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Seventeen patients transplanted with hematopoietic cells to correct severe T lymphocyte immunodeficiency resulting from complete DiGeorge anomaly were identified worldwide, and retrospective data were obtained using a questionnaire-based survey. Patients were treated at a median age of 5 months (range, 2-53 months) between 1995 and 2006. Bone marrow was used in 11 procedures in 9 cases: 6 from matched unrelated donors, 4 from human leukocyte antigen (HLA)-identical siblings, and one haploidentical parent with T-cell depletion. Unmobilized peripheral blood was used in 8 cases: 5 from HLA-identical siblings, one from a matched unrelated donor, one from an HLA-identical parent, and one unrelated matched cord blood. Conditioning was used in 5 patients and graft-versus-host disease prophylaxis in 11 patients. Significant graft-versus-host disease occurred in 9 patients, becoming chronic in 3. Median length of follow-up was 13 months, with transplantation from HLA-matched sibling showing the best results. Median survival among deceased patients (10 patients) was 7 months after transplantation (range, 2-18 months). The overall survival rate was 41%, with a median follow-up of 5.8 years (range, 4-11.5 years). Among survivors, median CD3 and CD4 counts were 806 (range, 644-1224) and 348 (range, 225-782) cells/mm(3), respectively, CD4(+)/CD45RA(+) cells remained very low, whereas mitogen responses were normalized.

Serologic testing results are one of the major reasons for discarding donor corneas. This study assessed the prevalence of serologic markers and the times of preanalytic steps. The prevalence of serologic markers in 705 cornea donors of the Lorraine region was studied. One hundred forty-one (20%) corneas were discarded on the basis of serologic testing. In a subsample of 180 consecutive cornea donors, data concerning the time of death, sampling, and serology testing were collected. When the time between death and sampling did not exceed 8 h (n = 122), immediate decantation (separation of serum from clot) led to less discarding of corneas than delayed decantation (2/46 [4.3%] discarded in the group with immediate decantation versus 13/76 [17.1%] discarded in the group with delayed decantation [P = 0.038]). For blood samples collected within 8 h of death, the rate of reactive results is significantly lower if samples are immediately decanted.

Background: The efficacy of numerous hyaluronic acid (HA)-based fillers has been demonstrated by semi-quantitative and qualitative methods, useful in clinical practice, but poorly reliable., Objective: To objectively evaluate the efficacy of a HA gel in treating nasolabial folds (NLFs) over a 9-12-month follow-up period., Methods: A total of 47 adult patients with moderate to severe NLFs received one or two injections of HA gel. Efficacy was assessed by measuring NLF depth at time intervals up to 12 months subjectively by blind and open clinical scoring using the Lemperle scale, and objectively using skin replicas and in vivo 3D imaging methods. Tissue characterization and dermal thickness were also assessed using radiofrequency ultrasonography and high-resolution ultrasound imaging, respectively., Results: The filler injection highly significantly decreased the depth of NLFs (p < 0.0001) at all time points, with an improvement of at least 1 grade in the Lemperle score in 77% and 89% of the subjects at 9 and 12 months, respectively. NLF volume measured on replicas and 3D images significantly decreased after injection and this improvement was maintained over 12 months., Conclusion: This HA gel is well tolerated and provides a significant and long-lasting correction of moderate to severe NLFs, as objectively demonstrated by instrumental methods.

Adenovirus (ADV) infections are one of the major causes of morbidity and mortality after hematopoietic stem cell transplantation, despite new antiviral treatment strategies. We describe here a complete clinical-grade generation of human anti-ADV cytotoxic T cells to propose an adoptive immunotherapy. Peripheral blood mononuclear cells (PBMC) from 7 healthy donors, known for their good cellular immunity against ADV, were stimulated for 6 hours with a synthetic peptide pool covering the ADV5 Hexon protein interferon-gamma (IFN-gamma) secreting cells were isolated on a clinical device. After immunoselection, a mean number of 1.01 +/- 0.84 x 10(6) total nucleated cells was obtained. The isolated ADV-specific T cells were mainly CD4+ (mean=56% +/- 20.8%, yield=51% +/- 32.4%) but also CD8+ (mean=42% +/- 27%, yield = 56% +/- 39.3%). Isolated T lymphocytes (CTL) were expanded to carry out functional tests. Ability of the expanded CTL to secrete IFN-gamma and to proliferate after restimulation with the ADV peptide pool was confirmed. A high cytotoxicity against autologous target cells loaded with ADV antigens was observed but not against nonloaded target cells. We observed a decrease of 1.27 log of the allogeneic reaction against non HLA identical healthy donor PBMC with CTL compared with the PBMC before selection. Clinical-grade generation of ADV-specific T cells was achieved with a synthetic antigen. This technology has the advantage of being fast, and is sufficiently reactive to be proposed for immunotherapy if antiviral treatment fails.

