48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis

PubMed Central

Zantour, Baha; Sfar, Mohamed Habib; Younes, Samia; Alaya, Wafa; Kamoun, Mahdi; Mkaouar, Emna; Jerbi, Saida

2010-01-01

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family. PMID:20827436

Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow aplasia mouse model: A study to explore the novel mechanism of pesticide toxicity.

PubMed

Chattopadhyay, Sukalpa; Chatterjee, Ritam; Law, Sujata

2016-10-01

According to case-control studies, long-term pesticide exposure can cause bone marrow aplasia like hematopoietic degenerative disease leading to impaired hematopoiesis and increased risk of aplastic anemia in human subjects. However, the exact mechanism of pesticide mediated hematotoxicity still remains elusive. In this study, we investigated the role of noncanonical Wnt signaling pathway, a crucial regulator of adult hematopoiesis, in pesticide induced bone marrow aplasia mouse model. Aplasia mouse model was developed following inhalation and dermal exposure of 5% aqueous mixture of common agriculturally used pesticides for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis and flowcytometric expression analysis of noncanonical Wnt signaling components, such as Wnt 5a, fzd5, NFAT, IFN-γ, intracellular Ca(2+) level were evaluated in the bone marrow hematopoietic stem/progenitor compartment of the control and pesticide induced aplasia groups of animals. Results showed that pesticide exposed mice were anemic with peripheral blood pancytopenia, hypocellular degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon pesticide exposure, Wnt 5a expression was severely downregulated with a decline in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp downregulation of NFATc2 transcription factor expression, the major target of pesticide toxicity and its target molecule IFN-γ. Taken together, our result suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the hematopoietic stem/progenitor compartment plays a crucial role behind the pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive hematopoietic stem cells' ability to maintain hematopoietic homeostasis and reconstitution mechanism in vivo during xenobiotic stress leading to ineffective hematopoiesis and evolution of bone marrow aplasia. �

Uterovaginal Anastomosis for Cases of Cryptomenorrhea Due to Cervical Atresia with Vaginal Aplasia: Benefits and Risks.

PubMed

Zayed, M; Fouad, R; Elsetohy, K A; Hashem, A T; AbdAllah, A A; Fathi, A I

2017-12-01

The objective of this study was to assess short-term benefits and risks of utero-vaginal anastomosis done for cases of cryptomenorrhea due to cervical atresia with vaginal aplasia. Prospective study. Surgical procedures were done between December 2013 and September 2015 at the department of Obstetrics and Gynecology, Cairo University Hospital. Five patients who had cryptomenorrhea due to cervical atresia associated with vaginal aplasia were included. Utero-vaginal anastomoses were performed in 2 stages; a stage of McIndoe vaginoplasty and a stage of excision of the atretic cervical tissue and anastomosing the uterus to the neovagina. Follow-up was done by gynecological and ultrasound examination in a duration ranged from 12 to 36 months. Occurrence of regular menstrual flow and relief of the severe cyclic pain. All patients had relief of the severe cyclic pain. Four patients had regular menstrual flow. One patient developed occlusion of the track after 1 year and needed dilatation once. Three patients developed low vaginal stenosis without occlusion of the track. One patient had rectal injury repaired without causing postoperative morbidity. Uterovaginal anastomosis is a promising conservative management option for cervical atresia with vaginal aplasia, which has benefits but is not free of risks. Long-term follow-up is still needed to judge its feasibility. We recommend performing McIndoe vaginoplasty as a starting stage before the anastomosis preferably in a separate setting. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Pure Red Cell Aplasia due to B19 Parvovirus Infection after Autologous Stem Cell Transplantation

PubMed Central

Tsirigotis, Panagiotis; Girkas, Konstantinos; Economopoulou, Christina; Bouchla, Anthoula; Papanicolaou, Nikolaos; Economopoulou, Panagiota; Papageorgiou, Sotirios; Pappa, Vassiliki; Dervenoulas, John

2011-01-01

Parvovirus B19 is recognized as a rare cause of pure red cell aplasia (PRCA) in allogeneic stem cell (SCT) and solid organ transplant patients. We report a patient with Hodgkin's disease who developed PRCA due to parvovirus B19 after autologous SCT and who had an excellent response after treatment with gamma-globulin. PMID:23198254

[Aplasia cutis congenita associated with epidermolysis bullosa].

PubMed

Muñoz-Guerrero, Félix; Muñoz-Solís, Adrián Antonio; Ornelas-Aguirre, José Manuel

2017-12-01

Aplasia cutis congenita (ACC) is a skin condition of rare presentation, this disease is characterized by absence of skin at birth and associated with facial, skin and bone skull deformities. The diagnosis is mainly clinical. Male 5 days after birth, unique product of primigravida mother and no family history of relevance. Physical examination revealed bilateral and symmetrical skin defects of both lower extremities, the disease is characterized by skin fragility, scabs, and coated pseudomembrane ulcers, decreased interdigital space between toes of the left foot, retraction of the foot and genu varum. It was handled with allograft of epidermis cultured in vitro, general wound care and clinical follow-up. ACC associated with epidermolysis bullosa is one of the rarer forms of presentation. It is necessary to rule out other skin diseases. Clinical management is recommended with biological or synthetic skin cover, infection prevention, early treatment of complications and clinical follow. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Like Father, Like Daughter-inherited cutis aplasia occurring in a family with Marfan syndrome: a case report.

PubMed

Islam, Yasmin Florence Khodeja; Williams, Charles A; Schoch, Jennifer Jane; Andrews, Israel David

2017-01-01

We present the case of a newborn with co-occurrence of Marfan syndrome and aplasia cutis congenita (ACC) and a family history significant for Marfan syndrome and ACC in the father. This case details a previously unreported mutation in Marfan syndrome and describes a novel coinheritance of Marfan syndrome and ACC.

Amelioration de l'efficacite energetique du procede d'electrolyse de l'aluminium conception d'un nouveau bloc cathodique

NASA Astrophysics Data System (ADS)

Blais, Mathieu

Au Quebec, les alumineries sont de grandes consommatrices d'energie electrique, soit pres de 14 % de la puissance installee d'Hydro-Quebec. Dans ce contexte, des petits gains en efficacite energetique des cuves d'electrolyse pourraient avoir un impact important sur la reduction globale de la consommation d'electricite. Le projet de maitrise decrit dans cette etude repond a la problematique suivante : comment l'optimisation de la geometrie d'un bloc cathodique en vue d'uniformiser la densite de courant peut augmenter l'efficacite energetique et la duree de vie de la cuve d'aluminium? Le but premier du projet est de modifier la geometrie en vue d'ameliorer le comportement thermoelectrique des blocs cathodiques et d'accroitre par le fait meme l'efficacite energetique du procede de production d'aluminium. La mauvaise distribution de la densite de courant dans la cuve est responsable de certains problemes energetiques ayant des impacts negatifs sur l'economie et l'environnement. Cette non-uniformite de la distribution du courant induit une usure prematuree de la surface de la cathode et contribue a reduire la stabilite magnetohydrodynamique de la nappe de metal liquide. Afin de quantifier les impacts que peut avoir l'uniformisation de la densite de courant a travers le bloc cathodique, un modele d'un bloc cathodique d'une cuve de la technologie AP-30 a ete concu et analyse par elements finis. A partir de son comportement thermoelectrique et de donnees experimentales d'une cuve AP-30 tirees de la litterature, une correlation entre le profil de densite de courant a la surface du bloc et le taux d'erosion local au meme endroit a ete creee. Cette relation correspond au modele predictif de la duree de vie de tout bloc du meme materiau a partir de son profil de densite de courant. Ensuite, une programmation a ete faite incorporant dans une meme fonction cout les impacts economiques de la duree de vie, de la chute de voltage cathodique et de l'utilisation de nouveaux materiaux

Studies on Red Cell Aplasia. V. PRESENCE OF ERYTHROBLAST CYTOTOXICITY IN γG-GLOBULIN FRACTION OF PLASMA

PubMed Central

Krantz, Sanford B.; Moore, W. H.; Zaentz, S. Donald

1973-01-01

The marrow cells of a patient with pure red cell aplasia markedly increased their rate of heme synthesis when they were freed from the host environment and were incubated in vitro. When the red cell aplasia was treated with cyclophosphamide and prednisone, marrow cell incorporation of 59Fe into heme in vitro increased several weeks before a reticulocytosis was apparent, and was the earliest effect noted. The plasma γG-globulins of this patient inhibited heme synthesis by normal marrow cells or the patient's own marrow cells obtained after remission of the disease. Since the inhibition of heme synthesis could be the result of damage to erythroblasts, the patient's posttreatment marrow cells or normal marrow cells were labeled with 59Fe and were then incubated with the patient's pretreatment, treatment, and posttreatment γG-globulins as well as normal γG-globulins. At the end of this incubation the supernatant and cells were separated and counted. Heme was extracted and also was counted. Treatment of the cells with the patient's pretreatment γG-globulins resulted in a release of 40% of the radioactive heme from the cells. This represented the loss of radioactive hemoglobin and was an index of erythroblast cytotoxicity. A progressive disappearance of the cytotoxic factor in the γG-globulins occurred in the 3 wk period preceding the onset of reticulocytes in the patient's blood. Posttreatment and normal γG-globulins did not produce this effect and increased injury of red cells and lymphocytes was not produced by the patient's pretreatment γG-globulins. These studies demonstrate a method for measuring erythroblast cytoxicity and show that red cell aplasia is associated with γG-globulins that specifically damage erythroblasts. Whether interference with new erythroblast development also occurs and contributes to the inhibition of heme synthesis has not yet been ascertained. Images PMID:4119161

From labyrinthine aplasia to otocyst deformity.

PubMed

Giesemann, Anja Maria; Goetz, Friedrich; Neuburger, Jürgen; Lenarz, Thomas; Lanfermann, Heinrich

2010-02-01

Inner ear malformations (IEMs) are rare and it is unusual to encounter the rarest of them, namely labyrinthine aplasia (LA) and otocyst deformity. They do, however, provide useful pointers as to the early embryonic development of the ear. LA is characterised as a complete absence of inner ear structures. While some common findings do emerge, a clear definition of the otocyst deformity does not exist. It is often confused with the common cavity first described by Edward Cock. Our purpose was to radiologically characterise LA and otocyst deformity. Retrospective analysis of CT and MRI data from four patients with LA or otocyst deformity. Middle and inner ear findings were categorised by two neuroradiologists. The bony carotid canal was found to be absent in all patients. Posterior located cystic structures were found in association with LA and otocyst deformity. In the most severe cases, only soft tissue was present at the medial border of the middle ear cavity. The individuals with otocyst deformity also had hypoplasia of the petrous apex bone. These cases demonstrate gradual changes in the two most severe IEMs. Clarification of terms was necessary and, based on these findings, we propose defining otocyst deformity as a cystic structure in place of the inner ear, with the cochlea, IAC and carotid canal absent. This condition needs to be differentiated from the common cavity described by Edward Cook. A clear definition of inner ear malformations is essential if outcomes following cochlear implantation are to be compared.

Immune-mediated pure red cell aplasia in a domestic ferret.

PubMed

Malka, Shachar; Hawkins, Michelle G; Zabolotzky, Shanon M; Mitchell, Elizabeth B; Owens, Sean D

2010-09-15

An 8-month-old spayed female domestic ferret (Mustela putorius furo) was referred for examination to determine the cause of lethargy and severe anemia. Initial examination revealed that the ferret was lethargic but with appropriate mentation. The only other abnormal findings were severe pallor of the mucous membranes, nasal planum, and skin and a PCV of 8%. Pure red cell aplasia (PRCA) was diagnosed on the basis of cytologic evaluation of a bone marrow biopsy specimen. Medical treatment included blood transfusions, IM administration of iron dextran, oral administration of antimicrobials and gastrointestinal tract protectants, and SC administration of erythropoietin. Once PRCA was diagnosed, the ferret was orally administered prednisone, cyclosporine, and azathioprine. Nine months after onset of treatment, the PRCA was in remission and the ferret was doing well. Immunosuppressive treatment was discontinued at 14 months after onset of treatment, and 36 months after initial examination, the ferret appeared to be healthy. It is important that PRCA be considered as a differential diagnosis for a ferret with severe anemia. Prolonged immunosuppressive treatment was successful in the ferret described here.

A Rare Case of Apical Root Resorption during Orthodontic Treatment of Patient with Multiple Aplasia.

PubMed

Agrawal, Chintan M; Mahida, Khyati; Agrawal, Charu C; Bothra, Jitendrakumar; Mashru, Ketan

2015-07-01

External apical root resorption is an adverse effect of orthodontic treatment. It reduces the length of root and breaks the integrity of teeth and dental arch. Orthodontics is the only dental specialty that clinically uses the inflammatory process to correct the mal-aligned teeth. Hence, it is necessary to know the risk factors of root resorption and do everything to reduce the rate of root resorption. Hence, all predisposing factors which are systemic as well as local should be considered before treatment begins. This case report describes the incidence of root resorption following orthodontic treatment and the teeth affected in the patient with multiple aplasia.

Thyroid aplasia in male sibling of heterozygotic twins born to the hyperthyroid mother treated with propylthiouracil during pregnancy (case report).

PubMed

Almarzouki, A A

2012-01-01

A 30-year-old pregnant female was diagnosed to have thyrotoxicosis (TSH= 0.005 µU/ml) at 13th week of gestation. Propylthiouracil (PTU; 200 mg daily) was prescribed to her and four weekly follow ups by the endocrinologist and obstetrician were ensured. At each examination TSH, FT4 and FT3 levels were normal and she became symptom free. Repeated ultrasound examination throughout the pregnancy did not reveal any fetal abnormality. The lady normally delivered heterozygotic twins. Umbilical cord blood of the baby boy twin showed a high TSH (541 µU/ml; reference range 0.270 - 4.20 μU/ml). He was started on thyroxine therapy (50 µg once daily). Ultrasound reported the absence of the thyroid gland. One month later TSH was within normal range and thyroxine dose was adjusted to 25 µg once daily. Repeated ultrasound confirmed the absence of thyroid gland. TSH was repeatedly normal. The boy is currently doing well on thyroxine replacement therapy. The other non-identical twin was a healthy girl with normal thyroid function tests and always thereafter. This case report suggested that PTU could be a hazardous drug to the fetus, since the mother gave birth to a baby with thyroid aplasia. PTU, Thyroid aplasia, Thyrotoxicosis, TSH.

Pulmonary anatomy and a case of unilateral aplasia in a common snapping turtle (Chelydra serpentina): developmental perspectives on cryptodiran lungs.

PubMed

Schachner, E R; Sedlmayr, J C; Schott, R; Lyson, T R; Sanders, R K; Lambertz, M

2017-12-01

The common snapping turtle (Chelydra serpentina) is a well studied and broadly distributed member of Testudines; however, very little is known concerning developmental anomalies and soft tissue pathologies of turtles and other reptiles. Here, we present an unusual case of unilateral pulmonary aplasia, asymmetrical carapacial kyphosis, and mild scoliosis in a live adult C. serpentina. The detailed three-dimensional (3D) anatomy of the respiratory system in both the pathological and normal adult C. serpentina, and a hatchling are visualized using computed tomography (CT), microCT, and 3D digital anatomical models. In the pathological turtle, the right lung consists of an extrapulmonary bronchus that terminates in a blind stump with no lung present. The left lung is hyperinflated relative to the normal adult, occupying the extra coelomic space facilitated by the unusual mid-carapacial kyphotic bulge. The bronchial tree of the left lung retains the overall bauplan of the normal specimens, with some minor downstream variation in the number of secondary airways. The primary difference between the internal pulmonary structure of the pathological individual and that of a normal adult is a marked increase in the surface area and density of the parenchymal tissue originating from the secondary airways, a 14.3% increase in the surface area to volume ratio. Despite this, the aplasia has not had an impact upon the ability of the turtle to survive; however, it did interfere with aquatic locomotion and buoyancy control under water. This turtle represents a striking example of a non-fatal congenital defect and compensatory visceral hypertrophy. © 2017 Anatomical Society.

[Thrombopenia and radial aplasia: 2 cases with platelet function and ultrastructural studies of megakaryocytes and platelets (author's transl)].

PubMed

Juhan, I; Bayle, J; Mattei, J F; Thevenieau, D; Perrimond, H; Muratore, R

1979-10-01

The authors report on two cases of congenital thrombopenia with radial aplasia. Both children display several formative abnormalities and a mild thrombopenia; hemorragic manifestations occurred in the first case only. Megacryoblastic to platelets series, as studied with electronic microscopy, show small-sized, "microcytic" and hypogranular megacaryocytes, displaying a maturative disorder (dysmegacaryocytopoiesis). In functional studies, platelets of the first patient show an imperfect nucleotidic release and do not agregate normally with ristocetin. The second case exhibits mostly a PF3 reduction. The variety of expression of the megacaryocytic-platelets disorders appears likewise in the squelettal and visceral malformations. The whole disorder could be ascribed to a pleiotropic abnormal gene with a variable expressivity.

[Clinical examination of children with tooth aplasia. Correlations between dental symptoms and the whole organism].

PubMed

Knolmayer, Judit; Bognár, Veronika; Szabó, Gyula

2008-10-01

The characteristic abnormalities of jaws, teeth, and salivation can be measured and expressed by numbers. The possible etiological factors, like the positive family history of noxas during the pregnancy can be explored. In our study we examined the symptoms of general organic system and teeth trait--jaw relation, seriousness of aplasia, abnormalities of teeth in size--defect of salivary glands and the presence of possible etiological factors. Thirty children were examined. The symptoms of general organic system were diagnosed. 60% of tooth agenesis occurs in the maxilla, the size of teeth reduced also in the upper jaw. Pseudoprogenia can be explained by these facts. The size reduction of extant teeth appeared stronger in the labiolingual direction. The salivary secretion rate in examined children proved significantly lower than in the control group. Seven siblings and eight parents were identified by examining the etiological factors. We did not find any noxas during the pregnancy by our questionnaire method.

Spontaneous hematologic recovery from bone marrow aplasia after accidental tenfold overdosage with radiophosphorus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gmuer, J.; Bischof, B.; Coninx, S.

1983-04-01

Two patients with polycythemia vera received intravenously an accidental tenfold overdosage of radiophosphorus therapy (60 and 50 mCi 32P, respectively). In both patients, the occurrence of hemorrhagic complications 3 wk after the 32P medication led to detection of the error and referral to our hospital. Upon admission they showed an agranulocytosis, severe thrombocytopenia, and bone marrow aplasia. In both cases, spontaneous recovery of the hematopoiesis was observed from day 40 posttreatment onward. In one patient, a slow but ultimately complete normalization of blood counts and marrow morphology took place, whereas in the other, a mild thrombocytopenia persists. Nearly 5 yrmore » after the accidental overdosage, both patients are clinically well. Symptoms of polycythemia vera have not reappeared up to now. Attempts were made to evaluate the radiation dose absorbed by the bone marrow. In the first patient, the daily 32P excretion was determined from day 22 to day 60, whereas in the other patient a whole body count was performed on day 78 after administration. From these results, an approximate cumulative bone marrow dose of 10 Sv (1000 rem) could be calculated.« less

Comparison of small intestinal submucosa graft with split-thickness skin graft for cervicovaginal reconstruction of congenital vaginal and cervical aplasia.

PubMed

Shen, Fang; Zhang, Xu-Yin; Yin, Chu-Yang; Ding, Jing-Xin; Hua, Ke-Qin

2016-11-01

What is the difference in vaginal-length gain and resumption of menstruation following cervicovaginal reconstruction using split-thickness skin (STS) graft versus small intestinal submucosa (SIS) graft for patients with congenital vaginal and cervical aplasia? No difference was found in the number of patients who resumed menstruation between the two groups; however, significantly greater vaginal-length gain was found in the STS group. Hysterectomy and vaginoplasty are typically recommended for patients without a cervix or without a sufficient cervix to avoid postoperative re-obstruction. Advances in surgical techniques have enabled the use of autologous tissues or heterologous biological grafts for reconstructive procedures, allowing patients undergoing these procedures to preserve the possibility of conception. This was a retrospective study of 26 women who were diagnosed with congenital vaginal and cervical aplasia with a functional endometrial cavity and underwent cervicovaginal reconstruction using STS or SIS grafts between January 2012 and October 2015 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. 15 women underwent cervicovaginal reconstruction using SIS graft and 11 underwent cervicovaginal reconstruction using STS graft. Clinical characteristics, perioperative data, resumption of menstruation, vaginal stenosis, length of the neovagina, vaginal-length gain, stricture of the cervix and body image were postoperatively assessed. At a median follow-up of 21 (2-46) months, all but one of the patients experienced relief of abdominal pain and resumed menstruation. Re-obstruction of the cervix occurred in only one patient in the SIS group. The SIS group reported significantly higher body image scores and cosmetic satisfaction. Although the two groups had a similar vaginal length before surgery, the vaginal-length gain was significantly greater in the STS group (4.9 ± 1.7 cm in the SIS group versus 7.5 ± 0.7 cm in the STS group

Efficacité de la gestion de vaccins et qualité de vaccination à l'antenne PEV Kisangani en République Démocratique du Congo

PubMed Central

Labama, Matthieu Betofe; Longembe, Eugène Basandja; Likwela, Joris Losimba

2017-01-01

Introduction La qualité des vaccins conditionne les résultats attendus de la vaccination. Elle est tributaire de l'efficacité de système de gestion technique et logistique mis en place. Cette étude est menée pour évaluer l'efficacité de la gestion des vaccins et d'en tirer des leçons. Méthodes Une étude rétrospective est menée pendant la période de 2010 à 2014 sur la gestion logistique de vaccins au niveau de l'antenne PEV Kisangani. La revue documentaire complétée par les entretiens semi-dirigés des gestionnaires et prestataires de services de vaccination ont permis d'évaluer la gestion de vaccins en se servant des modèle GEV de l'OMS, en vue de dégager les écarts. Résultats Il est observé une faible connaissance des prestataires sur les vaccins qui ne peuvent pas être congelés, sur les tests de congélation et d'autres dommages de vaccins. La gestion informatisée des données au niveau de l'antenne est correctement assurée. Aucun critère évalué n'a atteint l'objectif de 80%. Le respect de la température de stockage est de 70% au niveau de l'antenne ; le critère relatif à la gestion de vaccins est respectivement de 65% et 67% au niveau du BCZ et CS. Le critère relatif à la maintenance est nul à tous les niveaux. Conclusion Le dysfonctionnement de système logistique est remarquable à tous les niveaux de la pyramide sanitaire, ceci pourrait interférer avec la qualité et l'impact attendu de la vaccination. Une attention particulière doit être accordée à la maintenance des équipements. PMID:28748006

Ectrodactyly with aplasia of long bones (OMIM; 119100) in a large inbred Arab family with an apparent autosomal dominant inheritance and reduced penetrance: clinical and genetic analysis.

PubMed

Naveed, Mohammed; Al-Ali, Mahmoud T; Murthy, Sabita K; Al-Hajali, Sarah; Al-Khaja, Najib; Deutsch, Samuel; Bottani, Armand; Antonarakis, Stylianos E; Nath, Swapan K; Radhakrishna, Uppala

2006-07-01

Ectrodactyly with aplasia of long bones syndrome is one of the most recognizable defects involving the extremities. We have studied a very large eight-generation consanguineous Arab family from the United Arab Emirates (UAE) with multiple severe limb anomalies resembling this condition (OMIM; 119100), for which the affected gene is unknown. The pedigree consists of 145 individuals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had tibial aplasia (TA) usually on the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral TA with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant with reduced penetrance. There were 10 consanguineous marriages observed in this pedigree. This could suggest possible pseudodominance due to high frequency of the mutant allele. Candidate loci for the described syndrome include GLI3 (OMIM: 165240) on 7p13, sonic hedgehog; (OMIM: 600725) on 7q36, Langer-Giedion syndrome (OMIM: 150230) on 8q24.1 and split-hand/foot malformation 3 (OMIM: 600095) on 10q24. In addition, bilateral tibial hemimelia and unilateral absence of the ulna was previously observed to co-segregate with deletion of 8q24.1. Two-point linkage and haplotype analyses did not show the involvement of the above regions in this family. (c) 2006 Wiley-Liss, Inc.

Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): distinctive features and prenatal detection.

PubMed

Olney, R S; Hoyme, H E; Roche, F; Ferguson, K; Hintz, S; Madan, A

2001-11-01

Schinzel phocomelia syndrome is characterized by limb/pelvis hypoplasia/aplasia: specifically, intercalary limb deficiencies and absent or hypoplastic pelvic bones. The phenotype is similar to that described in a related multiple malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome. The additional important feature of large parietooccipital skull defects without meningocele, encephalocele, or other brain malformation has thus far been reported only in children with Schinzel phocomelia syndrome. We recently evaluated a boy affected with Schinzel phocomelia born to nonconsanguineous healthy parents of Mexican origin. A third-trimester fetal ultrasound scan showed severe limb deficiencies and an absent pelvis. The infant died shortly after birth. Dysmorphology examination, radiographs, and autopsy revealed quadrilateral intercalary limb deficiencies with preaxial toe polydactyly; an absent pelvis and a 7 x 3-cm skull defect; and extraskeletal anomalies including microtia, telecanthus, micropenis with cryptorchidism, renal cysts, stenosis of the colon, and a cleft alveolar ridge. A normal 46,XY karyotype was demonstrated, and autosomal recessive inheritance was presumed on the basis of previously reported families. This case report emphasizes the importance of recognizing severe pelvic and skull deficiencies (either post- or prenatally) in differentiating infants with Schinzel phocomelia from other multiple malformation syndromes that feature intercalary limb defects, including thalidomide embryopathy and Roberts-SC phocomelia. Copyright 2001 Wiley-Liss, Inc.

Use of Nandrolone Decanoate in Treatment of Pure Red Cell Aplasia Secondary to Diclofenac Administration: A Case Report.

PubMed

de Marchi, Paula Nassar; Sueur Vieira, André Nanny Le; Antunes Ribeiro, José Francisco; Geraldes, Silvano Salgueiro; Rodrigues Ramos, Paulo Roberto; Melchert, Alessandra; Guimarães-Okamoto, Priscylla Tatiana Chalfun

2017-03-01

Pure red cell aplasia (PRCA) is a disorder that leads to a nonregenerative anemia that results from erythroid precursors failing to reach maturity in the bone marrow, whereas the numbers of mature myeloid and megakaryocytic cells remain normal. PRCA can be induced by autoimmune processes, infections, drugs, toxins, and radiation, and is diagnosed by a bone marrow cytology examination after excluding the most common causes of nonregenerative anemia. Immunosuppressive therapies are used to treat PRCA, and usually involve the use of glucocorticoids, cyclosporin, or azathioprine. Alternatively, although little studied in veterinary medicine, drugs which stimulate bone marrow (e.g., nandrolone decanoate) have been mentioned as possible therapeutic agents. A case of PRCA that presented at the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine and Animal Science (UNESP)-Botucatu, Brazil showed a good therapeutic response to weekly administration of nandrolone decanoate. Therefore, it was concluded that bone marrow stimulants might improve the quality of life of PRCA patients, provided they are used with caution and under close clinical supervision. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk of pure red cell aplasia in patients with hepatitis C receiving antiviral therapy and an erythropoiesis-stimulating agent.

PubMed

Rossert, Jerome; Yue, Susan; Smirnakis, Karen; Mytych, Daniel T; Johnson, Larry; Kouchakji, Elias; Casadevall, Nicole

2014-02-01

Antibody-mediated pure red cell aplasia (PRCA) has been primarily observed in patients with chronic kidney disease treated with an erythropoiesis-stimulating agent (ESA); only a few anecdotal cases have been reported in other patient populations. We searched the Amgen Global Safety Adverse Event Database and identified 14 patients with hepatitis C who developed severe anemia, anti-erythropoietin antibodies, and bone marrow biopsy-proven PRCA, while receiving interferon therapy (with or without ribavirin) and an ESA. During the follow-up period and after ESA treatment stopped, 11 patients no longer required transfusions and 3 did. Analysis of antibody isotypes showed that, contrary to reports of patients with chronic kidney disease, immunoglobulin G1 was the predominant isotype rather than immunoglobulin G4 (immunoglobulin G4 was detected in only 1 of 6 patients). Epitope mapping showed the anti-erythropoietin antibodies bound domains required for receptor binding. Therefore, the potential benefits of ESA therapy must be weighed against the risk for PRCA in patients with hepatitis C who are receiving treatment with interferon and ribavirin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

[The course of pregnancy in congenital thyroid gland aplasia. Case report with special reference to maternal hypothyroidism].

PubMed

Bolz, M; Nagel, H

1994-01-01

A report is given on a 28 years old women with congenital aplasia of the thyroid gland. She was substituted with thyroxine (300 micrograms per day). Her first pregnancy was complicated by gestational hypertension and pre-eclampsia. Delivery was by forceps. During the first trimester of her second pregnancy, bleedings occurred. The thyroid-stimulating hormone level (TSH-level) was increased (18.3 microU/ml). The patient did not show clinical signs of manifested hypothyroidism. The thyroxine dosis was increased. Bleedings disappeared. Labour was terminated and induced. Labour intra partum was hypoactive. The delivery was again by forceps. The newborn did not show any signals of hypothyroidism. Dysfunction of thyroid gland is associated with reduced fertility. Hypothyroidism in pregnancy is associated with an adverse outcome in fetal health as well as an increase in obstetric complications. Thyroid hormones play a vital role in fetal development and maturation of brain. Women with a hypothyroidism have a lower rate of pregnancy and a higher rate of spontaneous miscarriages compared to a normal population. Recognition and treatment of thyroid disorders in reproductive age occur before conception. Iodoprophylaxis is necessary for prevention of congenital hypothyroidism (cretinism). Iodoprophylaxis is necessary to prevent endemic goiter in pregnancy. Euthyroid goiter is an indication for a combined treatment with jodid and levothyroxine. Treatment should be individualized. Assessment of efficacy of treatment is based on measurement of TSH- and free thyroid hormone (fT4)-levels.

Severe palmar-plantar erythrodysesthesia and aplasia in an adult undergoing re-induction treatment with high-dose cytarabine for acute myelogenous leukemia: a possible drug interaction between posaconazole and cytarabine.

PubMed

Alzghari, Saeed K; Seago, Susan E; Cable, Christian T; Herrington, Jon D

2017-09-01

High-dose cytarabine is recommended for re-induction chemotherapy in patients less than 60 years of age with acute myelogenous leukemia. This case describes a patient receiving high-dose cytarabine for re-induction and subsequently developed tingling and numbness in her hands and feet followed by severe pain, swelling, and erythema consistent with a diagnosis of palmar-plantar erythrodysesthesia. Furthermore, the patient's hemoglobin, platelets, and neutrophils did not recover after over 30 days post high-dose cytarabine. The patient was concurrently receiving posaconazole for fungal prophylaxis which was initiated after the induction therapy. We speculate that posaconazole may inhibit the cytarabine efflux through P-glycoprotein inhibition leading to the patient's palmar-plantar erythrodysesthesia and subsequent aplasia. Future pharmacokinetic studies need to be conducted to ascertain if posaconazole does influence the pharmacokinetics of cytarabine.

The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes.

PubMed

Boven, Katia; Stryker, Scott; Knight, John; Thomas, Adrian; van Regenmortel, Marc; Kemeny, David M; Power, David; Rossert, Jerome; Casadevall, Nicole

2005-06-01

The incidence of pure red cell aplasia (PRCA) in chronic kidney disease patients treated with epoetins increased substantially in 1998, was shown to be antibody mediated, and was associated predominantly with subcutaneous administration of Eprex. A technical investigation identified organic compounds leached from uncoated rubber stoppers in prefilled syringes containing polysorbate 80 as the most probable cause of the increased immunogenicity. This study investigated whether the incidence of PRCA was higher for exposure to the product form containing leachates than for leachate-free product forms. Antibody-mediated PRCA cases were classified according to indication, product form, and route of administration. Exposure estimates were obtained by country, indication, route of administration, and product form. For 2001 to 2003, the PRCA incidence rate for patients with subcutaneous exposure to Eprex in prefilled syringes with polysorbate 80 and uncoated rubber stoppers (leachates present) was 4.61/10,000 patient years (95% CI 3.88-5.43) versus 0.26/10,000 patient years (95% CI 0.007-1.44) for syringes with coated stoppers (leachates absent). The rate difference was 4.35/10,000 patient years (95% CI 3.44-5.26; P < 0.0001); the rate ratio was 17 (95% CI 3.14-707). A substantial rate difference remained in sensitivity analyses that adjusted for exposure to multiple product forms. The epidemiologic data, together with the chemical and immunologic data, support the hypothesis that leachates from uncoated rubber syringe stoppers caused the increased incidence of PRCA associated with Eprex. Currently, all Eprex prefilled syringes contain fluoro-resin coated stoppers, which has contributed to decreased incidence of PRCA with continued surveillance.

