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1.
Phys Rev Lett ; 127(20): 204501, 2021 Nov 12.
Article in English | MEDLINE | ID: mdl-34860033

ABSTRACT

We report on the collision-coalescence dynamics of drops in Leidenfrost state using liquids with different physicochemical properties. Drops of the same liquid deposited on a hot concave surface coalesce practically at contact, but when drops of different liquids collide, they can bounce several times before finally coalescing when the one that evaporates faster reaches a size similar to its capillary length. The bouncing dynamics is produced because the drops are not only in Leidenfrost state with the substrate, they also experience Leidenfrost effect between them at the moment of collision. This happens due to their different boiling temperatures, and therefore, the hotter drop works as a hot surface for the drop with lower boiling point, producing three contact zones of Leidenfrost state simultaneously. We called this scenario the triple Leidenfrost effect.

2.
Osteoarthritis Cartilage ; 28(11): 1432-1436, 2020 11.
Article in English | MEDLINE | ID: mdl-32860991

ABSTRACT

BACKGROUND: Sprifermin is under investigation as a potential disease-modifying osteoarthritis drug. Previously, 2-year results from the FORWARD study showed significant dose-dependent modification of cartilage thickness in the total femorotibial joint (TFTJ), medial and lateral femorotibial compartments (MFTC, LFTC), and central medial and lateral TFTJ subregions, by quantitative magnetic resonance imaging (qMRI) using manual segmentation. OBJECTIVE: To determine whether qMRI findings from FORWARD could be reproduced by an independent method of automated segmentation using an identical dataset and similar anatomical regions in a post-hoc analysis. METHOD: Cartilage thickness was assessed at baseline and 6, 12, 18 and 24 months, using automated cartilage segmentation with active appearance models, a supervised machine learning method. Images were blinded for treatment and timepoint. Treatment effect was assessed by observed and adjusted changes using a linear mixed model for repeated measures. RESULTS: Based on automated segmentation, statistically significant, dose-dependent structural modification of cartilage thickness was observed over 2 years with sprifermin vs placebo for TFTJ (overall treatment effect and dose response, both P < 0.001), MFTC (P = 0.004 and P = 0.044), and LFTC (both P < 0.001) regions. For highest dose, in the central medial tibial (P = 0.008), central lateral tibial (P < 0.001) and central lateral femoral (P < 0.001) regions. CONCLUSIONS: Cartilage thickness assessed by automated segmentation provided a consistent dose response in structural modification compared with manual segmentation. This is the first time that two independent quantification methods of image analysis have reached the same conclusions in an interventional trial, strengthening the conclusions that sprifermin modifies structural progression in knee osteoarthritis.


Subject(s)
Cartilage, Articular/diagnostic imaging , Knee Joint/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Cartilage, Articular/pathology , Fibroblast Growth Factors/therapeutic use , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Organ Size , Osteoarthritis, Knee/drug therapy
3.
Int J Obes (Lond) ; 42(3): 552-560, 2018 03.
Article in English | MEDLINE | ID: mdl-29135972

ABSTRACT

OBJECTIVE: Bariatric surgery appears as the most efficient therapeutic alternative in morbidly obese patients. In addition to its efficiency to decrease body weight, it also improves metabolic complications associated to morbid obesity, including dyslipidemia. Although the cholesterol-lowering effect varies with the bariatric procedures, the underlying molecular mechanisms remain poorly defined. This study aims to assess the consequence of both restrictive (sleeve gastrectomy; SG) and malabsorptive (Roux-en-Y gastric bypass; RYGB) procedures on cholesterol metabolism in mice. SUBJECTS: Ten-week-old C57BL6/J males were fed with a high-fat diet for 8-14 weeks before sleeve or RYGB surgery. RESULTS: SG has a modest and transient effect on plasma cholesterol levels, linked to a reduction in food intake. In contrast, modified RYGB led to a sustained ≈35% reduction in plasma cholesterol concentrations with a drastic increase in fecal cholesterol output. Mechanistically, RYGB exerts a synergystic effect on cholesterol metabolism by inducing the trans-intestinal cholesterol efflux and reducing the intestinal cholesterol absorption. CONCLUSIONS: In mice, RYGB, but not sleeve, strongly favors plasma cholesterol elimination by concomitantly increasing trans-intestinal cholesterol excretion and by decreasing intestinal cholesterol absorption. Our models open new perspective for deciphering the hypocholesterolemic effects of bariatric procedures.


