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1.
Clin Immunol ; 263: 110214, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38604255

ABSTRACT

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.


Subject(s)
Consensus , Lupus Erythematosus, Systemic , Remission Induction , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/diagnosis , Child , Immunosuppressive Agents/therapeutic use , Age of Onset , Delphi Technique , Advisory Committees
2.
Am J Med Genet A ; 194(7): e63585, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38459620

ABSTRACT

Germline gain of function variations in the AKT3 gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the AKT3 gene NM_005465.7:c.964G>T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2 years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6 months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and AKT3 gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the AKT3 gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.


Subject(s)
Germ-Line Mutation , Megalencephaly , Mutation, Missense , Proto-Oncogene Proteins c-akt , Humans , Megalencephaly/genetics , Megalencephaly/pathology , Mutation, Missense/genetics , Proto-Oncogene Proteins c-akt/genetics , Germ-Line Mutation/genetics , Male , Child, Preschool , Phenotype , Hypothyroidism/genetics , Hypothyroidism/pathology , Hypothyroidism/complications , Female , Human Growth Hormone/deficiency , Human Growth Hormone/genetics
3.
Eur J Med Genet ; 66(8): 104803, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37379879

ABSTRACT

Generalized Arterial Calcifications of Infancy (GACI) is an extremely rare autosomal recessive genetic condition, mostly due to pathogenic variations in the ENPP1 gene (GACI1, MIM #208000, ENPP1, MIM #173335). To date 46 likely pathogenic or pathogenic distinct variations in ENPP1 have been described, including nonsense, frameshift, missense, splicing variations, and large deletions. Here we report a case of GACI in a male newborn with a homozygous stop-loss variant in ENPP1 treated in Nancy Regional University Maternity Hospital. Based on proband main clinical signs, clinical exome sequencing was performed and showed a deletion of one nucleotide leading to frameshift and stop-loss (NM_006208.3 (ENPP1):c.2746del,p.(Thr916Hisfs*23)). Clinical presentation is characterized by primary neonatal arterial hypertension resulting in hypertrophic cardiomyopathy decompensated by three cardiogenic shocks and a neonatal deep right sylvian stroke. The child died at 24 days of life. This is the first report of a pathogenic stop-loss variant in ENPP1. It is an opportunity to remind clinicians of GACI disease, a rare and severe etiology in neonates with severe hypertension, and possibility of bisphosphonates therapy.


Subject(s)
Hypertension , Stroke , Vascular Calcification , Child , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Frameshift Mutation , Mutation , Vascular Calcification/drug therapy , Vascular Calcification/genetics , Vascular Calcification/pathology
4.
Rev Sci Tech ; 42: 75-82, 2023 05.
Article in English | MEDLINE | ID: mdl-37232317

ABSTRACT

The sharing of animal disease data should be encouraged. The analysis of such data will broaden our knowledge of animal diseases and potentially provide insights into their management. However, the need to conform to data protection rules in the sharing of such data for analysis purposes often poses practical difficulties. This paper sets out the challenges and the methods used for the sharing of animal health data in England, Scotland and Wales - Great Britain - using bovine tuberculosis (bTB) data as a case study. The data sharing described is undertaken by the Animal and Plant Health Agency on behalf of the Department for Environment, Food and Rural Affairs and the Welsh and Scottish Governments. It should be noted that animal health data are held at the level of Great Britain (rather than the United Kingdom - which includes Northern Ireland), as Northern Ireland's Department of Agriculture, Environment and Rural Affairs has its own separate data systems. Bovine tuberculosis is the most significant and costly animal health problem facing cattle farmers in England and Wales. It can be devastating for farmers and farming communities and the control costs for taxpayers in Great Britain are over £150 million a year. The authors describe two methods of data sharing - first, where data are requested by, and delivered to, an academic institution for epidemiological or scientific analysis, and second, where data are proactively published in an accessible and meaningful way. They provide details of an example of the second method, namely, the free-to-access website â€Ëœinformation bovine TB' (https://ibtb.co.uk), which publishes bTB data for the benefit of the farming community and veterinary health professionals.


