Onchocerca volvulus microfilariae in the anterior chambers of the eye and ocular adverse events after a single dose of 8 mg moxidectin or 150 µg/kg ivermectin: results of a randomized double-blind Phase 3 trial in the Democratic Republic of the Congo, Ghana and Liberia.

BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment. METHODS: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively). CONCLUSIONS: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.

Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?

Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Effect of a single dose of 8 mg moxidectin or 150 µg/kg ivermectin on O. volvulus skin microfilariae in a randomized trial: Differences between areas in the Democratic Republic of the Congo, Liberia and Ghana and impact of intensity of infection.

BACKGROUND: Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150µg/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). METHODOLOGY/PRINCIPAL FINDINGS: Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. CONCLUSIONS/SIGNIFICANCE: The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. CLINICAL TRIAL REGISTRATION: Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).

Urogenital symptoms in mitochondrial disease: overlooked and undertreated.

BACKGROUND AND PURPOSE: Bowel symptoms are well documented in mitochondrial disease. However, data concerning other pelvic organs is limited. A large case-control study has therefore been undertaken to determine the presence of lower urinary tract symptoms (LUTS) and sexual dysfunction in adults with genetically confirmed mitochondrial disease. METHODS: Adults with genetically confirmed mitochondrial disease and control subjects were recruited from a specialist mitochondrial clinic. The presence and severity of LUTS and their impact on quality of life, in addition to sexual dysfunction and bowel symptoms, were captured using four validated questionnaires. Subgroup analysis was undertaken in patients harbouring the m.3243A>G MT-TL1 mitochondrial DNA mutation. A subset of patients underwent urodynamic studies to further characterize their LUTS. RESULTS: Data from 58 patients and 19 controls (gender and age matched) were collected. Adults with mitochondrial disease had significantly more overactive bladder (81.5% vs. 56.3%, P = 0.039) and low stream (34.5% vs. 5.3%, P = 0.013) urinary symptoms than controls. Urodynamic studies in 10 patients confirmed that bladder storage symptoms predominate. Despite high rates of LUTS, none of the patient group was receiving treatment. Female patients and those harbouring the m.3243A>G MT-TL1 mutation experienced significantly more sexual dysfunction than controls (53.1% vs. 11.1%, P = 0.026, and 66.7% vs. 26.3%, P = 0.011, respectively). CONCLUSIONS: Lower urinary tract symptoms are common but undertreated in adult mitochondrial disease, and female patients and those harbouring the m.3243A>G MT-TL1 mutation experience sexual dysfunction. Given their impact on quality of life, screening for and treating LUTS and sexual dysfunction in adults with mitochondrial disease are strongly recommended.

The Red Kangaroo pericardium as a material source for the manufacture of percutaneous heart valves.

BACKGROUND: The kangaroo pericardium might be considered to be a good candidate material for use in the manufacture of the leaflets of percutaneous heart valves based upon the unique lifestyle. The diet consists of herbs, forbs and strubs. The kangaroo pericardium holds an undulated structure of collagen. MATERIAL AND METHOD: A Red Kangaroo was obtained after a traffic fatality and the pericardium was dissected. Four compasses were cut from four different sites: auricular (AUR), atrial (ATR), sternoperitoneal (SPL) and phrenopericardial (PPL). They were investigated by means of scanning electron microscopy, light microscopy and transmission electron microscopy. RESULTS: All the samples showed dense and wavy collagen bundles without vascularisation from both the epicardium and the parietal pericardium. The AUR and the ATR were 150±25µm thick whereas the SPL and the PPL were thinner at 120±20µm. The surface of the epicardium was smooth and glistening. The filaments of collagen were well individualized without any aggregation, but the banding was poorly defined and somewhat blurry. CONCLUSION: This detailed morphological analysis of the kangaroo pericardium illustrated a surface resistant to thrombosis and physical characteristics resistant to fatigue. The morphological characteristics of the kangaroo pericardium indicate that it represents an outstanding alternative to the current sources e.g., bovine and porcine. However, procurement of tissues from the wild raises supply and sanitary issues. Health concerns based upon sanitary uncertainty and reliability of supply of wild animals remain real problems.

Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness.

Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds. Patients were recruited through the Health Canada's Special Access Program. SASSs were grafted on debrided full-thickness wounds according to similar protocols used for AGs. The graft-take and the persistence of the SASS epithelium over time were evaluated. 14 patients received surgical care with SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation = 5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow-up time: 3.2 years), without noticeable deficiency in epidermal regeneration. Assessment of scar quality (skin elasticity, erythema, thickness) was performed on a subset of patients. Non-homogeneous pigmentation was noticed in several patients. These results indicated that the SASS allowed the successful coverage of full-thickness burns given its high graft-take, aesthetic outcome equivalent to autografting and the promotion of long-term tissue regeneration. When skin donor sites are in short supply, SASSs could be a valuable alternative to treat patients with full-thickness burns covering more than 50 % of their total body surface area.

Translating the combination of gene therapy and tissue engineering for treating recessive dystrophic epidermolysis bullosa.

The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vector as compared with the other pseudotypes. At least a 3.1-fold and a 1.3-fold increased transduction were obtained in fibroblasts and keratinocytes, respectively, with EF-C as compared with polybrene. A continuous and intense deposit of haemagglutinin (HA)-COLVII was observed at the dermal-epidermal junction of self-assembled TESs made of cells transduced with a HA-tagged COL7A1 vector. Furthermore, HA-tagged basal epidermal cells expressing keratin 19 were observed in TESs, suggesting stem cell transduction. This approach could be a valuable therapeutic option to further develop, in order to improve the long-term life quality of RDEB patients.

Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial.

BACKGROUND: The morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin. METHODS: This double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 µg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998. FINDINGS: Between April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3-1·0]) than in the ivermectin group (4·5 [3·5-5·9]; difference 3·9 [3·2-4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment. INTERPRETATION: Skin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination. FUNDING: UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

Protein-polyelectrolyte complexes to improve the biological activity of proteins in layer-by-layer assemblies.

A standard method of protein immobilization is proposed, based on the use of protein-polyelectrolyte complexes (PPCs) as building blocks for layer-by-layer assembly. Thicker multilayers, with a higher polyelectrolyte fraction, are obtained with PPCs compared to single protein molecules. Biological activity is not only maintained, but specific activity is also higher, as demonstrated for lysozyme-poly(styrene sulfonate) complexes. This is attributed to the more hydrated state of the assemblies. This new method of protein immobilization opens up perspectives for biotechnology and biomedical applications.

Microstructural alterations owing to handling of bovine pericardium to manufacture bioprosthetic heart valves: A potential risk for cusp dehiscence.

INTRODUCTION: Cross-linking and anti-calcification of prosthetic heart valves have been continuously improved to prevent degeneration and calcification. However, non-calcific structural deteriorations such as cuspal dehiscences along the stent still require further analysis. MATERIAL AND METHOD: Based upon the previous analysis of an explanted valve after 7 years, a fresh commercial aortic valve was embedded in poly(methyl methacrylate) (PMMA) and cut into slices to ensure the detailed observation of the assembly and material structures. A pericardial patch embossed to provide the adequate shape of the cusps was investigated after paraffin embedding and appropriate staining. The microstructural damages that occurred during manufacturing process were identified and evaluated by light microscopy, polarized microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: The wavy collagen bundles, the key structure of the pericardium patch, were damaged to a great extent at suture sites along the stent and in the compressed areas around the stent post. The fixation of the embossed pericardium patch along the plots of the stent aggravated the microstructural modifications. The damages mainly appeared as the elimination of collagen bundle waviness and delamination between the bundles. CONCLUSION: Considering the modes of failure of the explant, the damages to the collagen bundles may identify the vulnerable sites that play an important role in the cusp dehiscence of heart valve implants. Such information is important to the manufacturers. Recommendations to prevent in vivo cusp dehiscence can therefore be formulated.

Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry.

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a "real-world" context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management.

Correlation between structural changes and acute thrombogenicity in transcatheter pericardium valves after crimping and balloon deployment.

INTRODUCTION: Transcathether heart valve replacement has gained considerable acceptance during the last decades. It is now part of the armamentarium for aortic valve replacement. The procedure proved to be highly efficient. However the issues of the blood compatibility and tissue durability were not raised and the adverse events were probably under-reported, according to observations of thrombosis after deployment. MATERIAL AND METHOD: Bovine pericardium leaflets were sewn inside a 26mm diameter stainless steel stent to manufacture these valves (one control and two experimental). The correlation between the trauma and the acute thombogenicity of bovine pericardium leaflets, after crimping and ballooning, was investigated via an in vitro blood flow with labeled platelets. These leaflets were processed for histology: scanning electron microscopy, light microscopy, and transmission electron microscopy. RESULTS: The control specimens showed a regular pericardium structure with some blood cells deposited on the collagen fibrous surface (inflow) and scarce blood cells deposited on the serous surface (outflow). After crimping and ballooning, the structure of the pericardium was severely injured, eventually with delaminations and ruptures. The blood cell uptake was considerably increased compared to the control. CONCLUSION: It would therefore be appropriate to pay more attention to the design of the valves. Specifically, the incorporation of a buffer tissue or fabric between the pericardium and the metallic stent is suggested. The issue of ballooning deserves detailed and in depth investigation regarding the lifetime of the device.

Transcatheter heart valve crimping and the protecting effects of a polyester cuff.

INTRODUCTION: Prior to deployment, the percutaneous heart valves must be crimped and loaded into sheaths of diameters that can be as low as 6mm for a 23mm diameter valve. However, as the valve leaflets are fragile, any damage caused during this crimping process may contribute to reducing its long-term durability in vivo. MATERIAL AND METHOD: Bovine pericardium percutaneous valves were manufactured as follows. The leaflets were sutured on a nitinol frame. A polyester cuff fabric served as a buffer between the pericardium and the stent. Two valves were crimped and one valve was used as control. The valves were examined in gross observation and micro-CT scan and then the leaflets were processed for histology and analyzed in scanning electron microscopy, light microscopy and transmission electron microscopy. RESULT: Crimping of the valves resulted in the increase thickness of the leaflets and there was no evidence of additional delamination. The heavy prints of the stents were irregularly distributed on the outflow surface in the crimped devices and were shallow and did not penetrate throughout the thickness of the leaflets. However, the wavy microscopy of collagen fiber bundles was well preserved. They were found to remain individualized without any agglutination as shown by the regular banding appearance. CONCLUSION: Crimping of self-deployable valves per se caused only minor damages to the leaflets. However, the procedure could be refined in order to minimize areas of high pressure and swelling of the tissue that can be accompanied with flow surface disruption and increase of the hydraulic conductance. The incorporation of a polyester buffer serves to prevent the deleterious effects that may be caused if the pericardium tissue were in direct contact with the nitinol stent.

Effect of intense pulsed light treatment on human skin in vitro: analysis of immediate effects on dermal papillae and hair follicle stem cells.

BACKGROUND: Hair follicles house a permanent pool of epithelial stem cells. Intense pulsed light (IPL) sources have been successfully used for hair removal, but long-term hair reduction may require several treatments. Many questions remain regarding the impact of IPL treatment on the structure of the hair follicle, more specifically on hair follicular stem cells and dermal papilla cells, a group of specialized cells that orchestrate hair growth. OBJECTIVES: To characterize the destruction of human hair follicles and surrounding tissues following IPL treatment, with more attention paid to the bulge and the bulb regions. METHODS: Human scalp specimens of Fitzpatrick skin phototype II were exposed ex vivo to IPL pulses and were then processed for histological analysis, immunodetection of stem cell-associated keratin 19, and revelation of the endogenous alkaline phosphatase activity expressed in dermal papilla cells. RESULTS: Histological analysis confirmed that pigmented structures, such as the melanin-rich matrix cells of the bulb in anagen follicles and the hair shaft, are principally targeted by IPL treatment, while white hairs and epidermis remained unaffected. Damage caused by heat sometimes extended over the dermal papilla cells, while stem cells were mostly spared. CONCLUSIONS: IPL epilation principally targets pigmented structures. Our results suggest that, under the tested conditions, collateral damage does not deplete stem cells. Damage at the dermal papilla was observed only with high-energy treatment modalities. Extrapolated to frequently treated hairs, these observations explain why some hairs grow back after a single IPL treatment.