Objective: Natural killer (NK) cells are a lymphocyte subset that, in a hematopoietic stem cell transplantation setting, mediates a graft-vs-leukemia effect without any graft-vs-host disease. We aimed to evaluate an isolation method that can be used with Good Manufacturing Practices-grade reagents and to compare three cytokines for expansion in order to design future clinical protocols based on donor NK-cell infusions to cure relapse after allograft., Materials and Methods: NK cells were enriched using a CD3/CD19 depletion method and expanded for 13 days in the presence of 2, 10, and 50 ng/mL interleukin (IL)-2, IL-15, or IL-7. NK-cell cytotoxicity was evaluated after isolation and culture. Expression of NKG2D, KIR2DL2, and KIR2DL1 was monitored during expansion., Results: Highly T- and B-cell-depleted NK cells were obtained and enriched 2.6-fold. The optimal cytokine concentration for expansion was 10 ng/mL for IL-2 or 50 ng/mL for IL-15. NK-cell cytotoxicity was significantly improved after an overnight incubation with 10 or 50 ng/mL IL-2 or with 2, 10, or 50 ng/mL IL-15, and after 13 days with 50 ng/mL IL-15. The use of a combination of IL-2 and IL-15 showed no additional benefit and negative results were obtained with IL-7. The three NK cell receptors were significantly upregulated after culture, mainly with IL-2 or IL-15., Conclusion: In our study, 10 ng/mL IL-2 or 50 ng/mL IL-15 were the optimal concentrations for expansion and were equivalent in significantly enhancing cytotoxicity and modifying NK-cell receptor expression patterns., (2010 ISEH-Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

This study investigated the gene expression profile of human mesenchymal stem cells seeded in collagen sponge for 28 days in three different mediums: (1) basal medium as control containing ITS alone, (2) ITS+TGF-β1 alone or (3) ITS 1% supplemented sequentially by TGF-β1 (D3-D14) followed by BMP-2 (D15-D28). Differential expression of 84 genes implicated in chondrogenic and osteogenic differentiation of MSCs was analyzed at D28 by real-time RT-PCR array technology. TGF-β1 alone down-regulated two genes, CD36 and cathepsin K. Sixteen genes were significantly up-regulated, notably type 2 and type 10 collagens, COMP and Sox9. The sequential combination of TGF-β1 and BMP-2 produced a similar profile with prominent expression of type 2 collagen and the alkaline phosphatase gene. Interestingly, in this in vitro condition, RUNX2 was not up-regulated, suggesting that the sequential combination of TGF-β1/BMP2 enhances the hypertrophic chondrogenic profile without turning towards the osteoblastic pathway.

In 1997, the Joint Accreditation Committee ISCT & EBMT (JACIE) was created. The following year, it approved the first edition of standards for haemopoietic progenitor cell collection, processing and transplantation. The purpose of the standards is to ensure a minimal level of quality, alertness and homogeneity in the implementation of autologous and allogeneic haemopoietic stem cell transplantation (HSCT) programme in onco-hematology. The acquisition of accreditation is based upon the system of examination by trained medical professionals according to countries endorsements with the national regulation obligations applicable to HSCT. In 2008, the fourth edition has been launched. The range of application of the standards comprises both donors and recipients, and all phases of collection, processing, storage and administration of haemopoietic progenitor cells. Among the accredited processing facilities, a few have been integrated JACIE standards into their existing management quality system which is inspected by national health authority. In France, the comparison between JACIE standards and the good manufacturing practices of cellular therapy product reveals some common points and some differences to apply.