L'échange et le partage de données sur les maladies animales sont des pratiques à encourager. En effet, l'analyse de ces données permet d'étoffer les connaissances sur les maladies animales et peut aussi apporter un nouvel éclairage sur leur gestion. Néanmoins, la nécessité de se conformer aux règles sur la protection des données pose souvent des difficultés pratiques lors des échanges de ce type de données à des fins d'analyse. Les auteurs expliquent les difficultés rencontrées en matière d'échange de données de santé animale en Angleterre, en écosse et au Pays de Galles (Grande-Bretagne), ainsi que les méthodes utilisées, à partir de l'exemple concret des données relatives à la tuberculose bovine. L'échange et le partage de données sont réalisés par l'Agence britannique de santé animale et végétale, pour le compte du ministère britannique de l'Environnement, de l'Alimentation et des Affaires rurales et des gouvernements gallois et écossais. Il convient de préciser que les données de santé animale dont il s'agit sont celles conservées au niveau de la Grande-Bretagne seulement (et non du Royaume-Uni, qui inclut l'Irlande du Nord), étant donné que le ministère de l'Agriculture, de l'Environnement et des Affaires rurales de l'Irlande du Nord possède ses propres systèmes de données. La tuberculose bovine est le principal problème de santé animale auquel sont confrontés les éleveurs de bovins en Angleterre et au Pays de Galles, et le plus coûteux à traiter. La survenue de la tuberculose bovine est une catastrophe pour les éleveurs affectés et leur communauté. En outre, le coût annuel de son contrôle s'élève à plus de 150 millions de livres pour le contribuable britannique. Les auteurs décrivent deux méthodes d'échange et de partage de données : la première est celle où une institution de recherche demande et obtient l'accès à des données particulières afin de réaliser une étude épidémiologique ou scientifique ; la deuxième consiste à publier les données de manière proactive et constructive, en les rendant facilement accessibles. Un exemple concret de cette deuxième méthode est décrit en détail : il s'agit du site web d'information sur la tuberculose bovine (https://ibtb.co.uk), d'accès libre, qui diffuse des informations sur cette maladie à l'intention des éleveurs et des professionnels de la santé animale.


Convendría alentar la puesta en común de datos zoosanitarios, pues el análisis de estos datos nos ayudará a conocer más y mejor las enfermedades animales y, a la postre, puede darnos pistas sobre la mejor manera de afrontarlas. Ocurre a menudo, sin embargo, que el prescriptivo cumplimiento de las reglas de protección de datos plantee dificultades prácticas para poner estos datos en común con fines de análisis. Los autores, empleando como ejemplo un estudio sobre la tuberculosis bovina, describen esas dificultades y los métodos utilizados para compartir datos zoosanitarios en Inglaterra, Escocia y Gales (Gran Bretaña). En el ejemplo descrito, la Agencia de Sanidad Animal y Vegetal del Reino Unido fue la instancia que impulsó la puesta en común de los datos en nombre del Departamento de Medio Ambiente, Alimentación y Asuntos Rurales del Reino Unido y de los gobiernos galés y escocés. Conviene puntualizar que los datos zoosanitarios cubren el territorio de Gran Bretaña (y no de todo el Reino Unido, que incluye Irlanda del Norte), ya que el Departamento de Medio Ambiente, Alimentación y Asuntos Rurales norirlandés dispone de su propio sistema de datos independiente. La tuberculosis bovina es el problema zoosanitario más importante y oneroso al que hacen frente las explotaciones de vacuno en Inglaterra y Gales. Esta enfermedad no solo puede ser devastadora para los productores y profesionales del sector, sino que la lucha contra ella cuesta al contribuyente británico más de 150 millones de libras al año. Los autores describen dos métodos para compartir de datos: en el primero de ellos, un establecimiento universitario solicita y recibe los datos con fines de análisis científico o epidemiológico; en el segundo, una entidad toma la iniciativa de hacer públicos los datos de forma accesible y coherente. Los autores exponen en detalle un ejemplo del segundo procedimiento, a saber, el sitio web de información sobre la tuberculosis bovina (https://ibtb.co.uk) en libre acceso, en el cual se publican datos sobre la enfermedad dirigidos a los profesionales del sector pecuario y la sanidad animal.


