Feasibility, reproducibility, risks and benefits of face transplantation: a prospective study of outcomes.

Composite tissue allotransplantations can be indicated when autologous transfers fail to restore human appearance. We report the reproducibility, difficulties, serious adverse events and outcomes of our patients. Five patients were included in a registered clinical research protocol after thorough screenings assessed by an independent expert committee systematically discussing the alternative options. One patient suffered from plexiform neurofibromas, two from third degree burns and two from gunshot injuries. They were included on a national waiting list with a dedicated face procurement procedure. Transplants were harvested from heart beating brain-dead donors before other tissues and organs. Induction immunosuppressive therapy included antithymocyte globulins, steroids, mycophenolate mophetil and tacrolimus. Maintenance therapy included the last three ones associated with extracorporeal-photopheresis. Four patients were transplanted with 7- to 38-month follow-up. One could not due to multiple panel reactive antibodies after 18 months on waiting list. Acute cellular rejections were controlled by conventional treatment. Opportunistic infections affected all patients and lead one patient to die two month after the transplantation. Voluntary facial activity appeared from 3 to 5 month. Face transplantation has been reproducible under conventional immunosuppression. Major improvements in facial aesthetic and function allowed patients to recover social relations and improved their quality of life.

Skin penetration of epigallocatechin-3-gallate and quercetin from green tea and Ginkgo biloba extracts vehiculated in cosmetic formulations.

Green tea (Camellia sinensis) and Ginkgo biloba extracts in cosmetic formulations have been suggested to protect the skin against UV-induced damage and skin ageing. Thus, it is very important to assess the human skin penetration of their major flavonoids to verify if they penetrate and remain in the skin to exert their proposed effects. The aim of this study was to evaluate the human skin penetration of epigallocatechin-3-gallate (EGCG) and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations. This study was conducted with fresh dermatomed human Caucasian skin from abdominal surgery mounted on static Franz diffusion cells. Skin samples were mounted between two diffusion half-cells and 10 mg/cm(2) of formulations supplemented with 6% of green tea or G. biloba extract were applied on the skin surface. The receptor fluid was removed after 6 and 24 h and analyzed by high-performance liquid chromatography for the quantification of the flavonoids. The stratum corneum was removed by tape stripping and immersed in methanol and the epidermis was mechanically separated from the dermis and triturated in methanol to extract EGCG and quercetin. The results showed that the flavonoids under study penetrated into the skin, without reaching the receptor fluid. The majority of EGCG was quantified in the stratum corneum (0.87 microg/cm(2)), which was statistically higher than the EGCG concentrations found in viable epidermis (0.54 microg/cm(2)) and in the dermis (0.38 microg/cm(2)). The majority of quercetin was quantified in the viable epidermis (0.23 microg/cm(2)), which was statistically higher than the EGCG concentration found in the stratum corneum layer (0.17 microg/cm(2)). Finally, it can be concluded that EGCG and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations presented good skin penetration and retention, which can favor their skin effects.

Phenol biosensor based on Sonogel-Carbon transducer with tyrosinase alumina sol-gel immobilization.

A new biosensor for detection of phenols, based on tyrosinase immobilization with alumina sol-gel on Sonogel-Carbon transducer, has been developed. The electrode was prepared using high energy ultrasounds directly applied to the precursors. The alumina sol-gel provided a microenvironment for retaining the native structure and activity of the entrapped enzyme and a very low mass transport barrier to the enzyme substrates. Phenols are oxidized by tyrosinase biosensor to form a detectable product, which was determined at -300 mV vs. Ag/AgCl reference electrode. For phenol, the sensor exhibited a fast response which resulted from the porous structure and high enzyme loading of the sol-gel matrix. The linear range was from 5 x 10(-7)M to 3 x 10(-5)M, with a detection limit of 3 x 10(-7)M. The stability of the biosensor was also evaluated.

[Nociceptive cancer pain in adult patients: statement about guidelines related to the use of antinociceptive medicine]. / Douleurs cancéreuses par excès de nociception chez l'adulte: mise au point sur les recommandations concernant les traitements antalgiques médicamenteux.