Cardiovascular Morbidity and Pure Red Cell Aplasia Associated With Epoetin Theta Therapy in Patients With Chronic Kidney Disease: A Prospective, Noninterventional, Multicenter Cohort Study.

PubMed

Lammerich, Andreas; Balcke, Peter; Bias, Peter; Mangold, Simone; Wiesholzer, Martin

2016-02-01

The European Medicines Agency recommends limiting the hemoglobin (Hb) concentration to 10 to 12 g/dL in adults with chronic kidney disease (CKD) receiving erythropoiesis-stimulating agents such as epoetin theta. This postauthorization study assessed the incidence and intensity of cardiovascular events, including ischemic stroke, in patients receiving epoetin theta for anemia associated with CKD. A secondary end point was adverse drug reactions, including pure red cell aplasia. In this prospective, noninterventional, multinational cohort study, consecutive patients with advanced or end-stage renal disease and receiving epoetin theta were followed up for 6 months. Data on reportable adverse events (RAEs) (cardiac disorders, cardiac failure, myocardial infarction, and ischemic stroke and respective subterms), epoetin theta dosage, and Hb concentrations were collected. A post hoc exploratory analysis assessed the incidences of RAEs according to tertiles for individual mean Hb concentration (≤10.7, >10.7-11.47, and >11.47 g/dL for low, intermediate, and high, respectively) and mean weekly epoetin theta dosage (≤62, >62-125, and >125 IU/kg/wk for low, intermediate, and high). Data from 1039 patients were included (577 men, 462 women; mean age, 68.7 years). A total of 101 RAEs were documented in 89 patients (8.6%), for an event rate of 0.1985/person-year. Sixty-four patients (6.1%) died; none of the deaths was considered related to epoetin theta use. The incidence of RAEs was lowest at intermediate Hb concentrations (6.2%) compared with low (11.3%) and high (7.8%) Hb concentrations. The incidence of ischemic stroke was 1.5% at high Hb concentrations versus 0.6% at both the low and intermediate Hb concentrations. The incidence of any RAE was greater in the high-dose group (10.1%) than in the intermediate-dose (8.0%) and low-dose (7.6%) groups. The risk for any cardiovascular RAE or ischemic stroke was greatest in the high-dose/high-Hb group (13.3%), followed by high

Acute renal failure in a pediatric kidney allograft recipient treated with intravenous immunoglobulin for parvovirus B19 induced pure red cell aplasia.

PubMed

Subtirelu, Mihail M; Flynn, Joseph T; Schechner, Richard S; Pullman, James M; Feuerstein, Dianne; Del Rio, Marcela

2005-12-01

Infection with parvovirus B19 (PV-B19) after solid organ transplantation may cause pure red cell aplasia (PRCA). Intravenous immunoglobulin (IVIg) may be of benefit in clearing the infection. Acute renal failure is a known adverse effect of IVIg administration. A 14-yr-old male received a cadaveric renal transplant. Three weeks after surgery he developed symptomatic anemia (hemoglobin 4.5 g/dL, reticulocyte count 0.2%). Anti-PV-B19 IgM and IgG titers, which had been negative pretransplant, were positive. He received two IVIg infusions as treatment for the PV-B19 infection. Four days after the IVIg infusions he developed non-oliguric acute renal failure (ARF) with a rise in serum creatinine from 1 to 1.8 mg/dL. Allograft biopsy showed changes consistent with an osmotic load. Anemia and the renal failure resolved after transfusions and IVIg. PV-B19 infection in immunosuppressed transplant recipients is associated with significant morbidity and may respond to IVIg therapy. High sucrose IVIg preparations may be associated with renal failure in renal allograft recipients. Adding PV-B19 testing of the donor and recipient to the standard pretransplant evaluation may be beneficial in diagnosing and managing a potential infection. If IVIg is to be used it may be safer to use a sucrose-free IVIg preparation.

Linezolid Induced Twice Pure Red Cell Aplasia in a Patient with Central Nervous System Infection after Allogeneic Stem Cell Transplantation.

PubMed

Hu, Wenqing; Shi, Bing; Liu, Lihui; He, Shengke; Ye, Liping; Tian, DengMei; Zhang, Yongqing

2016-01-01

Linezolid (LZD), severed as the first oxazolidinone antibiotic, was active against multidrug-resistant gram-positive strains. LZD can induce thrombocytopenia, anemia and leukocytopenia. Currently, reports on pure red cell aplasia (PRCA) cases induced by LZD are relatively rare (4-7). In this paper, we reported a patient with PRCA twice induced by LZD. A 37-year-old man was diagnosed with myelodysplatic syndrome (MDS) and underwent allo-HSCT from an unrelated donor with ABO blood type and leukocyte antigen (HLA)-matching. After HSCT for 2 years, the patient suffered from refractory fever and headache. He was first treated with empirical antifungal agent and antibiotics for central nervous system (CNS) infection, but then changed to LZD therapy for little effect. Twenty-eight days after LZD treatment, the symptom improved significantly but the hemoglobin declined to 70 g/L and the reticulocyte level was only 0.23%. The LZD therapy was stopped and the fever and headache symptoms reoccurred 1 week latter. Then, erythropoietin (EPO) and halved dosage of LZD were used for treatment. The CNS infection and the anemia symptom relieved gradually and the level of hemoglobin and reticulocyte declined again. After blood transfusion, the half dose of LZD was sustained without anaemia recovery. In summary, patients with anemia, myelosuppressants history or potential abnormal proliferation of T cells may suffer PRCA with long term LZD treatment. The monitoring of complete blood count and reticulocyte count were necessary during LZD therapy. If the clinical condition permits, LZD dosage reduction and blood transfusion should be considered.

Integra®-Dermal Regeneration Template and Split-Thickness Skin Grafting: A Therapy Approach to Correct Aplasia Cutis Congenita and Epidermolysis Bullosa in Carmi Syndrome.

PubMed

Trah, Julian; Has, Christina; Hausser, Ingrid; Kutzner, Heinz; Reinshagen, Konrad; Königs, Ingo

2018-05-18

The association of junctional epidermolysis bullosa with pyloric atresia (JEB-PA) and aplasia cutis congenita (ACC) was described by El Shafie et al. (J Pediatr Surg 14(4):446-449, 1979) and Carmi et al. (Am J Med Genet 11:319-328, 1982). Most patients die in the first weeks of life, and no curative treatment options are available so far. We describe a patient with JEB-PA and ACC (OMIM # 226730) who was treated for extensive areas of ACC by Integra ® -Dermal Regeneration Template and split-thickness skin grafting (STSG). Clinically, the dermal template changed into well-vascularized neodermis, and after STSG, full take of the transplants was detected. No infections of the huge ACC areas were seen. Further studies must validate this treatment option in severe and acute cases of JEB-PA with ACC. Based on clinical findings, we postulate that placement of Integra ® -Dermal Regeneration Template with STSG could be a new treatment option for patients having JEB-PA with ACC to prevent severe infection, compartment-syndrome-like conditions, and deformities. Based on literature findings, we assume that Integra ® -Dermal Regeneration Template with STSG could even be able to prevent new blistering and thereby be a treatment option in cases of ACC and JEB.

Aplasia Ras homologue member Ⅰ overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture.

PubMed

Ye, Kaishan; Wang, Shuanke; Yang, Yong; Kang, Xuewen; Wang, Jing; Han, Hua

2015-09-01

Aplasia Ras homologue member Ⅰ (ARHI), an imprinted tumor-suppressor gene, is downregulated in various types of cancer. However, the expression, function and specific mechanisms of ARHI in human osteosarcoma (OS) cells remain unclear. The aim of the present study was to assess the effect of ARHI on OS cell proliferation and apoptosis and its associated mechanism. In the study, ARHI mRNA and protein levels were markedly downregulated in OS cells compared with the human osteoblast precursor cell line hFOB1.19. By generating stable transfectants, ARHI was overexpressed in OS cells that had low levels of ARHI. Overexpression of ARHI inhibited cell viability and proliferation and induced apoptosis. However, caspase‑3 activity was not changed by ARHI overexpression. In addition, phosphorylated Akt protein expression decreased in the ARHI overexpression group compared to that in the control vector group. The knockdown of ARHI also resulted in the promotion of cell proliferation and the attenuation of apoptosis in MG‑63 cells. Additionally, ARHI silencing increased the level of p‑Akt. The present results indicate that ARHI inhibits OS cell proliferation and may have a key role in the development of OS.

Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E

PubMed Central

Liu, Xue-song; Zhao, Xu-dong; Wang, Xiaoxing; Yao, Yi-xin; Zhang, Liang-liang; Shu, Run-zhe; Ren, Wei-hua; Huang, Ying; Huang, Lei; Gu, Ming-min; Kuang, Ying; Wang, Long; Lu, Shun-yuan; Chi, Jun; Fen, Jing-sheng; Wang, Yi-fei; Fei, Jian; Dai, Wei; Wang, Zhu-Gang

2010-01-01

Chromosomal instability during cell division frequently causes cell death or malignant transformation. Orderly chromosome congression at the metaphase plate, a paramount process to vertebrate mitosis and meiosis, is controlled by a number of molecular regulators, including kinesins. Kinesin-8 (Kif18A) functions to control mitotic chromosome alignment at the mid-zone by negative regulation of kinetochore oscillation. Here the authors report that disrupting Kif18a function results in complete sterility in male but not in female mice. Histological examination reveals that Kif18a−/− testes exhibit severe developmental impairment of seminiferous tubules. Testis atrophy in Kif18a−/− mice is caused by perturbation of microtubule dynamics and spindle pole integrity, leading to chromosome congression defects during mitosis and meiosis. Depletion of KIF18A via RNAi causes mitotic arrest accompanied by unaligned chromosomes and increased microtubule nucleating centers in both GC-1 and HeLa cells. Prolonged depletion of KIF18A causes apoptosis due to perturbed microtubule dynamics. Further studies reveal that KIF18A silencing results in degradation of CENP-E and BubR1, which is accompanied by premature sister chromatid separation. KIF18A physically interacts with BubR1 and CENP-E, and this interaction is modulated during mitosis. Combined, the studies indicate that KIF18A is essential for normal chromosome congression during cell division and that the absence of KIF18A function causes severe defects in microtubule dynamics, spindle integrity, and checkpoint activation, leading to germinal cell aplasia in mice. PMID:20981276

MURCS association.

PubMed

Balasubramanian, S; Muralinath, S; Shivbalan, So; Sripathi, V; Shivakumar, S

2004-07-01

The MURCS association i.e. MUllerian duct aplasia, Renal aplasia, Cervicothoracic Somite dysplasia is a rare developmental disorder. The authors report a case of MURCS association with supernumerary ribs in a 7-month-old infant who presented with failure to thrive.

Improved imaging of cochlear nerve hypoplasia using a 3-Tesla variable flip-angle turbo spin-echo sequence and a 7-cm surface coil.

PubMed

Giesemann, Anja M; Raab, Peter; Lyutenski, Stefan; Dettmer, Sabine; Bültmann, Eva; Frömke, Cornelia; Lenarz, Thomas; Lanfermann, Heinrich; Goetz, Friedrich

2014-03-01

Magnetic resonance imaging of the temporal bone has an important role in decision making with regard to cochlea implantation, especially in children with cochlear nerve deficiency. The purpose of this study was to evaluate the usefulness of the combination of an advanced high-resolution T2-weighted sequence with a surface coil in a 3-Tesla magnetic resonance imaging scanner in cases of suspected cochlear nerve aplasia. Prospective study. Seven patients with cochlear nerve hypoplasia or aplasia were prospectively examined using a high-resolution three-dimensional variable flip-angle turbo spin-echo sequence using a surface coil, and the images were compared with the same sequence in standard resolution using a standard head coil. Three neuroradiologists evaluated the magnetic resonance images independently, rating the visibility of the nerves in diagnosing hypoplasia or aplasia. Eight ears in seven patients with hypoplasia or aplasia of the cochlear nerve were examined. The average age was 2.7 years (range, 9 months-5 years). Seven ears had accompanying malformations. The inter-rater reliability in diagnosing hypoplasia or aplasia was greater using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence (fixed-marginal kappa: 0.64) than with the same sequence in lower resolution (fixed-marginal kappa: 0.06). Examining cases of suspected cochlear nerve aplasia using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence in combination with a surface coil shows significant improvement over standard methods. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Alternative Submarine Watch Systems: Recommendation for a New CF Submarine Watch Schedule (Systemes Differents d’Horaire de Garde a Bord des Sous-Marins: Nouvel Horaire Recommande Pour les Sous-Marins des FC)

DTIC Science & Technology

2010-01-01

comparativement à une efficacité cognitive de 96 % pour l’horaire de 1 tour sur trois de quatre heures ainsi que pour l’horaire de 1 tour sur trois de...tour sur 2 (8-4-4-8) comparativement à une efficacité cognitive de 96 % pour l’horaire de 1 tour sur trois de quatre heures ainsi que pour l’horaire...FAST™ (Fatigue Avoidance and Safety Tool), a computer application designed to predict and prevent fatigue in operational settings. The output of FAST

Estimation of the incubation period of invasive aspergillosis by survival models in acute myeloid leukemia patients.

PubMed

Bénet, Thomas; Voirin, Nicolas; Nicolle, Marie-Christine; Picot, Stephane; Michallet, Mauricette; Vanhems, Philippe

2013-02-01

The duration of the incubation of invasive aspergillosis (IA) remains unknown. The objective of this investigation was to estimate the time interval between aplasia onset and that of IA symptoms in acute myeloid leukemia (AML) patients. A single-centre prospective survey (2004-2009) included all patients with AML and probable/proven IA. Parametric survival models were fitted to the distribution of the time intervals between aplasia onset and IA. Overall, 53 patients had IA after aplasia, with the median observed time interval between the two being 15 days. Based on log-normal distribution, the median estimated IA incubation period was 14.6 days (95% CI; 12.8-16.5 days).

A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

PubMed

Sekiguchi, Yasunobu; Shimada, Asami; Imai, Hidenori; Wakabayashi, Mutsumi; Sugimoto, Keiji; Nakamura, Noriko; Sawada, Tomohiro; Komatsu, Norio; Noguchi, Masaaki

2014-01-01

The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/μL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

Association between an aplastic basilar artery, unaccompanied by a primitive carotid-vertebrobasilar anastomosis, and multiple aneurysms on the dominant posterior communicating artery.

PubMed

Behari, Sanjay; Krishna, Himanshu; Kumar, Marakani V Kiran; Sawlani, Vijay; Phadke, Rajendra V; Jain, Vijendra K

2004-05-01

Basilar artery (BA) aplasia when unaccompanied by a primitive carotid-vertebrobasilar anastomosis is exceedingly rare. The association of BA aplasia with two aneurysms on the dominant posterior communicating artery (PCoA) has not been previously reported. This 40-year-old man presented in a state of drowsiness and responded to simple commands only after being coaxed. He had complete left cranial third nerve palsy, right hemiparesis, and persisting signs of meningeal irritation. A computerized tomography (CT) scan revealed subarachnoid and intraventricular hemorrhage. An angiogram revealed BA aplasia. The right PCoA followed a sinuous course with multiple loops and provided the dominant supply to the posterior circulation. This vessel harbored two aneurysms, one at the origin of the PCoA from the internal carotid artery and the other at the looping segment just proximal to the brainstem. The left PCoA was extremely thin. The pterional transsylvian approach was used to clip the two aneurysms on the PCoA. The hemodynamic changes produced by the BA aplasia may have produced alterations in the cerebral vasculature leading to aneurysm formation and consequent subarachnoid hemorrhage.

Treatment of patients with a congenital transversal vaginal septum or a partial aplasia of the vagina. The vaginal pull-through versus the push-through technique.

PubMed

van Bijsterveldt, Chantal; Willemsen, Wim

2009-06-01

The aim of this study is to describe the different modalities of congenital obstructing vaginal malformations and the evaluation of techniques to solve the problem. A retrospective study. The University Hospital Nijmegen, the Netherlands. The medical records of 18 patients with congenital obstructive malformations of the vagina operated on by one gynecologist were retrospectively reviewed. The conditions were classified in three groups: group I with one uterus and vagina and with a transverse vaginal septum, group II with a partial vaginal agenesis and group III with a double genital system and a septum with occlusion of one vagina. Operating technique used, mold treatment after surgery, menstruation outflow, the possibility of having intercourse and the need for additional surgery. 18 patients were evaluated. Of 10 patients in group I, 8 patients were treated with the pull-through technique and 2 patients with the push-through technique. Four of the patients with a pull-through operation did not get mold treatment; of these patients, 3 needed repeat surgery because of the tendency for constriction. Of 4 patients in group II, 1 patient was treated with the pull-through technique and 3 with the push-through technique. The patient with the pull-through technique needed repeat surgery because of constriction. There was no mold treatment after the first procedure. Group III were 4 patients all treated with the pull-through technique. None of them received mold treatment, and none of these patients needed repeat surgery. The push-through method is a good surgical technique for the patients in whom problems of constriction after surgery are expected and for patients with difficulties during surgery. Mold treatment is recommended after surgery in patients with a thick transversal vaginal septum or a partial vaginal aplasia.

Evaluation d'une approche pedagogique respectant les facons d'apprendre des filles en sciences et en TIC en 9e annee au Nouveau-Brunswick

NASA Astrophysics Data System (ADS)

Lirette-Pitre, Nicole T.

2009-07-01

La reussite scolaire des filles les amene de plus en plus a poursuivre une formation postsecondaire et a exercer des professions qui demandent un haut niveau de connaissances et d'expertise scientifique. Toutefois, les filles demeurent toujours tres peu nombreuses a envisager une carriere en sciences (chimie et physique), en ingenierie ou en TIC (technologie d'information et de la communication), soit une carriere reliee a la nouvelle economie. Pour plusieurs filles, les sciences et les TIC ne sont pas des matieres scolaires qu'elles trouvent interessantes meme si elles y reussissent tres bien. Ces filles admettent que leurs experiences d'apprentissage en sciences et en TIC ne leur ont pas permis de developper un interet ni de se sentir confiante en leurs habiletes a reussir dans ces matieres. Par consequent, peu de filles choisissent de poursuivre leurs etudes postsecondaires dans ces disciplines. La theorie sociocognitive du choix carriere a ete choisie comme modele theorique pour mieux comprendre quelles variables entrent en jeu lorsque les filles choisissent leur carriere. Notre etude a pour objet la conception et l'evaluation de l'efficacite d'un materiel pedagogique concu specifiquement pour ameliorer les experiences d'apprentissage en sciences et en TIC des filles de 9e annee au Nouveau-Brunswick. L'approche pedagogique privilegiee dans notre materiel a mis en oeuvre des strategies pedagogiques issues des meilleures pratiques que nous avons identifiees et qui visaient particulierement l'augmentation du sentiment d'auto-efficacite et de l'interet des filles pour ces disciplines. Ce materiel disponible par Internet a l'adresse http://www.umoncton.ca/lirettn/scientic est directement en lien avec le programme d'etudes en sciences de la nature de 9e annee du Nouveau-Brunswick. L'evaluation de l'efficacite de notre materiel pedagogique a ete faite selon deux grandes etapes methodologiques: 1) l'evaluation de l'utilisabilite et de la convivialite du materiel et 2

Malformation of the eighth cranial nerve in children.

PubMed

de Paula-Vernetta, Carlos; Muñoz-Fernández, Noelia; Mas-Estellés, Fernando; Guzmán-Calvete, Abel; Cavallé-Garrido, Laura; Morera-Pérez, Constantino

2016-01-01

Prevalence of congenital sensorineural hearing loss (SNHL) is approximately 1.5-6 in every 1,000 newborns. Dysfunction of the auditory nerve (auditory neuropathy) may be involved in up to 1%-10% of cases; hearing losses because of vestibulocochlear nerve (VCN) aplasia are less frequent. The objectives of this study were to describe clinical manifestations, hearing thresholds and aetiology of children with SNHL and VCN aplasia. We present 34 children (mean age 20 months) with auditory nerve malformation and profound HL taken from a sample of 385 children implanted in a 10-year period. We studied demographic characteristics, hearing, genetics, risk factors and associated malformations (Casselman's and Sennaroglu's classifications). Data were processed using a bivariate descriptive statistical analysis (P<.05). Of all the cases, 58.8% were bilateral (IIa/IIa and I/I were the most common). Of the unilateral cases, IIb was the most frequent. Auditory screening showed a sensitivity of 77.4%. A relationship among bilateral cases and systemic pathology was observed. We found a statistically significant difference when comparing hearing loss impairment and patients with different types of aplasia as defined by Casselman's classification. Computed tomography (CT) scan yielded a sensitivity of 46.3% and a specificity of 85.7%. However, magnetic resonance imaging (MRI) was the most sensitive imaging test. Ten percent of the children in a cochlear implant study had aplasia or hypoplasia of the auditory nerve. The degree of auditory loss was directly related to the different types of aplasia (Casselman's classification) Although CT scan and MRI are complementary, the MRI is the test of choice for detecting auditory nerve malformation. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Traitement préventif intermittent à la sulfadoxine – pyriméthamine du paludisme chez les femmes enceintes: efficacité et observance dans deux hôpitaux urbains du Burkina Faso

PubMed Central

Bamba, Sanata; Séré, Adama; Nikiéma, Rodrigues; Halidou, Tinto; Thiéba, Blandine; Dao, Blami; Guiguemdé, Robert Tinga

2013-01-01

Introduction La présente étude prospective se propose dévaluer l'efficacité thérapeutique du traitement préventif intermittent à la sulfadoxine - pyriméthamine et son observance chez la femme enceinte dans deux hôpitaux urbains au Burkina Faso. Méthodes Chaque femme répondant aux critères d'inclusion a été soumise à un questionnaire pour la collecte des données socio - démographiques et des renseignements sur la grossesse. A l'accouchement, une apposition placentaire a été réalisée systématiquement. La lecture a été faite au microscope à lobjectif 100 à immersion. Résultats Au total, 542 femmes ont été incluses avec un âge moyen de 26,0 ± 6,45 ans (extrêmes 13- 43 ans). Le taux de couverture du TPI à la sulfadoxine- pyriméthamine a été de 80%. Le taux d'infestation placentaire a été de 4,7%. Il a diminué avec le nombre de dose de traitement préventif intermittent. Il a augmenté cependant de juillet à octobre. De 42,9% en octobre, il a diminué significativement à 9,5% en novembre (p < 0,05). Le taux global de bonne d'observance a été de 55%. Il a augmenté avec l’âge (p < 0,05). Conclusion Le taux de couverture de la sulfadoxine - pyriméthamine a été de 80%. Ce résultat est en conformité avec les objectifs du plan stratégique 2006-2010 de lutte contre le paludisme au Burkina Faso, qui préconisait un taux de couverture en sulfadoxine - pyriméthamine de 80% pour 2010. L'augmentation de la fréquence d'infestation de juillet à octobre, serait liée à la recrudescence de la transmission palustre pendant la saison des pluies (mai-octobre). PMID:23717719

[Genetic deafness].

PubMed

Marcolla, A; Bouchetemble, P; Lerosey, Y; Marie, J-P; Dehesdin, D

2006-06-01

The aim of this study was to review the different types of genetic deafness. We describe syndromic and isolated sensorineural deafness and transmission deafness. Genetic sensorineural syndromic deafness represents 30% of cases of genetic deafness. A frequent cause is Pendred syndrome, which associates congenital sensorineural deafness with goitre and malformations of the inner ear which can be identified on computed tomography scan. Isolated deafness which is responsible for 70% of cases of genetic deafness is then outlined. Among the different types of isolated deafness, 80% are autosomal recessive disorders. A frequent form of autosomal recessive deafness is due to mutations in the connexin 26 gene. Lastly, we detail transmission deafness dominated by aplasia. Major aplasia is characterized by a malformation of the external ear associated with malformations of the middle ear whereas, minor aplasia corresponds to a malformation of the middle ear, sometimes associated with minor external ear malformations. For each type of deafness we propose a systematic assessment.

Les recommandations relatives aux vaccins antigrippaux administrés aux enfants et aux adolescents pour la saison 2017-2018.

PubMed

Moore, Dorothy L

2018-02-01

La Société canadienne de pédiatrie continue d'encourager la vaccination antigrippale annuelle de TOUS les enfants et les adolescents, dès l'âge de six mois. Les recommandations du Comité consultatif national de l'immunisation (CCNI) pour la saison 2017-2018 n'ont pas subi de changements importants par rapport à la saison précédente. Le CCNI a analysé toutes les données sur l'efficacité du vaccin vivant atténué contre l'influenza (VVAI) sur le marché et conclut qu'elles en appuient l'utilisation au Canada, même si les États-Unis ne le recommandent pas en raison de doutes quant à son efficacité.

Case of pregnancy in two cows with unicorn horn of the uterus either by artificial insemination at ipsilateral or embryo transfer at contralateral corpus luteum in the ovary.

PubMed

Moriyama, C; Kobayashi, I; Tani, M; Oishi, T; Kajisa, M; Horii, Y; Kamimura, S

2008-06-01

Two Holstein heifers and a cow were diagnosed with White Heifer Disease by ultrasonography. Case 1 was a 14 month-old heifer with aplasia of both sides of the uterine horn. In case 2, a primiparous cow and case 3, an 18 month-old heifer, both showed aplasia of the right uterine horn. Case 2 became pregnant by artificial insemination at ipsilateral ovulatory follicle and corpus luteum in the left ovary, while case 3 became pregnant by embryo transfer at 7 days after oestrus with contralateral corpus luteum in the right ovary.

Microparticules magnetiques therapeutiques pour la chimio-embolisation ciblee du foie

NASA Astrophysics Data System (ADS)

Pouponneau, Pierre

The proposed project introduces a therapeutic vector for the liver tumor treatment based on a new magnetic targeting strategy. The hypothesis of this thesis is that it is possible to design a therapeutic vector compatible with the constraints of liver chemoembolization and MRN in the hepatic artery to target the right/left lobe of the liver. This vector, referred to as therapeutic magnetic microcarriers (TMMC) is loaded with an antitumor drug and magnetic nanoparticles. A design study, based on a mathematical modeling of microparticle steering and a literature review on the chemoembolization, was done to optimize TMMC properties (diameter, Ms, nanoparticle choice and loading). Iron-cobalt (FeCo) nanoparticles were synthesized and annealed under inert conditions to improve their magnetic properties. These ferromagnetic nanoparticles possessed a mean diameter of 200 nm, measured by transmission electronic microscopy, and an Ms of 205 emu g-1, determined with a vibrating sample magnetometer. These nanoparticles, by their high Ms, allowed reducing by half the magnetic material loading in TMMC compared with the encapsulation of iron oxide nanoparticles. The nanoparticles coated with 10-nm graphite shell were protected from oxidation and thus they maintained their excellent magnetic properties. The design study was experimentally confirmed by the encapsulation of FeCo nanoparticles into poly(lactic-co-glycolic acid (PLGA) biodegradable microparticles. The latter were steered in vitro in a phantom mimicking the hepatic artery and its right/left bifurcation. The steering efficiency was determined by steering video analysis and the iron and cobalt ion concentrations were assayed by atomic absorption spectrometry in each bifurcation. FeCo nanoparticles were then co-encapsulated with doxorubicin (DOX) into PLGA microparticles. DOX is an antitumor drug widely used for HCC treatments. TMMC possessed a mean diameter of 52 mum, an Ms of 72 emu g-1 and they were loaded with 37% (w/w) of nanoparticles and 3% (w/w) of DOX. In vitro, after 3 days of elution in phosphate buffered saline solution, 54% of the DOX encapsulated remained in the TMMC. The elution was characterized by a fast release phase during one hour and then a slow kinetics. The steering was evaluated in vitro in a phantom mimicking the hepatic artery under physiological and interventional radiology conditions (injection by catheter, variation of distance between the catheter and the bifurcation from 30 to 20 mm, magnetic gradient from 200 to 400 mT m -1, flow velocity from 7.5 to 12 cm s-1). Steering efficiency was defined as the reduction of the TMMC (or drug) dose in the untargeted area in the presence of magnetic steering versus the negative control (no steering). The steering efficiency increased when the magnetic gradient increased. The efficiency decreased when the flow velocity increased and the catheter was closer to the bifurcation. The efficiency decreased with microparticles with lower steering properties (diameter of 30 mum and Ms of 49 emu g-1). This result confirmed that the TMMC properties were specific to the vascular network being targeted. In the optimal conditions, the steering efficiency reached 70%. The steering of TMMC was measured in vivo. An interventional radiology protocol compatible with MRN was developed to place the catheters, to reduce the hepatic artery blood velocity during the steering and to determine the MRI sequence parameters. TMMC induced signal loss on T2*-weighted magnetic resonance images because of their high Ms which allowed their easy localization in the tissues. The embolization of the hepatic artery branches by TMMC was confirmed by histological analysis. The sustained release of DOX was verified by measuring its plasmatic concentration. TMMC distribution in the tissues was determined by the histological analysis and DOX and cobalt concentration measurements. A significant difference in the TMMC distribution in the liver lobes between the group with MRN and the control group was obtained. The MRN allowed reducing the microparticle concentration in the untargeted area. In the optimal conditions, the steering efficiency reached 50%. The parameters influencing the steering efficiency in vitro were confirmed during in vivo tests. (Abstract shortened by UMI.)

Congenital absence of the bilateral internal carotid artery: a review of the associated (ab)normalities from a newborn status to the eighth decade of life.

PubMed

Vasović, Ljiljana; Trandafilović, Milena; Vlajković, Slobodan; Radenković, Goran

2018-01-01

Due to the fact that the internal carotid artery (ICA) is responsible for nourishing two thirds of the brain volume, our aim was to inspect the morphofunctional consequences of the bilateral lack of this artery. In order to examine this condition, we referred to both the library archive of our Faculty of Medicine and electronic databases of anatomical and clinical reports that included the following keywords: "absence," "aplasia," or "agenesis" in combination with "internal carotid artery," "common carotid artery," or only "carotid artery." We found 60 recorded cases of the bilateral ICA absence in the subjects of newborn status to the eighth decade of life, which had been discovered in 20 countries. The following ten parameters were described: the embryological base, terminology, history, incidence, general data, differential diagnosis, collateral circulation, the associated vascular aplasia and/or other variants, pathophysiology, and the importance in praxis. This review noted all the cases of the bilateral ICA aplasia published for the past 104 years. Although there were 11.6% of cases of the associated cerebral aneurysms and 1-4 cases of 16 other diseases, approximately one quarter of the cases was without any pathology.

School Choice Options Limit Access to Higher Education for Various Groups of Students in Quebec

ERIC Educational Resources Information Center

Labrosse, Julie; Gaudreault, Marco; Picard, France

2017-01-01

The choice of selected school options by pupils in secondary school, particularly mathematics and physical sciences, have implications for future educational pathways in higher education [Felouzis, G. (1997). "L'efficacité des enseignants, Sociologie de la relation pédagogique." Paris: Presses Universitaires de France; Moreau, G. (2005).…

A previously undescribed syndrome combining fibular agenesis/hypoplasia, oligodactylous clubfeet, anonychia/ungual hypoplasia, and other defects.