This article reports the technique of percutaneous autologous bone marrow injection as a minimally invasive method alternative to open grafting techniques in the treatment of delayed unions and non-unions. Despite continuous advances in the treatment of long bone fractures, disturbances of healing processes remain a difficult challenge for orthopaedic surgeons. Percutaneous administration of substances with osteoinductive and osteogenic properties offers the advantage of decreased morbidity associated with the classic open grafting techniques. This makes it worth exploring before embarking on more extensive open surgery. The authors present the main technical stages of the percutaneous bone marrow grafting (bone marrow aspiration, concentration, intra-osseous re-injection and post-operative protocol) with a short literature review about this topic.

A young boy with a confirmed complete DiGeorge Syndrome (cDGS) underwent a peripheral blood mononuclear cell transplantation (PBMCT) from his HLA-identical sister at 4.5 years of age, without a conditioning regimen. Eight years later, he is healthy with good immunological functions in the presence of a stable mixed T-cell chimerism. Absence of recent thymic emigrants is confirmed. We observe an inverted CD4+/CD8+ ratio, related to the CD8 subset expansion, a skewing of the TCR repertoire, especially on the CD8+ subset and a telomere loss on the CD8+ cells compared to the donor. However, these anomalies do not seem to have an impact on functional immunity. PBMCT in cDGS using an HLA-matched sibling donor provides good long-lasting immunity and is an easy alternative to bone marrow transplantation and to thymic transplantation.

Fillers are numerous, and the products currently available have effects that may last from a few months to many years. These are used to treat facial wrinkles, and some of the new fillers exert a stimulatory effect, restoring volume in focal areas of the face by inducing collagen fibers. The dermasurgeon should thoroughly understand the indications and uses of these fillers to meet fully a patient's expectations. Some fillers are biodegradable (12-18 months), others slowly biodegradable (2-5 years), whereas others are permanent implants. The disadvantage of the traditional biodegradable fillers is their short duration (6-12 months). Over the past decade, semipermanent fillers (polylactic acid and ceramics) have been used: they do have a longer effect, but they might induce granulomas especially on the lips. Also, permanent fillers are traditionally linked to a higher incidence of granulomas and extrusions, although with the new formulations, the adverse events are decreased.

Thrombocytopenia frequently occurs in laboratory practice. The present work illustrates, through the presentation of a case report of Wiskott-Aldrich syndrome, the difficulties encountered to identify and characterize thrombocytopenia. The clinicobiological validation of a low platelet count involves both the biologist, who must assume the validation of numeration while mentioning the morphological characteristics of the platelets and other blood cells, as well as the physician who has to interpret these data according to the clinical context.

The WHIM syndrome is a rare immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Dominant heterozygous mutations of the gene encoding CXCR4, a G-protein-coupled receptor with a unique ligand, CXCL12, have been associated with this pathology. We studied patients belonging to 3 different pedigrees. Two siblings inherited a CXCR4 mutation encoding a novel C-terminally truncated receptor. Two unrelated patients were found to bear a wild-type CXCR4 open reading frame. Circulating lymphocytes and neutrophils from all patients displayed similar functional alterations of CXCR4-mediated responses featured by a marked enhancement of G-protein-dependent responses. This phenomenon relies on the refractoriness of CXCR4 to be both desensitized and internalized in response to CXCL12. Therefore, the aberrant dysfunction of the CXCR4-mediated signaling constitutes a common biologic trait of WHIM syndromes with different causative genetic anomalies. Responses to other chemokines, namely CCL4, CCL5, and CCL21, were preserved, suggesting that, in clinical forms associated with a wild-type CXCR4 open reading frame, the genetic anomaly might target an effector with some degree of selectivity for the CXCL12/CXCR4 axis. We propose that the sustained CXCR4 activity in patient cells accounts for the immune-hematologic clinical manifestations and the profusion of warts characteristic of the WHIM syndrome.

Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed.

CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.