Subject(s)
Cholesterol/blood , Gastric Bypass/methods , Intestinal Absorption/physiology , Obesity, Morbid , Animals , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity, Morbid/metabolism , Obesity, Morbid/surgery
4.
Acta Paediatr ; 107(7): 1140-1144, 2018 07.
Article in English | MEDLINE | ID: mdl-29193276

ABSTRACT

AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. METHOD: We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children. CONCLUSION: Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.


Subject(s)
Bronchodilator Agents/administration & dosage , Bronchopulmonary Dysplasia/prevention & control , Budesonide/administration & dosage , Pulmonary Surfactants/administration & dosage , Bronchopulmonary Dysplasia/diagnosis , Bronchopulmonary Dysplasia/etiology , Humans , Infant, Newborn
5.
Ann Dermatol Venereol ; 144(12): 759-767, 2017 Dec.
Article in French | MEDLINE | ID: mdl-28803665

ABSTRACT

BACKGROUND: Teledermatology is currently booming. Due to the shortage of dermatologists in hospitals access to dermatological consultations is very limited in some hospitals. We present our experience of collaboration between an expert center, the dermatology department of the Victor-Dupouy Hospital Centre in Argenteuil, and all medical structures under the André-Mignot Hospital in Versailles (CHV), including 2 prison medical centers (UCSA), traditional departments and emergency department. PATIENTS AND METHODS: Teledermatology, developed in the form of tele-expertise, began at the UCSA in November 2013. This expertise was then extended in June 2014 to the Internal Medicine department of CHV, and in December 2014 to all departments, including the emergency department. The rules and ethics of teledermatology were strictly adhered to. While UCSA could file all expertise dossiers, only urgent or difficult cases could be filed by other CHV departments. RESULTS: In 26 months, 347 expertise requests were filed: 231 by prisons and 116 by the other departments of the CHV. No patients refused teledermatology. The quality of information and photographs was considered good or excellent in over 95% of cases. A response was given within 3hours in more than 50% of cases and in all cases within 24hours (on working days). Analysis of diseases diagnosed illustrates the wide variety of conditions encountered in dermatology, with different structures having their own specific features. CONCLUSION: Our example illustrates the possibility of developing such an inter-hospital platform. However, it does not yet cater for requests made by patients to dermatologists, by dermatologists to dermatologists, or by dermatologists to the hospital teledermatology department. Acceptability was considered excellent by patients (with no refusals), physicians at the CHV, and the expert center.


Subject(s)
Dermatology/trends , Hospitals , Remote Consultation/trends , Skin Diseases/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Inpatients/statistics & numerical data , Male , Middle Aged , Prisoners/statistics & numerical data , Remote Consultation/statistics & numerical data , Retrospective Studies , Skin Diseases/epidemiology
6.
Int J Cancer ; 136(7): 1494-503, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-24622970

ABSTRACT

Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High-risk human papillomavirus (HR-HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de-escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de-escalation in HPV-positive OPSCC.


Subject(s)
Oropharyngeal Neoplasms/etiology , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/complications , Cancer Vaccines/therapeutic use , Clinical Trials as Topic , Combined Modality Therapy , Humans , Treatment Outcome
7.
Diabet Med ; 32(1): 90-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25186832

ABSTRACT

AIMS: Few reports have assessed the relationship between Type 1 diabetes and sleep disorders. The purposes of our study were to determine the prevalence of obstructive sleep apnoea in Type 1 diabetes and to compare the clinical profile of people with Type 1 diabetes with or without obstructive sleep apnoea. METHODS: In this cross sectional study of 67 consecutive people with Type 1 diabetes, we performed polysomnography as part of their yearly check-ups. RESULTS: In our cohort, with a mean BMI of 25.8 ± 4.7 kg/m(2), the prevalence of obstructive sleep apnoea [apnoea-hypopnoea index (AHI) > 10/h] was 46%. Severe obstructive sleep apnoea (AHI ≥ 30/h) was present in 19% of the patients. We found no significant differences in age, sex, body mass index, HbA1c or Epworth sleepiness scale score between people with or without obstructive sleep apnoea. People with obstructive sleep apnoea had a longer course of diabetes mellitus (P < 0.01) and a higher prevalence of retinopathy (P < 0.01), neuropathy (P = 0.05), cardiovascular disease (P < 0.01) and hypertension (P < 0.01). The occurrence of macrovascular complications was independently associated with the presence of OSA [odds ratio (OR) 8.28; 95% confidence interval (CI), 1.56-43.97; P = 0.013] and the duration of diabetes (OR 1.08; 95% CI, 1.02-1.15; P = 0.01). Moreover, retinopathy was independently associated with OSA (OR 4.54; 95% CI, 1.09-18.82; P = 0.04) and the duration of diabetes (OR 1.09; 95% CI, 1.04-1.15; P = 0.001). CONCLUSIONS: The prevalence of obstructive sleep apnoea was high in people with Type 1 diabetes. Obstructive sleep apnoea was independently associated with macrovascular complications and retinopathy. Obesity and excessive daytime sleepiness were uncommon in this population.


Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/epidemiology , Diabetic Neuropathies/epidemiology , Sleep Apnea, Obstructive/epidemiology , Adult , Body Mass Index , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Diabetes Mellitus, Type 1/epidemiology , Diabetic Angiopathies/etiology , Diabetic Neuropathies/etiology , Female , Humans , Male , Middle Aged , Polysomnography , Prevalence , Risk Factors , Sleep Apnea, Obstructive/etiology
8.
Horm Metab Res ; 46(13): 921-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25376550

ABSTRACT

Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is associated with systemic modifications and depends especially on pancreatic hormones. The aim of the study was to investigate the role of systemic factors released after two-thirds hepatectomy (2/3H) on early possible consequences of liver regeneration on endocrine pancreas structure and function. The pancreas and serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats. The HGF and VEGF serum concentrations and plasma microparticles levels were measured. The fate of endocrine pancreas was examined through islets histomorphometry and function in sham and 2/3H rats. ß-Cell line RIN-m5F viability was assessed after 24 h of growth in media supplemented with 10% serum from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p < 0.05) and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs. 15%, p < 0.05). Compared to Sham, sera obtained 3 days after hepatectomy were more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p < 0.01). Three days after surgery, no significant differences in serum HGF, a trend to significant increase in VEGF concentration and a significant increase in microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd Ser Eq., p < 0.05). Liver regeneration is associated with early effects on islets and could influence ß-cell viability and function by systemic effect.


Subject(s)
Hepatectomy , Insulin-Secreting Cells/pathology , Liver Regeneration , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell-Derived Microparticles/metabolism , Culture Media, Conditioned/pharmacology , Hepatocyte Growth Factor/blood , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Liver Regeneration/drug effects , Male , Models, Animal , Organ Size/drug effects , Rats, Inbred Lew , Vascular Endothelial Growth Factor A/blood
9.
Minerva Endocrinol ; 38(1): 29-46, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23435441

ABSTRACT

Recent technological innovations as insulin analogue formulation, devices for insulin delivery and glucose monitoring have allowed diabetic patients to improve their glycemic control and decrease their level of burden due to diabetes. Intensive insulin therapy via insulin pens, subcutaneous or intraperitoneal insulin infusions using pumps instead of vials and syringes, are associated with improved absorption reproducibility, HbA1c levels, reduced risk of hypo- or hyperglycemia, and increased quality of patient's life. These currently used systems are discussed in this review as well as the future of exogenous insulin therapy: closed loop system, the artificial pancreas, and oral insulin delivery. Glucose homeostasis is directly linked to glycemic regulated by portal insulin administration, thus endogenous insulin therapy might be the most promising treatment to "cure" diabetes. Consequently, pancreas and islet transplantation, and the bioartificial pancreas are described.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/prevention & control , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Biomarkers/blood , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnosis , Glycated Hemoglobin/metabolism , Humans , Infusions, Parenteral/methods , Infusions, Subcutaneous/methods , Insulin Infusion Systems , Quality of Life , Reproducibility of Results , Risk
10.
Proc Natl Acad Sci U S A ; 107(34): 14968-72, 2010 Aug 24.
Article in English | MEDLINE | ID: mdl-20679246

