Dynamical thermal dose models and dose time-profile effects.

Introduction: Models of dose-effect relationships seek systematic and predictive descriptions of how cell survival depends on the level and duration of the stressor. The CEM43 thermal dose model has been empirically derived more than thirty years ago and still serves as a benchmark for hyperthermia protocols despitethe advent of regulatory network models. Objective: In this paper, we propose and realize a simple experimental test to assess whether mechanistic models can prove more reliable indicators for some protocols. We define two time-asymmetric hyperthermia profiles, faster rise than decay or slower rise than decay, for which the CEM43 model predicts the same survival while a regulatory network model predicts significant differences. Materials: Experimental data (both control 37°C and hyperthermia assays) were collected from duplicate HeLa cell cultures. Cells were imaged before and 24, 48 and 72 h after the hyperthermia assay double-stained with fluorescein-5-isothiocyanate (FITC)-labeled annexin V and propidium iodide for detecting cell death. Results: Survival experiments of HeLa cells show that a fast temperature rise followed by a slow decay can be twice more lethal than the opposite, consistently with the prediction of the network model. Conclusions: Using a model reduction approach, we obtained a simple nonlinear dynamic equation that identifies the limited repair capacity as the main factor underlying the dose-asymmetry effect and that could be useful for refining thermal doses for dynamic protocols.

Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer.

Introduction: Standard treatment for early-stage invasive breast cancer (bca) consists of breast-conserving surgery and several weeks of adjuvant radiotherapy (rt). Neoadjuvant single-fraction rt is a novel approach for early-stage bca. We sought to investigate the effect of delaying surgery after neoadjuvant rt with respect to the rate of pathologic response (pr). Methods: Women 65 years of age or older with a new diagnosis of stage i luminal A bca were eligible for inclusion. A single 20 Gy dose to the primary breast tumour was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pr rate assessed by microscopic evaluation using the Miller-Payne system. Results: To date, 10 patients have been successfully treated. Median age of the patients was 72 years (range: 65-84 years). In 8 patients, neoadjuvant rt resulted in a tumour pr with median residual cellularity of 3%. No immediate rt complications other than mild dermatitis were noted. Conclusions: This study demonstrates a method for delivering single-fraction rt that can lead to a high level of pr in most patients. Continued accrual to this study and subsequent trials are needed to determine the feasibility, safety, and role of this novel technique in the management of early-stage bca.

Eotaxin promotes eosinophil transmigration via the activation of the plasminogen-plasmin system.

The effect of eotaxin, a potent eosinophil chemotactic factor, on eosinophil transmigration through a reconstituted basal membrane (Matrigel) was evaluated. Eotaxin induced significant eosinophil transmigration in the presence of 10% fetal bovine serum (FBS) and interleukin-5. Its effect was optimal at 0.01 microM, and it plateaued at 18 h. Eotaxin's effect was greater with eosinophils from asthmatic subjects (61.1 +/- 3.4%) than with eosinophils from normal subjects (38.7 +/- 4.2%) (P < 0.001). Inhibition of metalloproteinases decreased eotaxin-induced transmigration by < or = 10.4%, whereas inhibition of the plasminogen-plasmin system decreased eotaxin's effect by < or = 44.4% (P = 0.0002). Moreover, eotaxin-induced transmigration was largely diminished in medium with low concentrations of serum [0.5% FBS: 6.1 +/- 2.4%; 10% FBS: 40.2 +/- 5.8% (P = 0.0001)] but returned to its initial level with the addition of plasminogen (2 U/mL) to 0.5% FBS (43.1 +/- 6.5%). These data show that eotaxin is an efficient promoter of eosinophil transmigration in vitro, that it is more potent with cells from asthmatics than with normal cells, and that its effect depends predominantly on the activation of the plasminogen-plasmin system.

Somatosensory receptive field properties of corpus callosum fibres in the raccoon.