OBJECTIVE: The World Health Organization (WHO) published guidelines to improve cancer pain control which allow to relieve noceptive cancer pain in 80% of adult patients. Nevertheless WHO recommendations do not include: various ways to start morphine treatment, how to manage opioids adverse effects, severe cancer pain management, postoperative pain and procedure-relatived pain. The goal of this review is to discuss these issues. DATA SOURCES: The data were retrieved from PubMed years 2001 to 2006 (keywords used alone or in combination were: opioids, cancer, pain, pain killers, rotation, intraspinal, ketamine, side effects), the "Standard, Options and Recommendations on cancer nociceptive pain treatments for adult patients" published by the French Union of Comprehensive Cancer Centers (FNCLCC; Fédération nationale des centres de lutte contre le cancer) and the European Association for Palliative Care (EAPC) recommendations on morphine and alternative opioids in cancer pain. Data also include an analysis of studies before 2001 which give information about the pharmacokinetic data of transdermal and transmucosal fentanyl. STUDY SELECTION: Studies written in English or French related to the medical treatments (commercialized in France) for nociceptive cancer pain for adult patients were analyzed. Analyzed articles were clinical or experimental studies or metaanalyses. Studies on neuropathic cancer pain, editorials and letters to the editor were discarded. RESULTS: Nociceptive cancer pain is characterized by its frequent instability. More than 50% of patients have paroxystic painful accesses (PPA), either spontaneous or induced by care or mobilizations. Morphine is the main treatment but the prescription of controlled-release morphine must be associated with the prescription of immediate-release morphine to treat the PPA or to transmucosal fentanyl which has a faster onset of action than immediate-release morphine. Morphine treatment can be introduced either by immediate-release morphine or by controlled-release morphine. The introduction of immediate-release morphine is recommended for old or fragile patients, patients with denutrition, hepatic or renal failure. For patients suffering unbearable side effects under morphine or morphine resistant pain, opioid rotation or intravenous morphine or fentanyl are recommended. Spinal opioids administration (by epidural or intrathecal routes) is most often indicated in patients with very severe and resistant pain in terminal disease. In the postoperative period, previous pain treatment must be maintained or increased. Pain bounded to care procedures must be prevented with various and associated treatments: for example, mixed topics lidocaïne-prilocaine for venous or arterial punctures; infiltration of local anaesthetics and inhalation of an oxygen - nitrous oxide mixture for medullary biopsies. CONCLUSION: Oral immediate or controlled release morphine is the most common and effective pain treatment for most patients with nociceptive cancer pain but rotation with other opioids or alternative routes of administration must be discussed quickly if pain persits or if adverse effects occur.

[NMF and cosmetology of cutaneous hydration]. / NMF et cosmétologie de l'hydratation cutanée.

In the stratum corneum, the water binds to the intracellular hygroscopic and hydrosoluble substances called "natural moisturizing factors" or NMF. These "natural moisturizing factors" contained in the corneocytes are formed during epidermal differentiation and may represent up to 10 p. cent of the corneocyte mass. They are principally amino acids, carboxylic pyrrolidone acid, lactic acid, urea, glucose and mineral ions. Keratinization plays an important part in the formation of NMF that exhibit strong osmotic potential attracting the water molecules. The binding of water to NMF is the static aspect of cutaneous hydration. The second, dynamic, aspect is related to the selective permeability of the stratum corneum and to its lipid barrier properties, the permeability of which depends on the integrity and nature of the inter-corneocyte lipids and their lamellar organization between the cells. In these conditions, hydration cosmetics rely on two concepts that can be isolated or associated: the supply of hydrophilic substances to the stratum corneum, capable of attracting and retaining water (moisturizer) or capable of restoring the barrier in order to restore normal water loss or of protecting it against aggression (occlusive).

Enhanced antitumour activity of 6-hydroxymethylacylfulvene in combination with topotecan or paclitaxel in the MV522 lung carcinoma xenograft model.