ABSTRACT

Line defects on the surface of rutile TiO(2)(110) form in pairs separated by 1.2 nm creating a quantum well. The well is effectively closed by the presence of two charged structures at both ends separated by a distance in the 10-20 nm range. As expected for quantum confinement a long period oscillatory feature of the local density of states is observed and attributed to the formation of discrete quantum states inside the system. It is at first glance surprising that the lowest energy quantum state of the well can be observed at room temperature. The properties of the quantum state cannot be explained in an independent-electron, band-like theory. Instead, electron-electron correlation must be included to give a satisfactory picture of the spatial distribution of the charge density. Theory predicts charging energies of 1.30 eV and 1.14 eV for quantum well lengths of 14 nm and 16 nm, respectively, in good agreement with a classical calculation and the size dependence of the capacitance. This observation opens up the possibility of experimentally imaging the transition from a Coulomb blockade localized in a zero-dimensional system to an independent-particle or band-like behavior in an extended one-dimensional system.

11.
Parkinsonism Relat Disord ; 100: 41-44, 2022 07.
Article in English | MEDLINE | ID: mdl-35716627

ABSTRACT

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. METHODS: In a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. RESULTS: 7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). CONCLUSIONS: LCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.


Subject(s)
Multiple System Atrophy , Parkinson Disease , Antiparkinson Agents/therapeutic use , Carbidopa , Drug Combinations , Gels/therapeutic use , Humans , Levodopa/therapeutic use , Multiple System Atrophy/drug therapy , Parkinson Disease/drug therapy , Retrospective Studies
12.
AJNR Am J Neuroradiol ; 43(3): 376-380, 2022 03.
Article in English | MEDLINE | ID: mdl-35177550

ABSTRACT

BACKGROUND AND PURPOSE: There are limited data on the prevalence and outcome of intracranial atherosclerotic disease in patients with low-risk transient or persistent minor neurologic events. We sought to determine the prevalence and risk factors associated with intracranial atherosclerotic disease in patients with low-risk transient or persistent neurologic events. MATERIALS AND METHODS: Participants with available intracranial vascular imaging from the Diagnosis of Uncertain-Origin Benign Transient Neurologic Symptoms (DOUBT) study, a large prospective multicenter cohort study, were included in this post hoc analysis. The prevalence of intracranial atherosclerotic disease of ≥50% was determined, and the association with baseline characteristics and DWI lesions was evaluated using logistic regression. RESULTS: We included 661 patients with a median age of 62 years (interquartile range, 53-70 years), of whom 53% were women. Intracranial atherosclerotic disease was found in 81 (12.3%) patients; asymptomatic intracranial atherosclerotic disease alone, in 65 (9.8%); and symptomatic intracranial atherosclerotic disease, in 16 (2.4%). The most frequent location was in the posterior cerebral artery (29%). Age was the only factor associated with any intracranial atherosclerotic disease (adjusted OR, 1.9 for 10 years increase; 95% CI, 1.6-2.5). Multivariable logistic regression showed a strong association between intracranial atherosclerotic disease and the presence of acute infarct on MR imaging (adjusted OR, 3.47; 95% CI, 1.91-6.25). CONCLUSIONS: Intracranial atherosclerotic disease is not rare in patients with transient or persistent minor neurologic events and is independently associated with the presence of MR imaging-proved ischemia in this context. Evaluation of the intracranial arteries could be valuable in establishing the etiology of such low-risk events.


Subject(s)
Atherosclerosis , Intracranial Arteriosclerosis , Ischemic Attack, Transient , Stroke , Aged , Atherosclerosis/complications , Child , Cohort Studies , Female , Humans , Intracranial Arteriosclerosis/complications , Intracranial Arteriosclerosis/diagnostic imaging , Intracranial Arteriosclerosis/epidemiology , Ischemic Attack, Transient/diagnostic imaging , Ischemic Attack, Transient/epidemiology , Male , Middle Aged , Prevalence , Prospective Studies , Risk Factors , Stroke/complications
13.
Antimicrob Agents Chemother ; 55(10): 4692-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21825292