[Quality of life of living kidney donor: a national report]. / Rapport qualité de vie des donneurs vivants de rein. Étude QV DVR transversale.

The renal transplantation is nowadays the reference treatment of ESRD. Living donor kidney transplantation is less often performed in France than in other countries. Nevertheless, numerous French and international surveys have evidenced that it provides the recipients a longer life expectancy and a better quality of life. Donors themselves, what do they become? How are they? For the first time in France, a survey has been implemented to investigate the quality of life of living kidney donor to one of their close relations. This study has been undertaken by the Agency of the biomedecine and the service Clinical Epidemiology and Evaluation (EEC), of the University teaching hospital of Nancy. The main objective was to describe the quality of life of the living donors having given a kidney for more than a year and less than 5 years. The secondary objective was to contribute to the knowledge of the main factors associated to the living kidney donor quality of life, one year after the donation. Participants had to be living in France at the time of the donation which had taken place between June 30(th), 2005 and March 1(st), 2009. A folder gathering various self-administrated questionnaires was sent to the place of residence of the donor between March and April, 2010. These data were completed by medical data collected near the transplantation centres by the Agency of biomedecine within the framework of the register CRISTAL. They included the characteristics of the donation and of the donor at the very time of the donation, 3 months after the donation and at the last annual assessment. Three living donors in four, that is 501 persons, agreed to fully participate. They constituted a representative national sample of all the living donors of this period. The non participants were younger (4.5 years on average) and had a less adequate annual follow-up. The women were more represented (61 %) than men. The median age was 53 years. More of 2/3 were employed at the time of the survey. The three main categories of donors were ascendants (36 %), collateral (33 %) and spouses (26%). The donation decision was taken without hesitation (94 %) and at an early stage of the evolution of the recipient renal disease (64 %). The delivered information was considered globally satisfactory except for the painful consequences and for the scar. The living donors were, long after their donation, in an excellent physical health state according to the SF36 summarized physical score and this especially when they were old as compared to the same age and sex general population. This phenomenon highlights the drastic selection of the potential donors. The only factor influencing the level of long term physical health was the surgical technique: the 261 subjects having undergone a coelioscopy had less often presented post operative pain (OR=0.5; 0.3-0.8; P<0.002) and had more often recovered completely without any residual pain (OR=1.7; 1.2-2.5; P<0.004). The quality of life mental dimension according to the SF36 summarized mental score was very close to that of the same age and sex of the general population although a slightly lower. It is influenced by characteristics related to the way the donation had been lived, particularly the understanding of their donation by their circle of acquaintances (average score 74.2/100), the perception of a feeling of owing on behalf of the recipient (46.5 %) and the fact of having lived a competition to be retained as the donor (for 266 cases another potential donor did exist and 21 lived the donation as a strong competition). More than 84 % of the donors was still followed by a healthcare professional at the time of the survey. The main expressed complaints concern the quality of the medical follow-up (70 donors expressed themselves openly on this topic) and the pain and scar after effects of the intervention. In spite of the surgical complications, of the dissatisfactions regarding their medical follow-up, of dismissals or of necessary adjustments of their professional life (13 %), of their difficulties to carry heavy loads, of sometimes complex relations with the recipient (23 % positive, 10 % negative) or their circle of acquaintances, of expenses non reimbursement and of losses of salary (12 %), they would be 95 % to recommend the donation and if it was to be redone 98 % would do it again! Benefits brought to the recipient won largely over the encountered difficulties. This retrospective and cross-sectional study allows to state recommendations which have to be confirmed by the 2009-2012 longitudinal study: to favour the coelioscopy which offers an advantage in terms of less frequent pain and a better post operative recovery, to better understand the phenomena of competition between potential and donors recipients, to improve the information about the potential consequences of the donation on the pain and on the scar, to inform the donor about the importance to associate the proxies with the decisionmaking or at least with the discussion and finally to improve the society recognition of the donation.

