Realizing that insight in the developments in Afghanistan in general and the Taliban in particular will remain relevant to the Netherlands, the question rises to what extent the public communication by the Taliban could provide insight into the (future) positioning and conduct of this organization. This general question is divided into the following two research questions:To what extent is Taliban communication about their ideology, goals and strategy in line with their actual conduct?Can Taliban communication be used as a means to forecast the future positioning and conduct of this organization?Op 28 december 2014 is een einde gekomen aan de ISAF-missie (International Security and Assistance Force) in Afghanistan. De verantwoordelijkheid voor de veiligheidssituatie in het land werd op die dag overgedragen aan de Afghaanse regering in Kabul. Eén van de grootste uitdagingen voor Afghanistan is de voortdurende strijd met de Taliban. Door de in omvang afgenomen aanwezigheid van Nederlandse militairen in Afghanistan en andere Nederlandse belangen is de informatiepositie ten aanzien van de Taliban beperkter geworden. Het besef dat inzicht in de ontwikkelingen in Afghanistan in het algemeen en de Taliban in het bijzonder voor Nederland relevant blijven, roept de vraag op of de communicatie-uitingen van de Taliban inzicht zouden kunnen bieden in het toekomstig handelen van deze organisatie. Deze algemene vraag is in deze studie in de volgende twee hoofdvragen opgesplitst: In hoeverre komt de communicatie van de Afghaanse Taliban over hun ideologie, doelstellingen en strategie overeen met hun daadwerkelijke handelen? Kunnen op basis van de communicatie van de Taliban uitspraken gedaan worden over de toekomstige positie en het toekomstig handelen van de Taliban? INHOUD: 1. Introductie 2. De Taliban als organisatie 3. De Taliban tussen woord en daad 4. Conclusi

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n = 240) were randomised to receive gemcitabine 1125 mg m(-2) (days 1 and 8) plus either cisplatin 80 mg m(-2) (day 2) or epirubicin 100 mg m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status less than or equal to2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm

Prospective clinical and pharmacological evaluation of the Delcath System’s second generation (GEN2) hemofiltration system in patients undergoing percutaneous hepatic perfusion with melphalan

Surgical oncolog