Anatomical studies in a number of species have shown that most areas of the somatosensory cortex are callosally interconnected. This is also true for the raccoon, at least for those parts representing proximal and axial body regions. Electrophysiologically, studies carried out in cats and monkeys have demonstrated that all sensory sub-modalities cross in the callosum. Moreover, cells representing the paws and fingers, though occupying a large portion of areas SI and SII, seem to send proportionately fewer axons through the callosum than axial structures. No comparable study has been carried out in the raccoon. The purpose of the present experiment was therefore to investigate the functional organization of the callosal system in this animal by examining the receptive field properties of the somatosensory fibres crossing in the callosum. Axonal activity was recorded directly through tungsten microelectrodes in the corpus callosum of eight raccoons. Results indicated that somatosensory information is transmitted in its rostral portion. Most receptive fields concerned axial and proximal body regions and the head and face. Some receptive fields represented para-axial regions of the body and a few concerned the hands and fingers. Slowly and rapidly adapting fibres were found, as were all the sensory sub-modalities tested. A substantial proportion of the axons had bilateral receptive fields. These results are discussed in relation to those obtained in other species, with particular reference to: (1) the midline fusion hypothesis of callosal function; (2) the representation within this structure of the distal extremities, and (3) the origin of the bilateral receptive fields.

Somatosensory receptive fields of fibres in the rostral corpus callosum of the cat.

The corpus callosum is the principal neocortical commissure which transmits lateralized information between the hemispheres. The aim of the present experiment was to study the receptive field (RF) properties of somatosensory callosal fibres in the cat. The callosum was approached under direct visual control and axonic responses were recorded under N2O anaesthesia using tungsten microelectrodes or, mostly, glass micropipettes. RFs representing all the sensory submodalities tested (light touch, medium and deep pressure, joint movement and light pinches) were found to be present in the axons which travelled through the callosum. Rapidly adapting units were more common than slowly adapting ones. The axial and para-axial portions of the body accounted for about three-fifths of all RFs, followed by the head (about one-fifth), with the rest responding to stimulation of the extremities. The medial borders of most of the unilateral RFs situated on the trunk and, to a lesser degree, the head, extended to the mid-line. The results are interpreted in terms of the roles of the corpus callosum in mid-line fusion and interhemispheric transfer.

Endoscopic exploration and lymph node sampling of the axilla. Preliminary findings of a randomized pilot study comparing clinical and anatomo-pathologic results of endoscopic axillary lymph node sampling with traditional surgical treatment.

OBJECTIVE: To describe the technique of endoscopic exploration of the axilla. To compare this technique to open surgical treatment by comparing the following variables: operative time, peri-operative complications, duration of hospital stay, node's histology and morphologic aspects and esthetic results. MATERIALS: Standard instruments for traditional operative laparoscopy plus a lipo-aspirator (0.8 Bar). PATIENTS: Forty patients, 20 (group A) undergoing open surgery and 20 (group B) undergoing axilloscopy. All patients with early invasive breast cancer are eligible for conservative operative treatment. METHOD: Randomized study. The technique is described and preliminary results are presented. RESULTS: The operative time for axilloscopy is approximately double that for open surgery. A comparable number of lymph nodes is collected by axilloscopy and open surgery. The nodes collected by axilloscopy are more likely to be fractured. What is the clinical consequence? Two loco-regional relapses are observed in the endoscopic group. DISCUSSION: Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling. Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure. CONCLUSION: Operative time is increased for axilloscopy compared with open surgery. The techniques yield comparable anatomo-pathologic results. It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach.

[Vascular ligation for severe obstetrical hemorrhage: review of the literature]. / Ligatures vasculaires en obstétrique dans les hémorragies sévères de la délivrance.

OBJECTIVE: Assess the contribution of vascular ligation in the treatment of severe obstetrical hemorrhage. Method. We reviewed the anatomic and pathophysiological basis of vascular ligation analyzing the technique, results, and indications for this conservative procedure for the severe post-partum hemorrhage. New developments in suture techniques for uterine bleeding are under study. RESULTS: Outcome after uterine artery ligation is good. A stepwise procedure with progressive ligation of the uterine and ovarian arteries is a good solution (100% success). Bilateral ligation of the hypogastrics can provide success in 66% of cases. Vascular ligation can be an alternative between embolization and hysterectomy. CONCLUSION: Ligation of the bleeding vessels preserves the patient's life and uterus. More than fifty pregnancies have been reported after vascular ligation.