Background: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft., Study Design and Methods: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated. The statistical incidence of prefreeze and postthaw parameters as well as patient characteristics and conditioning regimens on hematologic recovery were analyzed., Results: By multivariate analysis, prefreeze and postthaw CD34+ cells were the only two variables significantly and independently correlated to hematologic recovery. Low prefreeze and postthaw CD34+ cell numbers associated to a low CD34+ yield characterize PBPC grafts from patients who have the slowest hematologic recovery. The postthaw PBPC CD34+ cell number can be estimated before conditioning regimen by thawing a small aliquot of the graft., Conclusion: In association to prefreeze CD34+ cell number and to CD34+ yield, postthaw CD34+ cell number may be useful in monitoring cell loss during processing and identifying patients at risk of slow PBPC engraftment.

To investigate the function of the main adhesion receptors (CD62L, CD49d, CD49e, CD11b and CD18) on CD34+ cells during homing, their expression was quantified by flow cytometry using calibration beads. CD34+ cells were isolated from bone-marrow (BM), cord blood (CB) or peripheral blood (PB) from patients with myeloma. As this process might mimic the mature leukocyte migration, we also observed the effect of exposing endothelial cells to shear stress (7 dyn/cm(2)) on the adhesion of CB CD34+ cells. The proportion of CD34+/CD62L+ cells was greater in PB than in BM (p<0.05). Likewise, we found a significantly greater expression of CD62L receptor on PB cells compared to BM cells (p<0.05) and on BM cells compared to CB cells (p<0.05). The proportions of CD34+/CD49d+ cells and CD34+/CD49e+ cells were significantly higher in the BM and CB than in PB. However, no significant difference in CD49d or CD49e antigen densities was observed. The beta&#95;2 integrins (CD11b and CD18) receptors are also implicated in CD34+ cells homing to BM. No significant variation in CD34+/CD11b+ and CD34+/CD18+ cells frequency was noted. However quantitative analysis revealed that CD18 was more strongly expressed on BM cells than on PB and CB cells. The adhesion assay showed that fluid flow may favour a firm adhesion of CB CD34+ cells to endothelial cells whereas static conditions just allowed CD34+ cells sedimentation. In conclusion, quantitative expression of the main receptors on CD34+ cells indicates that the three main sources of CD34+ cells currently used for transplantation have neither the same phenotype nor the same number of antigenic sites for a receptor. So, we hypothesize that migrational capacity of these cells might be different. Moreover, it seems that shear stress could favor adhesion of CD34+ cells to endothelial cells.

The aim of this study was to determine the comparative three-dimensional mechanical properties of healthy and atherosclerotic muscular human arteries. Using a previously developed experimental system, in vitro inflation tests were performed on twelve segments of arteries, in static conditions. Two different initial states were used to carry the mechanical study through (large deformation, thick-walled). Main significant differences between healthy and atherosclerotic tested segments are observed for axial traction force whatever the initial state and radial and circumferencial strains referenced to longitudinally pre-stretched state. We showed that strain energy allows to differentiate between both types of arteries only when absolute values of transversal components were considered. Differential values of energy were not discriminating. Our results also show the potential interest of studying arteries in vivo at low transmural pressure.

Receptors such as CD62L and CD11b/CD18, are transmembrane glycoproteins which regulate leukocyte adhesive phenotype. Flow cytometry (FCM) makes it possible to assess a characterization of the cell activation level by receptor quantifying, but that technique does not integrate other factors of adherence regulation, such as spatial distribution and molecular conformation. Our study consisted in exploring the main adherence receptors on Polymorphonuclear Neutrophils (PMN) that were simultaneously analyzed by FCM and Conventional Optical Scanning Microscopy (COSM). FCM analysis showed that TNFalpha induce a decrease in CD62L expression and an increase in beta2 integrins. COSM analysis distinguished three stages of cellular distribution of CD11b/CD18 within resting PMN: most of them (about 80%) had homogeneous distribution (heterogeneous spots distributed over the entire cell surface), for 10-15% of the cells, there was a crown distribution around the widest cell diameter and in less that 10% of them receptor distribution was polarized. CD62L was in the form of heterogeneous spots distributed in a circle on the surface on non-stimulated PMN. PMN stimulation by TNFalpha was associated to a randomized clustering involving both selectin and beta2 integrin. Three-dimensional analysis elicited data not shown by quantitative cytometry. For a single averaged value of the density determined by FMC, various spatial distributions of adherence receptors are found on the surface of non-stimulated PMN. The characterization of the leukocyte adhesive phenotype has to integrate adherence receptors density as well as their spatial distribution.