PubMed

Santos, Silvana C; Pardono, Eliete; Ferreira da Costa, Maria Ione; de Melo, Aurea Nogueira; Graciani, Zodja; de Albuquerque e Souza, Alessandra Cavalcanti; Lezirovitz, Karina; Thiele-Aguiar, Renata Soares; Mingroni-Netto, Regina Célia; Opitz, John M; Kok, Fernando; Otto, Paulo A

2008-12-15

We describe an apparently new genetic syndrome in six members of a family living in a remote area in Northeastern Brazil. This syndrome comprises: short stature due to a marked decrease in the length of the lower limbs (predominantly mesomelic with fibular agenesis/marked hypoplasia), grossly malformed/deformed clubfeet with severe oligodactyly, upper limbs with acromial dimples and variable motion limitation of the forearms and/or hands, severe nail hypoplasia/anonychia sometimes associated with mild brachydactyly and occasionally with pre-axial polydactyly. This syndrome is apparently distinct from the syndrome of brachydactyly-ectrodactyly with fibular aplasia or hypoplasia (OMIM 113310), the syndrome of fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly (OMIM 228930), and from other previously described conditions exhibiting fibular agenesis/hypoplasia. Copyright (c) 2008 Wiley-Liss, Inc.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

PubMed

O'Riordan, Aisling M; McGrath, Niamh; Sharif, Farhana; Murphy, Nuala P; Franklin, Orla; Lynch, Sally Ann; O'Grady, Michael J

2017-01-01

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

Research News: Debate on Learning Theory Is Shifting.

ERIC Educational Resources Information Center

Fox, Jeffrey L.

1983-01-01

Discusses current learning theories, indicating that though many psychologists and ethologists now agree on using a mechanistic approach, some linguists doubt its adequacy. Implications of research on the mollusk "Aplasia" to understand the learning process are included. (JN)

Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

ClinicalTrials.gov

2005-06-23

Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

In utero phthalate effects in the female rat: a model for MRKH syndrome##

EPA Science Inventory

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phen...

In Utero Phthalate Effects in the Female Rat: A Model for MRKH Syndrome

EPA Science Inventory

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly define etiology. Reproductive toxicity of phthlate esters (PEs) occurs in rat offspring exposed in utero. a phenome...

CAR T-cells merge into the fast lane of cancer care.

PubMed

Frey, Noelle V; Porter, David L

2016-01-01

Chimeric antigen receptors (CARs) can be introduced into T-cells redirecting them to target specific tumor antigens. CAR-modified T cells targeting CD19 have shown remarkable activity against CD19+ malignancies including B cell acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphomas (NHL). Complete remission rates as high as 90% have been observed for patients with relapsed and refractory ALL and greater than 50% response rates have been seen in heavily pre-treated CLL and NHL. Excitingly, some remissions have been durable without any additional therapy, a finding which correlates with in-vivo T-cell persistence and B-cell aplasia. The major treatment related toxicities include B-cell aplasia, neurologic toxicities, and a potentially severe cytokine release syndrome. This review summarizes outcomes for patients treated with CD19-CAR T-cells while exploring the field's challenges and future directions. © 2015 Wiley Periodicals, Inc.

Primary Fused Teeth and Findings in Permanent Dentition.

PubMed

Açıkel, Hatice; İbiş, Sevgin; Şen Tunç, Emine

2018-01-01

The aim of this study was to investigate the characteristics of primary fused teeth (PFT) and their effect on permanent dentition in a group of Turkish children. Dental records of 13,450 pediatric patients who attended the Pediatric Dental Clinic in northern Turkey between 2015 and 2017 were reviewed. Forty patients had been diagnosed with PFT and were included in the study. Clinical and radiographic examinations were conducted, and the distribution of PFT was calculated by type, sex, affected jaw, associated dental anomalies, and clinical complications. Data analysis involved descriptive statistics. A total of 50 PFT were detected in the 40 patients. The mean age of patients was 6.7 ± 0.3 years (range 3-10 years). The most common PFT were the mandibular lateral incisors and canines (34, 68%). The most prevalent type of PFT was type III (20, 40%). Of the 40 patients with PFT, 34 (85%) also ex-hibited other dental anomalies such as tooth aplasia, peg-shaped incisors, talon cusps, ectopic eruption, and delayed eruption in both related and unrelated areas. The most common complications of PFT were fusion-related tooth aplasia (n = 26 [76%]) and caries formation in the affected teeth (24 [48%]). In this study, PFT were frequently observed in the mandibular anterior region. Caries formation and dental anomalies, especially permanent tooth aplasia, were often encountered in areas where PFT were seen. Hence, parents should be informed about possible dental problems associated with PFT and be encouraged to schedule regular follow-up appointments. ©2018 The Author(s) Published by S. Karger AG, Basel.

[Poland's syndrome].

PubMed

Slezak, R; Sasiadek, M

2000-08-01

Poland's syndrome consists of the variable clinical features, but always includes unilateral aplasia of the chest wall muscles and ipsilateral anomalies of upper extremity. The incidence of Poland's syndrome, reported by different authors ranges from 1:10,000 to 1:100,000 and is observed more frequently in males than in females with the right side of the body affected more often than the left. The etiology of this syndrome is still discussed. However most of described cases were sporadic, rare familial incidence of Poland's syndrome were also presented. Therefore different etiologic factors of the Poland's syndrome are taken into account: genetic, vascular compromise during early stages of embriogenesis but also teratogenic effect of environmental xenobiotics (e.g. cigarette smoking by pregnant women). The authors present also the case of 20-years old man with inherited bilateral syndactyly with the right side aplasia of major pectoralis muscle and face asymmetry. The familial history was negative in respect to the features, associated with Poland's syndrome.

Acute human parvovirus b19 infection: cytologic diagnosis.

PubMed

Sharada Raju, Rane; Nalini Vinayak, Kadgi; Madhusudan Bapat, Vishnuprasad; Preeti Balkisanji, Agrawal; Shaila Chandrakant, Puranik

2014-09-01

Human parvovirus B19 is highly tropic to human bone marrow and replicates only in erythroid progenitor cells. It is causative agent of transient aplastic crisis in patients with chronic haemolytic anemia. In immunocompromised patients persistent parvovirus B19 infection may develop and it manifests as pure red cell aplasia and chronic anaemia. Bone marrow is characterised morphologically by giant pronormoblast stage with little or no further maturation. We encountered a case of 6 year old HIV positive male child presented with pure red cell aplasia due to parvovirus B19 infection. Bone marrow aspiration cytology revealed giant pronormoblast with prominent intranuclear inclusions led to suspicion of parvovirus B19 infection which was confirmed by DNA PCR. This case is presented to report classical morphological features of parvovirus B19 infection rarely seen on bone marrow examination should warrant the suspicion of human parvovirus B19 infection in the setting of HIV positive patient with repeated transfusions and confirmation should be done by PCR.

Pancytopenia in a patient with sickle cell anemia.

PubMed

Kim, K Y; Karayalcin, G; Rosner, F; Aballi, A

1975-10-01

An 11-year-old black boy with sickle cell anemia developed profound pancytopenia during the course of his disease, but fully recovered therefrom. The patient was receiving anticonvulsant drugs for a seizure disorder secondary to a "stroke," and, therefore, a drug-related marrow aplasia cannot be ruled out.

Bacterial flora of the sigmoid neovagina.

PubMed Central

Toolenaar, T A; Freundt, I; Wagenvoort, J H; Huikeshoven, F J; Vogel, M; Jeekel, H; Drogendijk, A C

1993-01-01

The bacterial microbiota of 15 sigmoid neovaginas, created in patients with congenital vaginal aplasia or male transsexualism, was studied. No specimen was sterile, and only normal inhabitants of the colon were cultured. The total counts of bacteria were lower than those reported for healthy sigmoid colons. PMID:8308126

Azoospermia in a Male with Klippel-Feil Anomaly.

PubMed

Uloko, Maria; Bearrick, Elizabeth; Bodie, Joshua

2017-07-01

Müllerian-duct aplasia, renal agenesis, and cervical somite dysplasia (MURCS) is a rare genetic disorder. Previously thought to be exclusive in females, there have now been a small number of case reports describing a male analogue. We describe a patient with obstructive azoospermia and Klippel-Feil anomaly.

Caudal articular process dysplasia of thoracic vertebrae in neurologically normal French bulldogs, English bulldogs, and Pugs: Prevalence and characteristics.

PubMed

Bertram, Simon; Ter Haar, Gert; De Decker, Steven

2018-02-20

The aims of this study were to evaluate the prevalence and anatomical characteristics of thoracic caudal articular process dysplasia in French bulldogs, English bulldogs and Pugs presenting for problems unrelated to spinal disease. In this retrospective cross-sectional study, computed tomography scans of the thoracic vertebral column of these three breeds were reviewed for the presence and location of caudal articular process hypoplasia and aplasia, and compared between breeds. A total of 271 dogs met the inclusion criteria: 108 French bulldogs, 63 English bulldogs, and 100 Pugs. A total of 70.4% of French bulldogs, 84.1% of English bulldogs, and 97.0% of Pugs showed evidence of caudal articular process dysplasia. Compared to French and English bulldogs, Pugs showed a significantly higher prevalence of caudal articular process aplasia, but also a lower prevalence of caudal articular process hypoplasia, a higher number of affected vertebrae per dog and demonstrated a generalized and bilateral spatial pattern more frequently. Furthermore, Pugs showed a significantly different anatomical distribution of caudal articular process dysplasia along the vertebral column, with a high prevalence of caudal articular process aplasia between T10 and T13. This area was almost completely spared in French and English bulldogs. As previously suggested, caudal articular process dysplasia is a common finding in neurologically normal Pugs but this also seems to apply to French and English bulldogs. The predisposition of clinically relevant caudal articular process dysplasia in Pugs is possibly not only caused by the higher prevalence of caudal articular process dysplasia, but also by breed specific anatomical characteristics. © 2018 American College of Veterinary Radiology.

Rhinencephalon changes in tuberous sclerosis complex.

PubMed

Manara, Renzo; Brotto, Davide; Bugin, Samuela; Pelizza, Maria Federica; Sartori, Stefano; Nosadini, Margherita; Azzolini, Sara; Iaconetta, Giorgio; Parazzini, Cecilia; Murgia, Alessandra; Peron, Angela; Canevini, Paola; Labriola, Francesca; Vignoli, Aglaia; Toldo, Irene

2018-06-17

Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. Eight of110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.

Use of Scientific and Technical Information in the NATO Countries

DTIC Science & Technology

1983-03-01

pouvoirs publics resultant de la coordination de 1’information dans les secteurs Defense et ASrospatlal sont pr^sent^s a travers 1’organisation du...et le secteur Aerospatial s’lmpose pour des raisons d’efficacit^ et d’Sconomie de moyens. Cette coordination devra cependant tenir compte de la sp...cificit§ des problemes de Defense et de 1’importance militaire et industrlelle du secteur aerospatial qui provient essentiellement : . du caractere

Renal Aplasia in Humans Is Associated with RET Mutations

PubMed Central

Skinner, Michael A.; Safford, Shawn D.; Reeves, Justin G.; Jackson, Margaret E.; Freemerman, Alex J.

2008-01-01

In animal models, kidney formation is known to be controlled by the proteins RET, GDNF, and GFRA1; however, no human studies to date have shown an association between abnormal kidney development and mutation of these genes. We hypothesized that stillborn fetuses with congenital renal agenesis or severe dysplasia would possess mutations in RET, GDNF, or GFRA1. We assayed for mutations in these genes in 33 stillborn fetuses that had bilateral or unilateral renal agenesis (29 subjects) or severe congenital renal dysplasia (4 subjects). Mutations in RET were found in 7 of 19 fetuses with bilateral renal agenesis (37%) and 2 of 10 fetuses (20%) with unilateral agenesis. In two fetuses, there were two different RET mutations found, and a total of ten different sequence variations were identified. We also investigated whether these mutations affected RET activation; in each case, RET phosphorylation was either absent or constitutively activated. A GNDF mutation was identified in only one fetus with unilateral agenesis; this subject also had two RET mutations. No GFRA1 mutations were seen in any fetuses. These data suggest that in humans, mutations in RET and GDNF may contribute significantly to abnormal kidney development. PMID:18252215

Intensité thérapeutique optimale : comment mesurer l'intensité d'une association radiothérapie-chimiothérapie ?

NASA Astrophysics Data System (ADS)

Ganem, G.; Dubray, B.

1998-04-01

Treatment intensification is needed to overcome the disappointing efficacy of anticancer treatments used as a single modality. The conception, comparison and optimization of radiotherapy - chemotherapy combinations is hampered by the lack of a common tool enabling the clinicians to quantify the effects of the association of different treatment modalities. Such a difficulty is mainly due to chemotherapy (large array of drugs, pharmacological uncertainties), but is also the consequence of end-point multiplicity (tumour control, normal tissue injury) and tumour biology complexity. L'intensification thérapeutique est une nécessité face à l'efficacité insuffisante des traitements anticancéreux utilisés séparément. La conception, la comparaison, et l'optimisation des modalités possibles d'association de radiothérapie et de chimiothérapie est considérablement gênée par l'absence d'un outil permettant de mesurer l'efficacitéé résultante de la combinaison d'agents thérapeutiques différents. Cette difficulté provient essentiellement de l'usage de la chimiothérapie (nombreuses drogues, pharmacocinétique mal connue), mais aussi de la multiplicité des critères de jugement (action anti-tumorale, lésions des tissus sains) et de la complexité de la biologie tumorale.

Development of Measures of Effectiveness and Performance from Cognitive Work Analysis Products

DTIC Science & Technology

2012-02-01

la Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2012 DRDC Atlantic CR 2011...le nouveau concept du système. Ce rapport vise à déterminer si les résultats du travail de conception peuvent aider à élaborer des mesures de ...l’information (IIDS). Le contrat actuel comportait deux objectifs : élaborer des mesures de l’efficacité (MOE) et du rendement (MOP) pour

Collaboration between the Canadian Forces and the Public in Operations

DTIC Science & Technology

2011-03-01

recueillir les recommandations relativement à la formation et à l’éducation dans le but d’accroître l’efficacité de la collaboration civilo-militaire en...intervenants en contexte public (p. ex., avec des ONG), et 2) recueillir les recommandations d’experts en la matière (EM) relativement aux possibilités de...CF might be the distribution of aid to those in need. On the other hand, an indirect impact of collaboration could be an “implicit ethical message

Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

DTIC Science & Technology

2015-12-01

abnormalities, and predisposition to cancer. The current treatment of steroids and chronic transfusions leads to significant morbidity. Approximately 25...more rigorously test this hypothesis and identify new downstream targets and microRNAs, we propose three specific aims. In Aim 1, we will...aplasia, congenital abnormalities, and predisposition to cancer. The current treatment of steroids and chronic transfusions leads to significant

Assessing Vulnerability of Biometric Technologies for Identity Management Applications

DTIC Science & Technology

2011-10-01

de vulnérabilité et d’analyse de la relation entre la performance du système et la force de sécurité de la fonction. En Octobre 2010, IBG-Canada...Les agences et ministères du gouvernement du Canada ont besoin d’information sur la performance , les vulnérabilités et l’efficacité des solutions...négligent des éléments humains qui peuvent stimuler la performance , de sécurité et les

Processes for Assessing Outcomes of Multi-national Missions (Processus d’evaluation des resultats de missions multinationales)

DTIC Science & Technology

2013-11-01

la raison d’être du recueil des données relatives aux variables centrales afin de soutenir ces efforts dans...communs utilisés par les pays membres et un ensemble central d’indicateurs complétant les Mesures de Performance (MOP) et Mesures d’Efficacité (MOE...dénomination « STO », « RTO » ou « AGARD » selon le cas, suivi du numéro de série. Des informations analogues, telles que le titre est la date de

Rare case of nephrotic syndrome: Schimke syndrome.

PubMed

Pedrosa, Anna Kelly Krislane de Vasconcelos; Torres, Luiz Fernando Oliveira; Silva, Ana Corina Brainer Amorim da; Dantas, Adrianna Barros Leal; Zuntini, Káthia Liliane da Cunha Ribeiro; Aguiar, Lia Cordeiro Bastos

2016-01-01

Schimke syndrome corresponds to dysplasia of bone and immunity, associated with progressive renal disease secondary to nephrotic syndrome cortico-resistant, with possible other abnormalities such as hypothyroidism and blond marrow aplasia. It is a rare genetic disorder, with few reports in the literature. The most frequent renal involvement is nephrotic syndrome with focal segmental glomerulosclerosis and progressive renal failure. The objective of this study was to report a case of Schimke syndrome, diagnostic investigation and management of the case. Resumo A síndrome Schimke corresponde à displasia imuno-óssea, associada à doença renal progressiva secundária à síndrome nefrótica córtico-resistente, podendo haver outras anormalidades como hipotireoidismo e aplasia de medula óssea. Trata-se de uma patologia genética rara, com poucos relatos na literatura. O acometimento renal mais frequente é uma síndrome nefrótica por glomeruloesclerose segmentar e focal e falência renal progressiva. O objetivo deste estudo foi relatar um caso de síndrome de Schimke, investigação diagnóstica e condução do caso.

The classification of frontal sinus pneumatization patterns by CT-based volumetry.

PubMed

Yüksel Aslier, Nesibe Gül; Karabay, Nuri; Zeybek, Gülşah; Keskinoğlu, Pembe; Kiray, Amaç; Sütay, Semih; Ecevit, Mustafa Cenk

2016-10-01

We aimed to define the classification of frontal sinus pneumatization patterns according to three-dimensional volume measurements. Datasets of 148 sides of 74 dry skulls were generated by the computerized tomography-based volumetry to measure frontal sinus volumes. The cutoff points for frontal sinus hypoplasia and hyperplasia were tested by ROC curve analysis and the validity of the diagnostic points was measured. The overall frequencies were 4.1, 14.2, 37.2 and 44.5 % for frontal sinus aplasia, hypoplasia, medium size and hyperplasia, respectively. The aplasia was bilateral in all three skulls. Hypoplasia was seen 76 % at the right side and hyperplasia was seen 56 % at the left side. The cutoff points for diagnosing frontal sinus hypoplasia and hyperplasia were '1131.25 mm(3)' (95.2 % sensitivity and 100 % specificity) and '3328.50 mm(3)' (88 % sensitivity and 86 % specificity), respectively. The findings provided in the present study, which define frontal sinus pneumatization patterns by CT-based volumetry, proved that two opposite sides of the frontal sinuses are asymmetric and three-dimensional classification should be developed by CT-based volumetry, because two-dimensional evaluations lack depth measurement.

Les médicaments à libération prolongée pour les enfants et les adolescents ayant un trouble de déficit de l’attention avec hyperactivité

PubMed Central

Feldman, M; Bélanger, S

2009-01-01

Le trouble de déficit de l’attention avec hyperactivité (TDAH) touche un enfant canadien sur 20 et s’associe à un dossier scolaire et à un registre d’emploi défavorables, à des taux élevés de blessures et de consommation de drogues ou d’alcool, à des relations interpersonnelles médiocres, à de mauvaises issues en santé mentale et à une qualité de vie insatisfaisante. Des essais contrôlés démontrent que les médica-ments sont efficaces pour traiter les symptômes de TDAH tandis que des études d’observation indiquent qu’ils s’associent à de meilleures issues sociales et de santé. De nombreuses familles, ainsi que leur médecin traitant, préfèrent les médicaments à libération prolongée (LP) contre le TDAH aux médicaments à libération immédiate (LI) et à action brève. Toutefois, les préparations à LP sont souvent inabor-dables pour les familles, dont un nombre disproportionné fait partie de la strate à faible statut socioéconomique. Le présent document de principes vise à proposer une évaluation critique des données probantes sur l’efficacité relative des médicaments à LP par rapport aux médicaments à LI ainsi que des recommandations au sujet de leur utilisation convenable dans le traitement du TDAH. Lorsque les médicaments sont indiqués, il faut envisager d’utiliser des préparations à LP comme traitement de première intention contre le TDAH parce qu’elles sont plus efficaces et moins susceptibles d’être détournées. Les futures recherches et les analyses coûts-avantages doivent tenir compte à la fois de l’efficacité de médicaments dans des études contrôlées et de leur efficacité clinique en situation réelle ainsi que du potentiel de détournement et de mésusage de ces médicaments. L’industrie, les sociétés d’assurance et le gouvernement doivent collaborer pour rendre ces médicaments accessibles à tous les enfants et adolescents ayant un TDAH.

[Approaches to the immunological problems of leukocyte transfusions].

PubMed

Gualde, N; Malinvaud, G; Gaillard, S

1975-01-01

51 leukocyte transfusions from healthy donors and 3 from chronic myelogenous leukemia were given to 16 patients with acute leukemia and 4 with aplasia. During 14 transfusions we have observed clinicals reactions which are of immunological origin. The part of the transfusions and of the pregnancies in the presence of antibodies is argued. The necessity of utilisation of HL-A compatible donors during leukocyte transfusions is asserted.

Cellules solaires photovoltaïques plastiques enjeux et perspectives

NASA Astrophysics Data System (ADS)

Sicot, L.; Dumarcher, V.; Raimond, P.; Rosilio, C.; Sentein, C.; Fiorini, C.

2002-04-01

Après avoir détaillé le fonctionnement d'une cellule photovoltaïque plastique et les paramètres photovoltaïques permettant de caractéiser son efficacité, un état de l'art des technologies de fabrication des cellules est présenté. Des moyens d'amélioration des performances des cellules photovoltaïques organiques sont ensuite illustrés par l'étude de dispositifs développés au Laboratoire Composants Organiques (LCO) du CEA Saclay.

CF Procedures and Practices Involving Information Aggregation

DTIC Science & Technology

2007-03-01

courants de doctrine ont été étudiés : la planification opérationnelle, le renseignement interarmées, la gestion des risques , les opérations...Aggregation Humansystems® Incorporated Résume L’efficacité opérationnelle des Forces canadiennes (FC) est tributaire de leur capacité de prendre des ...décisions opportunes et éclairées. La connaissance de toutes les variables à tenir compte dans la décision peut améliorer la démarche décisionnelle, mais

Annual Research Progress Report, Fiscal Year 1979,

DTIC Science & Technology

1979-10-01

Infusion on 58 Hemoglobin Oxygen Carrying Patterns in Man. (0) (PR) C-6-78 Minoxidil as an Anti-Hypertensive in Patients 59 Refractory to Available...aspirin. Ann. Int. Med. 89:1006, 1978. Rubin, E.N., Walker, B.K., Ersler, A.J., et al. Euthyroid aplasia complicating collagen vascular disease...Texas 78234 CLINICAL INVESTIGATION SERVICE INVESTIGATION PROJECT RESUME TITLE: Minoxidil as an Anti-Hypertensive in Patients Refractory to Available

Role of fibroblast growth factor receptor signaling in kidney development.

PubMed

Bates, Carlton M

2007-03-01

Fibroblast growth factor receptors (Fgfrs) are expressed in the ureteric bud and metanephric mesenchyme of the developing kidney. Furthermore, in vitro and in vivo studies have shown that exogenous fibroblast growth factors (Fgfs) increase growth and maturation of the metanephric mesenchyme and ureteric bud. Deletion of fgf7, fgf10, and fgfr2IIIb (the receptor isoform that binds Fgf7 and Fgf10) in mice lead to smaller kidneys with fewer collecting ducts and nephrons. Overexpression of a dominant negative receptor isoform in transgenic mice has revealed more striking defects including renal aplasia or severe dysplasia. Moreover, deletion of many fgf ligands and receptors in mice results in early embryonic lethality, making it difficult to determine their roles in kidney development. Recently, conditional targeting approaches revealed that deletion of fgf8 from the metanephric mesenchyme interrupts nephron formation. Furthermore, deletion of fgfr2 from the ureteric bud resulted in both ureteric bud branching and stromal mesenchymal patterning defects. Deletion of both fgfr1 and fgfr2 in the metanephric mesenchyme resulted in renal aplasia, characterized by defects in metanephric mesenchyme formation and initial ureteric bud elongation and branching. Thus, Fgfr signaling is critical for growth and patterning of all renal lineages at early and later stages of kidney development.

Role of fibroblast growth factor receptor signaling in kidney development.

PubMed

Bates, Carlton M

2011-09-01

Fibroblast growth factor receptors (Fgfrs) are expressed throughout the developing kidney. Several early studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB). Transgenic mice that over-express a dominant negative receptor isoform develop renal aplasia/severe dysplasia, confirming the importance of Fgfrs in renal development. Furthermore, global deletion of Fgf7, Fgf10, and Fgfr2IIIb (isoform that binds Fgf7 and Fgf10) in mice leads to small kidneys with fewer collecting ducts and nephrons. Deletion of Fgfrl1, a receptor lacking intracellular signaling domains, causes severe renal dysgenesis. Conditional targeting of Fgf8 from the MM interrupts nephron formation. Deletion of Fgfr2 from the UB results in severe ureteric branching and stromal mesenchymal defects, although loss of Frs2α (major signaling adapter for Fgfrs) in the UB causes only mild renal hypoplasia. Deletion of both Fgfr1 and Fgfr2 in the MM results in renal aplasia with defects in MM formation and initial UB elongation and branching. Loss of Fgfr2 in the MM leads to many renal and urinary tract anomalies as well as vesicoureteral reflux. Thus, Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.

A Challenge for Cochlear Implantation: Duplicated Internal Auditory Canal.

PubMed

Binnetoğlu, Adem; Bağlam, Tekin; Sarı, Murat; Gündoğdu, Yavuz; Batman, Çağlar

2016-08-01

Duplication of the internal auditory canal is an uncommon, congenital malformation that can be associated with sensorineural hearing loss owing to aplasia/hypoplasia of the vestibulocochlear nerve. Only 14 such cases have been reported to date. We report the case of a 13-month-old girl with bilateral, congenital, sensorineural hearing loss caused by narrow, duplicated internal auditory canals and discuss the challenges encountered in the diagnosis and treatment of this condition.

A novel KAL1 mutation is associated with combined pituitary hormone deficiency.

PubMed

Takagi, Masaki; Narumi, Satoshi; Hamada, Riku; Hasegawa, Yukihiro; Hasegawa, Tomonobu

2014-01-01

Using a next-generation sequencing strategy, we identified a novel KAL1 missense mutation (p.His568Gln) in a patient with combined pituitary hormone deficiency, right microphthalmia, right renal aplasia and severe developmental delay. Our findings will provide additional evidence that KAL1 mutations are associated with hypopituitarism, in addition to luteinizing hormone, and follicle-stimulating hormone deficiencies, and improve our understanding of the phenotypic features and developmental course associated with KAL1 mutations.

Ophthalmologic abnormalities in Mowat-Wilson syndrome and a mutation in ZEB2.

PubMed

Ariss, Michelle; Natan, Kristina; Friedman, Neil; Traboulsi, Elias I

2012-09-01

Mowat-Wilson syndrome is a genetic disorder characterized by a distinct facial appearance, moderate-to-severe mental retardation, microcephaly, agenesis of the corpus callosum, Hirschsprung disease, congenital heart disease, and genital anomalies. Ophthalmological abnormalities have been rarely described in patients with this condition which is caused by mutations in the ZEB2 gene. We report a 9-year-old female with this syndrome who has severe ocular abnormalities including bilateral microphthalmia, cataract, and retinal aplasia.

[Variants of radial hemimelia with and without vitium cordis (Holt-Oram syndrome) in 2 families].

PubMed

Pfeiffer, R A; Böwing, B; Deeg, K H

1989-05-01

In two families radial hemimelia is inherited as a dominant trait. The first proposita suffered from bilateral radial aplasia, the 2nd propositus exhibited (pseudo)phocomelia. In this case the diagnosis was Holt-Oram-syndrome. The affected mothers showed unilateral hypoplasia of the thumb only. Cases like these ones are likely to be overlooked or misinterpreted. The recurrence risk is 50%. Similar observations are quoted. The cause of "variable expressivity" is unknown.

Optimal RSOM-hub Locations for Northern Operations: A MAJAID Scenario Analysis

DTIC Science & Technology

2011-08-01

droit du Canada), telle que représentée par le ministre de la Défense nationale, 2011 Abstract …….. This paper presents an analysis of a...militaires et les opérations de maintien en puissance. Au cours de cette étude, les mesures de rendement ont été établies en vue d’évaluer l’efficacité...analyse plus approfondie des données réelles devrait être menée. • Au cours de l’analyse, la simulation du transport tactique était fondée sur le CH146

Stephen Neidle on cancer therapy and G-quadruplex inhibitors. Interview by Joanna De Souza.

PubMed

Neidle, Stephen

2004-09-15

Stephen Neidle was educated at Imperial College, London, where he graduated in chemistry and then proceeded to do a PhD in crystallography. After a period as an ICI Fellow, he joined the Biophysics Department at King's College, which ignited his interest in nucleic acid structural studies. He was appointed as one of the first Cancer Research Campaign Career Development Awardees, becoming a Life Fellow on moving to the Institute of Cancer Research. He was appointed to the Chair of Biophysics at the Institute of Cancer Research in 1990, and moved to the new Chair of Chemical Biology at the School of Pharmacy in the University of London in 2002, where he also directs the Cancer Research UK Biomolecular Structure Group. He is currently Chairman of the Chemical Biology Forum of the Royal Society of Chemistry, which is involved in developing the interface between chemistry and the life sciences. He will shortly assume the Directorship of the newly-established Centre for Cancer Medicines at the School. Stephen Neidle has received several awards for his work on drug-nucleic acid recognition and drug design, including the 2000 prize of the Biological and Medicinal Chemistry Sector of the Royal Society of Chemistry, and its 2002 Interdisciplinary Award. He was the 2004 Paul Ehrlich Lecturer of the French Societé de Chimie Therapeutique, and was recently awarded the 2004 Aventis Prize in Medicinal Chemistry.

UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep

ClinicalTrials.gov

2017-12-03

Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia/Lymphoma; Burkitt's Lymphoma; Natural Killer Cell Malignancies; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome; Large-cell Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Relapsed Chronic Lymphocytic Leukemia; Relapsed Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-cell Lymphoma; Prolymphocytic Leukemia; Bone Marrow Failure Syndromes; Myeloproliferative Neoplasms/Myelofibrosis; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias; MRD Positive Leukemia; Leukemia or MDS in Aplasia; Relapsed T-Cell Lymphoma; Relapsed Multiple Myeloma; Plasma Cell Leukemia

Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation

PubMed Central

Kopko, Patricia M.

2016-01-01

Summary ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation. PMID:27022318

A novel KAL1 mutation is associated with combined pituitary hormone deficiency

PubMed Central

Takagi, Masaki; Narumi, Satoshi; Hamada, Riku; Hasegawa, Yukihiro; Hasegawa, Tomonobu

2014-01-01

Using a next-generation sequencing strategy, we identified a novel KAL1 missense mutation (p.His568Gln) in a patient with combined pituitary hormone deficiency, right microphthalmia, right renal aplasia and severe developmental delay. Our findings will provide additional evidence that KAL1 mutations are associated with hypopituitarism, in addition to luteinizing hormone, and follicle-stimulating hormone deficiencies, and improve our understanding of the phenotypic features and developmental course associated with KAL1 mutations. PMID:27081504

EVALUATION AND DIAGNOSIS OF THE DYSMORPHIC INFANT

PubMed Central

Jones, Kelly L.; Adam, Margaret P.

2015-01-01

SYNOPSIS Neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate. In this review, multiple anomalies and physical features are discussed along with the potential associated genetic syndromes. The anomalies and physical features that are discussed include birth parameters, aplasia cutis congenita, holoprosencephaly, asymmetric crying facies, preauricular ear tags and pits, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, congenital heart defects, ventral wall defects, and polydactyly. PMID:26042903

Upper limb malformations in DiGeorge syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cormier-Daire, V.; Iserin, L.; Sidi, D.

1995-03-13

We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

Congenital malformations of human dermatoglyphs

PubMed Central

David, T. J.

1973-01-01

A classification for congenital malformations of dermatoglyphs is presented, dividing them into ridge aplasia, ridge hypoplasia, ridge dissociation, ridges-off-the-end, and a combination of the last two. The medical and genetic significance of these are considered in the light both of previous published cases and of new material. Malformations of dermatoglyphs are important as physical signs in paediatric diagnosis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4693462

Genetics Home Reference: congenital deafness with labyrinthine aplasia, microtia, and microdontia

MedlinePlus

... Tekin M, Hişmi BO, Fitoz S, Ozdağ H, Cengiz FB, Sirmaci A, Aslan I, Inceoğlu B, Yüksel-Konuk ... Tekin M, Oztürkmen Akay H, Fitoz S, Birnbaum S, Cengiz FB, Sennaroğlu L, Incesulu A, Yüksel Konuk EB, Hasanefendioğlu ...