ABSTRACT

MUT056399 is a highly potent new inhibitor of the FabI enzyme of both Staphylococcus aureus and Escherichia coli. In vitro, MUT056399 was very active against S. aureus strains, including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains, with MIC(90)s between 0.03 and 0.12 µg/ml. MUT056399 was also active against coagulase-negative staphylococci, with MIC(90)s between 0.12 and 4 µg/ml. The antibacterial spectrum is consistent with specific FabI inhibition with no activity against bacteria using FabK but activity against FabI-containing Gram-negative bacilli. In vitro, resistant clones of S. aureus were obtained at a low frequency. All of the resistant clones analyzed were found to contain mutations in the fabI gene. In vivo, MUT056399, administered subcutaneously, protected mice from a lethal systemic infection induced by MSSA, MRSA, and vancomycin-intermediate S. aureus strains (50% effective doses ranging from 19.3 mg/kg/day to 49.6 mg/kg/day). In the nonneutropenic murine thigh infection model, the same treatment with MUT056399 reduced the bacterial multiplication of MSSA and MRSA in the thighs of immunocompetent mice. These properties support MUT056399 as a very promising candidate for a novel drug to treat severe staphylococcal infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Benzamides/pharmacology , Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/antagonists & inhibitors , Escherichia coli Proteins/antagonists & inhibitors , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Phenyl Ethers/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Acetamides/pharmacology , Animals , Anti-Bacterial Agents/therapeutic use , Benzamides/therapeutic use , Drug Resistance, Multiple, Bacterial , Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/genetics , Escherichia coli Proteins/genetics , Fatty Acid Synthase, Type II/antagonists & inhibitors , Fatty Acid Synthase, Type II/genetics , Female , Linezolid , Mice , Microbial Sensitivity Tests , Mutation , Oxazolidinones/pharmacology , Phenyl Ethers/therapeutic use , Staphylococcal Infections/microbiology , Vancomycin/pharmacology
14.
Am J Transplant ; 10(7): 1707-12, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20642693

ABSTRACT

Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. In the present study, we report the long-term follow-up of four end-stage CF patients treated with combined bilateral lung and pancreatic islet transplantation from the same donor. All patients were C-peptide negative (<0.5 microg/L) and inadequately controlled despite intensive insulin treatment. One patient was transplanted with 4 019 +/- 490 islet equivalent/kg injected into the transverse colic vein using a surgical approach. In the remaining three patients, islets were cultured for 3-6 days and transplanted by percutaneous transhepatic catheterization of the portal vein. In all patients, islet allograft recovery was recognized by elevation in the plasma level of C-peptide (>0.5 microg/L). At 6 months after transplantation, one patient showed multiple episodes of acute lung transplant rejection and a progressive decline in pancreatic islet cell function. Three out of four patients experienced an improved control of glucose levels with a HbA1c of 5.2%, 7% and 6% respectively at 1.5, 2 and 15 years follow-up. Compared with the pretransplant period, there was a 50% reduction in mean daily insulin needs. Pulmonary function remained satisfactory in all patients. In conclusion, our cases series shows that combined bilateral lung and pancreatic islet transplantation may be a viable therapeutic option for patients with end-stage CF and CFRD.


Subject(s)
Cystic Fibrosis/surgery , Islets of Langerhans Transplantation/methods , Lung Transplantation/methods , Adolescent , Adult , Age of Onset , C-Peptide/blood , Combined Modality Therapy , Cystic Fibrosis/complications , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Diabetes Complications/surgery , Forced Expiratory Volume , Humans , Male , Mutation , Sequence Deletion , Transplantation, Homologous , Treatment Outcome , Vital Capacity , Young Adult
15.
Rev Med Interne ; 41(8): 510-516, 2020 Aug.
Article in French | MEDLINE | ID: mdl-32680715

ABSTRACT

INTRODUCTION: A consultation dedicated to symptomatic health professionals was opened at the beginning of the COVID-19 epidemic in order to meet the specific needs of this population. The objective of this work was to estimate the frequency of SARS-Cov-2 nasopharyngeal carriage in symptomatic healthcare workers suspected of having COVID-19 and to determine the factors associated with this carriage. METHODS: Of the 522 consultants, 308 worked in the Hospital and 214 outside. They had mild forms of COVID-19 and non-specific clinical signs with the exception of agueusia/anosmia, which was significantly more common in those with positive RT-PCR. The rate of RT-PCR positivity was 38% overall, without significant difference according to profession. It was higher among external consultants (47% versus 31%). In the hospital, this rate was significantly lower for symptomatic staff in the care sectors, compared to staff in the technical platforms and laboratories (24%, versus 45%, p = 0.006 and 54%, respectively, p < 0.001), but did not differ between staff in COVID units and other care sectors (30% versus 28%). Among the external consultants, the positivity rates of nursing home and private practices staff (53% and 55% respectively) were more than double that of acute care hospital staff (24%, p < 0.001). CONCLUSIONS: These data confirm the strong impact of COVID-19 on health professionals. The higher positivity rates among symptomatic professionals working outside the hospital compared to those working in hospital may be explained in part by a shortage of protective equipment and by difficulties in accessing virological diagnosis, which were greater outside the hospital when the epidemic began.