Complete DiGeorge syndrome (cDGS) is a congenital disorder characterized by typical facies, thymic aplasia, susceptibility to infections, hypoparathyroidism and conotruncal cardiac defect. Fetal thymus or post-natal thymus tissue transplantations and human leucocyte antigen (HLA)-genoidentical bone marrow transplantations were followed in a few cases by immune reconstitution. More recently, a peripheral blood mononuclear cell transplantation (PBMCT) was performed with an HLA-genoidentical donor and followed by a partial T-cell engraftment and immune reconstitution. We report a boy with cDGS, without cardiac defect, who suffered recurrent severe infections. At the age of 4 years, he underwent PBMCT from his HLA-genoidentical sister. He received no conditioning regimen, but graft-versus-host disease (GVHD) prophylaxis was with oral cyclosporin A and mycophenolate mofetil. Toxicity was mild, with grade I acute GVHD. The patient is currently 2.5 years post-PBMCT with excellent clinical performances. Mixed chimaerism can only be observed on the T-cell population (50% donor T cells). T-lymphocyte count fluctuated (CD3 more than 400 x 10(6)/l at d 84 and CD4 more than 200 x 10(6)/l at d 46). Exclusive memory phenotype T cells and absence of new thymic emigrants suggest expansion of infused T cells. T-cell mitogen and tetanus antigen responses normalized a few months after transplantation. After immunizations, specific antibodies were produced. PBMCT from an HLA identical sibling could be an efficient treatment of immune deficiency in cDGS.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies or inherited disorders. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevent the development of graft-versus-host disease (GVHD). However, the consequence of these nonspecific approaches is a long-lasting immunodeficiency associated with increased disease relapse, graft rejection, and reactivation of viral infections. Donor lymphocyte infusion, to treat leukemic relapse after allogeneic HSCT, can cause severe GVHD. Several strategies are being optimized to specifically inactivate anti-host T cells while preserving antileukemic or antimicrobial immunocompetence, based on ex vivo or in vivo elimination of anti-host T cells or on the modulation of their anti-host activity., (Copyright 2002 by W.B. Saunders Company.)

The purpose of the present study was to investigate the intracellular IL-1beta production and beta1 integrins (alpha4/beta1 and alpha5/beta1) expression on chondrocytes. Chondroytes monolayer (human chondrosarcoma cell line HEM-C55) were incubated for 12, 24 and 48 hours in the presence of Tumor Necrosis Factor-alpha (TNF-alpha, Sigma, France) or recombinant human IL-1alpha (rh-IL1alpha, Becton Dickinson, France). After direct immunolabelling, cells were either analyzed on FACScan flow cytometer (Becton Dickinson, France), or observed under an epi-fluorescence inverted microscope equipped with the CellScan EPR optical scanning acquisition system (IPLab-Scanalytics, USA). We found that the IL-1beta mean fluorescence intensity in flow cytometry and in 3D microscopy was increased in the presence of TNF-alpha or rh-IL-1alpha, and alpha4/beta1 or alpha5/beta1 expression was higher on stimulated cells than on control cells. On the other hand, we have evaluated the in vitro effects of rhein (10(-5) M, Negma, France), an active metabolite of diacerein, on the intracellular IL-1beta and beta1 integrins expressed by stimulated or no-stimulated chondrocytes. The results indicated that rhein leads to a reduction of IL-1beta synthesis whereas a weak decrease of beta1 integrins receptors expression is observed. From this study, it seems that rhein partially reduce cytokine-induced intracellular IL-1beta production, and it has a weak action on alpha4/beta1 or alpha5/beta1 receptors.