Salivary glands abnormalities in oculo-auriculo-vertebral spectrum.

PubMed

Brotto, Davide; Manara, Renzo; Vio, Stefania; Ghiselli, Sara; Cantone, Elena; Mardari, Rodica; Toldo, Irene; Stritoni, Valentina; Castiglione, Alessandro; Lovo, Elisa; Trevisi, Patrizia; Bovo, Roberto; Martini, Alessandro

2018-01-01

Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p < 0.001). Submandibular salivary gland hypoplasia was associated to Goldenhar phenotype (p < 0.05). Parotid gland abnormalities were associated with ipsilateral fifth (p < 0.001) and seventh cranial nerve (p = 0.001) abnormalities. No association was found between parotid gland anomaly and ipsilateral internal carotid artery, inner ear, brain, eye, or spine abnormalities (p > 0.6). Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment.

Treatment posibilities in ectromelia.

PubMed

Nemeş, Dan; Poenaru, Dan; Bereteu, Oana; Onofrei, Roxana; Amaricai, Elena; Totorean, Alina

2007-01-01

Ectromelia is a congenital abnormality characterised by limb growth disturbances (aplasia or hypoplasia) during the period from 4th to 8th gestation week. We present a case of hemimezomelic longitudinal ectromelia of the right upper limb associated with other skeletal abnormalities, surgically treated. An important role in the management of this case is attributed to the complex rehabilitation programme done before and after each surgical intervention. The aim of the complex therapy is to diminish the permanent invalidity of these patients.

Adsorption de gaz sur les materiaux microporeux modelisation, thermodynamique et applications

NASA Astrophysics Data System (ADS)

Richard, Marc-Andre

2009-12-01

Nos travaux sur l'adsorption de gaz dans les materiaux microporeux s'inscrivent dans le cadre des recherches visant a augmenter l'efficacite du stockage de l'hydrogene a bord des vehicules. Notre objectif etait d'etudier la possibilite d'utiliser l'adsorption afin d'ameliorer l'efficacite de la liquefaction de l'hydrogene des systemes a petite echelle. Nous avons egalement evalue les performances d'un systeme de stockage cryogenique de l'hydrogene base sur la physisorption. Comme nous avons affaire a des plages de temperatures particulierement etendues et a de hautes pressions dans la region supercritique du gaz, nous avons du commencer par travailler sur la modelisation et la thermodynamique de l'adsorption. La representation de la quantite de gaz adsorbee en fonction de la temperature et de la pression par un modele semi-empirique est un outil utile pour determiner la masse de gaz adsorbee dans un systeme mais egalement pour calculer les effets thermiques lies a l'adsorption. Nous avons adapte le modele Dubinin-Astakhov (D-A) pour modeliser des isothermes d'adsorption d'hydrogene, d'azote et de methane sur du charbon actif a haute pression et sur une grande plage de temperatures supercritiques en considerant un volume d'adsorption invariant. Avec cinq parametres de regression (incluant le volume d'adsorption Va), le modele que nous avons developpe permet de tres bien representer des isothermes experimentales d'adsorption d'hydrogene (de 30 a 293 K, jusqu'a 6 MPa), d'azote (de 93 a 298 K, jusqu'a 6 MPa) et de methane (de 243 a 333 K, jusqu'a 9 MPa) sur le charbon actif. Nous avons calcule l'energie interne de la phase adsorbee a partir du modele en nous servant de la thermodynamique des solutions sans negliger le volume d'adsorption. Par la suite, nous avons presente les equations de conservation de la niasse et de l'energie pour un systeme d'adsorption et valide notre demarche en comparant des simulations et des tests d'adsorption et de desorption. En plus de l

Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

NASA Astrophysics Data System (ADS)

Belanger, Simon

La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

PubMed

Ramalho, Fernando S; Yamamoto, Aparecida Y; da Silva, Luis L; Figueiredo, Luiz T M; Rocha, Lenaldo B; Neder, Luciano; Teixeira, Sara R; Apolinário, Letícia A; Ramalho, Leandra N Z; Silva, Deisy M; Coutinho, Conrado M; Melli, Patrícia P; Augusto, Marlei J; Santoro, Ligia B; Duarte, Geraldo; Mussi-Pinhata, Marisa M

2017-08-15

We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The position of symbrachydactyly in the classification of congenital hand anomalies.

PubMed

Miura, T; Nakamura, R; Horii, E

1994-06-01

The clinical features of 53 cases of intercalated hypoplasia and 113 cases of distal aplasia are reviewed and compared with each other and with 129 cases of syndactyly. Tri-, di- and mono-phalangeal symbrachydactyly, and adactyly with nubbin digits are consecutive anomalies. Transverse deficiency may result if the mesenchyme is damaged severely, and if damage is mild and formation has continued, intercalated transverse deficiency may occur. Webbing in symbrachydactyly may result from failure of the apical ectodermal ridge under the influence of damaged mesenchyme.

An electrochemical study of the action of a poly(vinylpyridine) derivative as inhibitor for corrosion of iron in 1M H2SO4

NASA Astrophysics Data System (ADS)

Abed, Y.; Arrar, Z.; Hammouti, B.; Aouniti, A.; Kertit, S.; Mansri, A.

1999-09-01

The influence of the addition of poly(4-vinylpyridine poly-3-oxide ethylene) (P4VPP3OE) on the corrosion of Armco iron in molar sulphuric acid has been investigated by potentiodynamic and polarisation resistance measurements. The polymer studied reduces the corrosion current densities. The inhibition efficiency (E%) of P4VPP3OE increases wiht its concentration and attains 99% at 3.33 10-5 M. E% obtained from cathodic Tafel plots and polarisation resistance methods were in good agreement. The inhibitor was adsorbed on the iron surface according to the Frumkin adsorption isotherm model. Polarisation measurements show also that the compound acts as a cathodic inhibitor. L'influence de l'addition du Poly(4-vinylpyridine poly-3-oxyde éthylène) nouvellement synthétisé au laboratoire sur la corrosion du fer Armco dans l'acide sulfurique molaire a été étudié par les méthodes potentiodynamique et la résistance de polarisation. La présence du polymère réduit la densité du courant cathodique et augmente la résistance de polarisation. Ce phénomène s'accentue avec la concentration du produit. Les pentes de Tafel obtenues à partir des courbes cathodiques sont parallèles indiquant qu'en absence et en présence de l'inhibiteur, la réduction du proton se fait selon le même mécanisme d'activation pure. L'efficacité d'inhibition augmente avec la concentration et atteint 99 % à 3.3 10-5 M. Les efficacités obtenues par les deux méthodes sont en bon accord. L'inhibiteur s'adsorbe sur la surface métallique selon l'isotherme de Frumkin. Les mesures de polarisation montrent ainsi que le composé agit essentiellement comme inhibiteur cathodique.

Impact of anatomical variations of the circle of Willis on the incidence of aneurysms and their recurrence rate following endovascular treatment.

PubMed

Songsaeng, D; Geibprasert, S; Willinsky, R; Tymianski, M; TerBrugge, K G; Krings, T

2010-11-01

To analyse the impact of anatomical variations of the parent arteries on the incidence and recurrence rate following coil embolization of aneurysms of the anterior (AcoA), posterior communicating artery (PcoA) and basilar artery (BA) tip. Two hundred and two (96 AcoA, 67 PcoA, and 29 BA) aneurysms in 200 patients were treated with coil embolization between January 2000 and April 2008. Parent artery variations at each location were classified as: AcoA: A1 aplasia versus hypoplasia versus symmetrical size; PcoA: foetal origin versus medium versus small size, BA: cranial versus caudal versus asymmetrical fusion. The incidence of aneurysms and difference between recurrence rates for each group were recorded on follow-up. AcoA, PcoA, and BA aneurysms were more often associated with embryonically earlier vessel wall dispositions (A1 aplasia, foetal PcoA, asymmetrical fusion). Two of these variations were also associated with aneurysm recurrence following coil embolization: asymmetrical A1 segment (p=0.01), and asymmetrical BA tip (p=0.02). AcoA, PcoA, and BA tip aneurysms tend to occur more often in anatomically variant parent artery dispositions, some of which are related to aneurysm recurrence following coil embolization. This may relate to a more fragile vessel disposition as it is not fully matured or to altered haemodynamics secondary to the anatomical variations. Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial.

PubMed

Schetelig, J; Schaich, M; Schäfer-Eckart, K; Hänel, M; Aulitzky, W E; Einsele, H; Schmitz, N; Rösler, W; Stelljes, M; Baldus, C D; Ho, A D; Neubauer, A; Serve, H; Mayer, J; Berdel, W E; Mohr, B; Oelschlägel, U; Parmentier, S; Röllig, C; Kramer, M; Platzbecker, U; Illmer, T; Thiede, C; Bornhäuser, M; Ehninger, G

2015-05-01

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.

Holt-Oram syndrome and diaphragmatic hernia associate with paracentric inversion of chromosome 8

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eswara, M.S.; Batanian, J.R.

1994-09-01

Holt-Oram syndrome (HOS) consists of congenital heart disease, usually atrial septal defect, along with thumb anomalies and occasionally more extensive limb defects. Inheritance is autosomal dominant. Previous reports have associated HOS with cytogenetic abnormalities on chromosomes 4, 14 and 20. Recently a linkage study has suggested a HOS locus on chromosome 12. We describe another case of HOS with a de novo cytogenetic abnormality. On prenatal ultrasound, IUGR, oligohydramnios and left diaphragmatic hernia were noted. Following delivery, patient was placed on extra-corporeal membrane oxygenation because of severe lung hypoplasia; diaphragmatic hernia was repaired with mesh graft. He expired on daymore » 17 of life. On exam, he had subtle dysmorphic features with hypotelorism and abnormal folding of the ear lobes. He had bilateral radial aplasia, aplasia of thumbs, index and middle fingers, along with the metacarpals. On autopsy he was found to have atrial septal defect of the ostium secundum type, right side aortic arch with vascular ring formation, bicuspid pulmonic valve and severe lung hypoplasia worse on the left. Cytogenetic analysis on blood and skin showed 48,XX,inv(8)(q24.2q13). Chromosome fragility study was negative. Parental chromosomes were normal. Our observation of inv(8)q with HOS and diaphragmatic hernia may indicate genetic heterogeneity with this condition. Regulation of morphogenesis is likely under the control of a hierarchy of genes; multiple loci for conditions such as HOS would not be surprising.« less

Congenital oval or round window anomaly with or without abnormal facial nerve course: surgical results for 15 ears.

PubMed

Thomeer, Henricus; Kunst, Henricus; Verbist, Berit; Cremers, Cor

2012-07-01

To describe the audiometric results in a consecutive series of patients with congenital ossicular aplasia (Class 4a) or dysplasia of the oval and/or round window (Class 4b), which might include a possible anomalous course of the facial nerve. Retrospective chart study. Tertiary referral center. A tertiary referral center study with a total of 14 patients with congenital minor ear anomalies as part of a consecutive series (n = 89) who underwent exploratory tympanotomies (15 ears). Audiometric results. In 8 of 15 ears, ossicular reconstruction was attempted. In the short term (1 mo), there was a serviceable hearing outcome (air-bone gap closure to within 25 dB) in 4 ears. However, the long-term results showed deterioration because of an increased air-bone gap in all but 1 ear. No facial nerve lesion was observed postoperatively. Congenital dysplasia or aplasia of the oval and/or round window is an uncommon congenital minor ear anomaly. Classical microsurgical opportunities are rare in this group of anomalies. Newer options for hearing rehabilitation, such as the osseointegrated passive bone conduction devices, have become viable alternatives for conventional air conduction hearing devices. In the near future, upcoming active bone conduction devices might become the most preferred surgical option. In cases in which the facial nerve is only partially overlying the oval window, a type of malleostapedotomy procedure might result in a serviceable postoperative hearing level.

[Bilateral hypoplasia of the internal carotid arteries associated with aneurysm of the right posterior communicating artery. Apropos of a case].

PubMed

el Khamlichi, A; Amrani, F; el Azzusi, M; el Oufir, M; Khamlichi, A M

1989-01-01

The authors report a case of bilateral hypoplasia of the internal carotid arteries associated with aneurysm of the right posterior communicating artery in a 17 year old female patient. This anomaly was discovered following a meningeal haemorrhage, which recurred 18 months later, causing the patient's death. Surgical operation was refused by the patient and her family. Bilateral hypoplasia of the internal carotid arteries is a rare congenital malformation (16 cases have been reported in the literature, our case constitutes the 17th). It is distinguished from aplasia by the presence of a patent but very reduced vascular lumen, while aplasia is associated with vestiges of non-patent vessels. The mechanism of development of such a malformation is unclear: some authors have suggested secondary regression of the internal carotid artery following a phase of normal development, while others consider it to represent arrest of the development of the internal carotid artery, at a given moment in time. The frequency of associated aneurysm would be due to the haemodynamic disruption induced by the malformation, especially as parietal defects are more frequent in a malformed vasculature. Bilateral hypoplasia of the internal carotid arteries may be compatible with normal life for an indefinite period of time due to the development of a large number of collateral vessels. However, the new vasculature is threatened by rupture with meningeal haemorrhage and by acute ischaemia, which would probably involve another aetiological factor.

L'Apport de la Greffe de Peau Totale dans le Traitement des Sequelles des Brulures de la Main: a Propos de 14 Cas

PubMed Central

Ettalbi, S.; Ibnouzahir, M.; Rachid, M.; Bahaichar, N.; Boukind, H.

2007-01-01

Summary La main est fréquemment exposée aux brûlures, ce qui entraîne des séquelles cutanées. A partir d'une série de 14 patients suivis dans notre service sur une année, nous avons essayé d'établir la simplicité, l'efficacité et le rôle de la greffe de peau totale dans le traitement de ces séquelles (les organes nobles ne sont pas mis à nu). La greffe de peau totale associée à une rééducation efficace permet aux patients de reprendre la mobilité des mains dans les brefs délais. PMID:21991094

Long-term survival of donor bone marrow multipotent mesenchymal stromal cells implanted into the periosteum of patients with allogeneic graft failure.

PubMed

Kuzmina, L A; Petinati, N A; Sats, N V; Drize, N J; Risinskaya, N V; Sudarikov, A B; Vasilieva, V A; Drokov, M Y; Michalzova, E D; Parovichnikova, E N; Savchenko, V G

2016-09-01

The present study involved three patients with graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We obtained multipotent mesenchymal stromal cells (MSCs) from the original hematopoietic cell donors and implanted these cells in the periosteum to treat long-term bone marrow aplasia. The results showed that in all patients endogenous blood formation was recovered 2 weeks after MSC administration. Donor MSCs were found in recipient bone marrow three and 5 months following MSC implantation. Thus, our findings indicate that functional donor MSCs can persist in patient bone marrow.

Bone marrow transplantation in a patient with drug-induced aplastic anemia.

PubMed

Banerjee, T K; Band, P R; Pabst, H; Goldsand, G; Armstrong, W D; Brown, J; Hill, J R; Dossetor, J B

1972-09-09

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.

Hepatitis A and parvovirus B19 infections in an infant with fulminant hepatic failure.

PubMed

Ozçay, Figen; Bikmaz, Y Emre; Canan, Oğuz; Ozbek, Namik

2006-06-01

Acute viral hepatitis with hepatitis A, B, C, D, and E viruses in the etiology of fulminant hepatic failure either single or in combinations has been described. Parvovirus B19 is also an etiologic agent of acute liver failure and hepatitis-associated aplastic anemia. We present a patient diagnosed with fulminant hepatitis A referred for liver transplantation. Parvovirus B19 superinfection was detected when the patient developed anemia during the course of the disease. We discuss possible roles of both viruses in fulminant hepatitis and pure red cell aplasia.

[Parvovirus B19 infection as the cause of hepatitis and neutrophil granulocytosis in a 20-year old woman].

PubMed

Wiggers, H; Rasmussen, L H; Møller, A

1995-10-23

A case of Parvovirus B19 infection (erythema infectiosum) in a 20 year old woman is presented. The patient presented with fever, arthritis in one knee, neutrophil granulocytosis and biochemical evidence of hepatitis. Serological evidence of Parvovirus B19 infection was found as the only explanation of the clinical picture. Hepatitis was due to Parvovirus B19 infection as there was no serological evidence of EBV or CMV reactivation. Neutrophil granulocytosis and thrombocytosis were found and were probably due to an active bone marrow in the recovery phase of bone marrow aplasia.

How many breaks do we need to CATCH on 22q11?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dallapiccola, B.; Pizzuti, A.; Novelli, G.

1996-07-01

The major clinical manifestations of DiGeorge syndrome (DGS; MIM 188400), which reflect developmental abnormalities of the 3d and 4th pharyngeal pouch derivatives, include thymus- and parathyroid-gland aplasia or hypoplasia and conotruncal cardiac malformations. The additional dysmorphic facial features, such as hypertelorism, cleft lip and palate, bifid uvula, and small/low-set ears, which are also common, presumably reflect the same defect. The DGS phenotype has been associated with chromosome abnormalities and, sometimes, is the effect of teratogenic agents such as retinoic acid and alcohol. 53 refs., 1 fig.

Colovaginoplasty in a Case of Mayer-Rokitansky-Kuster-Hauser Syndrome

PubMed Central

Iqbal, Muhammad Zafar; Jam, Mazher Rafee; Ahmad, Mushtaq; Mirza, Bilal

2014-01-01

Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS) is characterized by various abnormalities of paramesonephric duct structures; vaginal aplasia being the commonest anomaly in the spectrum. We report a 17-year-old girl; a case of MRKHS with vaginal agenesis. The cervix was present but atretic; uterus, fallopian tubes and ovaries were normal. There were no associated renal or skeletal defects. Colovaginoplasty was done to bridge the gap between uterus and introitus. Postoperatively, small part of colovaginoplasty flap became necrotic posteriorly, which was ultimately managed by insetting of labial flap. PMID:24834388

Colovaginoplasty in a case of mayer-rokitansky-kuster-hauser syndrome.

PubMed

Saleem, Muhammad; Iqbal, Muhammad Zafar; Jam, Mazher Rafee; Ahmad, Mushtaq; Mirza, Bilal

2014-01-01

Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS) is characterized by various abnormalities of paramesonephric duct structures; vaginal aplasia being the commonest anomaly in the spectrum. We report a 17-year-old girl; a case of MRKHS with vaginal agenesis. The cervix was present but atretic; uterus, fallopian tubes and ovaries were normal. There were no associated renal or skeletal defects. Colovaginoplasty was done to bridge the gap between uterus and introitus. Postoperatively, small part of colovaginoplasty flap became necrotic posteriorly, which was ultimately managed by insetting of labial flap.

Effets potentiels d’un modèle rationnel de prescription sur les dépenses nationales en santé

PubMed Central

Littman, Jordan; Halil, Roland

2016-01-01

Résumé Objectif Estimer les économies que pourrait engendrer la mise en œuvre d’un modèle rationnel de prescription pour des classes de médicaments équivalents sur les plans de l’efficacité, de la toxicité et de la commodité. Conception L’Institut canadien d’information sur la santé a fourni des renseignements sur les 10 principales classes de médicaments en fonction des dépenses annuelles qui leur sont attribuables. Ces classes ont été examinées en vue de leur inclusion potentielle dans l’étude selon qu’il était possible de comparer les médicaments à l’intérieur d’une même classe. Lorsqu’à la suite d’une recherche documentaire, une équivalence a été établie en fonction de l’efficacité, de la toxicité et de la commodité des médicaments, les données annuelles sur les prescriptions ont été recueillies à partir de la base de données du Système national d’information sur l’utilisation des médicaments prescrits. Les économies potentielles de coûts ont ensuite été calculées en comparant les parts de marché actuelles avec les parts potentielles futures de ce marché. Contexte Le Canada. Principaux paramètres à l’étude Les différences estimées dans les dépenses que produirait un modèle rationnel de prescription. Résultats Une équivalence a été établie sur les plans de l’efficacité, de la toxicité et de la commodité dans les classes de statines, d’inhibiteurs de la pompe à protons, d’inhibiteurs de l’enzyme de conversion de l’angiotensine et d’inhibiteurs sélectifs du recaptage de l’angiotensine. Les dépenses annuelles totales dans ces classes se situent à 856 millions $ dans les programmes publics de médicaments et à 1,97 milliard $ environ à l’échelle nationale. Grâce à des prescriptions rationnelles, on estime que les économies annuelles pourraient atteindre 222 millions $ pour les programmes publics et 521 millions $ à l’échelle nationale. Conclusion La

The cerebral arterial circle (circulus arteriosus cerebri): an anatomical study in fetus and infant samples.

PubMed

Ardakani, Shahab Kamali; Dadmehr, Majid; Nejat, Farideh; Ansari, Saeed; Eftekhar, Behzad; Tajik, Parvin; El Khashab, Mostafa; Yazdani, Shahrooz; Ghodsi, Mohammad; Mahjoub, Fatemeh; Monajemzadeh, Maryam; Nazparvar, Bashir; Abdi-Rad, Afshin

2008-01-01

Many studies have investigated the variations in the anatomy of each segment of the cerebral arterial circle while a few have addressed the variations of the cerebral arterial circle as a whole. Thirty brains of recently deceased Iranian infants and fetuses were dissected. The dissection process was filmed and digitized so as to be readily available for further studies. The variations of the circle as a whole and segmental variations were evaluated. Variants with uni- and bilateral hypoplasia of posterior communicating arteries (PcoAs) were the most common in our study, similar to previous works. No aplasia of the precommunicating part of the anterior cerebral artery (A1), the precommunicating part of the posterior cerebral artery (P1) and anterior communicating artery was seen. Hypoplasia of the right and left PcoA was observed in 8 and 5 cases, respectively. Aplasia of the right PcoA was found in 16.6% and of the left PcoA in 3.3%. In this study, we confirmed the previously described finding that the symmetrical, circular configuration of the circulus arteriosus cerebri is present in only about 42.1%. The main differences between the fetal and adult disposition are the diameter of the PcoA and the circular part of the posterior cerebral artery. According to previous studies, the fetal brain older than 4 months has anatomical characteristics very similar to the adult's circle; our finding was mostly similar to adult samples as most samples were from infants, not fetuses. (c) 2008 S. Karger AG, Basel.

Ultrasonography of Various Thyroid Diseases in Children and Adolescents: A Pictorial Essay

PubMed Central

Lee, Eun Hye; Jeong, Sun Hye; Park, Jisang; Lee, Heon

2015-01-01

Thyroid imaging is indicated to evaluate congenital hypothyroidism during newborn screening or in cases of a palpable thyroid mass in children and adolescents. This pictorial essay reviews the ultrasonography (US) of thyroid diseases in children and adolescents, including normal thyroid gland development, imaging features of congenital thyroid disorders (dysgenesis, [aplasia, ectopy, hypoplasia], dyshormonogenesis, transient hypothyroidism, thyroglossal duct cyst), diffuse thyroid disease (Grave's disease, Hashimoto's thyroiditis, and suppurative thyroiditis), and thyroid nodules. The primary imaging modalities for evaluating thyroid diseases are US and radionuclide scintigraphy. Additionally, US can be used to guide aspiration of detected nodules. PMID:25741204

Acquired Aplastic Anemia: What Have We Learned and What Is in the Horizon?

PubMed

Savaşan, Süreyya

2018-06-01

Acquired aplastic anemia (aAA) characterized by peripheral pancytopenia and bone marrow aplasia is a rare and serious disorder. Differential diagnosis includes constitutional bone marrow failure syndromes and myelodysplastic disorders. Autoimmune reaction to altered hematopoietic stem cells highlights the underlying mechanism. Matched related donor allogeneic hematopoietic stem cell transplantation is the ideal pediatric treatment; alternative approaches include immunosuppressive therapy and use of eltrombopag. Progression to clonal disorders can occur. Recently, alternative donor hematopoietic stem cell transplantation outcomes have significantly improved. Despite advances, aAA continues to be a challenge for hematologists. Copyright © 2018 Elsevier Inc. All rights reserved.

2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

PubMed

Gejyo, Fumitake; Saito, Akira; Akizawa, Tadao; Akiba, Takashi; Sakai, Tatsuya; Suzuki, Masashi; Nishi, Shinichi; Tsubakihara, Yoshiharu; Hirakata, Hideki; Bessho, Masami

2004-12-01

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic

Le Sommeil et l’Age: de la Physiopathologie a la Therapeutique (Sleep and Age: From Physiopathology to Therapeutics)

DTIC Science & Technology

2000-08-01

the pineal gland , presents a - Sleep hygiene circadian rhythm with a maximal production at 02:00. It Sleep being sensible to each behavioral...widely used in sports and military - a calcification of the pineal gland , scopes to allow a better tolerance to sleep deprivation. It - a more intensive...the genetic expression level in the performance (Dinges & Broughton, 1989). However, suprachiasmatic nucleus and/or the pineal gland , this method can

Developpement de mesures non destructives, par ondes ultrasonores, d'epaisseurs de fronts de solidification dans les reacteurs metallurgiques

NASA Astrophysics Data System (ADS)

Floquet, Jimmy

Dans les cuves d'electrolyse d'aluminium, le milieu de reaction tres corrosif attaque les parois de la cuve, ce qui diminue leur duree de vie et augmente les couts de production. Le talus, qui se forme sous l'effet des pertes de chaleur qui maintiennent un equilibre thermique dans la cuve, sert de protection naturelle a la cuve. Son epaisseur doit etre controlee pour maximiser cet effet. Advenant la resorption non voulue de ce talus, les degats generes peuvent s'evaluer a plusieurs centaines de milliers de dollars par cuve. Aussi, l'objectif est de developper une mesure ultrasonore de l'epaisseur du talus, car elle serait non intrusive et non destructive. La precision attendue est de l'ordre du centimetre pour des mesures d'epaisseurs comprenant 2 materiaux, allant de 5 a 20 cm. Cette precision est le facteur cle permettant aux industriels de controler l'epaisseur du talus de maniere efficace (maximiser la protection des parois tout en maximisant l'efficacite energetique du procede), par l'ajout d'un flux thermique. Cependant, l'efficacite d'une mesure ultrasonore dans cet environnement hostile reste a demontrer. Les travaux preliminaires ont permis de selectionner un transducteur ultrasonore a contact ayant la capacite a resister aux conditions de mesure (hautes temperatures, materiaux non caracterises...). Differentes mesures a froid (traite par analyse temps-frequence) ont permis d'evaluer la vitesse de propagation des ondes dans le materiau de la cuve en graphite et de la cryolite, demontrant la possibilite d'extraire l'information pertinente d'epaisseur du talus in fine. Fort de cette phase de caracterisation des materiaux sur la reponse acoustique des materiaux, les travaux a venir ont ete realises sur un modele reduit de la cuve. Le montage experimental, un four evoluant a 1050 °C, instrumente d'une multitude de capteurs thermique, permettra une comparaison de la mesure intrusive LVDT a celle du transducteur, dans des conditions proches de la mesure

Déclenchement du travail à terme par le misoprostol: expérience d'une maternité tunisienne

PubMed Central

Ouerdiane, Nadia; Tlili, Nihel; Othmani, Kaouther; Daaloul, Walid; Masmoudi, Abdelwaheb; Hamouda, Sonia Ben; Bouguerra, Badreddine

2016-01-01

Evaluer l'efficacité et l'innocuité de l'utilisation du misoprostol par voie vaginale pour le déclenchement du travail à terme. Etude prospective réalisée au service de gynécologie obstétrique B de l'hôpital Charles Nicolle de Tunis sur une durée de 4 mois. La population sélectionnée concernait les patientes à terme devant bénéficier d'une maturation cervicale. Le misoprostol à la dose de 50 µg par voie vaginale toutes les 12 h était utilisé. Les paramètres étudiés étaient les anomalies contractiles, les anomalies du RCF, le mode d'accouchement, le délai d'accouchement et l’état néonatal. 44 patientes ont bénéficié d'une maturation cervicale par misoprostol. Le terme moyen était de 40 SA. Le taux de nullipare était de 23/44 (52%). Le taux d'accouchement par voie basse était de 31/44 (70.4%). 84% des patientes ont reçu une seule dose de misoprostol. Les anomalies du RCF ont été notées dans 14/44 (32%). Le taux de liquides méconiaux était de 12/44 (27%). Un score d'Apgar à 5 mn inférieur à 7 était noté chez 7/44 (16%). Un cas de rupture utérine était survenue chez une primipare et ce après une seule prise de misoprostol. Nos résultats sont décevants en raison de la survenue d'une rupture utérine et d'une morbidité néonatale importante. D'autres études prospectives multicentriques restent utiles pour mieux s'assurer de l'efficacité mais surtout de l'innocuité du misoprostol à dose faible pour le déclenchement du travail à terme. PMID:27583092

Assessment of liver and cardiac iron overload using MRI in patients with chronic anemias in Latin American countries: results from ASIMILA study.

PubMed

Cancado, Rodolfo; Watman, Nora P; Lobo, Clarisse; Chona, Zulay; Manzur, Fernando; Traina, Fabiola; Park, Miriam; Drelichman, Guillermo; Zarate, Juan Pablo; Marfil, Luis

2018-04-17

A multicenter, noninterventional, observational study was conducted in the Latin American countries including Argentina, Brazil, Colombia, Mexico, and Venezuela to assess the prevalence of liver and cardiac iron overload using magnetic resonance imaging (MRI) in patients with chronic anemias except thalassemia. Patients aged >10 years with transfusion-dependent anemias, except thalassemia, either with <20 units of red blood cell (RBC) transfusions with serum ferritin (SF) levels >2000 ng/mL or with ≥20 units of RBC transfusions regardless of SF level in their lifetime, were enrolled. Iron overload was assessed using MRI. Among 175 patients included, the majority had sickle cell disease (SCD; 52%), followed by aplastic anemia (AA; 17.7%), myelodysplastic syndrome (MDS; 8.6%), Diamond-Blackfan anemia (DBA; 4%), pure red cell aplasia (1.1%), and others (16.6%). Liver iron overload was observed in 76.4% of patients, while cardiac iron overload was seen in 19.2% when assessed by MRI. The prevalence of iron overload was 80.2% in patients with SCD, 73.3% in MDS, 77.4% in AA, 100% in pure red cell aplasia, 71.4% in DBA, and 68.9% in other transfusion-related disorders. A moderate correlation between liver iron concentration (LIC) and SF was observed in patients with SCD and MDS (r = 0.47 and r = 0.61, respectively). All adverse events reported were consistent with the published data for deferasirox or underlying disease. A high prevalence of iron overload in this patient population in Latin American countries indicates that a better diagnosis and management of iron overload is required in these countries.

Phocomelia: Case report and differential diagnosis.

PubMed

Osadsky, Captain Rasto

2011-01-01

While rarely seen in the present-day Western world, phocomelia is not uncommon in underdeveloped countries. Phocomelia is an abnormality in which the limbs are not fully formed. It may be inherited as an autosomal recessive or dominant disorder. This case concerns a 12-year-old Afghan boy with multiple skeletal anomalies, most prominently of his right arm, including aplasia of the entire proximal humerus, hypoplasia of the clavicle and scapula, and absence of the radial ray and thumb. A hypoplastic left thumb was also present. Other anomalies included thoracic scoliosis, upper thoracic hemivertebrae, and mild cardiomegaly. The differential diagnosis and likely diagnosis are discussed.

Biochemistry of seminal plasma in azoospermic men.

PubMed

Perez-Pelaez, M; Jeyendran, R S; Alagaratnam, D

1985-01-01

Seminal plasma from 20 azoospermic and 4 vasectomized men and 75 samples from normal ejaculates were quantitated colorimetrically for zinc, fructose, and glycerylphosphorylcholine (GPC) contents. The results were similar to those obtained in the normal ejaculates, in 17 of 21 azoospermic ejaculates, whereas in the vasectomized ejaculates, GPC values were reduced. In the remaining 4 azoospermic ejaculates, less than 15% of fructose and GPC and a zinc content three times higher than normal were detected. Vasogram performed in these 4 azoospermic men revealed occlusion or aplasia of the ampula. The data suggest that biochemical evaluation may aid in differential diagnosis of the etiology of azoospermia.

PET/CT in a Patient Diagnosed With Dandy-Walker Syndrome.