Subject(s)
Cattle Diseases , Tuberculosis, Bovine , Cattle , Animals , Humans , Tuberculosis, Bovine/epidemiology , Tuberculosis, Bovine/prevention & control , United Kingdom/epidemiology , Agriculture , Farmers , Farms , Risk Factors
5.
Clin Immunol ; 250: 109296, 2023 05.
Article in English | MEDLINE | ID: mdl-36934849

ABSTRACT

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.


Subject(s)
Immunosuppressive Agents , Lupus Erythematosus, Systemic , Adult , Child , Humans , Severity of Illness Index , Immunosuppressive Agents/therapeutic use , Prednisolone , Consensus , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy
6.
Int J Appl Posit Psychol ; 7(3): 271-300, 2022.
Article in English | MEDLINE | ID: mdl-35600501

ABSTRACT

Positive psychology interventions hold great promise as schools around the world look to increase the wellbeing of young people. To reach this aim, a program was developed to generate positive emotions, as well as improve life satisfaction, mental toughness and perceptions of school kindness in 538 expatriate students in Dubai, United Arab Emirates. Starting in September 2019, the program included a range of positive psychology interventions such as gratitude, acts of kindness and mental contrasting as examples. Life satisfaction and mental toughness at mid-year were sustained or grew by the end of the year. Positive affect, emotional wellbeing and social wellbeing increased at post-intervention 1, compared to baseline. However, this improvement reverted to baseline levels at post-intervention 2, when data were collected during the COVID-19 pandemic. Only psychological wellbeing, negative affect, perceptions of control, and school kindness were increased at post-intervention 2. During the lockdown, students moved less, but slept and scrolled more. Those who extended their sleep duration reported greater wellbeing. Boosting wellbeing through the use of positive psychology interventions works - even in a pandemic - and extended sleep duration appears to be a driving factor for this observation.

7.
Drug Alcohol Depend ; 234: 109391, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35306397

ABSTRACT

INTRODUCTION: Low clinical insight in psychiatry is defined as poor recognition of one's mental illness, including disability to self-evaluate symptom severity. It has been reported as common in addiction and is associated with lower treatment compliance. Longitudinal studies suggest that low clinical insight could be linked to more relapse. However, association with successful quit attempts remains unknown. OBJECTIVE: Our objective was to examine the prospective link between baseline clinical insight level and self-reports of successful attempts to quit / control use during the first 3 months of outpatient addiction treatment. METHODS: Participants were recruited from the ADDICTAQUI cohort at outpatient treatment intake for substance or behavioral addictions. They completed a baseline evaluation using the Addiction Severity Index (ASI), the Mini International Neuropsychiatric Interview (MINI), and the modified Hanil Alcohol Insight Scale (m-HAIS) with a follow-up ASI 3 months later. Data were analyzed using multiple logistic regression and non-parametric tests. RESULTS: Lower clinical insight level at baseline was associated with less successful quit / control attempts during the first 3 months of outpatient treatment compared to a higher clinical insight level, controlling for sociodemographic factors, baseline addiction severity, and comorbidities (n = 54; exp(B) = 0.76; p (FDRcor) = 0.033). CONCLUSION: Poor clinical insight may be a barrier to treatment success, and future studies should examine underlying mechanisms.


Subject(s)
Behavior, Addictive , Mental Disorders , Smoking Cessation , Humans , Outpatients , Prospective Studies , Smoking Cessation/psychology
8.
Encephale ; 48(2): 163-170, 2022 Apr.
Article in French | MEDLINE | ID: mdl-34099245

ABSTRACT

BACKGROUND: In the fields of psychology and psychiatry, the use of the terms impulsivity, sensation-seeking and ordalie to refer to risk-taking behaviors can sometimes be confusing. OBJECTIVE: The objective of this study was to establish a clinical definition of the concepts of ordalie, sensation-seeking and impulsivity, in order to analyze the similarities and differences between these concepts. METHODS: We prioritized literature review articles with or without meta-analysis from the Medline database and supplemented with the Google-Scholar database. The articles were included in this review if their objectives were in line with ours. The research was conducted in November 2018. RESULTS: Twenty-seven articles were selected. There are similarities in the clinical definitions of these concepts with measurable heterogeneous constructions, and an exacerbation in adolescence for engagement in harmful behaviors, but there are also nuances that highlight their differences. CONCLUSION: We were able to describe areas of divergence and convergence between these three concepts but not to establish a quantitative diagram of the areas of divergence and convergence. It would seem that the coexistence of sensation-seeking and impulsivity in the same individual could explain that individual's involvement in ordalique behaviors. Further studies approaching this hypothesis would seem useful in terms of preventing risk-taking behaviors such as addictive behaviors.