Subject(s)
Betacoronavirus , Coronavirus Infections , Nasal Cavity , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Carrier State , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Health Personnel , Hospitals, University , Humans , Nasal Cavity/virology , Paris , Real-Time Polymerase Chain Reaction , Risk Factors , SARS-CoV-2
16.
Am J Transplant ; 9(8): 1961-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19522877

ABSTRACT

We describe the decline in islet function, in relation to HLA sensitization, in an islet transplant recipient and the recovery of this function after treatment with anti-CD20 monoclonal antibody and IV immunoglobulins. A 51-year-old woman with type 1 diabetes received one intraportal islet infusion. Following this transplantation, she became insulin independent. A search for HLA antibodies by using an ELISA technique remained consistently negative for HLA class I and II. It was only 2 years after the islet transplantation that this search became positive against class II antigens, reaching a peak of reactivity concomitantly with the appearance of a deterioration of glucose control requiring low-dose insulin therapy. Luminex screening and single-antigen assays then revealed the presence of both nondonor-specific and donor-specific antibodies against HLA class II molecules. This immunization, already present in the pretransplant serum, had increased during the 6 months preceding the clinical deterioration. Since these data nevertheless pointed to antibody-mediated rejection of the islet allograft, treatment with anti-CD20 monoclonal antibody and IV immunoglobulins was initiated. One month later, the search by ELISA for antibodies against HLA class II antigens became negative, the Luminex tests normalizing more gradually. As the result of an improvement in glucose control, the patient was again insulin-free.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/immunology , Immunity, Humoral/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Islets of Langerhans Transplantation/immunology , Antibodies, Monoclonal, Murine-Derived , Female , Humans , Middle Aged , Rituximab , Treatment Outcome
17.
Biotechnol Bioeng ; 102(4): 1259-67, 2009 Mar 01.
Article in English | MEDLINE | ID: mdl-18949749

ABSTRACT

Articular cartilage has a low capacity for spontaneous repair. To promote the repair of this tissue, the transfer of autologous chondrocytes using a three-dimensional matrix appears promising. In this context, the aim of the present work was to investigate the potential use of autologous rabbit nasal chondrocytes (RNC) associated with an injectable self-setting cellulose-based hydrogel (Si-HPMC). Firstly, the influence of Si-HPMC on chondrocytic phenotype was investigated by real-time PCR for specific chondrocyte markers (type II collagen and aggrecan) and type I collagen. Thereafter, autologous RNC were amplified in vitro for 4 weeks before transplantation with Si-HPMC into a rabbit articular cartilage defect followed by analysis 6 weeks later. Implants were histologically characterized for the presence of sulfated GAG and type II collagen. Transcripts analysis indicated that dedifferentiated RNC recovered expression of the main chondrocytic markers after in vitro three-dimensional culture within Si-HPMC. Histological analysis of autologous RNC transplanted in an articular cartilage defect revealed the formation of repair tissue with a histological organization similar to that of healthy articular cartilage. In addition, immunohistological analysis of type II collagen suggested that the repair tissue was a hyaline-like cartilage. Si-HPMC hydrogel associated with nasal chondrocytes therefore appears a promising injectable tissue engineering device for the repair of articular cartilage.


Subject(s)
Cartilage, Articular/injuries , Chondrocytes/transplantation , Hydrogel, Polyethylene Glycol Dimethacrylate/therapeutic use , Tissue Engineering/methods , Transplantation, Autologous/methods , Animals , Cells, Cultured , Chondrocytes/physiology , Collagen Type II/metabolism , Gene Expression Profiling , Glycosaminoglycans/metabolism , Injections , Rabbits
18.
Ann Endocrinol (Paris) ; 70(2): 129-32, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18995843

ABSTRACT

Retroperitoneal fibrosis is characterized by the presence of a retroperitoneal tissue, consisting of chronic inflammation and marked fibrosis, which entraps the retroperitoneal organs. In two-thirds of cases, the retroperitoneal fibrosis is idiopathic. The pathogenic mechanism is not clearly identified. We report a case of idiopathic retroperitoneal fibrosis associated with type 1 diabetes mellitus. A 61-year-old woman with C peptide negative insulindependent diabetes developed retroperitoneal fibrosis revealed by bilateral hydronephrosis. Anti-GAD 65 antibodies were positive. There were no signs of autoimmune pancreatitis: no steatorrhea, normal IgG4 isotype levels, and absence of pancreas morphological abnormalities.