PubMed

Infante, Jose R; Garcia, Lucia; Rayo, Juan I; Serrano, Justo; Dominguez, Maria L; Moreno, Manuel

2016-01-01

The Dandy-Walker syndrome (DWS) is a rare congenital posterior fossa malformation characterized by aplasia or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. We present a 52-year-old Caucasian man diagnosed with gastrointestinal stromal tumor and submitted to 18F-FDG PET/CT as a staging procedure. The patient was previously diagnosed with DWS in brain CT scan. PET/CT images revealed an ametabolic large cyst in the posterior fossa and hypoplasia of cerebellar vermis. The case is presented with the aim to show the appearance of this syndrome on PET/CT study.

Epidermal nevus syndrome and didymosis aplasticosebacea.

PubMed

Demerdjieva, Zdravka; Kavaklieva, Svetlana; Tsankov, Nikolay

2007-01-01

The epidermal nevus syndrome is a disease complex consisting of the association of an epidermal nevus with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular, and urogenital systems. The epidermal nevi are classified according to their predominant component; nevus sebaceus (sebaceous glands), nevus comedonicus (hair follicles), and nevus verrucosus (keratinocytes). We report a neonate who presented with a nevus sebaceus on the scalp and face as well as a coloboma and dermoid on his left eye. Within the sebaceous nevus on the scalp, circumscribed lesions of aplasia cutis congenita were detected, which is consistent with the recently proposed term in the literature didymosis aplasticosebacea.

Human parvovirus B19 infection during the inactive stage of systemic lupus erythematosus.

PubMed

Suzuki, Takashiro; Saito, Shinichiro; Hirabayashi, Yasuhiko; Harigae, Hideo; Ishii, Tomonori; Kodera, Takao; Fujii, Hiroshi; Munakata, Yasuhiko; Sasaki, Takeshi

2003-06-01

A 42-year-old woman with systemic lupus erythematosus (SLE) had an episode of fever, arthralgia and anemia. In order to treat the suspected activation of SLE, the daily dose of steroid was increased, however, the anemia progressed and pancytopenia developed. Both IgM anti-B19 antibodies to human parvovirus B19 (B19) and B19 DNA were positive, and bone marrow analysis revealed pure red cell aplasia with giant proerythroblasts. High dose gamma globulin was administered and the daily dose of steroid was tapered, resulting in the improvement of her condition. B19 infection should be ruled out in cases with reactivation of autoimmune diseases.

Management of Congenital Chest Wall Deformities

PubMed Central

Blanco, Felix C.; Elliott, Steven T.; Sandler, Anthony D.

2011-01-01

Congenital chest wall deformities are considered to be anomalies in chest wall growth. These can be categorized as either rib cage overgrowth or deformities related to inadequate growth (aplasia or dysplasia). Rib cage overgrowth leads to depression of the sternum (pectus excavatum) or protuberance of the sternum (pectus carinatum) and accounts for greater than 90% of congenital chest wall deformities. The remaining deformities are a result of inadequate growth. Evolution in the management of congenital chest wall deformities has made significant progress over the past 25 years. This article will review chest wall deformities and the current management strategies of these interesting anomalies. PMID:22294949

[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].

PubMed

Levy, A; Guitera, P; Kerob, D; Ollivaud, L; Archimbaud, A; Dubertret, L; Basset-Seguin, N

2006-02-01

Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis. Its clinical and hematological safety is usually good. Hypersensitivity in hepatic failure patients is the most serious side effect described. This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003. Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values). Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded. Twenty patients were included, 11 women and 9 men of median age 58.6 years (22-82 years) with multiple metastases in all cases. DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status. Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group. In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment. In 2 patients, treatment was stopped after the second course because of disease progression. In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment. Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively. In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology. Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment. Hypersensitivity with DTIC seems to be frequent, being observed in 20

Thrombophlébite cérébrale inhabituelle du post-partum

PubMed Central

El Hassani, Moulay Elmehdi; Habib, Abdellah Baba; Kouach, Jaouad; Sekkach, Youssef; Bakkali, Hicham; Jira, Mohamed; Elqatni, Mohamed; Abouzahir, Ali; Ghafir, Dris; Moussaoui, Dris; Dehayni, Mohamed

2014-01-01

La thrombophlébite cérébrale du post-partum immédiat constitue un événement rare et gravissime pouvant mettre en jeu le pronostic vital à court terme. Celle-ci doit être systématiquement évoquée devant la persistance d'une fièvre dans les suites de couches. La prise en charge associera le plus souvent, des antibiotiques à large spectre et des anticoagulants. Le suivi évolutif est indispensable, afin d'apprécier l'efficacité thérapeutique. A travers une observation singulière et à présentation inhabituelle, nous insistons sur le grand intérêt des moyens d'imagerie dont nous disposons afin de porter le diagnostic et de choisir le traitement le mieux adapté. PMID:25478039

Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation.

PubMed

Yoshihara, Ai; Noh, JaedukYoshimura; Yamaguchi, Takuhiro; Ohye, Hidemi; Sato, Shiori; Sekiya, Kenichi; Kosuga, Yuka; Suzuki, Miho; Matsumoto, Masako; Kunii, Yo; Watanabe, Natsuko; Mukasa, Koji; Ito, Kunihiko; Ito, Koichi

2012-07-01

Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy. We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women. We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations. The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation. In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

[Retrospective study of 25 cases of pulmonary mucormycosis in acute leukaemia].

PubMed

Caillot, D; Legouge, C; Lafon, I; Ferrant, E; Pagès, P B; Plocque, A; Estivalet, L; Valot, S; Dalle, F; Abou Hanna, H; Chretien, M-L

2018-04-01

In acute leukaemia (AL), the occurrence of pulmonary mucormycosis (PM), the incidence of which is increasing, as a result of chemotherapy induced marrow aplasia, remains a life threatening complication. Analysis of clinical, biological and thoracic CT characteristics of patients with PM developing during the treatment of AL between 2000 and 2015. Day 0 (D0) was defined as the day with first CT evidence of PM. Among 1193 patients, 25 cases of PM were recorded during 2099 episodes of bone marrow aplasia. At time of diagnosis of PM, 24/25 patients had been neutropenic for a median of 12 days. None of the patients had diabetes mellitus. On initial CT (D0), the lesion was solitary in 20/25 cases and a reversed halo sign (RHS) was observed in 23/25 cases. From D1 to D7, D8 to D15 and after D15, RHS was seen in 100 %, 75 % and 27 % of cases, respectively. A tissue biopsy was positive in 17/18 cases. The detection of circulating Mucorales DNA in serum was positive in 23/24 patients and in 97/188 serum specimens between D-9 and D9. Bronchoalveolar lavage contributed to diagnosis in only 3/21 cases. The antifungal treatment was mainly based on liposomal amphotericin B combined with, or followed by, posaconazole. A pulmonary surgical resection was performed in 9/25 cases. At 3 months, 76 % of patients were alive and median overall survival was 14 months. In AL, early use of CT could improve the prognosis of PM. The presence of a RHS on CT suggests PM and is an indication for prompt antifungal treatment. Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.

[Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008].

PubMed

Buitrón-Santiago, Natalie; Arteaga-Ortiz, Luis; Rosas-López, Adriana; Aguayo, Alvaro; López-Karpovitch, Xavier; Crespo-Solís, Erick

2010-01-01

Acute myeloid leukemia (AML) comprises a group of diseases with different biologic characteristics; despite knowledge improvements, these are not reflected in long term survival. To describe characteristics of adults with AML in a hospital of Mexico City, their treatment response, complications and to evaluate survival related factors. Cohort study. Between January 2003 and July 2008, patients with AML diagnosis were included (except promyelocitic). Treatment protocols used: 3 + 7, high doses of cytarabine and autologous bone marrow transplant as consolidation therapy. 53 patients were included. Median age: 44 years (15-79). At diagnosis: tumor lysis syndrome in 4/ 53 (7.5%), 3/51 (5.9%) with altered liver function test and hyperleukocytosis in 8/53 (15.1%). 46 patients had available cytogenetic and this was successful in 28/46 (60.8%), 12/28 (42.8%) had adverse cytogenetic; 16/28 (57.1%) intermediate risk and none was favorable. There were 2 losses during follow up, 7 patients did not receive chemotherapy with curative intent and 1 died at diagnosis. 43 patients received 3 + 7, 13.9% died during aplasia, complete remission was achieved in 27/43 (62.7%) and 10/43 (23.2%) were refractory to treatment. A second induction attempt was required in 39.5% (17/43). Median disease free survival (DFS) was 491 days (366-615), with a median follow up of 993 days (105-1744). The median overall survival (OS) was 531 days (312-749). Aplasia related mortality decreased (p = 0.09) between the actual cohort (13.9%) and the historical cohort (37%). Long term survival in AML patients remains poor despite improvements in diagnosis, classification, and treatment. In our institution, it is required to improve induction protocols and cytogenetic analysis in order to adequately choose the group of patients that could be benefit from stem cell transplant.

Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia.

PubMed

Feben, Candice; Kromberg, Jennifer; Wainwright, Rosalind; Stones, David; Poole, Janet; Haw, Tabitha; Krause, Amanda

2015-03-01

Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease. Copyright © 2014 Elsevier Inc. All rights reserved.

22q11 deletions in fetuses with malformations of the outflow tracts or interruption of the aortic arch: impact of additional ultrasound signs.

PubMed

Volpe, Paolo; Marasini, Maurizio; Caruso, Gilda; Marzullo, Andrea; Buonadonna, Antonia Lucia; Arciprete, Paolo; Di Paolo, Salvatore; Volpe, Gennaro; Gentile, Mattia

2003-09-01

One hundred and forty-one consecutive cases of malformations of the outflow tracts or interrupted aortic arch (IAA), detected by fetal echocardiography, underwent detailed anatomy scan, karyotyping and fluorescence in situ hybridization analysis (FISH) to detect the prevalence of 22q11 microdeletion and to evaluate neonatal clinical findings and outcome according to the presence of the genetic defect. Then, we sought to investigate whether some prenatal ultrasound findings could help identify fetuses at higher risk of carrying the 22q11 microdeletion. Echocardiography and FISH for the DiGeorge critical region (22q11) were performed in all cases. 22q11 microdeletion was detected in 28 of 141 fetuses (19.8%). Intrauterine growth restriction (IUGR) appeared to be associated with the worst prognosis, being present in 2/2 intrauterine fetal deaths and 5/6 post-natal deaths. IUGR, additional aortic arch anomalies and thymic hypo/aplasia were significantly more frequent in fetuses with 22q11 microdeletion (p=0.011, 0.011 and <0.0001, respectively). Prenatal ultrasound thymus examination, performed on the last 84 fetuses, showed 75% sensitivity and 94% specificity. The combination of 2 predictors, namely, thymus defects and IUGR associated with additional aortic arch anomalies reached more than 90% sensitivity and 100% specificity. Our study demonstrates that 22q11 microdeletion occurs in 20% of malformations of the outflow tracts and IAA type B, as detected in utero, and that this association is significantly predicted by the presence of associated ultrasound findings: thymic hypo/aplasia, IUGR and additional aortic arch anomalies. The feasibility of a correct prenatal diagnosis should enable clinicians to provide the couple with further informative counselling and to plan adequate post-natal medical interventions. Copyright 2003 John Wiley & Sons, Ltd.

Experiences from Auditory Brainstem Implantation (ABIs) in four paediatric patients.

PubMed

Lundin, Karin; Stillesjö, Fredrik; Nyberg, Gunnar; Rask-Andersen, Helge

2016-01-01

Indications for auditory brainstem implants (ABIs) have been widened from patients with neurofibromatosis type 2 (NF2) to paediatric patients with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, or cochlear ossification after meningitis. We present four ABI surgeries performed in children at Uppsala University Hospital in Sweden since 2009. Three children were implanted with implants from Cochlear Ltd. (Lane Cove, Australia) and one child with an implant from MedEl GMBH (Innsbruck, Austria). A boy with Goldenhar syndrome was implanted with a Cochlear Nucleus ABI24M at age 2 years (patient 1). Another boy with CHARGE syndrome was implanted with a Cochlear Nucleus ABI541 at age 2.5 years (patient 2). Another boy with post-ossification meningitis was implanted with a Cochlear Nucleus ABI24M at age 4 years (patient 3). A girl with cochlear aplasia was implanted with a MedEl Synchrony ABI at age 3 years (patient 4). In patients 1, 2, and 3, the trans-labyrinthine approach was used, and in patient 4 the retro-sigmoid approach was used. Three of the four children benefited from their ABIs and use it full time. Two of the full time users had categories of auditory performance (CAP) score of 4 at their last follow up visit (6 and 2.5 years postoperative) which means they can discriminate consistently any combination of two of Ling's sounds. One child has not been fully evaluated yet, but is a full time user and had CAP 2 (responds to speech sounds) after 3 months of ABI use. No severe side or unpleasant stimulation effects have been observed so far. There was one case of immediate electrode migration and one case of implant device failure after 6.5 years. ABI should be considered as an option in the rehabilitation of children with similar diagnoses.

A rare case of 46,XX gonadal dysgenesis and Mayer-Rokitansky-Kuster-Hauser syndrome.

PubMed

Manne, Sriharibabu; Veeraabhinav, C H; Jetti, Mounica; Himabindu, Yalamanchali; Donthu, Kiranmai; Badireddy, Mutyalarayudu

2016-01-01

46,XX gonadal dysgenesis is a rare genetically heterogeneous disorder characterized by underdeveloped ovaries with consequent, impuberism, primary amenorrhea, and hypergonadotropic hypogonadism. Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in a woman with normal development of secondary sexual characteristics and a normal 46,XX karyotype. The phenotypic manifestations of MRKH syndrome may sometimes overlap with various other syndromes and require accurate delineation. The coexistence of both these disorders is extremely rare. Here, we report a case of 46,XX gonadal dysgenesis and MRKH syndrome with anatomically dispersed congenital anomalies unique among reported cases.

Loss of GATA-1 Full Length as a Cause of Diamond–Blackfan Anemia Phenotype

PubMed Central

Parrella, Sara; Aspesi, Anna; Quarello, Paola; Garelli, Emanuela; Pavesi, Elisa; Carando, Adriana; Nardi, Margherita; Ellis, Steven R.; Ramenghi, Ugo; Dianzani, Irma

2015-01-01

Mutations in the hematopoietic transcription factor GATA-1 alter the proliferation/differentiation of hemopoietic progenitors. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond–Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. We sequenced GATA-1 in 23 patients that were negative for mutations in the most frequently mutated DBA genes. One patient showed a c.2T > C mutation in the initiation codon leading to the loss of the full-length GATA-1 isoform. PMID:24453067

Parvovirus B19 infection as a cause of acute myositis in an adult.

PubMed

Cakirca, Mustafa; Karatoprak, Cumali; Ugurlu, Serdal; Zorlu, Mehmet; Kıskaç, Muharrem; Çetin, Güven

2015-01-01

Parvovirus B19 infection is often asymptomatic, but clinical expressions may include transient aplastic crisis, erythema infectiosum, non-immune hydrops fetalis, and chronic red cell aplasia. This virus has also been associated with rheumatoid arthritis and other autoimmune connective tissue diseases; however, we could not identify any acute adult myositis case developed after a Parvovirus B19 infection in the literature. For this reason, we would like to present a rare case of acute myositis developed after Parvovirus B19 infection. In patients presenting with symptoms of fever, rash on the legs and myositis, viral infections such as Parvovirus B19 should be kept in mind. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Ehrlichia canis infection in a dog with no history of travel outside the United Kingdom.

PubMed

Wilson, H E; Mugford, A R; Humm, K R; Kellett-Gregory, L M

2013-08-01

A two-year-old female neutered Tibetan terrier was referred following a one-month history of lethargy, inappetence and pancytopenia, which had been poorly responsive to immunosuppressive and fluoroquinolone treatment. The dog was diagnosed with pure red cell aplasia and was found to be positive for Ehrlichia canis by both antibody titre measurement and polymerase chain reaction. The dog lived in London and had not travelled outside the UK. The dog was treated with doxycycline, prednisolone and ciclosporin, but died as a result of gastrointestinal tract haemorrhage. To the authors' knowledge, this represents the first reported case of Ehrlichia canis in a dog in the UK with no previous travel history. © 2013 British Small Animal Veterinary Association.

Modelisation frequentielle de la permittivite du beton pour le controle non destructif par georadar

NASA Astrophysics Data System (ADS)

Bourdi, Taoufik

Le georadar (Ground Penetrating Radar (GPR)) constitue une technique de controle non destructif (CND) interessante pour la mesure des epaisseurs des dalles de beton et la caracterisation des fractures, en raison de ses caracteristiques de resolution et de profondeur de penetration. Les equipements georadar sont de plus en plus faciles a utiliser et les logiciels d'interpretation sont en train de devenir plus aisement accessibles. Cependant, il est ressorti dans plusieurs conferences et ateliers sur l'application du georadar en genie civil qu'il fallait poursuivre les recherches, en particulier sur la modelisation et les techniques de mesure des proprietes electriques du beton. En obtenant de meilleures informations sur les proprietes electriques du beton aux frequences du georadar, l'instrumentation et les techniques d'interpretation pourraient etre perfectionnees plus efficacement. Le modele de Jonscher est un modele qui a montre son efficacite dans le domaine geophysique. Pour la premiere fois, son utilisation dans le domaine genie civil est presentee. Dans un premier temps, nous avons valide l'application du modele de Jonscher pour la caracterisation de la permittivite dielectrique du beton. Les resultats ont montre clairement que ce modele est capable de reproduire fidelement la variation de la permittivite de differents types de beton sur la bande de frequence georadar (100 MHz-2 GHz). Dans un deuxieme temps, nous avons montre l'interet du modele de Jonscher en le comparant a d'autres modeles (Debye et Debye-etendu) deja utilises dans le domaine genie civil. Nous avons montre aussi comment le modele de Jonscher peut presenter une aide a la prediction de l'efficacite de blindage et a l'interpretation des ondes de la technique GPR. Il a ete determine que le modele de Jonscher permet de donner une bonne presentation de la variation de la permittivite du beton dans la gamme de frequence georadar consideree. De plus, cette modelisation est valable pour differents

Les bisphosphonates dans le traitement de l’ostéoporose

PubMed Central

Brown, Jacques P.; Morin, Suzanne; Leslie, William; Papaioannou, Alexandra; Cheung, Angela M.; Davison, Kenneth S.; Goltzman, David; Hanley, David Arthur; Hodsman, Anthony; Josse, Robert; Jovaisas, Algis; Juby, Angela; Kaiser, Stephanie; Karaplis, Andrew; Kendler, David; Khan, Aliya; Ngui, Daniel; Olszynski, Wojciech; Ste-Marie, Louis-Georges; Adachi, Jonathan

2014-01-01

Résumé Objectif Exposer l’efficacité et les risques du traitement par les bisphosphonates dans la prise en charge de l’ostéoporose et décrire les patients qui seraient de bons candidats aux congés thérapeutiques. Qualité des données Une recherche dans MEDLINE (PubMed, jusqu’au 31 décembre 2012) a permis de relever les publications pertinentes pour l’inclusion. La plupart des données probantes citées sont de niveau II (tirées d’essais non randomisés, de cohorte et d’autres essais comparatifs). Message principal L’efficacité des bisphosphonates de premier recours homologués pour la prévention des fractures a été éprouvée dans le cadre d’essais cliniques randomisés et contrôlés. Cependant, l’usage clinique répandu et prolongé des bisphosphonates a donné lieu à des rapports de manifestations indésirables rares, mais graves. L’ostéonécrose maxillaire et les fractures atypiques sous-trochantériennes ou diaphysaires du fémur seraient liées à l’emploi des bisphosphonates dans le traitement de l’ostéoporose, mais ces manifestations sont extrêmement rares et lorsqu’elles surviennent, elles sont accompagnées d’autres comorbidités ou de l’emploi concomitant de médicaments. Les congés thérapeutiques ne peuvent être envisagés que chez les patients à faible risque et dans un groupe restreint de patients dont le risque de fracture est modéré après un traitement de 3 à 5 ans. Conclusion Lorsque les bisphosphonates sont prescrits à des patients dont le risque de fracture est élevé, leur effet de prévention des fractures l’emporte de loin sur leurs torts potentiels. Chez les patients qui prennent des bisphosphonates depuis 3 à 5 ans, il faut réévaluer le besoin de poursuivre le traitement.

CONCLUSIONS ET RECOMMANDATIONS À L’ISSUE DE LA CONSULTATION DE L’OMS SUR LA LUTTE CONTRE LA CARENCE MARTIALE CHEZ LE NOURRISSON ET LE JEUNE ENFANT DANS LES PAYS D’ENDÉMIE PALUSTRE

PubMed Central

Allen, L.; Black, R.E.; Brandes, N.; Brittenham, G.; Chazot, G.; Chunming, C.; Crawley, J.; de Benoist, B.; Dalmiya, N.; Darnton-Hill, I.; Dewey, K.; El-Arifeen, S.; Fontaine, O.; Geissler, C.; Haberle, H.; Harvey, P.; Hasler, J.; Hershko, C.; Hurrell, R.; Juma, M.A.; Lönnerdal, B.; Lozoff, B.; Lynch, S.; Salgado, H. Martines; McLean, E.; Metz, J.; Oppenheimer, S.; Premji, Z.; Prentice, A.; Ramsan, M.; Ratledge, C.; Stoltzfus, R.; Tielsch, J.; Winachagoon, P.

2011-01-01

Cet article présentent les résultats d'une Consultation d'Experts dont l'objectif était d'évaluer l'efficacité et l'innocuité des suppléments de fer administrés aux nourrissons et aux jeunes enfants dans les zones d’endémie palustre, ainsi que les conséquences d’une telle mesure pour la santé publique. Les participants à cette Consultation, qui s’est déroulée à Lyon (France) les 12–14 juin 2006, se sont entendus sur plusieurs questions importantes concernant l’administration d’une supplémentation martiale aux nourrissons et aux jeunes enfants dans les zones d’endémie palustre. Les conclusions du présent rapport s’appliquent plus particulièrement aux pays où le paludisme est endémique. PMID:18630054

Total anomalous pulmonary venous connection and a constellation of craniofacial, skeletal, and urogenital anomalies in a newborn and similar features in his 36-year-old father.

PubMed

Pierson, D M; Taboada, E M; Lofland, G K; Begleiter, M L; Smith, G S; Hall, F; Butler, M G

2001-04-01

We report on a newborn male born to non-consanguineous parents with total anomalous pulmonary venous connection (TAPVC) and additional findings of malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY karyotype. His 36-year-old father had similar craniofacial and limb anomalies suggesting an autosomal dominant syndrome with variable expression. Our patients may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe brachyphalangy in the hands, and a micropenis.

Neurocutaneous Melanosis in Association with Dandy-Walker Complex with Extensive Intracerebral and Spinal Cord Involvement

PubMed Central

Sung, Kyoung-Su

2014-01-01

Neurocutaneous melanosis (NCM) is a rare congenital syndrome consisting of benign or malignant melanotic tumors of the central nervous system with large or numerous cutaneous melanocytic nevi. The Dandy-Walker complex (DWC) is characterized by an enlarged posterior fossa with high insertion of the tentorium, hypoplasia or aplasia of the cerebellar vermis, and cystic dilatation of the fourth ventricle. These each two conditions are rare, but NCM associated with DWC is even more rare. Most patients of NCM with DWC present neurological symptoms early in life such as intracranial hemorrhage, hydrocephalus, and malignant transformation of the melanocytes. We report a 14-year-old male patient who was finally diagnosed as NCM in association with DWC with extensive intracerebral and spinal cord involvement. PMID:25289129

Anti-M Antibody Induced Prolonged Anemia Following Hemolytic Disease of the Newborn Due to Erythropoietic Suppression in 2 Siblings.

PubMed

Ishida, Atsushi; Ohto, Hitoshi; Yasuda, Hiroyasu; Negishi, Yutaka; Tsuiki, Hideki; Arakawa, Takeshi; Yagi, Yoshihito; Uchimura, Daisuke; Miyazaki, Toru; Ohashi, Wataru; Takamoto, Shigeru

2015-08-01

Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

The first case of Horn Kolb Syndrome in Turkey, diagnosed prenatally at the 23(rd) week of a pregnancy: A very rare and unusual case far from the original geography.

PubMed

Temur, Ismail; Ulker, Kahraman; Volkan, Islim; Karaca, Mehmet; Ersoz, Mustafa; Gul, Abdulaziz; Adiguzel, Esat

2012-01-01

The aim of this report was to evaluate and announce the first documented appearance of Horn Kolb syndrome in Turkey. Acheiropodia (Horn Kolb Syndrome) is the bilateral congenital amputation of the distal parts of the 4 extremities. It is an autosomal recessive developmental disorder. The characteristic features are amputation of the upper and lower extremities with aplasia of the hands and feet. The disorder affects only the extremities without other systemic manifestations. In this report, we present the first known case of Horn Kolb syndrome in Turkey, along with the diagnostic features. Severe dysmorphic skeletal anomalies should be excluded as soon as the earlier gestational weeks in every pregnancy by visualizing all 4 limbs of the fetus in routine prenatal ultrasound screening.

Poland syndrome with bilateral features: case description with review of the literature.

PubMed

Baban, Anwar; Torre, Michele; Bianca, Sebastiano; Buluggiu, Anna; Rossello, Mario Igor; Calevo, Maria Grazia; Valle, Maura; Ravazzolo, Roberto; Jasonni, Vincenzo; Lerone, Margherita

2009-07-01

Poland syndrome (PS) has been described as unilateral pectoral muscle deficiency variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia/aplasia of the pectoralis muscle and upper limb defects in association with variable thoracic muscles, chest wall deformities and lower limb defects have been infrequently reported in the literature. We report on a 3(1/2)-year-old girl with clinical features consisting in bilateral asymmetric pectoral muscle defects (complete agenesis on the left side and agenesis of the sternocostal head on the right side), nipple hypoplasia, left rib defect, and right hand symbrachydactyly. In this study, we reviewed the bilateral features present in our patient and those described in the literature. Hypotheses explaining bilateral features in PS are reviewed.

Anomalous optic discs in a patient with a Dandy-Walker cyst.

PubMed

Orcutt, J C; Bunt, A H

1982-03-01

A 19-month-old female infant with a Dandy-Walker cyst had anomalous optic discs, each of which appeared to divide to form an accessory optic nerve. The discs probably lie within the spectrum of anomalous discs including optic nerve aplasia and hypoplasia, megallopapillae, morning glory disc, optic disc dysplasia, and optic nerve colobomas. The association of anomalous optic discs with a Dandy-Walker cyst has not been previously recognized. The ocular and brain malformations in this patient likely occurred during the fourth to eighth week of gestation, when the retinal ganglion cell axons were penetrating the optic nerve, and the rhombic lips were enlarging in early cerebellar development. The etiology of these anomalies is not known; however, teratogens, sporadic events, and genetic disorders should be considered.

LAMM syndrome with middle ear dysplasia associated with compound heterozygosity for FGF3 mutations.

PubMed

Sensi, Alberto; Ceruti, Stefano; Trevisi, Patrizia; Gualandi, Francesca; Busi, Micol; Donati, Ilaria; Neri, Marcella; Ferlini, Alessandra; Martini, Alessandro

2011-05-01

We report on the first cases of FGF3 compound heterozygotes in two European families from non-consanguineous marriages, affected with labyrinthine aplasia, microtia, and microdontia (LAMM) Syndrome. Three not previously described mutations (p.W153VfsX51, p.Y106C, and p.Y49C) and a recurrent one (p.R104X) were found. Analysis of 50 unrelated control subjects (100 chromosomes) of the same European background did not show any of the two newly reported missense variations. We confirm the absence of otodental syndrome in heterozygous carriers, but report unilateral microtia in one of them. We also report on the involvement of the middle ear structures in LAMM Syndrome. Copyright © 2011 Wiley-Liss, Inc.

Un nouveau cristal laser largement accordable le BOYS dopé à l'ytterbium

NASA Astrophysics Data System (ADS)

Chénais, S.; Druon, F.; Balembois, F.; Georges, P.; Gaumé, R.; Aka, G.; Viana, B.; Vivien, D.

2002-06-01

Nous avons étudié les performances laser en pompage par diode de puissance d'un nouveau cristal : le Sr3Y(BO3)3 (acronyme : BOYS), dopé à l'ytterbium. Son spectre d'émission particulièrement large en fait un matériau particulièrement prometteur pour la réalisation de lasers femtosecondes directement pompés par diode. Ses performances ont été comparées à celles d'un verre phosphate ainsi qu'à celles du cristal d' Yb:GdCOB dans les mêmes conditions. Nous démontrons que, tant du point de vue de l'efficacité laser que de la tenue aux fortes puissances, GdCOB et BOYS sont supérieurs au verre ; le BOYS est de surcroît plus accordable (sur 50 nm), mais son comportement thermique limite a priori son usage à des puissances de pompe modérées.

Epigenetic and microenvironmental alterations in bone marrow associated with ROS in experimental aplastic anemia.

PubMed

Chatterjee, Ritam; Law, Sujata

2018-01-01

Aplastic anemia or bone marrow failure often develops as an effect of chemotherapeutic drug application for the treatment of various pathophysiological conditions including cancer. The long-term bone marrow injury affects the basic hematopoietic population including hematopoietic stem/progenitor cells (HSPCs). The present study aimed in unearthing the underlying mechanisms of chemotherapeutics mediated bone marrow aplasia with special focus on altered redox status and associated effects on hematopoietic microenvironment and epigenetic status of hematopoietic cells. The study involves the development of busulfan and cyclophosphamide mediated mouse model for aplastic anemia, characterization of the disease with blood and marrow analysis, cytochemical examinations of bone marrow, flowcytometric analysis of hematopoietic population and microenvironmental components, determination of ROS generation, apoptosis profiling, expressional studies of Notch-1 signaling cascade molecules, investigation of epigenetic modifications including global CpG methylation of DNA, phosphorylation of histone-3 with their effects on bone marrow kinetics and expressional analysis of the anti-oxidative molecules viz; SOD-2 and Sdf-1. Severe hematopoietic catastrophic condition was observed during aplastic anemia which involved peripheral blood pancytopenia, marrow hypocellularity and decreased hematopoietic stem/progenitor population. Generation of ROS was found to play a central role in the cellular devastation in aplastic marrow which on one hand can be correlated with the destruction of hematopoiesis supportive niche components and alteration of vital Notch-1 signaling and on other hand was found to be associated with the epigenetic chromatin modifications viz; global DNA CpG hypo-methylation, histone-3 phosphorylation promoting cellular apoptosis. Decline of anti-oxidant components viz; Sdf-1 and SOD-2 hinted towards the irreversible nature of the oxidative damage during marrow aplasia

Efficacy and safety data of subsequent entry biologics pertinent to nephrology practice: a systematic review.

PubMed

Marin, Judith Genevieve; Leung, Marianna; Lo, Clifford; Tsao, Nicole W; Martinusen, Daniel J

2014-01-01

Subsequent entry biologics (SEBs) may soon be a reality in Canadian nephrology practice. Understanding the worldwide experience with these agents will be valuable to Canadian clinicians. To compare the efficacy and safety data between SEBs used in nephrology practice and their reference biologic. Systematic review. Ovid MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, Cochrane Central Register of Controlled Trials. Adult patients with chronic kidney disease (CKD). Our systematic review follows the process outlined by Cochrane Reviews. For efficacy data, all randomized controlled trials (RCTs), quasi-RCTs and observational trials in nephrology practice were included. For safety data, case series, case reports, review articles in nephrology practice and pharmacovigilance programs were included as well. Only epoetin SEBs trials were published in the literature. Ten studies involving three different epoetin SEBs (epoetin zeta, HX575 and epoetin theta) were included. The mean epoetin dose used did not differ significantly between the SEBs and the reference product. For epoetin zeta and epoetin theta, the mean hemoglobin levels achieved in the studies were similar between the SEBs and the reference epoetin. The HX 575 studies reported a mean absolute change in hemoglobin within the predefined equivalence margin, when compared with the reference biologic. In terms of safety data, 2 cases of pure-red-cell aplasia were linked to the subcutaneous administration of HX 575. Otherwise, the rate of adverse drug reactions was similar when epoetin SEBs were compared with the reference biologic. Our analysis is limited by the paucity of information available on SEB use in nephrology with the exception of epoetin SEBs. Methodological flaw was found in one of the epoetin zeta studies which accounted for 45% of pooled results. Little clinical difference was found between epoetin SEBs and the reference product. Although not deemed

[Clinical effects of the transfusion of leukocytes isolated by filtration from continuous flux].

