Methods to control anticancer chemotherapy preparations ranked by risk analysis.

The observed increase in cancer led to a continuous rise in anticancer drug preparations in Hospital Centres. The quality and security of these preparations are essential to ensure the efficacy and to limit the risk of iatrogenic toxicity. Several methods have been described to secure the process of preparation (i.e. non-analytical methods for the control during the fabrication; analytical methods for the final product evaluation). These different methods have been presented in many studies, in particular in descriptive studies, but in practice, selecting a method is difficult and related to needs and hospital priorities. Therefore, we decided to conduct this present review focused on various existing methods allowing enhancement in security of anti-cancer drugs preparation process. A proactive hazard analysis method was applied, considering preparation and control steps, to discuss the choice of a method in terms of quality and security and to identify potential risks of failure. The results show that none method is perfect. Methods with the lowest criticality score are the robotization closely followed by Drugcam® in the case of re-labelling of all containers. According to these elements a University Hospital Centre could consider these risk indexesimplementing control methods.

Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report.

Five patients with endogenous depression were asked to participate in a phase-advance procedure consisting in advancing by 5 h the time schedule of the major external synchronizers such as light/dark, sleep/wake, meal time and social activity cycles. Clinical and biological parameters were observed throughout this 2-week process which followed one night of partial sleep deprivation. All patients improved with partial sleep deprivation and four of the five showed continuing remission during the phase-advance process. The antidepressant effects of the phase-advance process are discussed in light of different chronobiological models for depression.

Charcoal suspension for tumor labelling modifies macrophage activity in mice.

We have previously developed a charcoal suspension for injection into human breast cancers in order to facilitate their location during surgery. We observed that charcoal particles were ingested by intra and peritumoral macrophages, some of which carried the particles at some distance from the injection site. We studied the influence of the formulation parameters of the charcoal suspension for intratumoral injection on in vitro and in vivo activation and in vivo mobilization of mouse peritoneal macrophages after intra-peritoneal injection of 2 mL of each preparation. The influence of the charcoal origin (peat vs wood), granulometry, suspension vehicle (water for parenteral injection, vs saline), concentration and excipients were studied. Micronized peat charcoal in water for injection at the highest studied concentration reduced macrophage activation in vitro and in vivo. However, macrophage mobilization was weaker than after thioglycolate injection and did not seem to be charcoal dose-dependent. The additives incorporated in the charcoal suspension led in vivo to increased peritoneal macrophage activation and mobilization (mannitol, and glucose), only increased activation (polysorbate 80 and pluronic F68) or mobilization (dextran 40, egg lecithin, and cabosil), or inhibited both activation and mobilization (cremophor EL).

Effects of tail alkyl chain length (n), head group structure and junction (Z) on amphiphilic properties of 1-Z-R-D,L-xylitol compounds (R = CnH2n+1).

In the family of 1-Z-R-D,L-xylitol, we have determined the main amphiphilic properties of esters (Z = OCO) as a function of alkyl chain length (R = CnH2n+1, n = 4-17). A classical decrease of critical micelle concentration with the increase in the alkyl chain has been found. With water, esters displayed lamellar phases at temperatures of 25 degrees C or higher. The extent of hydrophilic/lipophilic balance range obtained by emulsification method can be proven to be of interest for pharmaceutical applications. The results were compared with those obtained in previous investigations, i.e. for alkyl-substituted xylitol, with thioether (Z=S) and ether (Z=O) linking groups in order to discuss the role of the junction nature. Likewise, they were compiled with the results related to their D-glucose homologues, in order to put forward the effects of the head group configuration, cyclic or acyclic.

[The long-term effects of dual-chamber stimulation in 8 patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy]. / Effetti a lungo termine della stimolazione bicamerale in otto pazienti portatori di cardiomiopatia ipertrofica ostruttiva con sintomi refrattari a terapia medica.

BACKGROUND: The issue of DDD pacing as a therapeutic option for patients with obstructive hypertrophic cardiomyopathy is still under debate. Moreover, some authors stress the concept of the placebo effect of electrical therapy in this particular setting. METHODS: We retrospectively evaluated 8 symptomatic patients with obstructive hypertrophic cardiomyopathy despite medical therapy, who underwent DDD pacemaker implantation as an adjunctive therapeutic strategy. All patients were evaluated with a two-dimensional/Doppler echocardiogram at baseline, shortly after the beginning of DDD pacing and at follow-up. In 3 patients dobutamine stimulation was necessary to elicit the intraventricular gradient. RESULTS: At follow-up (21 +/- 19 months, range 1-54 months) the peak gradient declined from 86 +/- 27 to 34 +/- 27 mmHg (55.2%). In 4 patients the peak gradient sharply declined after pacemaker implantation with active pacing and remained stable throughout the follow-up. In 2 patients we noted a continuous reduction in the peak gradient during the follow-up, while in 2 patients it returned to baseline values after 1 year and 1 month, respectively, despite an early reduction with DDD pacing. All patients experienced symptomatic amelioration throughout the follow-up. Two patients developed angina at the end of our observation together with an increase in the peak gradient. CONCLUSIONS: We believe that DDD pacing may be considered as a practical therapeutic option for patients with obstructive hypertrophic cardiomyopathy who would otherwise be regarded as candidates for surgery.