6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the toxin illudin S, which is a product of the Omphalotus mushroom. MGI 114 induces cytotoxicity against a broad range of solid tumours in vivo, including the drug-refractory MV522 human lung cancer xenograft. In this study, the potential application of MGI 114 in the treatment of lung cancer was explored by evaluating the activity of MGI 114 in combination with either topotecan (TPT) or paclitaxel. Groups of eight nude mice bearing MV522 xenografts were treated with MGI 114, TPT or paclitaxel as single agents and with MGI 114 in combination with TPT or paclitaxel. MGI 114 was administered at doses of 2.5 and 5.0 mg/kg intraperitoneally (i.p.) daily on days 1-5, while TPT and paclitaxel were administered at doses of 0.5 or 1.0 mg/kg and 20 mg/kg, respectively, i.p. on days 1-5. In the single-agent studies, MGI 114, TPT and paclitaxel all resulted in decreased final tumour weights compared with vehicle-treated controls. As single agents, TPT, at the 0.5 mg/kg dose level, and paclitaxel, at the 20 mg/kg dose level, produced partial shrinkages (PSs). All combinations of MGI 114, and either TPT or paclitaxel, produced decrements in final tumour weights compared with monotherapy with the same doses of MGI 114, TPT and paclitaxel. Although all animals treated with the combination of MGI 114 and paclitaxel experienced PSs or complete shrinkages (CSs) (or died), analysis of the time to tumour doubling revealed that the combination of MGI 114 and TPT at 2.5 and 0.5 mg/kg, respectively, was synergistic. These results suggest that cytotoxic activity is enhanced when MGI 114 is combined with either TPT or paclitaxel, and clinical trials to further evaluate these combination regimens are warranted.

[Efficiency of etidronic acid in the case of cutaneous radiocontamination by actinid elements: in vitro evaluation]. / Efficacité de l'acide étidronique dans les radiocontaminations cutanées par les actinides: évaluation in vitro.

Ethane 1 hydroxy 1.1. biphosphonate (EHBP) is a medicine named Didronel, which inhibits bone resorption in the case of Paget's disease. This molecule could offer a new application in radiotoxicology. Our works describe its efficiency as decontaminating agent in uranium and plutonium cutaneous radiocontamination. Its effect on uranium and plutonium is demonstrated by two in vitro techniques using human cutaneous explants. Both techniques are usually used in dermopharmacology to estimate the action of topic drugs.

[Wasting and postoperative infection in cancer patients]. / Dénutrition et infection postopératoire chez le cancéreux.

Denutrition decreases immunological responses of non-cancer patients, the healing is altered whereas infectious complications increase. Now during hospitalization, malnutrition prevails in cancer patients. The suppression of the adaptability to fasting which reduces the expenditure of energy at rest, an a normal metabolic response to nutrients' supply with the impossibility to compensate totally the metabolic deficits with the artificial nutrition alone, raise the fear of postoperative disorders, particularly an increase of the infectious risk. The key point is therefore to identify the cachexia's degree owing to a simple, predictive and consensual index. This check-up allows a postoperative complications' prevention by starting up a perioperative refeeding in high-risk subjects: that is to say all severe wasting patients, the people booked for a severe surgical procedure, especially for oesophageal and gastric neoplasms. Actually, we consider that the quality of the results depend more on the making up of the different nutritional solutions dispensed than to strictly providing for cancer patients' wants, which could be harmful in the postoperative period. Supplementation with antioxidant micronutrients or arginine, glutamine, ribonucleic acids and omega-3 fatty acids would allow an immuno- modulation of the renutrition. But complications strictly due to preoperative denutrition are still to be established.

Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts.