PubMed

Malinvaud, G; Gailiard, S; Gualde, N

1977-09-01

The present work studies clinical effects of leukocyte transfusions to patients with medular aplasis. Leukocytes were collected by filtration on a continuous flow, according to the technique earlier described in this review [9]. Two major points are stressed on tolerance by the patients of the injected products and clinical efficiency. Seventy eight suspensions were prepared and transfused to 30 patients in the course of 36 incidents of myeloid insufficiency. All patients but two evidenced by the time of transfusion a number of polynuclears inferior to 500 per cubic millimeter. The infection was quite serious with increased gravity despite the antibiotherapy. Intolerance was noticeable in about one third of the cases, half of which consisted only in chillis by the end or after transfusion. Only one accident consisting in acute respiration troubles and shock was observed. This however does not occur by chance. It involves sensitization which may be related to HLA system but may also be of different nature, although not clearly identified. Nevertheless is efficiency of the injected products demonstrated by recirculation of the transfused leukocytes. This was noticed within an hour following transfusion for more than 50 percent of the cases. Furthermore it lasted for 16 hours in more than one fourth of the patients. In addition following results are in favour of real clinical efficiency. Certainly in the course of 16 aplasic incidents, no improvement was observed. For most patients however transfusions were late and not renewed or the patients were highly immunized. Conversely the infection state did improve in 8 patients, the disease responsible for aplasia running its course on its own. Lastly in the course of 12 aplasic incidents, infection and acute aplasia did cure. All these observations should lead one to study with great care the immunological state of the recipient. Instructions being known, the number of transfused leukocytes should be sufficient and

Al-Awadi/Raas-Rothschild Syndrome in a Newborn with Additional Anomalies

PubMed Central

Alp, Esma; Atabek, Mehmet Emre; Pirgon, Özgür

2010-01-01

Al-Awadi/Raas-Rothschild (AARR) syndrome is a rare phocomelia syndrome characterized by limb/pelvic hypoplasia/aplasia, renal anomalies such as horseshoe and polycystic kidney, and abnormal facial features including cleft palate, hypertelorism and micro-retrognatia. Autosomal recessive inheritance has been proposed for AARR syndrome. In this report a boy affected with AARR syndrome is presented. The previous pregnancy of the mother was terminated because of lower limb agenesis detected at 14th week of gestation. This report emphasizes the importance of recognizing severe pelvic and limb deficiencies in newborns with AARR syndrome and differentiating the syndrome from other multiple malformation syndromes. Fetal ultrasonography at 15th week of gestation is helpful in diagnosing the major extremity anomalies in the fetus. Conflict of interest:None declared. PMID:21274338

[Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid leukemia].

PubMed

Eddou, Hicham; Zinebi, Ali; Khalloufi, Abdelaziz; Sina, Mohammed; Mahtat, Mehdi; Doghmi, Kamal; Mikdame, Mohammed; Moudden, Mohammed Karim; Baaj, Mohammed El

2017-01-01

Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.

Multifactorial neutropenia in a patient with acute promyelocytic leukemia and associated large granular lymphocyte expansion: A case report.

PubMed

Reda, Gianluigi; Fattizzo, Bruno; Cassin, Ramona; Flospergher, Elena; Orofino, Nicola; Gianelli, Umberto; Barcellini, Wilma; Cortelezzi, Agostino

2017-03-01

Neutropenia in the setting of acute hematological malignancies may impact disease prognosis, thus affecting therapy dose intensity. This is often due to chemotherapy-induced aplasia as well as to the disease itself. However, chronic neutropenia deserves further investigation, as the management of reversible concomitant causes may avoid treatment delay. The present study describes a case of an acute promyelocytic leukemia patient with chronic severe neutropenia of multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune activation with anti-platelets and anti-neutrophil antibodies positivity, and the rare association of large granular lymphocyte (LGL) expansion. As neutropenia may challenge the diagnosis and treatment of acute malignancies, clinicians and hematopathologists must discuss the differential diagnosis in order to avoid misdiagnosing and undertreating concomitant diseases. In particular, LGL chronic expansion and autoimmunity should be considered.

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

ClinicalTrials.gov

2018-06-13

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Assessment of environmental factors affecting male fertility

PubMed Central

Dixon, R. L.; Sherins, R. J.; Lee, I. P.

1979-01-01

Exposure to drinking water containing as much as 500 ppm aluminum chloride for periods of 30, 60, and 90 days had no apparent effect on male reproductive processes. In an attempt to correlate enzyme activity with particular spermatogenic cell types, postnatal development of testicular enzymes was studied. Eight enzymes were selected: hyaluronidase (H), lactate dehydrogenase isoenzyme-X (LDH-X), dehydrogenases of sorbitol (SDH), α-glycerophosphate (GPDH), glucose-6-phosphate (G6PDH), malate (MDH), glyceraldehyde-3-phosphate (G3PDH), and isocitrate (ICDH). Enzyme specific activities in testicular homogenates were determined. Two types of enzyme developmental patterns were observed. One was represented by H, LDH-X, SDH, and GPDH; and the other by G6PDH, MDH, G3PDH, and ICDH. The former was characterized by a change in enzyme activities from low in newborn to high in adult while in the latter this pattern was reversed. The two complementary enzyme systems crossed each other at puberty. Prior to puberty, only spermatogonial cells are present; sperm differentiation initiated at puberty adds spermatocytes and spermatids to the testicular cell population. Male rats were exposed to borax in their diet for periods of 30 and 60 days. Concentrations of boron were 0, 500, 1000, and 2000 ppm. At the end of each experimental period, the specific activities of the selected enzymes were determined in the testis and prostate. Correlations of enzyme activity with testicular histology and androgen activities of the male accessory organs were sought. In addition, plasma FSH, LH, and testosterone levels were measured to assess pituitary-testicular interaction. Plasma and testicular boron concentrations were determined and a minimum boron concentration which induced germinal aplasia and male infertility was estimated. In both 30 and 60 day feeding studies, male rats receiving 500 ppm failed to demonstrate any significant adverse effects. In contrast, male rats receiving 100 and 2000 ppm

Improving the Organisational Effectiveness of Coalition Operations (Amelioration de l’efficacite structurelle des operations en coalition)

DTIC Science & Technology

2012-11-01

peak capacity 2. Prosthesis or visual aids 3. Adaptation 4. Selection Motives 1. Assessment of people‘s motives to work 2. Recruitment of people to...after each rotation. In addition, feelings of isolation, frustration, and deprivation of a group identity [35] or difficulties in adopting new...people feel uncomfortable by feedback”. Finally, trust may be a sensitive issue in a multi-national environment, and can cause dilemma situations. In

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

PubMed Central

Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.

2016-01-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies. PMID:27760047

Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

PubMed

Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

2016-04-07

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

PubMed

Paszkiewicz, Paulina J; Fräßle, Simon P; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C; Riddell, Stanley R; Busch, Dirk H

2016-11-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.

Orthodontic space closure without counterbalancing extractions in patients with bilateral aplasia of the lower second premolars.

PubMed

Zimmer, Bernd; Rottwinkel, Yvonne

2002-09-01

Orthodontic space closure in situations with bilateral aplastic lower second premolars without maxillary extractions is a rarely practiced treatment method. Due to the high risk of severe side effects, preference is currently given to the maintenance of deciduous second molars and subsequent prosthodontic solutions. As a combination of Class I push and Class II pull mechanics seemed likely to reduce secondary effects by transferring the anchorage site from the reactive lower anterior teeth to the more resistant upper arch, a clinical study was carried out in order to investigate effects and secondary effects of the mechanics. Casts, panoramic radiographs and lateral headfilms of 13 consecutively treated, non-selected adolescents (seven boys, six girls, mean age at start of treatment 13 years 4 months) were evaluated. In six patients a Jasper Jumper trade mark was inserted in addition for a mean period of 6 months. The treatment outcome after a mean period of 3 years and 1 month showed in almost all cases the desired Class III molar occlusion of one cusp width (+/- 1/4 cw) with overbite and overjet within the normal range. Analyses of static and dynamic occlusion revealed anterior/canine protected articulation and a satisfactory number of centric contact points. A significant space gain (p

Prescrire du cannabis fumé pour la douleur chronique non cancéreuse

PubMed Central

Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

2014-01-01

Résumé Objectif Offrir des conseils préliminaires sur la prescription de cannabis fumé pour la douleur chronique avant la publication de lignes directrices officielles. Qualité des données Nous avons examiné les ouvrages scientifiques sur l’efficacité analgésique du cannabis fumé et les dommages causés par la consommation de cannabis à des fins médicales et récréatives. Nous avons élaboré des recommandations concernant les indications et les contre-indications du cannabis fumé, les précautions à prendre et son dosage et nous avons classé les recommandations en fonction du niveau des données probantes. La plupart des données probantes sont de niveau II (études observationnelles bien effectuées) et de niveau III (opinion d’experts). Message principal Le cannabis fumé pourrait être indiqué chez des patients souffrant de douleurs neuropathiques sévères qui n’ont pas répondu à des essais suffisants de cannabinoïdes pharmaceutiques et d’analgésiques standards (données probantes de niveau II). Le cannabis fumé est contre-indiqué chez les patients de 25 ans ou moins (données probantes de niveau II); ceux qui font actuellement ou ont fait par le passé une psychose ou encore ont de forts antécédents familiaux de psychose (données probantes de niveau II); ceux qui ont ou ont eu un problème de consommation de cannabis (données probantes de niveau III); ceux qui ont un problème actuel de toxicomanie ou d’alcoolisme (données probantes de niveau III); ceux qui ont une maladie cardiovasculaire ou respiratoire (données probantes de niveau III); ou celles qui sont enceintes ou planifient une grossesse (données probantes de niveau II). Il devrait être utilisé avec précaution par les patients qui fument du tabac (données probantes de niveau II), qui sont à risque accru de maladies cardiovasculaires (données probantes de niveau III), qui ont des troubles d’anxiété ou de l’humeur (données probantes de niveau II) ou

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Woods, C G; Stricker, S; Seemann, P; Stern, R; Cox, J; Sherridan, E; Roberts, E; Springell, K; Scott, S; Karbani, G; Sharif, S M; Toomes, C; Bond, J; Kumar, D; Al-Gazali, L; Mundlos, S

2006-08-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome

PubMed Central

Woods, C. G.; Stricker, S.; Seemann, P.; Stern, R.; Cox, J.; Sherridan, E.; Roberts, E.; Springell, K.; Scott, S.; Karbani, G.; Sharif, S. M.; Toomes, C.; Bond, J.; Kumar, D.; Al-Gazali, L.; Mundlos, S.

2006-01-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development. PMID:16826533

Case report: recurrent abdominal symptoms in a child with panhypopituitarism - there is always a differential.

PubMed

Olbrich, Laura; Schmidt, Eva; Mayatepek, Ertan; Vogel, Markus

2016-01-01

We report the case of a 6 year old boy suffering from adenohypophysis aplasia as well as ectopic neurohypophysis and delayed diagnosis of familial Mediterranean fever (FMF). The boy was diagnosed with panhypopituitarism during the neonatal period and suffered from recurrent episodes during the following years suggesting infections. He also showed signs of adrenal insufficiency. Finally, at the age of 6 years, an additional diagnosis of familial Mediterranean fever (FMF) was clinically suspected and later confirmed by molecular analysis. The clinical pictures of panhypopituitarism and FMF can be overlapping. It is imperative to take a detailed and accurate history in order to find the right diagnosis, particularly a precise family history. In conditions like FMF an early diagnosis is crucial, as initiation of treatment with colchicine is important to prevent long-term complications due to amyloid fibril deposition.

Pelizaeus-Merzbacher disease. The Löwenberg-Hill type.

PubMed

Bruyn, G W; Weenink, H R; Bots, G T; Teepen, J L; van Wolferen, W J

1985-01-01

The clinical and neuropathological findings are reported of two sibs with adult type PMD. Clinical features deviating from the usual pattern included: no psychosis, no measurable dementia, no dwarfism, no microcephaly, no (marked) involuntary movements, but conspicuous generalised muscle atrophy and denervation, impairment of vital and gnostic sensation, thoracolumbar vertebral anomalies, and aplasia of os coccygis. Neuropathological findings were as usual, with additional unusual features: pinhead-size areas of acute myelin-abbau products, involvement of grey in addition to white matter, and upon ultrastructure, the new finding of intra-oligodendroglial fingerprint bodies, both in neuronal satellite and in white matter oligoglia, but not in astrocytes, ganglion cells, or pericytes. This excludes the origin of the stored material in the lysosomes as to derive exclusively from demyelination and would possibly imply PMD to be an oligodendroglial lysosomal storage disease.

Parvovirus B19-triggered Acute Hemolytic Anemia and Thrombocytopenia in a Child with Evans Syndrome.

PubMed

Zikidou, Panagiota; Grapsa, Anastassia; Bezirgiannidou, Zoe; Chatzimichael, Athanassios; Mantadakis, Elpis

2018-01-01

Human parvovirus B19 (HPV-B19) is the etiologic agent of erythema infectiosum, of transient aplastic crises in individuals with underlying chronic hemolytic disorders, and of chronic pure red cell aplasia in immunocompromised individuals. We describe a 14-year-old girl with long-standing Evans syndrome, who presented with severe anemia, reticulocytopenia and thrombocytopenia. A bone marrow aspirate revealed severe erythroid hypoplasia along with the presence of giant pronormoblasts, while serological studies and real-time PCR of whole blood were positive for acute parvovirus B19 infection. The patient was initially managed with corticosteroids, but both cytopenias resolved only after administration of intravenous gamma globulin 0.8g/kg. Acute parvovirus B19 infection should be suspected in patients with immunologic diseases, who present reticulocytopenic hemolytic anemia and thrombocytopenia. In this setting, intravenous gamma globulin is effective for both cytopenias.

Pneumococcal vaccine failure: can it be a primary immunodeficiency?

PubMed

Moinho, Rita; Brett, Ana; Ferreira, Gisela; Lemos, Sónia

2014-06-12

Vaccine failure is a rare condition and the need to investigate a primary immunodeficiency is controversial. We present the case of a 4-year-old boy, with complete antipneumococcal vaccination, who had necrotising pneumonia with pleural effusion and severe pancytopaenia with need for transfusion. A vaccine-serotype Streptococcus pneumoniae was isolated in the blood culture. On follow-up, detailed medical history, laboratory and genetic investigation led to the diagnosis of X linked dyskeratosis congenita. Dyskeratosis congenita is an inherited disorder that causes shortening or dysfunction of telomeres, affecting mainly rapidly dividing cells (particularly in the skin and haematopoietic system). It leads to bone marrow failure, combined immunodeficiency and predisposition to cancer. The confirmation of this diagnosis allows genetic counselling and medical monitoring of these patients, in order to detect early complications such as bone marrow aplasia or malignancies. 2014 BMJ Publishing Group Ltd.

MURCS Association: a rare association with patent ductus arteriosus and bicuspid aortic valve.

PubMed

Ramakrishna; Kotecha, Nikunj; Patel, Chetan A; Pipavat, Rushi

2013-11-01

An 18 yr old female referred to us as hypertrophic obstructive cardiomyopathy with bicuspid aortic valve. On Initial history and examination patient also had primary amenorrhoea, differential cyanosis in lower limbs, differential clubbing, polydactyly, syndactyly, high arched foot, pectus carinatum and scoliosis. Oxygen saturation was 94% at room air and complete blood count was suggestive of polycythaemia (Hb 20 g/dl, Hct 60%, Tc-16500, RBC count--6.29 million/cumm, Platelet count--1,88000). Imaging studies were done, ultrasonography showed absent uterus, absent left kidney, right ectopic kidney.X-ray foot showed 6th metatarsal with phalanx. 2D ECHO was suggestive of Patent Ductus Arteriosus with reversal of shunt with severe aortic stenosis and bicuspid aortic valve. All these anomalies form part of a syndrome complex called MURCS ASSOCIATION (Mullerian agenesis/aplasia, renal anomalies, and Cervicothoracic Somite deformities).

La réfrigération des grandes machines supraconductrices

NASA Astrophysics Data System (ADS)

Gistau, Guy

1991-02-01

The large scale superconducting devices which are now in operation for deviation of heavy particles, acceleration of light particles or plasma confinement need very large powers of refrigeration. After a short survewing of the different functions of refrigerators and the special requirements for large units, the paper describes some existing or envisaged cooling systems which have an equivalent cooling power in the range of 5 kW at 4.5 K. Les grands appareils de physique utilisant les supraconducteurs demandent des puissances cryogéniques de plus en plus importantes. Après un examen des fonctions élémentaires assurées par un réfrigérateur liées au cahier des charges spécifique à chaque utilisation, les spécificités des grosses unités de réfrigération (fiabilité, efficacité, flexibilité, automatisme) sont mises en évidence. Les solutions proposées dans plusieurs grands projets nécessitant des puissances froides supérieures à 5 kW à 4,5 K sont discutées.

Lasers solides pompés par diode émettant des impulsions picosecondes à haute cadence dans l'ultraviolet

NASA Astrophysics Data System (ADS)

Balembois, F.; Forget, S.; Papadopoulos, D.; Druon, F.; Georges, P.; Devilder, P.-J.; Lefort, L.

2005-06-01

De nombreuses applications requièrent des sources lasers impulsionnelles ultraviolettes, présentant des durées d'impulsion et des cadences spécifiques. Grâce à l'utilisation de structures d'oscillateurs et d'amplificateurs originales il est possible de réaliser de telles sources à partir de lasers solides pompés par diodes et de profiter ainsi de la compacité, de l'efficacité et de la robustesse de ces sources. Nous présentons ici la réalisation d'un laser à verrouillage de modes et d'un microlaser déclenché permettant d'obtenir des impulsions ultraviolettes picosecondes à une cadence de quelques MHz en vue d'application à la microscopie de fluorescence résolue en temps, ainsi que la mise en œuvre pour le traitement des matériaux d'un système oscillateur-amplificateur produisant plus de 600 mW de rayonnement UV à 266 ou 355 nm avec des impulsions sub-nanosecondes.

Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials.

PubMed

Brown, Jennifer R

2013-03-01

Ibrutinib is a potent covalent kinase inhibitor that targets BTK. BTK, or Bruton's tyrosine kinase, is an obvious target for therapy of B cell diseases because inactivating mutations lead to B cell aplasia in humans and the disease X-linked agammaglobulinemia. Ibrutinib has modest cytotoxicity against CLL cells in vitro but also blocks trophic stimuli from the microenvironment. As with other inhibitors of the BCR pathway, ibrutinib causes rapid nodal reduction and response associated with rapid increase in lymphocytosis, which then returns to baseline over time. The ORR of ibrutinib in relapsed refractory CLL is 67 % with PFS 88 % at 15 months. In a cohort of untreated patients 65 years and over, the estimated 15 month PFS is 96 %. Registration trials have been initiated, and the difficult task that remains is to determine where in the course of CLL therapy this drug will have the greatest impact and benefit for patients.

Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism.

PubMed

Brang, David; Ramachandran, V S

2010-05-01

Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.

Neurocutaneous melanosis in association with Dandy-Walker malformation: case report and literature review.

PubMed

Schreml, S; Gruendobler, B; Schreml, J; Bayer, M; Ladoyanni, E; Prantl, L; Eichelberg, G

2008-08-01

Neurocutaneous melanosis (NCM) is a rare congenital noninheritable phacomatosis characterized by large and/or numerous cutaneous congenital melanocytic naevi (CMN) in combination with melanocytic leptomeningeal tumours. Dandy-Walker malformation (DWM) consists of a cystic dilatation of the fourth ventricle communicating with the posterior fossa, and a high insertion of the tentorium and hypoplasia/aplasia of the cerebellar vermis (partially caused by Zic1(+/-)Zic 4(+/-) on 3q2). An association of NCM and DWM is very rare, with only 15 previously reported cases to our knowledge. We present an 8-year-old girl with multiple CMN and DWM. A ventriculoperitoneal shunt operation was performed when she was 1 day old. Her neurological symptoms to date comprise headaches, nausea and vomiting as a result of ventriculoperitoneal shunt dislocation at the age of 4 years. The diagnosis is provisional asymptomatic multiple CMN-type NCM in association with DWM.

Dandy Walker Variant and Bipolar I Disorder with Graphomania

PubMed Central

Karakaş Uğurlu, Görkem; Çakmak, Selcen

2014-01-01

Cerebellum is known to play an important role in coordination and motor functions. In some resent studies it is also considered to be involved in modulation of mood, cognition and psychiatric disorders. Dandy Walker Malformation is a congenital malformation that is characterized by hypoplasia or aplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of the posterior fossa. When the volume of posterior fossa is normal, the malformation is called Dandy Walker Variant. Case is a 32 year old male with a 12 year history of Bipolar I Disorder presented with manic and depresive symptoms, including dysphoric and depressive affect, anhedonia, suicidal thoughts and behaviours, thoughts of fear about future, overtalkativeness and graphomania, increased energy, irregular sleep, loss of appetite, increased immersion in projects, irritability, agressive behavior, impulsivity. Cranial Magnetic Resonance Imaging was compatible to the morphological features of Dandy Walker Variant. PMID:25110509

Optic disc dysplasia in poland syndrome.

PubMed

Maxfield, Steven D; Strominger, Mitchell B

2014-06-01

To report optic disc dysplasia in a case of Poland syndrome. Non-interventional case report. A 2-year-old boy with Poland syndrome was referred for ophthalmic evaluation after abnormal optic discs were found on exam. Physical exam at birth revealed right-sided aplasia of the pectoralis major muscle, symbrachydactyly, hypoplastic scapula, and an abnormal third rib. On dilated examination the optic nerve heads were dysplastic. The findings included multiple cilioretinal vessels, situs inversus, inferotemporal excavation, and surrounding pigmentary disturbances. Only one case of optic disc anomaly has been reported in Poland syndrome and was described as morning glory syndrome. The optic discs in our patient do not fit well with other optic disc excavation syndromes but are most reminiscent of those in papillorenal syndrome. As both Poland syndrome and papillorenal syndrome share vascular dysfunction as a possible etiology, this case adds to the literature of vascular dysgenesis in Poland syndrome.

[Mayer-Rokitansky-Küster-Hauser syndrome: two cases report].

PubMed

Ávila-Vergara, Marco Antonio; León-Álvarez, Damián Alfredo; López-Villegas, Miriam Nayeli; Quintero-Medrano, Samantha Melissa; Angulo-Bueno, Gladys Fabiola; Vadillo-Ortega, Felipe

2015-03-01

Agenesia of the Müllerian ducts is a low-frequency congenital disease but with devastating effects on women's reproductive health. In this paper we present two cases of women affected by Mayer-Rokitansky-Küster-Hauser syndrome (MRKH). First case was a 17-year-old woman with aplasia of the upper vagina and absence of uterus. No other defects were found and was classified as type 1-MRKH. Second case was 18-year-old woman with absence of uterus, escoliosis and polycystic ovary syndrome, classified as type II-MRKH. Patients were seen at the Hospital with primary amenorrhea and fully developed secondary sexual characteristics. A clinical follow-up protocol, including the use of high-resolution image studies was used for diagnosis. Diagnostic procedures and current medical approaches to the treatment of MRKH are discussed, including psychological advisory, surgical procedures and new tissue-engineering techniques.

Cytokine profile of nasal and middle ear polyps in a patient with Woakes' syndrome and eosinophilic otitis media.

PubMed

De Loof, Marie; De Leenheer, Els; Holtappels, Gabriële; Bachert, Claus

2016-05-03

Woakes' syndrome is characterised by severe recurrent nasal polyps in early childhood with broadening of the nose, nasal dyscrinia, frontal sinus aplasia and bronchiectasis. Eosinophilic otitis media (EOM) is an intractable condition that can cause gradual or sudden deterioration of hearing and is associated with comorbid asthma. For these reasons, both diseases must be recognised and treated appropriately. We present a case of a 20-year-old man with Woakes' syndrome complicated by EOM, with polyps in both middle ears; this condition has so far not been described as an entity of eosinophilic disease in the literature. We have, from reviewing the literature, learned that this is the first time that results of tissue examination on nasal polyposis with respect to tissue IgE, eosinophil-cationic protein, interleukin (IL)-17 and IL-5 in a patient with Woakes' syndrome and EOM, has been reported and discussed. 2016 BMJ Publishing Group Ltd.

Anterior segment developmental anomalies in a 33-week-old fetus with MIDAS syndrome.

PubMed

Herwig, Martina C; Loeffler, Karin U; Gembruch, Ulrich; Kuchelmeister, Klaus; Müller, Annette M

2014-01-01

We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.

Development and applications of groundwater remediation technologies in the USA

NASA Astrophysics Data System (ADS)

Barcelona, Michael J.

2005-03-01

The future of the development and application of groundwater remediation technologies will unfold in an atmosphere of heightened public concern and attention. Cleanup policy will undergo incremental change towards more comprehensive efforts which account for the impact of remediation on nearby resources. Newly discovered contaminants will cause the re-examination of "mature" technologies since they may be persistent, mobile and difficult to treat in-situ. Evaluations of the effectiveness of remedial technologies will eventually include by-product formation, geochemical consequences and sustainability. Long-term field trials of remedial technologies alone can provide the data necessary to support claims of effectiveness. Dans le futur, le développement et les applications des technologies de traitement des eaux souterraines seront déroulés en tenant compte de l'inquiétude et l'attention croissante de l'opinion publique. La politique de nettoyage va subir un changement vers des efforts plus compréhensifs qui prendront en compte l'impact du traitement sur les ressources voisines. Les nouveaux contaminants seront persistants, mobiles et difficile de traiter in situ; par conséquence ils vont provoquer la reexamination des technologies consacrées. L'évaluation de l'efficacité des technologies de traitement doit considérer l'apparition des produits secondaires ainsi que les conséquences géochimiques et le développement durable. Seulement les essais in situ, pendant des longues périodes sur les technologies peuvent fournir les éléments nécessaires pour démontrer leur efficacité. El futuro del desarrollo y de la aplicación de las tecnologías para la recuperación del agua subterránea, se revelará en una atmósfera de gran atención e interés público elevado. La política de limpieza sufrirá un cambio adicional hacia esfuerzos más tangibles, los cuales incluyan el impacto de la recuperación en los recursos circundantes. Los contaminantes

Improving Human Effectiveness Through Embedded Virtual Simulation (Amelioration de l’efficacite humaine grace a la simulation virtuelle integree)

DTIC Science & Technology

2014-01-01

mesurer leur expérience. Le groupe a rencontré des experts des technologies associées : les environnements virtuels, la réalité augmentée, les agents...virtuels, l’entraînement, l’ergonomie et la performance humaine. Les réflexions et conclusions issues de ces réunions et discussions sont résumées dans...en matière de EVS/ET (incluant les caractéristiques de l’utilisateur, la mission et l’environnement) et la gestion de l’entraînement est un

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis

PubMed Central

Garg, Ankur; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven

2017-01-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development. PMID:29028795

A newborn with combined pituitary hormone deficiency developing shock and sludge.

PubMed

Ueda, Yasuhiro; Aoyagi, Hayato; Tajima, Toshihiro

2017-11-27

A male neonate was born at 41 weeks of gestation with a birth weight of 3320 g. Artificial respiratory management was required due to respiratory disturbance 1 h after birth, and subsequently catecholamine-refractory low cardiac output-induced shock occurred. Severe combined pituitary hormone deficiency (CPHD) was considered based on the presence of his respiratory disturbance, hypoglycemia and micropenis. After hydrocortisone (HDC) administration, circulatory dynamics rapidly improved. Brain magnetic resonance imaging (MRI) showed aplasia of the anterior pituitary gland and ectopic posterior gland. γ-Glutamyltranspeptidase (γ-GTP) increased from day 10 after birth and direct bilirubin increased from day 18. On ultrasonography, sludge filling the common bile duct and gall bladder was observed. After initiating treatment with both ursodeoxycholic acid and recombinant human growth hormone (rhGH), cholestasis improved and the sludge disappeared at 3 months after birth. In newborns with CPHD, severe central adrenal insufficiency might induce cardiogenic shock after birth. Early diagnosis and intervention are necessary.

Management of Hyperthyroidism during the Preconception Phase, Pregnancy, and the Postpartum Period.

PubMed

Sarkar, Sudipa; Bischoff, Lindsay A

2016-11-01

Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurocutaneous melanosis in association with the Dandy-Walker complex, complicated by melanoma: report of a case and literature review.

PubMed

Mena-Cedillos, Carlos Alfredo; Valencia-Herrera, Adriana M; Arroyo-Pineda, Alma Iris; Salgado-Jiménez, M Angeles; Espinoza-Montero, Rubén; Martínez-Avalos, Armando Bernardo; Perales-Arroyo, Antonio

2002-01-01

Neurocutaneous melanosis is a rare congenital neurocutaneous syndrome in which benign and malignant melanocytic tumors of the leptomeninges with large or numerous congenital melanocytic nevi develop. The Dandy-Walker malformation occurs as a broad posterior fossa with high insertion of the tentorium, hypoplasia or aplasia of the cerebellar vermis, and cystic dilation of the fourth ventricle communicating with the posterior fossa. Association of these entities is very unusual and only 10 previous reports were found in the literature. Our patient had multiple, medium-size to small melanocytic nevi present since birth. At 5 years of age the patient has intracranial pressure secondary to hydrocephalus. A diagnosis of Dandy-Walker malformation and suspected neurocutaneous melanosis was established after a skull computed tomography (CT) scan. Three months later the patient developed a right frontal tumor shown on the CT scan. The histologic finding was nevomelanocytic infiltration with strong pleomorphism. The tumor grew rapidly, producing neurogenic shock and death. The postmortem report indicated malignant melanoma.

Biology and clinical application of CAR T cells for B cell malignancies.

PubMed

Davila, Marco L; Sadelain, Michel

2016-07-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

A gene for cleidocranial dysplasia to the short arm of chromosome 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feldman, G.F.; Muenke, M.; Robin, N.H.

1995-04-01

Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia characterized by mild-to-moderate short stature, clavicular aplasia or hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth, a characteristic craniofacial appearance, and a variety of other skeletal anomalies. We have performed linkage studies in five families with CCD, with 24 affected and 20 unaffected individuals, using microsatellite markers spanning two candidate regions on chromosomes 8q and 6. The strongest support for linkage was with chromosome 6p microsatellite marker D6S282 with a two-point lod score of 4.84 ({theta} = .03). Furthermore, the multipoint lod score was 5.70 in the intervalmore » between D6S282 and D6S291. These data show that the gene for autosomal dominant CCD is located within a 19-cM interval on the short arm of chromosome 6, between D6S282 and D6S291. 25 refs., 3 figs., 1 tab.« less

Drug-Induced Hematologic Syndromes

PubMed Central

Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

2009-01-01

Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

Thymus Transplantation

PubMed Central

Markert, M. Louise; Devlin, Blythe H.; McCarthy, Elizabeth A.

2013-01-01

Thymus transplantation is a promising investigational therapy for infants born with no thymus. Because of the athymia, these infants lack of T cell development and have a severe primary immunodeficiency. Although thymic hypoplasia or aplasia is characteristic of DiGeorge anomaly, in “complete” DiGeorge anomaly, there is no detectable thymus as determined by the absence of naïve (CD45RA+, CD62L+) T cells. Transplantation of postnatal allogeneic cultured thymus tissue was performed in sixty subjects with complete DiGeorge anomaly who were under the age of 2 years. Recipient survival was over 70%. Naïve T cells developed 3–5 months after transplantation. The graft recipients were able to discontinue antibiotic prophylaxis, and immunoglobulin replacement. Immunosuppression was used in a subset of subjects but was discontinued when naïve T cells developed. The adverse events have been acceptable with thyroid disease being the most common. Research continues on mechanisms underlying immune reconstitution after thymus transplantation. PMID:20236866

Laparoscopic promontofixation for the treatment of recurrent sigmoid neovaginal prolapse: case report and systematic review of the literature.