The aim of this work was to quantify by flow cytometry the main adhesion receptors on CD34+ cells. These cells were isolated from bone marrow (BM) or mobilized peripheral blood (PB). The proportions of CD34+/CD49d+ and CD34+/CD49e+ are weaker on PB cells, without quantitative expression variation. This phenotypic variation may induce CD34+ cells exist from BM into circulation, promoting the mobilization. The homing to the BM implicate the CD62L receptor, which expression was found more frequently and stronger on PB cells than on BM. The CD11b, CD18 and CD54 receptors are implicated in CD34+ cells adhesion to BM micro-environment. No significant variation in CD34+/CD11b+ and CD34+/CD18+ cells frequency was noted. Moreover, CD54 receptor was more frequently expressed on PB cells. Quantitative analysis revealed that CD18 was more strongly expressed on BM than on PB cells. This quantitative variation could promote progenitor adhesion by interacting with stromal cells. Finally, quantitative expression of the main receptors on CD34+ cells provides an original option for studying CD34+ cells during the mobilization, the homing or the adhesion to BM micro-environment.

Vascular engineering developed through advancing knowledge of the physiological and pathological processes operating in cells and tissues subjected to environmental mechanical stress. We review briefly the more relevant cellular and general mechanism characteristic of vascular tissue examining the performances obtained with prosthetic materials (allografts, synthetic grafts) and current research and development of new vessel substitutes (biohybrids or biovessels).

Objective: To study the efficacy of the nutritional education software, Nutri-Expert, in the management of obese adult patients., Material and Methods: Two groups of obese patients were followed up over one year in a randomized study: the first group received close traditional management (seven nutritional visits over the year, with physicians and dietitians conjointly) and the second one also used at home by Minitel the Nutri-Expert system. 557 patients were enrolled in the study by 16 French centers of diabetology and nutrition. Body mass index (BMI), tests of dietetic knowledge, dietary records and centralized biological measurements were assessed at inclusion, 6 and 12 months. 341 patients were evaluable at the end of the year., Results: The group using Nutri-Expert scored significantly better in the tests of dietetic knowledge than the control group. For all patients, nutritional education led to a significant improvement in BMI, dietary records and biological measurements, without significant difference between the two groups. Five years after the end of the study, the weight of 148 patients was recorded; mean BMI was significantly lower than the initial value but there was no significant difference between the two groups., Conclusion: In the management of obese patients, Nutri-Expert system has a role to play in reinforcing nutritional knowledge; if regular follow-up is not possible, or if a large series of obese patients is to be treated, Nutri-Expert could partly replace traditional management, for example between visits.

A group of 18 patients with mycosis fungoides (M.F.) was treated by PUVAtherapy. According to VanScott classification, they have been set in:--5 parapsoriasis in large plaques = 5 stages I;--6 stages II;--3 stages III;--2 stages IV;--1Sézary syndrom.--1 erythrodermia. There was complete clearing of 12 patients (66 p. 100); 2 patients (11 p. 100) improved cutaneous lesions without a complete clearing, and there was no response to treatment for 3 patients (22 p. 100) (1 with erythrodermia, 1 with Sézary syndrom and 1 stage IV, and 1 forsaking). The method applied here was different in several points: orally administered methoxalen were given according to the body area (mg/m2) and some of the patients had twice a day puvatherapy. Puvatherapy seems to be the least dangerous and most effective treatment for the patients in the early stages of mycosis fongoides (I, II) and nitrogen mustard, electron therapy, corticoids and even mono- or polychimiotherapy could be associated to puvatherapy, if necessary, for the stages III and IV.

As impairment in coagulation and platelet function has been reported following acute administration of somatostatin, a reevaluation of the effects of the cyclic and linear form of the peptide was undertaken. In vitro somatostatin had no effect by itself on platelet aggregation and no effect on ADP- or ristocetin-induced aggregation. In vivo ten healthy men infused with cyclic or linear somatostatin (loading dose of 250 microgram and three hour-infusion with 1,500 microgram) and five control subjects were investigated during the infusion and for three hours after the end of the infusion. With this dose, sufficient in man for maintaining plasma growth hormone and insulin at fasting levels under arginine stimulation, no abnormalities in platelet count, in ADP-induced platelet aggregation and in plasma VIII von Willebrand factor, factor VIII procoagulant activity and factor VIII related antigen levels were observed.