Subject(s)
Adolescent Behavior , Behavior, Addictive , Adolescent , Adolescent Behavior/psychology , Humans , Impulsive Behavior , Risk-Taking , Sensation
9.
Epidemiol Infect ; 149: e20, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33327978

ABSTRACT

Arctic rabies virus variant (ARVV) is enzootic in Quebec (Canada) north of the 55th parallel. With climate change, increased risk of re-incursion of ARVV in more densely populated southern regions raises public and animal health concerns. The objective of this study was to prioritise geographical areas to target for an early detection of ARVV incursion south of the 55th parallel based on the historical spatio-temporal trends of reported rabies in foxes in Quebec. Descriptive analyses of fox rabies cases from 1953 to 2017 were conducted. Three periods show increases in the number of fox rabies cases in southern regions and indicate incursion from northern areas or neighbouring provinces. The available data, particularly in central and northern regions of the province, were scarce and of low spatial resolution, making it impossible to identify the path of spread with precision. Hence, we investigated the use of multiple criteria, such as historical rabies cases, human population density and red fox (Vulpes vulpes) relative abundance, to prioritise areas for enhanced surveillance. This study underscores the need to define and maintain new criteria for selecting samples to be analysed in order to detect rapidly ARVV cases outside the current enzootic area and any potential re-incursion of the virus into central and southern regions of the province.


Subject(s)
Foxes/virology , Rabies/veterinary , Animals , Population Surveillance , Quebec/epidemiology , Rabies/epidemiology , Retrospective Studies
10.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 39(5): 279-283, sept.-oct. 2020. ilus, tab
Article in Spanish | IBECS | ID: ibc-198289

ABSTRACT

ANTECEDENTES: El hiperinsulinismo congénito (HIC) es una enfermedad neuroendocrina con anomalías focales o difusas en el páncreas. Mientras que las formas difusas resistentes a los medicamentos requieren una pancreatectomía casi total o una farmacoterapia prolongada, el HIC focal podría ser tratado por resección quirúrgica dirigida. Por tanto, evaluamos la utilidad del 18F-DOPA PET/TC para identificar la forma pancreática focal. Objetivos y metodología: Diecinueve niños (11 niños y 8 niñas de 2 a 54meses de edad) con signos clínicos de HIC neonatal y exámenes genéticos positivos fueron registrados en el estudio. Después de la administración intravenosa del 18F-DOPA, una primera PET y posteriormente otra PET/TC cubriendo longitudinalmente la región toracoabdominal fueron llevadas a cabo. Ambas adquisiciones fueron realizadas en modo dinámico para permitir la exclusión de imágenes con artefactos de movimiento. Los valores de absorción estandarizados fueron ajustados al peso corporal (SUVbw). El hallazgo fue considerado como focal cuando la proporción de SUVbwmax entre la región sospechosa y el resto del páncreas fue mayor que 1,2. RESULTADOS: Las formas focales fueron registradas en 10/19 niños y 4 de ellos se sometieron a una resección quirúrgica con recuperación completa. La captación focal fue significativamente mayor que la captación en el tejido pancreático normal (p = 0,0059). Las formas focales y difusas del HIC no difieren significativamente en la captación del tejido pancreático normal. No encontramos ninguna ventaja en la medición de la relación SUVbwmean en comparación con la relación SUVbwmax (p = 0,50). CONCLUSIONES: 18F-DOPA PET/TC es una herramienta útil para la localización de HIC focal y la planificación de un tratamiento quirúrgico