PubMed

Kondo, William; Ribeiro, Reitan; Tsumanuma, Fernanda Keiko; Zomer, Monica Tessmann

2012-01-01

Prolapse of a sigmoid neovagina, created in patients with congenital vaginal aplasia, is rare. In correcting this condition, preservation of coital function and restoration of the vaginal axis should be of primary interest. A 34-year-old woman with vaginal agenesis underwent vaginoplasty using sigmoid colon. Almost 6 years after the initial operation, she started complaining of a bearing-down sensation and an increase in vaginal discharge. She underwent 2 open surgeries and one vaginal surgery to treat the prolapse with no success. She came to our service and at vaginal examination the neovagina protruded approximately 5 cm beyond the hymen. The prolapse was treated successfully using a laparoscopic approach to suspend the neovagina to the sacral promontory (laparoscopic promontofixation). Prolapse of an artificially created vagina is a rare occurrence, without a standard treatment. Laparoscopy may be an alternative approach to restore the neovagina without compromising its function. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

[Clinical and magnetic resonance imaging characteristics of isolated congenital anosmia].

PubMed

Liu, Jian-feng; Wang, Jian; You, Hui; Ni, Dao-feng; Yang, Da-zhang

2010-05-25

To report a series of patients with isolated congenital anosmia and summarize their clinical and magnetic resonance imaging (MRI) characteristics. Twenty patients with isolated congenital anosmia were reviewed retrospectively. A thorough medical and chemosensory history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, sinonasal computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Neither ENT physical examination nor nasal endoscopy was remarkable. Subjective olfactory testing indicated all of them were of anosmia. No olfactory event-related potentials to maximal stimulus were obtained. Computed tomography scan was normal. MRI revealed the absence of olfactory bulbs and tracts in all cases. And hypoplasia or aplasia of olfactory sulcus was found in all cases. All the patients had normal sex hormone level. The diagnosis of isolated congenital anosmia is established on chief complaints, physical examination, olfactory testing and olfactory imaging. MRI of olfactory pathway is indispensable.

Effects of tributyltin on metamorphosis and gonadal differentiation of Xenopus laevis at environmentally relevant concentrations.

PubMed

Shi, Huahong; Zhu, Pan; Guo, Suzhen

2014-05-01

Tributyltin (TBT), a well known endocrine disruptor, has high teratogenicity to embryos of amphibian (Xenopus tropicalis). An amphibian metamorphosis assay (AMA) and a complete AMA (CAMA) were conducted for TBT. In AMA, the body weight, the snout-to-vent length and the hind limb length of X. laevis tadpoles were decreased in tributyltin chloride (TBTCl; 12.5-200 ng/L) treatment groups after 7 days exposure. TBT greatly retarded the development of tadpoles, decreased the number of follicle and induced thyroid follicle cell hyperplasia after 19 days exposure. In CAMA, 10 and 100 ng/L TBTCl led to various malformations of gonad, including intersex, segmental aplasia and multiple ovary cavities of X. laevis following exposure from stages 46 to stage 66. The sex ratio was male-biased in TBT treatment groups. These results suggest that TBT delayed the metamorphosis, inhibited the growth of tadpoles and disrupted the gonadal differentiation of X. laevis at environmentally relevant concentrations.

[Erythropoiesis-stimulating agents in chronic kidney disease: which route of administration?].

PubMed

Borrelli, S; Baldanza, D; Scigliano, R; Catapano, F; Grimaldi, M; Calabria, M; Zamboli, P; Minutolo, R; De Nicola, L; Conte, G

2009-01-01

In the last twenty years, erythropoiesis-stimulating agents (ESAs) have improved the management of renal anemia, with significant amelioration of quality of life in patients on hemodialysis. ESAs can be administered both intravenously and subcutaneously. In predialysis chronic kidney disease and in peritoneal dialysis, the administration route is necessarily subcutaneous. In hemodialysis the intravenous route was initially preferred because of the presence of ready vascular access for drug administration. Subsequent studies have demonstrated that the subcutaneous route allowed the achievement of optimal levels of hemoglobin with a reduction of mean administered dose, number of injections, and costs. A few years ago, the finding of a higher risk of pure red cell aplasia associated with subcutaneous administration of epoetin reopened the debate about the route of administration. We here review the studies on the preferable route of administration of epoetin and darbepoetin- alpha, in terms of efficacy and safety, and take a look at future perspectives.

Today's challenges in pharmacovigilance: what can we learn from epoetins?

PubMed

Ebbers, Hans C; Mantel-Teeuwisse, Aukje K; Moors, Ellen H M; Schellekens, Huub; Leufkens, Hubert G

2011-04-01

Highly publicized safety issues of medicinal products in recent years and the accompanying political pressure have forced both the US FDA and the European Medicines Agency (EMA) to implement stronger regulations concerning pharmacovigilance. These legislative changes demand more proactive risk management strategies of both pharmaceutical companies and regulators to characterize and minimize known and potential safety concerns. Concurrently, comprehensive surveillance systems are implemented, intended to identify and confirm adverse drug reactions, including the creation of large pharmacovigilance databases and the cooperation with epidemiological centres. Although the ambitions are high, not much is known about how effective all these measures are, or will be. In this review we analyse how the pharmacovigilance community has acted upon two adverse events associated with the use of erythropoiesis-stimulating agents: the sudden increase in pure red cell aplasia and the possible risk of tumour progression associated with these products. These incidents provide important insight for improving pharmacovigilance, but also pose new challenges for regulatory decision making.

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.

PubMed

Garg, Ankur; Bansal, Mukesh; Gotoh, Noriko; Feng, Gen-Sheng; Zhong, Jian; Wang, Fen; Kariminejad, Ariana; Brooks, Steven; Zhang, Xin

2017-10-01

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.

PCI-32765, the First BTK (Bruton’s Tyrosine Kinase) Inhibitor in Clinical Trials

PubMed Central

2013-01-01

Ibrutinib is a potent covalent kinase inhibitor that targets BTK. BTK, or Bruton’s tyrosine kinase, is an obvious target for therapy of B cell diseases because inactivating mutations lead to B cell aplasia in humans and the disease X-linked agammaglobulinemia. Ibrutinib has modest cytotoxicity against CLL cells in vitro but also blocks trophic stimuli from the microenvironment. As with other inhibitors of the BCR pathway, ibrutinib causes rapid nodal reduction and response associated with rapid increase in lymphocytosis, which then returns to baseline over time. The ORR of ibrutinib in relapsed refractory CLL is 67 % with PFS 88 % at 15 months. In a cohort of untreated patients 65 years and over, the estimated 15 month PFS is 96 %. Registration trials have been initiated, and the difficult task that remains is to determine where in the course of CLL therapy this drug will have the greatest impact and benefit for patients. PMID:23296407

Biology and clinical application of CAR T Cells for B cell malignancies

PubMed Central

Davila, Marco L; Sadelain, Michel

2017-01-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma (NHL) and B cell acute lymphoblastic leukemia (B-ALL), including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors. PMID:27262700

De Novo Mutations of the Gene Encoding the Histone Acetyltransferase KAT6B Cause Genitopatellar Syndrome

PubMed Central

Simpson, Michael A.; Deshpande, Charu; Dafou, Dimitra; Vissers, Lisenka E.L.M.; Woollard, Wesley J.; Holder, Susan E.; Gillessen-Kaesbach, Gabriele; Derks, Ronny; White, Susan M.; Cohen-Snuijf, Ruthy; Kant, Sarina G.; Hoefsloot, Lies H.; Reardon, Willie; Brunner, Han G.; Bongers, Ernie M.H.F.; Trembath, Richard C.

2012-01-01

Genitopatellar syndrome (GPS) is a rare disorder in which patellar aplasia or hypoplasia is associated with external genital anomalies and severe intellectual disability. Using an exome-sequencing approach, we identified de novo mutations of KAT6B in five individuals with GPS; a single nonsense variant and three frameshift indels, including a 4 bp deletion observed in two cases. All identified mutations are located within the terminal exon of the gene and are predicted to generate a truncated protein product lacking evolutionarily conserved domains. KAT6B encodes a member of the MYST family of histone acetyltranferases. We demonstrate a reduced level of both histone H3 and H4 acetylation in patient-derived cells suggesting that dysregulation of histone acetylation is a direct functional consequence of GPS alleles. These findings define the genetic basis of GPS and illustrate the complex role of the regulation of histone acetylation during development. PMID:22265017

Systeme microfluidique d'analyse sanguine en temps reel pour l'imagerie moleculaire chez le petit animal

NASA Astrophysics Data System (ADS)

Convert, Laurence

De nouveaux radiotraceurs sont continuellement développés pour améliorer l'efficacité diagnostique en imagerie moléculaire, principalement en tomographie d'émission par positrons (TEP) et en tomographie d'émission monophotonique (TEM) dans les domaines de l'oncologie, de la cardiologie et de la neurologie. Avant de pouvoir être utilisés chez les humains, ces radiotraceurs doivent être caractérisés chez les petits animaux, principalement les rats et les souris. Pour cela, de nombreux échantillons sanguins doivent être prélevés et analysés (mesure de radioactivité, séparation de plasma, séparation d'espèces chimiques), ce qui représente un défi majeur chez les rongeurs à cause de leur très faible volume sanguin (˜1,4 ml pour une souris). Des solutions fournissant une analyse partielle sont présentées dans la littérature, mais aucune ne permet d'effectuer toutes les opérations dans un même système. Les présents travaux de recherche s'insèrent dans le contexte global d'un projet visant à développer un système microfluidique d'analyse sanguine complète en temps réel pour la caractérisation des nouveaux radiotraceurs TEP et TEM. Un cahier des charges a tout d'abord été établi et a permis de fixer des critères quantitatifs et qualitatifs à respecter pour chacune des fonctions de la puce. La fonction de détection microfluidique a ensuite été développée. Un état de l'art des travaux ayant déjà combiné la microfluidique et la détection de radioactivité a permis de souligner qu'aucune solution existante ne répondait aux critères du projet. Parmi les différentes technologies disponibles, des microcanaux en résine KMPR fabriqués sur des détecteurs semiconducteurs de type p-i-n ont été identifiés comme une solution technologique pour le projet. Des détecteurs p-i-n ont ensuite été fabriqués en utilisant un procédé standard. Les performances encourageantes obtenues ont mené à initier un projet de ma

La problématique du coût des nouvelles thérapeutiques en oncologie: qu'en-est-il du Maroc?

PubMed Central

Brahmi, Sami Aziz; Zahra, Ziani Fatima; Seddik, Youssef; Afqir, Said

2016-01-01

Le cancer est un problème majeur de santé public en Afrique. Les progrès réalisé dans le traitement des cancers ces dix dernières années est indéniable. L’émergence des thérapies ciblés en oncologie a permit de modifier l'histoire naturelle de certains cancers réputés de mauvais pronostic. En dépit de leurs efficacité, ces thérapeutiques pose un problème majeur de coût qui les rend inaccessible à la majorité des patients dans les pays en voie développement. Au Maroc, le cancer est reconnu comme a une affection de longue durée et les patients bénéficient de ce fait d'une couverture médicale totale. L'implication de la société civile a permis aussi d'améliorer la prise en charge ainsi qu'un accès plus élargi aux médicaments innovants pour les patients les plus démunis. PMID:27642392

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

PubMed Central

Mirabelli, Peppino; Di Noto, Rosa; Lo Pardo, Catia; Morabito, Paolo; Abate, Giovanna; Gorrese, Marisa; Raia, Maddalena; Pascariello, Caterina; Scalia, Giulia; Gemei, Marica; Mariotti, Elisabetta; Del Vecchio, Luigi

2008-01-01

Background Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007). The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i) multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii) fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii) detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively). As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a). Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA). Conclusion Our study, comparing surface antigen expression of ALDH+/CD34+, ALDH

Etude energetique et modelisation d'un Systeme Hybride Eolien-Diesel avec stockage d'Air Comprime (SHEDAC)

NASA Astrophysics Data System (ADS)

Martinez, Nicolas

Actuellement le Canada et plus specialement le Quebec, comptent une multitude de sites isoles dont !'electrification est assuree essentiellement par des generatrices diesel a cause, principalement, de l'eloignement du reseau central de disuibution electrique. Bien que consideree comme une source fiable et continue, 1 'utilisation des generatrices diesel devient de plus en plus problematique d'un point de vue energetique, economique et environnemental. Dans le but d'y resoudre et de proposer une methode d'approvisionnement plus performante, mains onereuse et plus respectueuse de l'environnement, l'usage des energies renouvelables est devenu indispensable. Differents travaux ont alors demontre que le couplage de ces energies avec des generauices diesel, formant des systemes hybrides, semble etre une des meilleures solutions. Parmi elles, le systeme hybride eolien-diesel avec stockage par air comprime (SHEDAC) se presente comme une configuration optimale pour 1 'electrification des sites isoles. En effet, differentes etudes ont permis de mettre en avant l'efficacite du stockage par air comprime, par rapport a d'autres technologies de stockage, en complement d'un systeme hybride eolien-diesel. Plus precisement, ce systeme se compose de sous-systemes qui sont: des eoliennes, des generatrices diesel et une chaine de compression et de stockage d'air comprime qui est ensuite utilisee pour suralimenter les generatrices. Ce processus permet ainsi de reduire Ia consommation en carburant tout en agrandissant la part d'energie renouvelable dans Ia production electrique. A ce jour, divers travaux de recherche ont pennis de demontrer I' efficacite d 'un tel systeme et de presenter une variete de configurations possibles. A travers ce memoire, un logiciel de dimensionnement energetique y est elabore dans le but d'unifom1iser !'approche energetique de cette technologie. Cet outil se veut etre une innovation dans le domaine puisqu'il est actuellement impossible de dimensionner un

Microgenerateurs electriques a base d'oscillateurs thermiques

NASA Astrophysics Data System (ADS)

Leveille, Etienne

Dans un contexte de developpement durable et d'automatisation de notre environnement, l'utilisation de capteurs sans-fil distribues est croissante. Hors l'usage et le remplacement de piles s'avere couteux. La consommation energetique de plus en plus faible de l'electronique rend l'extraction energetique de l'energie ambiante envisageable. La chaleur residuelle est une source d'energie interessante puisqu'elle est la forme finale de la majeure partie de l'energie utilisee par l'humain. Cependant, a petite echelle, seuls les elements thermoelectriques sont disponibles. Les presents travaux s'interessent donc a explorer et comparer des mecanismes de generation alternatifs. Puisque la majorite des mecanismes de transduction alternatifs sont dynamiques, leur utilisation requiert une transformation de l'energie thermique continue en oscillations. Les mecanismes etudies ont donc tous en commun de posseder un oscillateur thermique en plus d'un mecanisme de transduction vers la forme d'energie electrique. Parmi les divers mecanismes identifies, deux sont etudies en details pour comprendre leurs comportements ainsi que connaitre leur efficacite et leur puissance potentielle. Le premier generateur etudie theoriquement est base sur le changement de ferromagnetisme d'une masse suspendue par des ressorts au-dessus d'un aimant. Les comportements du modele developpe correspondent aux comportements reportes dans la litterature. Deux parametres de conception principaux ont ete identifies, permettant un controle de la frequence, de la plage de temperatures d'operation. De plus le mecanisme peut operer avec de faibles differences de temperature et des temperatures proches de l'ambiant, ouvrant la porte a des applications utilisant la chaleur du corps humain. L'utilisation de materiau pyroelectrique comme mecanisme de transduction pourrait offrir des densites de puissance electrique envisageables de l'ordre de 1mW/cm3. Le second generateur etudie experimentalement est base sur l

Inguinal ovary as a rare diagnostic sign of Mayer-Rokitansky-Küster-Hauser syndrome.

PubMed

Demirel, Fatma; Kara, Ozlem; Esen, Ihsan

2012-01-01

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare syndrome characterized by complete or partial agenesis of the uterus and vagina, due to a congenital defect of the Mullerian duct. Affected individuals have a 46,XX karyotype and a normal female phenotype. MRKH syndrome may be isolated (type I MRKH syndrome) or associated with renal, cardiac, and skeletal anomalies, short stature, and auditory defects. The latter is defined as type II MRKH syndrome or the Müllerian duct aplasia/hypoplasia, renal agenesis/ectopy, and cervicothoracic somite dysplasia (MURCS) association. The majority of patients with MRKH syndrome present with primary amenorrhea. We report a case of type II MRKH syndrome who has been referred by a pediatric surgeon for detection of gonadal function. During an inguinal hernia operation, the left ovary had been observed in the hernia sac. Clinical and radiological evaluation of the patient showed an absence of the uterus and left kidney, and cervical hemi vertebra. Based on these findings, the patient was diagnosed as having type II MRKH syndrome.

Birt-Hogg-Dubé syndrome and intracranial vascular pathologies.

PubMed

Kapoor, Rahul; Evins, Alexander I; Steitieh, Diala; Bernardo, Antonio; Stieg, Philip E

2015-12-01

Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

Rare case of tibial hemimelia, preaxial polydactyly, and club foot

PubMed Central

Granite, Guinevere; Herzenberg, John E; Wade, Ronald

2016-01-01

A seven-month old female presented with left tibial hemimelia (or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot (congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb’s superficial dissection, X-rays, and computed tomography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, and no middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature. PMID:28035313

Rare case of tibial hemimelia, preaxial polydactyly, and club foot.

PubMed

Granite, Guinevere; Herzenberg, John E; Wade, Ronald

2016-12-16

A seven-month old female presented with left tibial hemimelia (or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot (congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb's superficial dissection, X-rays, and computed tomography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, and no middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature.

De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome.

PubMed

Vaccari, Carlotta Maria; Romanini, Maria Victoria; Musante, Ilaria; Tassano, Elisa; Gimelli, Stefania; Divizia, Maria Teresa; Torre, Michele; Morovic, Carmen Gloria; Lerone, Margherita; Ravazzolo, Roberto; Puliti, Aldamaria

2014-05-30

Poland Syndrome (PS) is a rare disorder characterized by hypoplasia/aplasia of the pectoralis major muscle, variably associated with thoracic and upper limb anomalies. Familial recurrence has been reported indicating that PS could have a genetic basis, though the genetic mechanisms underlying PS development are still unknown. Here we describe a couple of monozygotic (MZ) twin girls, both presenting with Poland Syndrome. They carry a de novo heterozygous 126 Kbp deletion at chromosome 11q12.3 involving 5 genes, four of which, namely HRASLS5, RARRES3, HRASLS2, and PLA2G16, encode proteins that regulate cellular growth, differentiation, and apoptosis, mainly through Ras-mediated signaling pathways. Phenotype concordance between the monozygotic twin probands provides evidence supporting the genetic control of PS. As genes controlling cell growth and differentiation may be related to morphological defects originating during development, we postulate that the observed chromosome deletion could be causative of the phenotype observed in the twin girls and the deleted genes could play a role in PS development.

Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells.

PubMed

Gan, Jingyi; Meng, Fanwei; Zhou, Xin; Li, Chan; He, Yixin; Zeng, Xiaoping; Jiang, Xingen; Liu, Jia; Zeng, Guifang; Tang, Yunxia; Liu, Muyun; Mrsny, Randall J; Hu, Xiang; Hu, Jifan; Li, Tao

2015-04-01

Acute radiation syndrome (ARS) leads to pancytopenia and multi-organ failure. Transplantation of hematopoietic stem cells provides a curative option for radiation-induced aplasia, but this therapy is limited by donor availability. We examined an alternative therapeutic approach to ARS with the use of human extracellular superoxide dismutase (ECSOD)-modified umbilical cord mesenchymal stromal cells (UCMSCs). This treatment combines the unique regenerative role of UCMSCs with the anti-oxidative activity of ECSOD. We demonstrated that systemically administered ECSOD-UCMSCs are able to protect mice from sub-lethal doses of radiation and improve survival by promoting multilineage hematopoietic recovery. The therapeutic effect of this treatment is related to the decrease in radiation-induced O(2)(-) and apoptosis. Our data highlight the clinical potential of this two-pronged approach to the treatment of ARS, thereby serving as a rapid and effective first-line strategy to combat the hematopoietic failure resulting from a radiation accident, nuclear terrorism and other radiologic emergencies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum*

PubMed Central

Mathé, G.; Amiel, J. L.; Schwarzenberg, L.; Choay, J.; Trolard, P.; Schneider, M.; Hayat, M.; Schlumberger, J. R.; Jasmin, Cl.

1970-01-01

Allogeneic bone marrow grafts carried out after previous administration of antilymphocytic serum alone were attempted in 16 patients. Of these, six had acute myeloblastic leukaemia, four acute lymphoblastic leukaemia, and one a blast cell crisis in polycythaemia vera. Ten of these patients were in an overt phase of the disease and resistant to chemotherapy, while nine had complete agranulocytosis. In five of these patients erythrocyte and leucocyte antigenic markers demonstrated the establishment of the graft. One patient had thalassaemia major, and four others had aplasia of the bone marrow, in one case due to chloramphenicol poisoning and in another to virus hepatitis. The grafts were successful in the last two patients and transformed their clinical condition. No signs of early acute secondary disease were noted in any of the patients, either when the donor had been given antilymphocytic serum or when he was untreated. The grafts had no adoptive immunotherapeutic effect on the acute leukaemia. These observations have clearly shown that antilymphocytic serum has an immunosuppressive effect in man when it is used alone. PMID:4909449

Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis.

PubMed

Shears, D J; Vassal, H J; Goodman, F R; Palmer, R W; Reardon, W; Superti-Furga, A; Scambler, P J; Winter, R M

1998-05-01

Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited skeletal dysplasia characterized by disproportionate short stature with predominantly mesomelic limb shortening. Expression is variable and consistently more severe in females, who frequently display the Madelung deformity of the forearm (shortening and bowing of the radius with dorsal subluxation of the distal ulna). The rare Langer Mesomelic Dysplasia (LD; OMIM 249700), characterized by severe short stature with hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD (refs 4-6). In a six-generation pedigree with LWD, we established linkage to the marker DXYS6814 in the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max=6.28; theta=0). Linkage analysis of three smaller pedigrees increased the lod score to 8.68 (theta=0). We identified submicroscopic PAR1 deletions encompassing the recently described short stature homeobox-containing gene SHOX (refs 7,8) segregating with the LWD phenotype in 5 families. A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family.

MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement.

PubMed

Brancati, Francesco; Iannicelli, Miriam; Travaglini, Lorena; Mazzotta, Annalisa; Bertini, Enrico; Boltshauser, Eugen; D'Arrigo, Stefano; Emma, Francesco; Fazzi, Elisa; Gallizzi, Romina; Gentile, Mattia; Loncarevic, Damir; Mejaski-Bosnjak, Vlatka; Pantaleoni, Chiara; Rigoli, Luciana; Salpietro, Carmelo D; Signorini, Sabrina; Stringini, Gilda Rita; Verloes, Alain; Zabloka, Dominika; Dallapiccola, Bruno; Gleeson, Joseph G; Valente, Enza Maria

2009-02-01

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the "molar tooth sign", a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs. (c) 2008 Wiley-Liss, Inc.

Safety issues related to erythropoiesis-stimulating agents used to treat anemia in patients with chronic kidney disease.

PubMed

Del Vecchio, Lucia; Locatelli, Francesco

2012-11-01

Erythropoiesis-stimulating agents (ESAs) have been the main therapy for anemia in CKD patients since the late eighties. Since then, treatment indications have progressively changed, together with a progressive increase in therapeutic targets, in terms of hemoglobin levels. This paper discusses possible concerns about ESA use and increased cardiovascular risk (in particular stroke), hypertension, cancer progression and the development of pure red cell aplasia. A literature search was done on PubMed to obtain studies about the adverse effects of ESA in the CKD population. The publication of the TREAT study has largely contributed to the concerns about ESA use, indicating that complete anemia correction may not be safe in the CKD population. This may be particularly true in high-risk patients, especially if hyporesponsive to ESA treatment. However, there is a gray area of no evidence either way for intermediate levels (11.5 - 13 g/dl), in comparison with higher or lower levels. New recommendations about ESA use in the CKD population by the Food and Drug Administration seem to move toward treatment individualization.

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis.

PubMed

Aranda-Orgilles, Beatriz; Saldaña-Meyer, Ricardo; Wang, Eric; Trompouki, Eirini; Fassl, Anne; Lau, Stephanie; Mullenders, Jasper; Rocha, Pedro P; Raviram, Ramya; Guillamot, María; Sánchez-Díaz, María; Wang, Kun; Kayembe, Clarisse; Zhang, Nan; Amoasii, Leonela; Choudhuri, Avik; Skok, Jane A; Schober, Markus; Reinberg, Danny; Sicinski, Piotr; Schrewe, Heinrich; Tsirigos, Aristotelis; Zon, Leonard I; Aifantis, Iannis

2016-12-01

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin.

PubMed

Happle, R

1987-04-01

A genetic concept is advanced to explain the origin of several sporadic syndromes characterized by a mosaic distribution of skin defects. It is postulated that these disorders are due to the action of a lethal gene surviving by mosaicism. The presence of the mutation in the zygote will lead to death of the embryo at an early stage of development. Cells bearing the mutation can survive only in a mosaic state, in close proximity with normal cells. The mosaic may arise either from a gametic half chromatid mutation or from an early somatic mutation. This concept of origin is proposed to apply to the Schimmelpenning-Feuerstein-Mims syndrome, the McCune-Albright syndrome, the Klippel-Trenaunay syndrome, the Sturge-Weber syndrome, and neurocutaneous melanosis. Moreover, this etiologic hypothesis may apply to two other birth defects that have recently been delineated, the Proteus syndrome (partial gigantism of hands or feet, hemihypertrophy, macrocephaly, linear papillomatous epidermal nevus, subcutaneous hemangiomas and lipomas, accelerated growth, and visceral anomalies), and the Delleman-Oorthuys syndrome (orbital cyst, porencephaly, periorbital appendages, and focal aplasia of the skin.

Recent advances in nephrology: highlights from the 35th annual meeting of the American society of nephrology.

PubMed

Cases, Aleix

2002-12-01

The 35th Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, United States (October 30 to November 4, 2002) presented the newest advances in basic and clinical nephrology science. Several presentations and symposia discussed the effects of various interventions and risk factors in clinical outcomes in dialysis patients. The recent evidences of pure red cell aplasia secondary to neutralizing antibodies against erythropoietin were also extensively discussed in a special symposium. Recent advances in the management of calcium phosphorus metabolism and secondary hyperparathyroidism, such as the clinical efficacy and safety of AMG-073, a new calcimimetic agent in the control of hyperparathyroidism in chronic kidney disease patients, or the use of sevelamer or lanthanum carbonate as phosphate binders, were presented. The results in animal models on improved sparing of renal function with rapamycin versus cyclosporin A represent a promising advance in renal transplantation. Finally, the recent discoveries with the newly identified disease gene PKHD1, which causes autosomal recessive polycystic kidney disease, were also presented at the meeting. (c) 2002 Prous Science. All rights reserved.

Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18.

PubMed

Hu, Biliang; Ren, Jiangtao; Luo, Yanping; Keith, Brian; Young, Regina M; Scholler, John; Zhao, Yangbing; June, Carl H

2017-09-26

The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model. Antigen-propelled activation of cytokine helper ensemble (APACHE) CAR T cells displayed inducible expression of IL-18 and enhanced antitumor immunity. In an intact mouse tumor model, CD19-IL-18 CAR T cells induced deeper B cell aplasia, significantly enhanced CAR T cell proliferation, and effectively augmented antitumor effects in mice with B16F10 melanoma. These findings point to a strategy to develop universal CAR T cells for patients with solid tumors. Copyright © 2017. Published by Elsevier Inc.

MKS3/TMEM67 Mutations Are a Major Cause of COACH Syndrome, a Joubert Syndrome Related Disorder with Liver Involvement

PubMed Central

Brancati, Francesco; Iannicelli, Miriam; Travaglini, Lorena; Mazzotta, Annalisa; Bertini, Enrico; Boltshauser, Eugen; D’Arrigo, Stefano; Emma, Francesco; Fazzi, Elisa; Gallizzi, Romina; Gentile, Mattia; Loncarevic, Damir; Mejaski-Bosnjak, Vlatka; Pantaleoni, Chiara; Rigoli, Luciana; Salpietro, Carmelo D.; Signorini, Sabrina; Stringini, Gilda Rita; Verloes, Alain; Zabloka, Dominika; Dallapiccola, Bruno; Gleeson, Joseph G.; Valente, Enza Maria

2008-01-01

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs. PMID:19058225

MOON-test - determination of motor performance in the pediatric oncology.

PubMed

Götte, M; Kesting, S; Albrecht, C; Worth, A; Bös, K; Boos, J

2013-05-01

Pediatric cancer patients suffer from various negative consequences due to the disease, the medical therapy and the inactivity during the intensive treatment. Only few studies have systematically identified the adverse effects of cancer on motor performance in childhood. To determine the motor performance of pediatric cancer patients, a motor performance test was developed which is applicable for this specific patient group. Eight test items with reference values for healthy children were merged to the MOON-test (test for motor performance in the oncology). MOON was tested for feasibility and acceptance in 33 patients aged 4-18 years. Feasibility was confirmed for children with different types of cancer (hematological malignancies and solid tumors) and with amputation, endoprosthesis, during aplasia as well as reduced general condition. Furthermore the patients showed a broad acceptance. Based on the study findings, the use of MOON-test as a standardized motor performance diagnostic tool in clinical routine of oncological acute clinics as well as rehabilitation clinics can be recommended.· © Georg Thieme Verlag KG Stuttgart · New York.

Kallman syndrome versus idiopathic hypogonadotropic hypogonadism at MR imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogl, T.J.; Stemmler, J.; Bergman, C.

To identify morphologic differences between Kallman syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) and establish a role for magnetic resonance (MR) imaging in these disorders. Twenty-eight patients were compared with 10 eugonal male volunteers. Eighteen patients had KS (hypogonadotropic hypogonadism with anosmia) and 10 had IHH. All participants underwent hormone analysis, a sniff-bottle smell test, and gadolinium-enhanced MR imaging. Changes in the hypothalamic-hypophyseal region and the rhinencephalon were evaluated. MR imaging revealed intracranial morphologic changes in all patients on plain T1-weighted sections. Seventeen patients with KS demonstrated aplasia of an olfactory bulb; one olfactory sulcus was absent in six, rudimentarymore » in four, and normal in eight. Olfactory bulbs were present in all 10 IHH patients and three showed one slightly hypoplastic bulb. Ten patients with KS and three with IHH showed an enlarged paranasal sinus system. Further MR findings were similar. MR imaging demonstrates abnormalities of the rhinencephalon present in KS patients and occasionally absent in IHH patients. 18 refs., 10 figs., 1 tab.« less

Mise à jour sur la vaccination contre la méningococcie invasive chez les enfants et les adolescents canadiens.

PubMed

Robinson, Joan L

2018-02-01

La méningococcie invasive (MI) est une maladie grave qui est souvent à l'origine d'un sepsis fulminant ou d'une méningite. Au Canada, elle est surtout attribuable aux sérogroupes B et C. Des programmes de vaccination systématique contre le méningocoque du sérogroupe C sont prévus à l'âge de 12 mois, et dans certaines régions sociosanitaires, le calendrier comprend l'administration de doses supplémentaires aux enfants plus jeunes. Les adolescents reçoivent systématiquement une dose de rappel du vaccin contre le sérogroupe C ou d'un vaccin quadrivalent (sérogroupes A, C, W et Y). L'utilisation systématique des vaccins contre le sérogroupe B n'est pas recommandée tant qu'on n'aura pas recueilli de données supplémentaires sur l'efficacité des vaccins sur le marché et la durée de la protection qu'ils confèrent. Cependant, les enfants d'au moins deux mois qui courent un risque accru de MI devraient être vaccinés contre les sérogroupes B et C dans les plus brefs délais.

