Diffusion intra-amygdalienne et pharmacodynamies comparées de la roxithromycine,de la clarithromycine et de la 14-OH hydroxyclarithromycine

The purpose of the present work was to evaluate the intra-tonsillar concentrations of roxithromycin (ROX), clarithromycin (CLR) and 14-OH-CLR at steady state in children, and then to compare them with their respective MICs against group A Streptococci. It was a monocenter, pharmacokinetic study in children hospitalized for a tonsillectomy and receiving in a randomized manner either roxithromycin 3 mg/kg bid, or clarithromycin 7.5 mg/kg bid, for three days. The last dose in both groups was randomly administered either 2, or 4 or 12 hours before the bilateral tonsillectomy. The tissue sample was concomitent to a blood sample. Blood and tissue concentrations of macrolides were performed by HPLC.ResultsMean blood (mg/l) and tissue (mg/kg) concentrations are as follows (mean+/-SD) : serum concentrations (mg/L) (mg/kg) (mean, SD), as decreasing from 2^d to 12^th hour, are respectively 7.51±4.28 to 2.34±0.67 for ROX, of 1.83±1.15 to 0.62±0.53 for CLR and of 0.81±0.35 à 0.51±0.16 for 14-OH-CLR. For tonsils decreasing concentrations at the same sampling times were 0.81±0.48 to 0.29±0.14 for ROX, of 1.81±0.48 to 0.78±0.14 for CLR, of 0.78±0.49 to 0.51±0.14 for 14-OH-CLR. The areas under the serum concentrations curves (AUC) for ROX and CLR+ 14-OH-CLR (CLRtot) were respectively 53.8 and 22.5 μg.h.ml-1. The corresponding values for the tonsils were respectively 7.0 and 26.15. The rate of penetration as determined by the AUC serum/AUC tissue ratios are 13% and 116.2% for ROX and CLR tot respectively.As a consequence in terms of antibacterial activity, and as far as CLR and 14-OH-CLR MICs are regularly four times lower than those of ROX, and considering that intra-tonsillar concentrations of CLRtot vs ROX were 3.6 (2 h), 2.3 (4 h) and 4.4 (12 h) times higher than those of ROX, the resulting inhibitory quotients are up to 13-18 times higher for CLR, without taking into account the synergy that is likely to occur between CLR and 14-OH-CLR.ConclusionThe better antibacterial activity and tonsillar pharmacokinetics of CLR and its active metabolite 14-OH-CLR confer to these components pharmacodynamic properties which are more in adequation with the pre-requisites correlating with a suitable bacterio-clinical efficacy when compared with ROX.     

Tissue physiology and the response to heat.

The most important physiological parameter influencing tissue response to heat is blood flow. At mild hyperthermia temperatures blood perfusion increases in many tumours and this effect is heating time-, temperature- and tumour-dependent. These flow increases can improve tumour oxygenation. When heating is terminated, perfusion and oxygenation commonly recover, although how quickly this occurs appears to be tumour-specific. While these effects are unlikely to have any anti-tumour activity they can be exploited to improve the combination of heat with other therapies. However, since similar physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity by changing the tumour micro-environmental parameters, primarily an increase in tumour acidity. Such changes are generally not seen in normal tissues, thus resulting in a therapeutic benefit.     

Laparoscopic Local Resection Based on Sentinel Node Evaluation for Early Gastric Cancer: A Preliminary Report

We previously reported that lymphatic mapping using isosulfan blue can be used to identify sentinel nodes (SNs). This study was undertaken to evaluate the feasibility of using the SN technique in treating early gastric cancer and to explore its usefulness for minimal invasive surgery. Twenty-three patients with early gastric cancer who underwent SN biopsy were retrospectively evaluated. Based on SN evaluation, individualized surgery was performed in five patients with T1N0M0 gastric cancer. When pathological examination of frozen sections revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic local resection was applied when the SN biopsy was negative. Our results showed that the success rate with SN biopsy in early gastric cancer was 100%, as were the accuracy, sensitivity, and specificity. All five patients with early gastric cancer had SNs negative for metastases both by frozen section and by postoperative pathology. Thus, all these patients underwent laparoscopic local resection without extended lymphadenectomy. We conclude that SN biopsy is a useful tool to individualize the operative procedure, and laparoscopic local resection can be safely performed using SN guidance in selected patients with early gastric cancer.