BACKGROUND: Congenital hyperinsulinism (CHI) is a neuroendocrine disease with focal or diffuse abnormalities in pancreas. While drug-resistant diffuse forms require near-total pancreatectomy or prolonged pharmacotherapy, focal CHI may be treated by targeted surgical resection. We evaluated the usefulness of 18F-DOPA PET/CT to identify the focal pancreatic form. Subjects and methods: Nineteen children (11 boys, 8 girls, aged 2-54 months) with clinical signs of neonatal CHI and positive genetic examinations were enrolled in the study. After i.v. administration of 18F-DOPA, early PET and late PET/CT acquisition covering one-bed length over thoraco-abdominal region were performed. Both acquisitions were done in dynamic mode to allow exclusion of frames with motion artefacts. Standardized uptake values were adjusted to bodyweight (SUVbw). The finding was considered as focal when the ratio of SUVbwmax between the suspicious region and the rest of pancreas was greater than 1.2. RESULTS: Focal forms were recorded in 10/19 children and 4 of them underwent surgical resection with complete recovery. Focal uptake was significantly higher than the uptake in the normal pancreatic tissue (p = 0.0059). Focal and diffuse forms of CHI did not differ significantly in normal pancreatic tissue uptake. We found no advantage in the measurement of SUVbwmean ratio compared to SUVbwmax ratio (p = 0.50). CONCLUSION: 18F-DOPA PET/CT is a useful tool for the localization of focal CHI and planning of surgical treatment


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Congenital Hyperinsulinism/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Pancreas/diagnostic imaging , Radiopharmaceuticals/administration & dosage , Insulinoma/diagnostic imaging , Radioactive Tracers , Octreotide/therapeutic use , Diazoxide/therapeutic use
11.
Article in English, Spanish | MEDLINE | ID: mdl-32448747

ABSTRACT

BACKGROUND: Congenital hyperinsulinism (CHI) is a neuroendocrine disease with focal or diffuse abnormalities in pancreas. While drug-resistant diffuse forms require near-total pancreatectomy or prolonged pharmacotherapy, focal CHI may be treated by targeted surgical resection. We evaluated the usefulness of 18F-DOPA PET/CT to identify the focal pancreatic form. SUBJECTS AND METHODS: Nineteen children (11 boys, 8 girls, aged 2-54 months) with clinical signs of neonatal CHI and positive genetic examinations were enrolled in the study. After i.v. administration of 18F-DOPA, early PET and late PET/CT acquisition covering one-bed length over thoraco-abdominal region were performed. Both acquisitions were done in dynamic mode to allow exclusion of frames with motion artefacts. Standardized uptake values were adjusted to bodyweight (SUVbw). The finding was considered as focal when the ratio of SUVbwmax between the suspicious region and the rest of pancreas was greater than 1.2. RESULTS: Focal forms were recorded in 10/19 children and 4 of them underwent surgical resection with complete recovery. Focal uptake was significantly higher than the uptake in the normal pancreatic tissue (p=0.0059). Focal and diffuse forms of CHI did not differ significantly in normal pancreatic tissue uptake. We found no advantage in the measurement of SUVbwmean ratio compared to SUVbwmax ratio (p=0.50). CONCLUSION: 18F-DOPA PET/CT is a useful tool for the localization of focal CHI and planning of surgical treatment.


Subject(s)
Congenital Hyperinsulinism/diagnostic imaging , Dihydroxyphenylalanine/analogs & derivatives , Fluorine Radioisotopes , Pancreatectomy/methods , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals , Surgery, Computer-Assisted , Child, Preschool , Combined Modality Therapy , Congenital Hyperinsulinism/drug therapy , Congenital Hyperinsulinism/physiopathology , Congenital Hyperinsulinism/surgery , Diazoxide/therapeutic use , Dihydroxyphenylalanine/pharmacokinetics , Female , Fluorine Radioisotopes/pharmacokinetics , Humans , Infant , Insulinoma/complications , Insulinoma/surgery , Male , Neuroendocrine Cells/metabolism , Octreotide/therapeutic use , Pancreas/physiopathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Positron-Emission Tomography , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , Sirolimus/therapeutic use , Sulfonylurea Receptors/genetics , Tissue Distribution
12.
Rozhl Chir ; 98(6): 233-238, 2019.
Article in English | MEDLINE | ID: mdl-31331178

ABSTRACT

The development of a low-flow vascular prosthesis is a very topical issue. The authors present a pathway for the development of a prosthesis with optimal properties based on the idea of mimicking the characteristics of a biological model (saphenous vein graft) and programming these properties in the model of the prosthetic substitute. The vascular prosthesis presented consists of three layers - a non-absorbable scaffold representing vascular “media”, and two absorbable collagen layers - pseudointima and pseudoadventitia. The basic methods of physical testing are presented - the single axis stretch test and inflation-extension test, as well as other procedures that affect the final properties. These include collagen curing, antithrombotic treatment of the inner layer and the use of sterilization methods. The designed new graft was successfully implanted in an ovine model.