[Prevention of pulmonary collapse during bronchography under general anesthesia in children]. / Prophylaxie du collapsus pulmonaire lors des bronchographies sous anesthésie générale chez l'enfant.

The inhalation of halothane with oxygen and air facilitates bronchography without pulmonary collapse or alveolar obstruction by contrast medium. This anaesthetic technic used in 15 paediatric investigations is more secure under transcutaneous PO2 and PCO2 monitoring.

[Recurrent vulvovaginal mycoses]. / Mycoses vulvo-vaginales récidivantes (MVVR).

The treatment of recurrent vulvovaginal fungal infections is difficult. Pathogenic mechanisms are discussed. Available pharmacologic treatments and their mechanisms of action are reviewed. Patients clearly prefer oral treatment. Ketoconazole is toxic. Only topical or nonabsorbed oral agents can be used during pregnancy. Agents absorbed via the digestive tract can be used in women who use effective contraceptive methods. Published data demonstrate that trifluconazole (which has not yet been granted a license in France) is potent and less toxic than ketoconazole, and that recurrences at discontinuation of this drug are less common. A few hypotheses for future research are presented.

[The tracheal intubation of children suffering from congenital cranio-facial anomalies. Pre-operative anticipation of its technical problems (author's transl)]. / L'intubation trachéale chez les enfants atteints de dysmorphies cranio-faciales congénitales. Détection pré-opératoire des difficultés.

In order to anticipate the technical problems of the tracheal intubation of children suffering from congenital cranio-facial anomalies, the authors suggest, in addition to the routine examination of the nasal and buccal cavities, different clinical and radiological measurements such as mandible angle, maxillo-pharyngeal angle and the mouth opening. These parameters explore the extent of the mandibular asymmetry and hypoplasia, the limits of the mouth opening and the cervical spine extension. Three data are reported, showing the interest of the scheme of examination proposed.

5-Oxo-6,8,11,14-eicosatetraenoic acid induces important eosinophil transmigration through basement membrane components: comparison of normal and asthmatic eosinophils.

Basement membrane transmigration is an important step in tissue recruitment of eosinophils into inflamed tissue. Recent reports showed that this phenomenon is modulated by platelet-activating factor (PAF) in combination with cytokines and proteinases. We investigated the in vitro efficacy of 5-oxo-6,8,11, 14-eicosatetraenoic acid (5-oxo-ETE), a metabolite of arachidonic acid and known as a potent eosinophil chemotactic factor, in promoting the transmigration of blood eosinophils from normal and asthmatic subjects through a Matrigel basement membrane. 5-Oxo-ETE proved to be a more potent (> 10-fold) inducer of eosinophil transmigration than PAF, and this effect was similar in cells from normal and asthmatic subjects (82.0 +/- 3.7% and 88.1 +/- 3.7%, respectively). Moreover, 5-oxo-ETE was active in the absence of interleukin (IL)-5, although this cytokine amplified the effect of 5-oxo-ETE from 61.3 +/- 3.3% to 92.8 +/- 1.8% (p = 0.003). The membrane receptor for urokinase plasminogen activator (CD87), a serine protease, was observed on eosinophils, and its expression was increased by IL-5. The inhibition of both metalloproteinases (MMP) and plasmin/plasminogen complex with inhibitor or monoclonal antibodies decreased cell transmigration by about 50%. Combination of an MMP inhibitor with anti-CD87 antibodies had no additive effect. These data show that 5-oxo-ETE is an efficient promoter of eosinophil transmigration in vitro, and is much more potent in this respect than PAF. The data suggest that 5-oxo-ETE could play an important role in eosinophil recruitment in vivo. Moreover, they demonstrate that in addition to MMP, the plasmin/plasminogen system could be involved in eosinophil transmigration.