Water-soluble 20(S)-glycinate esters of two highly potent 10,11-methylenedioxy analogues of camptothecin (CPT) have been synthesized and evaluated for their ability to eradicate human breast cancer tumor xenografts. The glycinate ester moiety increases the water solubility of the 10,11-methylenedioxy analogues 4-16-fold. However, in contrast to CPT-11, a water-soluble CPT analogue that was recently approved for second line treatment of colorectal cancer, the 20(S)-glycinate esters do not require carboxylesterase for conversion to their active forms. The glycinate esters are hydrolyzed to their parent, free 20(S)-hydroxyl active analogues in phosphate buffer (pH 7.5) and in mouse and human plasma. The glycinate esters are also 20-40-fold less potent than CPT-11 in inhibiting human acetylcholinesterase. In vivo, we examined 20(S)-glycinate-10,11-methylenedioxycamptothecin, 20(S)-glycinate-7-chloromethyl-10,11-methylenedioxycamptothecin, and CPT-11. We found that the two 10,11-methylenedioxy analogues had antitumor activity against breast cancer xenografts that was comparable to that of CPT-11. Our results indicate that water-soluble 20(S)-glycinate esters of highly potent CPT analogues provide compounds that maintain biological activity, do not require interactions with carboxylesterases, and do not inhibit human acetylcholinesterase.

Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model.

6-Hydroxymethylacylfulvene (MGI-114) is a semisynthetic analogue of the toxin illudin S, a product of the Omphalotus mushroom. MGI-114 induces cytotoxicity in a variety of solid tumors in vivo, including the refractory HT29 human colon cancer xenograft. In this study, the potential application of MGI-114 in the treatment of colon cancer was further explored by evaluating the activity of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU). Groups of 9 nude mice bearing HT29 xenografts were treated with either single agent MGI-114, CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU. MGI-114 was administered at doses of 3.5 and 7 mg/kg i.p. daily on days 1 through 5, and CPT-11 and 5FU were administered at doses of 50 and 100 mg/kg i.p. on days 1, 12, and 19. In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in decreased final tumor weights compared with vehicle-treated controls (P<0.05), but only MGI-114 at 7 mg/kg produced partial responses. When MGI-114 at 3.5 mg/kg was combined with CPT-11, significant decrements in final tumor weights occurred compared with monotherapy with the same doses of MGI-114 and CPT-11 (P< or =0.001). Also, administration of the low-dose combination (MGI-114 at 35 mg/kg and CPT-11 at 50 mg/kg) resulted in final tumor weights similar to those achieved after administration of high-dose MGI-114 as a single agent. Moreover, the combination of MGI-114 and CPT-11 produced partial responses in nearly all of the animals, with some animals achieving complete responses. The outcome with the combination of MGI-114 and 5FU was less striking, with fewer partial responses and no complete responses. These results suggest enhanced activity when MGI-114 is combined with CPT-11, and clinical trials to further evaluate this combination regimen are planned.

[Block of the superior laryngeal nerve for ORL endoscopy. Description of a simplified technique]. / Le bloc du nerf laryngé supérieur pour les endoscopies ORL. Description d'une technique simplifiée.

The usual anterior and lateral routes used for superior laryngeal (SL) nerve blocks are not often used because too difficult to carry out. A simpler and easier technique is described, which blocks the SL nerve at the level of the greater cornu of the hyoid bone. Because the nerve is not located accurately with this technique, a larger volume of local anaesthetic is required. This technique was tested in 31 patients scheduled for endoscopies with rigid tubes. The mean duration of endoscopy was 30 +/- 10 min. The use of 8 ml 1% lidocaine for the block 30 min surgical anaesthesia. In 2 patients, the SL nerve block alone was sufficient. In 26 others a complement with a benzodiazepine (flunitrazepam, n = 9, mean dose 0.8 mg; midazolam, n = 17, mean dose 5 mg) was required. In 4 of these patients, attempts of oesophagoscopy gave rise to hypertension and tachycardia. General anaesthesia with propofol and tracheal intubation were therefore used. In the last 3 patients, intercricothyroid jet ventilation was used, requiring general anaesthesia (propofol and succinylcholine). The SL nerve block was satisfactory in 24 patients with total vocal cord paralysis and no haemodynamic reaction to painful stimuli in the blocked area. No complication was observed. It is concluded that this technique is useful and easier to carry out than the usual ones.