Subject(s)
Blood Substitutes , Blood Vessel Prosthesis , Vascular Patency , Vascular Surgical Procedures , Animals , Humans , Saphenous Vein , Sheep
13.
Physiol Res ; 68(4): 603-610, 2019 08 29.
Article in English | MEDLINE | ID: mdl-31177797

ABSTRACT

We compared graft outcome between two types of a novel composite three-layer carp-collagen-coated vascular graft in low-flow conditions in a sheep model. Collagen in group A underwent more cycles of purification than in group B in order to increase the ratio between collagen and residual fat. The grafts were implanted end-to-side in both carotid arteries in sheep (14 grafts in 7 sheep in group A, 18 grafts in 9 sheep in group B) and artificially stenosed on the right side. The flow in the grafts in group A decreased from 297±118 ml/min to 158±159 ml/min (p=0.041) after placement of the artificial stenosis in group A, and from 330±164ml/min to 97±29 ml/min (p=0.0052) in group B (p=0.27 between the groups). From the five surviving animals in group A, both grafts occluded in one animal 3 and 14 days after implantation. In group B, from the six surviving animals, only one graft on the left side remained patent (p=0.0017). Histology showed degradation of the intimal layer in the center with endothelization from the periphery in group A and formation of thick fibrous intimal layer in group B. We conclude that the ratio between collagen and lipid content in the novel three-layer graft plays a critical role in its patency and structural changes in vivo.


Subject(s)
Blood Vessel Prosthesis/trends , Carotid Arteries/surgery , Collagen/administration & dosage , Collagen/isolation & purification , Prosthesis Design/trends , Vascular Patency/physiology , Animals , Carotid Arteries/physiology , Carps , Prosthesis Design/methods , Sheep
14.
Leukemia ; 33(5): 1124-1134, 2019 05.
Article in English | MEDLINE | ID: mdl-30635631

ABSTRACT

KIT D816 mutations (KIT D816mut) are strongly associated with systemic mastocytosis (SM) but are also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor in combination with core binding factor (CBF) fusion genes. Here, we evaluated the clinical and molecular features of KIT D816mut/CBF-negative (CBFneg) AML, a previously uncharacterized combination. All KIT D816mut/CBFneg cases (n = 40) had histologically proven SM with associated AML (SM-AML). Molecular analyses revealed at least one additional somatic mutation (median, n = 3) beside KIT D816 (e.g., SRSF2, 38%; ASXL1, 31%; RUNX1, 34%) in 32/32 (100%) patients. Secondary AML evolved in 29/40 (73%) patients from SM ± associated myeloid neoplasm. Longitudinal molecular and cytogenetic analyses revealed the acquisition of new mutations and/or karyotype evolution in 15/16 (94%) patients at the time of SM-AML. Median overall survival (OS) was 5.4 months. A screen of two independent AML databases (AMLdatabases) revealed remarkable similarities between KIT D816mut/CBFneg SM-AML and KIT D816mut/CBFneg AMLdatabases (n = 69) with regard to KIT D816mut variant allele frequency, mutation profile, aberrant karyotype, and OS suggesting underlying SM in a significant proportion of AMLdatabases patients. Bone marrow histology and reclassification as SM-AML has important clinical implications regarding prognosis and potential inclusion of KIT inhibitors in treatment concepts.