[Treatment of gestational diabetes with oral hypoglycemic agents]. / Traitement du diabète gestationnel par hypoglycémiants oraux.

AIM: To study the accuracy of an oral therapy for gestational diabetes (GD) and literature review. PATIENTS AND METHODS: Glibenclamide (Daonil) was prescribed in pregnant women with GD diagnosed by O'Sullivan test and hyperglycemic tolerance test. Capillary glycemic control follow up was performed to check the accuracy of the oral treatment all along the pregnancy. RESULTS: Thirty-seven pregnant women have been involved at an average of 26.7 weeks of amenorrhea. Five of them had a non insulin dependent diabetes mellitus previously diagnosed. The glycemic control was obtained in 64.8 % and two women required metformin in addition. Hypoglycaemia has been noticed in 17 % of cases. In 18.9 %, macrosomia (birth weight upper than 4000 g) was reported. We carried out a cesarean section in 31.8 %. A short hypoglycaemic episode was observed in 10.8 % of new born babies. CONCLUSION: Oral therapy for GD is more and more often used and demonstrates an efficacy around 80 % and safety similar as insulin therapy. Our experience showed glibenclamide was useful in two third of cases and easier than insulin in clinical practice.

Skin substitutes and wound healing.

Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are not life threatening. Nowadays, more than 20 products are commercially available, more are undergoing clinical trials and a large number of new models are being investigated in various research laboratories worldwide. Many of the current products do not contain any living cells and vary in their capacity to harness the innate capacity of the body to heal itself. Others include living cells, of allogeneic or autologous origin, and are often referred to as 'cellular therapy' or 'tissue-engineered' products. Modifications and improvements are currently investigated that aim at improving the healing potential of those products through the use of recombinant growth factors and additional features such as microvascularization. Fundamental research into wound healing and scar-free regeneration raises the hope that we will eventually be able to restore almost completely the appearance and function of skin after the healing of wounds.

[Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering]. / La médecine régénératrice : les cellules souches, les interactions cellulaires et matricielles dans la reconstruction cutanée et cornéenne par génie tissulaire.

Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

Determination of parent orientation maps in advanced titanium-based alloys.

In the past few years, reconstruction methods have been developed and applied successfully to restore the beta microtexture in titanium alloys. This contribution shows how these methods are extended to other transformations often encountered in advanced titanium alloys: the alpha (hcp)-->gamma (tetragonal) and the beta (bcc)-->O (orthorhombic) transformation. The efficiency of the restitution depends on specific crystallographic features of the investigated phase transformations. Therefore, the paper outlines these crystallographic specificities for some advanced titanium alloys. To illustrate the capability of the method to reconstruct the parent phase, different restored parent microtextures of these alloys are presented. The results show that the reconstruction methods are an efficient tool to study the microstructure and texture modifications induced by these phase transformations.

Reliability of reconstructed beta-orientation maps in titanium alloys.

This paper demonstrates that parent beta-orientation maps of titanium alloys can reliably be reconstructed from inherited alpha maps in most cases. Important aspects of the calculation that ensure an accurate determination of the parent orientation as well as a reliable restitution of the beta boundaries are discussed. The limits of the reconstruction method, according to the inherited alpha microstructure are also pointed out. Finally, the method is applied to a beta metastable titanium alloy, which contained enough retained beta phase so that its orientation could be measured by EBSD. The comparison between the measured and the reconstructed beta maps shows the efficiency of the method.