[Penetration of solid particles in the respiratory system. Secondary immunity reactions to the inhalation of a dry aerosol (author's transl)]. / Pénétration des particules solides dans l'appareil respiratoire. Réactions immunitaires secondaires à l'inhalation d'un aérosol sec.

Deposition in the respiratory system of an inhaled dry particle depends on many factors, particularly its aerodynamic diameter. The quantity deposited in each compartment of the respiratory tract can be approximately determined by mathematical laws, but ther are still controversies about large size particles. Thus pollens have been found by the authors beyond the larynx deep in the lung. The bronchopulmonary system is divided in two parts, anatomically and immunologically different. The local response, closely related to the antigen, depends also on the intimate contact between particles and the immunity defense system of the individual. Liberation and solubility of some antigenic fractions, perhaps enzymatic, would help their intra-epithelial penetration and contact with the secretory immunity system. The additional intervention of an extraepithelial response has been observed in bronchi after instillation of pollen in the rat. There is in the sensitized animal an intense cellular reaction amidst the mucous of bronchial lumen with macrophages adhering to pollen granules and forming rosettes.

Enzyme determination and RAST inhibition assays for orchard grass (Dactylis glomerata): a comparison of commericial pollen extracts.

Pollens release enzymes when they are dropped into water. Orchard Grass extracts were tested by two methods. The Api-Zym System determined 19 enzymes and colorimetric amounts of Leucine Aminopeptidases, Acid phosphatase and trypsin. These were compared with RAST inhibition assays. A good correlation was shown between the techniques. Thus the enzyme dosage may be useful for the standardization of pollen extracts.

Penetration of inhaled pollen into the respiratory tract.

The pathophysiologic mechanisms of pollen-induced asthma have heretofore remained unclear, because pollen particles have generally been considered too large to penetrate into the lower respiratory tract. Such grains are therefore believed to be unable to induce an immunologic response in the lower respiratory tract. Nevertheless, experimental curves of particle penetration into the respiratory tract indicate that a small percentage of large-sized particles may penetrate into the peripheral areas of the lungs. Under the conditions of our study, a radioisotopic method using labeled pollen grains was not effective in detecting the very small number of grains expected to be found in the lung. We used another simpler and more effective method derived from techniques used by palynologists in the detection of pollen grains in sediments. According to our results, which showed pollen grains normally present in tracheobronchial secretions and in lung parenchyma, we can safely assume that inhaled pollen does penetrate into the distal lower respiratory tract. At present, we do not know the precise number of pollen grains necessary to trigger a response, and we do not know the behavior of these grains with regard to the mucous membranes of the small bronchi and the alveoli. It is important to determine whether these grains have an effect on these areas and whether a direct mechanism is involved in the genesis of pollen-induced asthma.

Qualitative and quantitative comparison of pollen calendars for plain and mountain areas.

A comparison of the quantity and the quality of pollen content in the atmosphere of two regions, one of the plains bordering the Mediterranean sea (altitude 40 m), the other of the mountains of the Pyrenees (altitude 1550 m), was made during the climatological year 1974-1975. The method which was used intercepts the pollen flux of the atmosphere with a vertical filtering unit, which is exposed facing the direction of wind on the filtering door of the weather-vane and collects much larger quantities of pollen than the other techniques of collection. The atmospheric currents displace from one region to another numerous spores and pollens, the trajectories of which are directly influenced by the general circulation of the atmosphere. The density of these fluxes can be very large, reaching 2500 grains/m3 of air at M.T.P.R. in the last week of January; the taxons collected are very numerous (more than 700). The atmospheric transfer of pollen modifies largely the pollen content of the atmosphere of different flowering domains. These interferences manifest themselves in the simplest cases by the presence of two peaks of concentration, the principal corresponding to the local efflorescence, the second to the pollen transferred from other regions. The pollen concentrations in the mountains are one-third of those in the plains. Pollination in the mountains is several weeks late in comparison to the plain during the first semester, whereas during the second semester, it is the plains that show a certain delay. These findings show why some allergic patients who go to the mountains during summer are affected twice by pollination.