Subject(s)
Alleles , Core Binding Factors/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Proto-Oncogene Proteins c-kit/genetics , Adult , Aged , Aged, 80 and over , Biomarkers , Bone Marrow/pathology , Cytogenetic Analysis , Female , Gene Frequency , High-Throughput Nucleotide Sequencing , Humans , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Mastocytosis, Systemic/genetics , Mastocytosis, Systemic/metabolism , Mastocytosis, Systemic/pathology , Middle Aged
15.
Rozhl Chir ; 97(10): 478-481, 2018.
Article in English | MEDLINE | ID: mdl-30590934

ABSTRACT

INTRODUCTION: Pulmonary embolism is a life-threatening condition that causes obstruction of the pulmonary arteries by an embolus, most often originating from the venous system of the lower limbs or pelvic veins. Depending on the extent of the embolism, an acute right-sided heart failure may result, with subsequent death. Paradoxical embolism is a condition in which a venous thrombus is embolized into the systemic circulation arteries by a right-to-left heart shunt. This condition most commonly occurs in the interatrial septum. The aim of treatment for pulmonary embolism is to remove the obstruction of the lung. Depending on the extent of the embolism and the patients hemodynamic status, thrombolytic or surgical treatment can be chosen. Thrombolytic therapy has become the basis of treatment for all types of acute pulmonary embolism. Currently, open surgery is indicated in hemodynamically unstable patients with massive pulmonary embolism, and increasingly frequently in submassive embolism where thrombolytic therapy is not effective or contraindicated. CASE REPORT: The case report describes a less common condition of pulmonary and concurrently systemic embolization in the subclavian artery. Thrombolytic therapy was contraindicated in this case due to the high risk of secondary embolism to the brain. Surgical embolectomy was performed from the pulmonary arteries simultaneously with direct embolectomy from the subclavian and brachiocephalic artery. The surgical management of acute pulmonary embolism is a suitable method of treatment for both massive pulmonary embolism where the procedure is performed as a life-saving indication, and submassive embolism where less invasive treatment would not be effective. CONCLUSION: Direct embolectomy of subclavian and brachiocephalic artery is associated with minimal risk of iatrogenic embolism into the arteries supplying the brain compared to indirect embolectomy performed from the cubital or brachial artery. Key words: embolism paradoxical embolization - embolectomy foramen ovale stroke.


Subject(s)
Embolectomy , Pulmonary Embolism , Thrombosis , Humans , Lower Extremity , Pulmonary Artery , Pulmonary Embolism/diagnosis , Pulmonary Embolism/surgery , Thrombosis/diagnosis , Thrombosis/surgery
16.
Biomicrofluidics ; 12(6): 064101, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30473738

ABSTRACT

This paper presents micro-particle tracking velocimetry measurements over cultured bovine aortic endothelial cell monolayers in microchannels. The objective was to quantify fluid forces and cell morphology at the sub-cellular scale for monolayers subjected to steady shear rates of 5, 10, and 20 dyn/cm2. The ultimate goal of this study was to develop an experimental methodology for in vitro detailed study of physiologically realistic healthy and diseased conditions. Cell topography, shear stress, and pressure distributions were calculated from sets of velocity fields made in planes parallel to the microchannel wall. For each experiment, measurements were made in 3 h intervals for 18 h. It was found that there is a three-dimensional change in cell morphology as a result of applied shear stress. That is, cells flatten and become more wedge shaped in the stream direction while conserving volume by spreading laterally, i.e., in the cross-stream direction. These changes in cell morphology are directly related to local variations in fluid loading, i.e., shear stress and pressure. This paper describes the first flow measurements over a confluent layer of endothelial cells that are spatially resolved at the sub-cellular scale with a simultaneous temporal resolution to quantify the response of cells to fluid loading.