Subject(s)
Diabetes Mellitus, Type 1/complications , Retroperitoneal Fibrosis/complications , Anti-Inflammatory Agents/therapeutic use , C-Peptide/blood , Diabetes Mellitus, Type 1/diagnostic imaging , Diabetes Mellitus, Type 1/pathology , Female , Glutamate Decarboxylase/immunology , Glutamate Decarboxylase/metabolism , Humans , Hydronephrosis/complications , Hydronephrosis/pathology , Middle Aged , Retroperitoneal Fibrosis/diagnostic imaging , Retroperitoneal Fibrosis/pathology , Retroperitoneal Space/diagnostic imaging , Retroperitoneal Space/pathology , Steroids/therapeutic use , Tomography, X-Ray Computed , Ureter/pathology
19.
Bioorg Med Chem Lett ; 18(14): 4022-6, 2008 Jul 15.
Article in English | MEDLINE | ID: mdl-18571407

ABSTRACT

Heptosyltransferases such as WaaC represent promising and attractive targets for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms. We report herein our approach to the identification of the first micromolar inhibitors of WaaC and the preliminary SAR generated from this family of 2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-ones identified by virtual screening.


Subject(s)
Glycosyltransferases/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Binding Sites , Chemistry, Pharmaceutical/methods , Crystallography, X-Ray/methods , Drug Design , Drug Resistance, Multiple, Bacterial/drug effects , Kinetics , Microbial Sensitivity Tests , Models, Biological , Models, Chemical , Molecular Conformation , Molecular Structure , Structure-Activity Relationship
20.
Transplant Proc ; 40(2): 470-2, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18374105

ABSTRACT

The aim of this work was to evaluate the effects of rapamycin on rat macrophage viability and chemotaxis toward allogereic pancreatic islet supernates. Macrophages were isolated from rats by peritoneal lavage at 3 days after intraperitoneal injection of thioglycolate. Macrophage viability was studied after 7 days of culture by Cell Titer assays in the presence of rapamycin at 0.1, 1, and 10 ng/mL (n = 6). After 48 hours of culture, pancreatic rat islet supernates were studied for there chemotactic properties toward freshly isolated macrophages in the presence of rapamycin at 0.1, 1, and 10 ng/mL. Chemotaxis was expressed as a migration index defined as the number of macrophages attracted by the test solution (islet supernate +/- rapamycin)/number of macrophages attracted by the supernate (n = 6). After 3 days of culture, macrophage viability decreased significantly by 22%, 36%, and 32% in the presence of 0.1, 1, and 10 ng/mL rapamycin, respectively (P = .008). Macrophage viability remained stable at about 70% after 7 days of culture. In the presence of islet supernates, macrophage migration increased two-fold compared with those obtained by culture medium. Rapamycin did not influence macrophage migration toward culture medium. However, the drug significantly reduced the migration of macrophages toward islet supernates from 2 +/- 0.6 to 0.9 +/- 0.4, 0.7 +/- 0.3, or 0.8 +/- 0.4 in the presence of 0.1, 1, or 10 ng/mL rapamycin, respectively (P = .04). Rapamycin decreased the survival of cultured rat macrophages and their migration toward allogenic islet supernates. These results suggested that, besides its anti-proliferative effect on T cells, rapamycin reduced macrophage attraction to the graft site.


Subject(s)
Cell Survival/drug effects , Chemotaxis/physiology , Islets of Langerhans Transplantation/physiology , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/physiology , Sirolimus/pharmacology , Animals , Cell Movement/drug effects , Cell Movement/physiology , Chemotaxis/drug effects , Culture Media , Macrophages, Peritoneal/drug effects , Male , Rats , Rats, Wistar , Transplantation, Homologous
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