17.
Physiol Res ; 67(6): 857-862, 2018 12 18.
Article in English | MEDLINE | ID: mdl-30204459

ABSTRACT

The geometry of the distal anastomosis of a femoropopliteal bypass influences local hemodynamics and formation of intimal hyperplasia. We hypothesized that the distal anastomosis of an above-knee femoropopliteal bypass undergoes remodeling that results in displacement of the original course of the popliteal artery and change in the anastomosis angle. We identified 43 CT angiography examination with proximal femoropopliteal bypass and either a preserved contralateral popliteal artery or previous CTA before construction of the bypass for comparison. In these examinations, we measured the displacement distance and angle at the level of the distal anastomosis and compared these measurements with clinical and imaging data. The displacement distance was 8.8+/-4.9 mm (P<0.0001) and the displacement angle was -1° (IQR=44°). The angle between the inflow and outflow artery was 153+/-16° (P<0.0001). There was a negative association between the displacement angle and the angle between the bypass and the outflow artery (r=-0.318, P=0.037). Patients with reversed venous grafts had a greater displacement of the anastomosis (14.7+/-3.0 mm) than patients with prosthetic grafts (8.0+/-4.5 mm, P=0.0011). We conclude that construction of a distal anastomosis of proximal femoropopliteal bypass results in displacement of the original course of the popliteal artery towards the bypass and this effect is more pronounced in reversed venous grafts.


Subject(s)
Computed Tomography Angiography/trends , Femoral Artery/diagnostic imaging , Lower Extremity/diagnostic imaging , Plastic Surgery Procedures/trends , Popliteal Artery/diagnostic imaging , Vascular Remodeling , Aged , Anastomosis, Surgical/trends , Female , Femoral Artery/physiology , Femoral Artery/surgery , Humans , Lower Extremity/blood supply , Lower Extremity/surgery , Male , Middle Aged , Popliteal Artery/physiology , Popliteal Artery/surgery , Retrospective Studies , Vascular Remodeling/physiology , Vascular Surgical Procedures/trends
18.
Mucosal Immunol ; 11(1): 290, 2018 01.
Article in English | MEDLINE | ID: mdl-28853440

ABSTRACT

This corrects the article DOI: 10.1038/mi.2017.46.

19.
Mucosal Immunol ; 11(1): 249-256, 2018 01.
Article in English | MEDLINE | ID: mdl-28537249

ABSTRACT

Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8+ Trm cells (CD103+/CD69+) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased interferon-γ in the airways of recipient mice, while CD4 transfer reduced tumor necrosis factor-α in the airways. Because DNA vaccines induce a systemic T-cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV-specific CD8 T cells, but they were immunopathogenic and not protective. Notably, there was a marked difference in the induction of Trm cells; infection but not immunization induced antigen-specific Trm cells in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen-specific airway cells.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Lung/immunology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/physiology , Respiratory System/immunology , Viral Vaccines/immunology , Adoptive Transfer , Animals , Cells, Cultured , Female , Humans , Immunologic Memory , Interferon-gamma/metabolism , Lung/virology , Mice , Mice, Inbred BALB C , Respiratory System/virology , Tumor Necrosis Factor-alpha/metabolism , Vaccination , Vaccines, DNA , Viral Load
20.
Rozhl Chir ; 97(11): 509-513, 2018.
Article in English | MEDLINE | ID: mdl-30646741

ABSTRACT

INTRODUCTION: Pedal bypass is a therapeutic option for limb salvage in critical limb ischemia. METHOD: Retrospective analysis of 20 patients who underwent either simple (14 patients) or branched (6 patients) pedal bypass in a single center and had at least one postoperative follow-up. In patients with branched pedal bypass, the main trunk was connected to the pedal artery of better quality and the side branch to an artery on the opposite side of the foot. The main trunk was constructed as a reverse saphenous bypass in all patients with branched bypass. From patients with simple bypass, nine had reverse saphenous graft, three had an allograft, one patient had in situ saphenous graft, and one PTFE prosthesis. RESULTS: The difference in the operation time was not significant. One patient with simple bypass required reoperation for wound bleeding and there was one case of perioperative mortality in the same group. The difference between the groups in the primary or secondary patency rates, limb salvage and overall survival was not significant. CONCLUSIONS: We did not find any significant difference in patency rates, limb salvage, or perioperative complications between patients with simple and branched pedal bypass in our cohort. We believe that the anticipated benefits of constructing an additional branch are masked by the disadvantageous presence of an additional anastomosis. Adoption of a branched pedal bypass may therefore require further improvements - perhaps the utilization of a branched saphenous graft. Key words:  critical limb ischemia - peripheral arterial disease - bypass - revascularization - amputation.


Subject(s)
Ischemia , Limb Salvage , Humans , Ischemia/surgery , Reoperation , Retrospective Studies , Saphenous Vein , Treatment Outcome , Vascular Patency
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