Evaluation experimentale de l'efficacite des gants de protection contre les nanoparticules de dioxyde de titane dans des conditions de travail

NASA Astrophysics Data System (ADS)

Vinches, Ludwig

Manufactured titanium dioxide nanoparticles (nTiO2) enter into the formulation of several commercial products including cosmetics, paints, varnishes or food. An increasing number of people will be exposed to nanoparticles (NP), in particular, scientists during their research and workers in companies. As such, they are an emerging source of hazard. Indeed, an increasing number of studies are warning against their likely harmful effects on health. The International Agency for Research against Cancer has classified nTiO2 as being possibly carcinogenic to humans. Furthermore some studies have shown that the skin is not an impervious membrane to the NP and that NP penetration is possible when the skin is injured by abrasion, after repeated flexions or even intact. Therefore, dermal protection will be necessary in order to thoroughly protect NP users. Based upon the precautionary principle, gloves should be used as protection against chemicals. However, to the best of our knowledge, no study on their resistance towards NP has been conducted. In this study, the performance of protective gloves was evaluated with respect to nTiO2 solutions and powders, under conditions simulating occupational use. Mechanical deformations, simulating those produced by hand flexing, were applied to nitrile and butyl rubber and latex samples that were in contact with nTiO2 in water, in propylene glycol or in powder form. nTiO 2 penetration through the protective gloves was determined after deformations of the materials. Following these results, the physicochemical and mechanical phenomena that facilitate the penetration of nTiO2 were identified and studied. It was shown that mechanical deformations caused both damage to the sample surface but also a change in the degree of crystallinity of the glove material. Strain energy was also measured. It decreased significantly in presence and absence of nTiO2, indicating a weakening of the polymer chains. A qualitative study showed that repetitive deformations also lead to a decrease in the size of the agglomerates that were contained in the nTiO2 powder. Glove materials that were in contact with colloidal solutions produced a swelling phenomenon. Finally, measurements of the elongation of glove samples immersed in colloidal solutions were used to determine diffusion coefficients across the materials. The transport of the nanoparticles was driven by that of the carrier liquid (water or propylene glycol). Given the carrier solutions and nanoparticles could be transported through the gloves, exposure to skin could occur.

Developpement d'un catalyseur nickel-alumine efficace pour le reformage de diesel a la vapeur d'eau et etude du systeme reactionnel

NASA Astrophysics Data System (ADS)

Fauteux-Lefebvre, Clemence

Le developpement de sources d'energie alternatives fiables et efficaces est aujourd'hui une necessite. L' interet dans le reformage d'hydrocarbures liquides est ainsi croissant puisqu'il s'agit d'une voie pour l'alimentation des piles a combustible. Les piles a combustible ont une efficacite pour la conversion d'energie en electricite plus grande que celle des moteurs a combustion et font ainsi partie de la recherche de solution en efficacite energetique. Ces piles consomment de l'hydrogene comme combustible pour produire de l'electricite, d'ou l'interet pour le reformage. En effet, cette reaction permet de produire de l'hydrogene et du monoxyde de carbone (un autre combustible des piles a combustible a electrolyte solide) a partir d'hydrocarbure liquide, notamment le diesel. Les piles pourraient donc etre integrees avec une unite de reformage leur fournissant directement le combustible necessaire a partir de diesel. Dans ce projet de recherche, un nouveau catalyseur de nickel sous forme de spinelle nickel-alumine (spinelle NiAl2O4 sur support d'alumine et de zircone stabilisee avec yttria) a ete developpe et teste en laboratoire pour du reformage de propane, d'hydrocarbures liquides et de diesel, a la vapeur d'eau. Par ailleurs, une methode d'ajout des reactifs novatrice a ete utilisee afin de diminuer la pyrolyse precedant le reformage, en utilisant une emulsion. Les resultats de reformage d'hydrocarbures purs ont montre des concentrations tres pres de l'equilibre thermodynamique et une activite constante sans desactivation du catalyseur ni formation de carbone, et ce avec des ratios H2O/C de moins de 2.5 et des temperatures d'operation variant entre 630 °C et 750 °C. Lors de tests effectues en utilisant du diesel fossile, a 705°C, avec un debit volumique des reactifs de plus de 50 000 cm3gcat-1h-1 et un ratio H2O/C de moins de 2.5, l'activite a ete maintenue pendant plus de 15 heures, malgre une operation en cycles. L'analyse du catalyseur apres cette

Bilateral arcuate foramen associated with partial defect of the posterior arch of the atlas in a medieval skeleton: case report and review of the literature. Looking backward to go forward.

PubMed

Travan, Luciana; Saccheri, Paola; Sabbadini, Gastone; Crivellato, Enrico

2011-08-01

We observed a complex atlas (C1) dysmorphism in a human medieval skeleton dug up from the sixth to the seventh century necropolis located in the north-eastern Italy. We analyzed such a dysmorphism in the light of pertinent literature and discussed the functional and clinical implications related to this type of C1 structural malformation. Macroscopical and CT-SCAN examinations of the atlas were carried out. Bone findings consisted of partial aplasia of the posterior arch of the C1 accompanied by a bilateral arcuate foramen. In addition, the spinous processes of C7 and T1 were found to be bifid. Although such abnormalities are supposed to be clinically inconspicuous, yet they may become challenging or even dangerous in the context of trauma. They may even complicate specific diagnostic or surgical procedures. In addition, they may cause a great number of symptoms, ranging from headache and neck pain to loss of postural muscle tone and consciousness, due to the close and complex relationship of bone structures with nerves, blood vessels, muscles, and ligaments. As a result, radiologists, clinicians, surgeons, and chiropractors should consider in their clinical reasoning the possibility that atlas dysmorphisms may occur.

Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference

PubMed Central

Vlachos, Adrianna; Ball, Sarah; Dahl, Niklas; Alter, Blanche P; Sheth, Sujit; Ramenghi, Ugo; Meerpohl, Joerg; Karlsson, Stefan; Liu, Johnson M; Leblanc, Thierry; Paley, Carole; Kang, Elizabeth M; Leder, Eva Judmann; Atsidaftos, Eva; Shimamura, Akiko; Bessler, Monica; Glader, Bertil; Lipton, Jeffrey M

2008-01-01

Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference. PMID:18671700

Biallelic BRCA2 mutations in two black South African children with Fanconi anaemia.

PubMed

Feben, Candice; Spencer, Careni; Lochan, Anneline; Laing, Nakita; Fieggen, Karen; Honey, Engela; Wainstein, Tasha; Krause, Amanda

2017-07-01

Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition, characterized cytogenetically by chromosomal instability and breakage secondary to impaired DNA repair mechanisms. Affected individuals typically manifest growth restriction and congenital physical abnormalities and most progress to hematological disease including bone marrow aplasia. A rare genetic subtype of FA (FA-D1) is caused by biallelic mutations in the BRCA2 gene. Affected individuals manifest severe congenital anomalies and significant pigmentary changes and are additionally at risk for early onset leukemia and certain solid organ malignancies, including Wilms tumors and brain tumors. Parents of affected individuals are obligate carriers for heterozygous BRCA2 mutations and are thus potentially at risk for adult onset cancers which fall within the hereditary breast and ovarian cancer spectrum. We present two cases of black South African patients with FA diagnosed with biallelic BRCA2 mutations and discuss the phenotypic consequences and implications for them and their families. Recognition of this severe end of the phenotypic spectrum of FA is critical in allowing for confirmation of the diagnosis as well as cascade screening and appropriate care of family members.

Klippel-Trenaunay syndrome in a Border collie.

PubMed

de Cock, H; Mols, N; van Roy, M R; Ducatelle, R; Simoens, P

1996-10-01

A Border collie was presented at the age of 9 weeks with several lesions of the right forelimb, including a reddish-blue haemangiomatous macula in the medio-dorsal part of the elbow, multiple, scattered small cavernous haemangioma-like lesions at the plantar part of the foot and a general hypertrophy of the limb. X-rays of the limb showed osteolysis. On skin biopsy, telangiectatic veins were observed. The rest of the body did not show any skin lesions or hypertrophy. The dog was otherwise healthy. Due to the extension of the lesions and worsening of the limb swelling, it was decided to amputate the affected limb. The dog remained healthy for 2 weeks, but then passed through episodes of anaemia, and finally died suddenly with signs of shock. Dissection of the limb after amputation revealed hypoplasia and aplasia of the deep venous system in the lower part of the leg. No arterio-venous shunts were noticed. ln man, this syndrome, characterised by an insufficiently developed deep venous system associated with local overgrowth of the limb and cutaneous telangiectasia, is known as Klippel-Trenaunay syndrome.

Immunophenotypic analysis of hematopoiesis in patients suffering from Shwachman-Bodian-Diamond Syndrome.

PubMed

Mercuri, Angela; Cannata, Elisa; Perbellini, Omar; Cugno, Chiara; Balter, Rita; Zaccaron, Ada; Tridello, Gloria; Pizzolo, Giovanni; De Bortoli, Massimiliano; Krampera, Mauro; Cipolli, Marco; Cesaro, Simone

2015-10-01

Shwachman-Diamond syndrome is a rare disorder characterized by exocrine pancreatic insufficiency, skeletal abnormalities, and bone marrow failure, with high risk of leukemic evolution. The aim of the study was the immunophenotypic characterization of bone marrow cells from patients with Shwachman-Diamond syndrome to assess the maturation pathway of blood progenitor cells and to identify the presence of recurrent abnormalities. Bone marrow samples from nineteen patients and eleven controls were analyzed by multiparameter flow cytometry. We found a low frequency of CD34+ cells (P = 0.0179) and myeloid progenitors (P = 0.025), in the bone marrow of patients with Shwachman-Diamond syndrome as compared to the controls. A significant reduction in the percentage of granulocytes (P = 0.002) and an increase of monocytes (P < 0.001) were also evident in the bone marrow of patients. On the basis of these observations, future prospective assessments may be useful to verify the contribution of bone marrow immunophenotype in the early identification of the evolution toward aplasia or myelodysplasia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hyperthyroidism during pregnancy

PubMed Central

Inoue, Miho; Arata, Naoko; Koren, Gideon; Ito, Shinya

2009-01-01

ABSTRACT QUESTION I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it? ANSWER In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight. PMID:19602653

How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

PubMed

Halim, Liem Andhyk; Brinks, Vera; Jiskoot, Wim; Romeijn, Stefan; Praditpornsilpa, Kearkiat; Assawamakin, Anunchai; Schellekens, Huub

2014-05-01

The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand. Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination. Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit. Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

Parvovirus-B19-associated complications in renal transplant recipients.

PubMed

Waldman, Meryl; Kopp, Jeffrey B

2007-10-01

Parvovirus B19 is a common human pathogen, causing erythema infectiosum in children, hydrops fetalis in pregnant women, and transient aplastic crisis in patients with chronic hemolytic anemia. Immunosuppressed patients can fail to mount an effective immune response to B19, resulting in prolonged or persistent viremia. Renal transplant recipients can develop symptomatic B19 infections as a result of primary infection acquired via the usual respiratory route or via the transplanted organ, or because of reactivation of latent or persistent viral infection. The most common manifestations of B19 infection in immunosuppressed patients are pure red cell aplasia and other cytopenias. Thus, this diagnosis should be considered in transplant recipients with unexplained anemia and reticulocytopenia or pancytopenia. Collapsing glomerulopathy and thrombotic microangiopathy have been reported in association with B19 infection in renal transplant recipients, but a causal relationship has not been definitively established. Prompt diagnosis of B19 infection in the renal transplant recipient requires a high index of suspicion and careful selection of diagnostic tests, which include serologies and polymerase chain reaction. Most patients benefit from intravenous immunoglobulin therapy and/or alteration or reduction of immunosuppressive therapy. Conservative therapy might be sufficient in some cases.

An overview on safety issues related to erythropoiesis-stimulating agents for the treatment of anaemia in patients with chronic kidney disease.

PubMed

Del Vecchio, Lucia; Locatelli, Francesco

2016-08-01

Erythropoiesis stimulating agents (ESA) are effective drugs, which have been used for decades in patients with chronic kidney disease (CKD) with few side effects. More recently, concern has been raised around their safety, from higher cardiovascular and thrombosis risk to cancer progression and increased mortality. We made a literature search on PubMed looking for adverse effects of ESA in CKD patients. The topics covered are cardiovascular adverse events, thrombosis, increased mortality, hypertension, cancer progression, diabetic retinopathy, pure red cell aplasia and anaphylactic reactions. Concerns around ESA therapy have questioned treatment indications in high-risk CKD patients (those with cancer, diabetes and cardiovascular comorbidities). A more cautious approach has then prevailed. In our opinion, intermediate Hb values (Hb 10-12 g/dl) should be aimed with ESA therapy, being more cautious in high-risk patients. As a consequence, IV iron is administered more frequently. However, excessive iron use may cause iron overload and in rare cases severe anaphylactic reactions. There are expectations of new erythropoietic agents, such as those manipulating the hypoxia-inducible transcription factors (HIF) system. Differing from ESAs, they stimulate the production of endogenous EPO, avoiding over-physiological plasmatic levels.

Birth defects observed with maternal carbimazole treatment: Six cases reported to Nice's Pharmacovigilance Center.

PubMed

Koenig, D; Spreux, A; Hiéronimus, S; Chichmanian, R-M; Bastiani, F; Fénichel, Patrick; Brucker-Davis, F

2010-12-01

To report cases of embryopathy occurring following first trimester exposure to anti-thyroid drugs. Retrospective screening of the database of our Pharmacovigilance Center from 1987 to date. We report six cases of embryopathy, all following carbimazole exposure during the first trimester: two cases of abdominal wall defect, including one associated with facial dysmorphia; one case of digestive malformation (patent omphalomesenteric duct); two cases of aplasia cutis including one with facial dysmorphism; one case of bilateral choanal atresia with aorta coarctation associated with poorly controlled insulin dependent diabetes. Four out of five patients were euthyroid with treatment during the first trimester. We found a context suggesting genetic predisposition to congenital malformation in three cases: two cases of parental cleft lip/palate, one case of consanguinity. Outcome was favorable in all cases. We want to raise awareness about the potential teratogenicity of carbimazole, probably on a predisposed genetic background. We suggest better reporting of congenital anomalies in children of women with Graves'disease, with or without in utero exposure to anti-thyroid drugs. In light of current literature, propylthiouracil should be the first line treatment for hyperthyroid women wishing a pregnancy. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

An update on ABO incompatible hematopoietic progenitor cell transplantation.

PubMed

Staley, Elizabeth M; Schwartz, Joseph; Pham, Huy P

2016-06-01

Hematopoietic progenitor cell (HPC) transplantation has long been established as the optimal treatment for many hematologic malignancies. In the setting of allogenic HLA matched HPC transplantation, greater than 50% of unrelated donors and 30% of related donors demonstrate some degree of ABO incompatibility (ABOi), which is classified in one of three ways: major, minor, or bidirectional. Major ABOi refers to the presence of recipient isoagglutinins against the donor's A and/or B antigen. Minor ABOi occurs when the HPC product contains the isoagglutinins targeting the recipient's A and/or B antigen. Bidirectional refers to the presence of both major and minor ABOi. Major adverse events associated with ABOi HPC transplantation includes acute and delayed hemolysis, pure red cell aplasia, and delayed engraftment. ABOi HPC transplantation poses a unique challenge to the clinical transplantation unit, the HPC processing lab, and the transfusion medicine service. Therefore, it is essential that these services actively communicate with one another to ensure patient safety. This review will attempt to globally address the challenges related to ABOi HPC transplantation, with an increased focus on aspects related to the laboratory and transfusion medicine services. Copyright © 2016 Elsevier Ltd. All rights reserved.

Congenital basis of posterior fossa anomalies

PubMed Central

Cotes, Claudia; Bonfante, Eliana; Lazor, Jillian; Jadhav, Siddharth; Caldas, Maria; Swischuk, Leonard

2015-01-01

The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies. PMID:26246090

Electro-oculography of smooth pursuit and optokinetic nystagmus eye movements in type I Duane's retraction syndrome.

PubMed

Melek, Nélida B; Blanco, Susana; Garcia, Horacio

2006-01-01

These two eye movements have not been previously studied in this condition by this method. Five cases were studied. Both visual acuity and eye examination of anterior and posterior segments were normal. A Nicolet Nystar Plus system with chloride silver electrodes was used to record the EOG. Of the two systems under study, the smooth pursuit system showed the most relevant anomalies, both in the Duane's eye and in the apparently healthy eye. No correlation was found between the pursuit and optokinetic nystagmus disorders. In some cases, more significant abnormalities were observed in the clinically normal eye. The results clearly demonstrated a significant impairment of the pursuit system. This suggests that this motor disorder is not exclusively caused by hypoplasia or aplasia of the nucleus of the abducens nerve (VIth cranial nerve). These abnormalities might be related to a poor development of the rhombencephalon since both supramotor nuclei as well as the pathways of this system arise from this region of the embryonic brain. In the particular case of OKN, the supramotor nuclei have a different origin. Therefore, these systems might be affected differently.

[Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma].

PubMed

Marguglio, A; Hoyoux, C; Dresse, M F; Chantraine, J M; Thiry, A; Gillet, P

1998-03-01

Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.

[Integration of Internal and Clinical Laboratory Medicine].

PubMed

Hirokawa, Makoto

2015-03-01

The mission of our department is to contribute to diagnostic improvement in medicine in order to promote better outcomes. We have clinical expertise in internal medicine including primary care medicine, hematology, allergy, rheumatology, and nephrology. We also have expertise in clinical laboratory medicine and hospital infection control. Specific areas of academic interest include immune-mediated hematological diseases, allergic diseases, autoimmune diseases, and chronic kidney disease. Immune recovery following hematopoietic stem cell transplantation and the immunopathophysiology of bone marrow failure syndrome have been our main topics of interest, and we have been applying our knowledge of T-cell receptor diversity to these areas in order to explore the mechanisms of immunodeficiency and autoimmunity in hematological disorders. We have found that the peripheral expansion of mature T cells in grafts plays an important role in immune reconstitution after stem cell transplantation in humans, and have also found altered T-cell repertoires in immune-mediated chronic acquired pure red cell aplasia. Thus, quantitative and qualitative analyses of immune receptors could be a promising method for assessing immunocompetence and exploring the pathophysiology of autoimmune diseases. Research and development of novel approaches in this field should be intensively conducted.

The genetic basis of female reproductive disorders: Etiology and clinical testing ☆

PubMed Central

Layman, Lawrence C.

2013-01-01

With the advent of improved molecular biology techniques, the genetic basis of an increasing number of reproductive disorders has been elucidated. Mutations in at least 20 genes cause hypogonadotropic hypogonadism including Kallmann syndrome in about 35–40% of patients. The two most commonly involved genes are FGFR1 and CHD7. When combined pituitary hormone deficiency includes hypogonadotropic hypogonadism as a feature, PROP1 mutations are the most common of the six genes involved. For hypergonadotropic hypogonadism, mutations in 14 genes cause gonadal failure in 15% of affected females, most commonly in FMR1. In eugonadal disorders, activating FSHR mutations have been identified for spontaneous ovarian hyperstimulation syndrome; and WNT4 mutations have been described in mullerian aplasia. For other eugonadal disorders, such as endometriosis, polycystic ovary syndrome, and leiomyomata, specific germline gene mutations have not been identified, but some chromosomal regions are associated with the corresponding phenotype. Practical genetic testing is possible to perform in both hypogonadotropic and hypergonadotropic hypogonadism and spontaneous ovarian hyperstimulation syndrome. However, clinical testing for endometriosis, polycystic ovary syndrome, and leiomyomata is not currently practical for the clinician. PMID:23499866

Nanoparticules d'or: De l'imagerie par resonance magnetique a la radiosensibilisation

NASA Astrophysics Data System (ADS)

Hebert, Etienne M.

Cette thèse approfondit l'étude de nanoparticules d'or de 5 nm de diamètre recouvertes de diamideéthanethioldiethylènetriaminepentacétate de gadolinium (DTDTPA:Gd), un agent de contraste pour l'imagerie par résonance magnétique (IRM). En guise de ciblage passif, la taille des nanoparticules a été contrôlée afin d'utiliser le réseau de néovaisseaux poreux et perméable des tumeurs. De plus les tumeurs ont un drainage lymphatique déficient qui permet aux nanoparticules de demeurer plus longtemps dans le milieu interstitiel de la tumeur. Les expériences ont été effectuées sur des souris Balb/c femelles portant des tumeurs MC7-L1. La concentration de nanoparticules a pu être mesurée à l'IRM in vivo. La concentration maximale se retrouvait à la fin de l'infusion de 10 min. La concentration s'élevait à 0.3 mM dans la tumeur et de 0.12 mM dans le muscle environnant. Les nanoparticules étaient éliminées avec une demi-vie de 22 min pour les tumeurs et de 20 min pour le muscle environnant. Les nanoparticules ont été fonctionnalisées avec le peptide Tat afin de leur conférer des propriétés de ciblage actif La rétention de ces nanoparticules a ainsi été augmentée de 1600 %, passant d'une demi-vie d'élimination de 22 min à 350 min. La survie des souris a été mesurée à l'aide de courbes Kaplan-Meier et d'un modèle mathématique évalue l'efficacité de traitements. Le modèle nous permet, à l'aide de la vitesse de croissance des tumeurs et de l'efficacité des traitements, de calculer la courbe de survie des spécimens. Un effet antagoniste a été observé au lieu de l'effet synergétique attendu entre une infusion de Au@DTDTPA:Gd et l'irradiation aux rayons X. L'absence d'effet synergétique a été attribuée à l'épaisseur du recouvrement de DTDTPA:Gd qui fait écran aux électrons produits par l'or. De plus, le moyen d'ancrage du recouvrement utilise des thiols qui peuvent s'avérer être des capteurs de radicaux. De plus

"Nature cures:" An alternative herbal formulation as a denture cleanser.

PubMed

Sushma, R; Sathe, Tanuja Tanaji; Farias, Anand; Sanyal, Pronob Kumar; Kiran, Shashi

2017-01-01

Candida albicans is one of the microorganisms which harbor the oral cavity, especially in elderly. However, the incidence of existence of this increases in patients using removable dental prosthesis. There is therefore a need to test the anticandidal efficacy of these cost-effective, easily available products to be used as routine denture cleansers. (1) To evaluate antifungal properties of triphala churna on the heat cure denture base material. (2) To evaluate the antifungal effect of chlorhexidine gluconate on the heat cure denture base material. (3) To compare the antifungal effect of triphala churna and chlorhexidine gluconate with a control. (4) To evaluate which among triphala churna and chlorhexidine gluconate has a better antifungal property on the heat cure denture base material. Study population consisted of sixty dentures wearers from those attending the Outpatient Department of Prosthodontics of the School of Dentistry, Krishna Institute of Medical Sciences Deemed University, Karad. Swabs were collected from the dentures before and after the use of triphala and chlorhexidine. The swabs were cultured on Sabouraud dextrose agar and the total Candida counts were determined. Triphala as an antifungal is shown to have more efficacy than the conventional chlorhexidine mouthwash. Résumé Arrière-plan: Candida albicans est l'un des micro-organismes qui abritent la cavité buccale surtout chez les personnes âgées. Cependant, l'incidence de l'existence de cette augmentation chez les patients utilisant des prothèses dentaires amovibles. Il est donc nécessaire de tester l'efficacité anticancédique de ces produits rentables et faciles à utiliser pour être utilisés comme nettoyants de routine pour prothèses dentaires. Buts et Objectifs: (1) Évaluer les propriétés antifongiques de Triphala churna sur le matériau de base de la prothèse thermo-durcissable. (2) Évaluer l'effet antifongique du gluconate de chlorhexidine sur le matériau de base de la

Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor.

PubMed

MacVittie, T J; Farese, A M; Herodin, F; Grab, L B; Baum, C M; McKearn, J P

1996-05-15

Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitution after bone marrow myelosuppression. This study evaluated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine-SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [QD], 15 micrograms/kg/d, n = 10), Synthokine (twice daily [BID], 100, micrograms/kg/d, n = 15), rhG-CSF (QD, 10 micrograms/kg/d, n = 5), or a combination of Synthokine and rhG-CSF (BID, 100 and 10 micrograms/kg/d, respectively, n = 5) for 23 days beginning on d1. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count < 500/microL) and thrombocytopenia (platelet count < 20,000/microL) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period neutropenia (P < .05). The combined Synthokine/rhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The Synthokine/rhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animals for Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA. These data showed that the combination of Synthokine, SC-55494, and rhG-CSF further decreased the cytopenic periods and nadirs for both platelets and neutrophils relative to Synthokine and rhG-CSF monotherapy and suggest that this combination therapy would be effective against both neutropenia and thrombocytopenia consequent to drug- or radiation- induced myelosuppression.

Allier théorie et pratique dans la lutte contre la pandémie du Sida

PubMed Central

Zerbo, Roger

2014-01-01

Le premier cas d'infection par le VIH a été notifié en 1986 au Burkina Faso. L'ignorance qui entourait cette infection et l'absence de traitement curatif a amplifié ses conséquences sociales et économiques. La mise en œuvre des interventions communautaire est un enjeu majeur actuel qui recommande la compréhension des logiques sociales endogènes qui influencent les comportements individuels et collectifs. C'est en cela que l'implication des sciences sociales dans la lutte contre les maladies, en particulier le Sida constitue un enjeu, en termes de définition et d'identification de leur contribution. Dans notre propos, nous pouvons mettre en évidence trois niveaux de contribution des sciences sociales, notamment la sociologie, l'anthropologie, la psychologie et dans une certaine mesure le droit et l’économie, à la prévention du Sida et la prise en charge des personnes infectées par le VIH. Il faut noter que ces disciplines contribuent à la lutte contre le VIH d'une part, par des réflexions et des éléments d'analyses constructives, et d'autre part, l'aptitude des porteurs de ces disciplines est parfois sollicitée pour l'efficacité de la mise en œuvre des actions et l'organisation des systèmes de soins. PMID:25722761

Les biofilms bactériens : leur importance en santé animale et en santé publique

PubMed Central

Tremblay, Yannick D.N.; Hathroubi, Skander; Jacques, Mario

2014-01-01

Résumé Les biofilms bactériens sont des amas structurés de cellules bactériennes enrobés d’une matrice polymérique et attachés à une surface. Le biofilm protège les bactéries et leur permet de survivre dans des conditions environnementales hostiles. Les bactéries du biofilm peuvent résister à la réponse immunitaire de l’hôte et sont beaucoup plus résistantes aux antibiotiques et aux désinfectants que les cellules bactériennes planctoniques. La capacité de former un biofilm est maintenant reconnue comme une caractéristique propre à plusieurs microorganismes. La présence de biofilms lors d’infections demande donc de nouvelles méthodes de prévention, de diagnostic et de traitement. De même, la présence de biofilms sur des surfaces retrouvées à la ferme, à l’abattoir ou à l’usine de transformation affectera l’efficacité du protocole de désinfection. De façon surprenante, la formation de biofilms chez les bactéries pathogènes des animaux et les bactéries zoonotiques est un sujet relativement peu étudié. Ce bref compte rendu a pour objectif de sensibiliser les intervenants en santé animale à l’importance des biofilms. PMID:24688172

Influence de l'introduction de défauts colonnaires amorphes sur les propriétés de transport d'un monocristal supraconducteur à haute Tc

NASA Astrophysics Data System (ADS)

Warmont, Franck; Hébert, Sylvie; Hardy, Vincent; Martin, Christine; Simon, Charles; Provost, Jackie

1997-12-01

Columnar defects can be introduced in high T_c superconductors by irradiation with high energy heavy ions. The concentration of these artificial pinning centers with a well characterized morphology is easily controlled. The pinning efficiency of these defects has been often demonstrated, mainly from magnetization measurements. In the present work, measurements of the electrical resistance along the c axis, R_c(T), in the presence of columnar defects are presented. They show the ability of these defects to prevent the thermal fluctuations effects. The measurements have been performed on the same crystal before and after the heavy ion irradiation. L'irradiation aux ions lourds de haute énergie permet d'introduire des défauts colonnaires amorphes dans les supraconducteurs à haute T_c. Ces centres de pinning artificiel, de morphologie connue, sont introduits en concentration facile à maîtriser. L'efficacité de ces défauts a été très souvent démontrée à partir de mesures d'aimantation. L'étude présentée ici : mesure de la résistance selon l'axe c, R_c(T), en présence de défauts colonnaires parallèles à l'axe c, montre que ces défauts sont capables de s'opposer efficacement à l'effet des fluctuations thermiques. Les mesures ont été faites sur le même monocristal avant et après l'irradiation.

Appendicite aigue non compliquée: y a-t- il une place pour le traitement conservateur

PubMed Central

El Khader, Ahmed; Lahkim, Mohamed; El Barni, Rachid; Achour, Abdessamad

2015-01-01

Le but de cette étude a été d’évaluer l'efficacité de l'antibiothérapie seule dans le traitement des appendicites aigues non compliquées. C'est une étude prospective, intéressant 68 patients ayant eu une appendicite aigue simple, de confirmation radiologique, traités par l'amoxicilline associée à l'acide clavulanique pendant 10 jours. L'appendicectomie a été réalisée en cas d'aggravation ou en cas de non amélioration au bout de 48heures de traitement. Le traitement conservateur a été efficace dans 82,35% avec une résolution complète des symptômes chez 56 patients. Les 12 cas restants (17,65%) ont subit une appendicectomie. l'appendicite a été gangréneuse dans 8 cas et phlegmoneuse dans 4 cas. Cinq des 56 patients, qui ont bien évolué sous traitement conservateur, ont été réadmis et opérés pour récidive, soit 8,9%. Deux cas ont eu une appendicite compliquée. L'appendicectomie reste le traitement de référence pour l'appendicite aigue, mais le traitement antibiotique peut être proposé en première intension à des patients présentant une appendicite aigue non compliquée. PMID:26327981

Evaluation of the immuno-stimulatory potential of stopper extractables and leachables by using dendritic cells as readout.

PubMed

Mueller, Robert; Karle, Anette; Vogt, Anne; Kropshofer, Harald; Ross, Alfred; Maeder, Karsten; Mahler, Hanns-Christian

2009-10-01

Recombinant protein pharmaceuticals may bear some risks and undesirable side effects, such as the appearance of immunogenic reactions. The increased incidence of antibody-mediated pure red cell aplasia (PRCA) outside the United States after administration of a human serum albumin (HSA)-free EPREX (recombinant human erythropoietin alpha) formulation was explained with the generation of rubber stopper related leachables, possibly acting as immunogenic adjuvants. In our study, we have investigated the potential of extractable and leachable preparations of three different pharmaceutical relevant stoppers to generate a "danger signal" in a dendritic cell assay. Furthermore, the investigated extractable and leachable preparations were characterized by NMR and a micelle-based polysorbate quantification method. In summary, we could demonstrate that stopper extractables, either generated by extraction or by leaching conditions, were not acting as danger signals for dendritic cells. Instead we identified degradation products of polysorbate 80, oleic acid and follow-up products, occur only under very accelerated conditions (100 degrees C for 4 days) as a potential stimulator for these immune cells. As this degradation did not occur at real-time, the authors however do not consider their finding to be linked to any direct safety implications of polysorbate-containing formulations in clinical practice.

Anatomical Variations of the Circulus Arteriosus in Cadaveric Human Brains

PubMed Central

Gunnal, S. A.; Farooqui, M. S.; Wabale, R. N.

2014-01-01

Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic channel at the base of the brain which unites the internal carotid and vertebrobasilar system. It maintains the steady and constant supply to the brain. The variations of CW are seen often. The Aim of the present work is to find out the percentage of normal pattern of CW, and the frequency of variations of the CW and to study the morphological and morphometric aspects of all components of CW. Methods. Circulus arteriosus of 150 formalin preserved brains were dissected. Dimensions of all the components forming circles were measured. Variations of all the segments were noted and well photographed. The variations such as aplasia, hypoplasia, duplication, fenestrations, and difference in dimensions with opposite segments were noted. The data collected in the study was analyzed. Results. Twenty-one different types of CW were found in the present study. Normal and complete CW was found in 60%. CW with gross morphological variations was seen in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and 40%, respectively. Conclusion. As it confirms high percentage of variations, all surgical interventions should be preceded by angiography. Awareness of these anatomical variations is important in neurovascular procedures. PMID:24891951

Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

PubMed

Tangen, Jon-Magnus; Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

2015-01-01

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

Immunomodulatory Effects of the Agaricus blazei Murrill-Based Mushroom Extract AndoSan in Patients with Multiple Myeloma Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation: A Randomized, Double Blinded Clinical Study

PubMed Central

Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

2015-01-01

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021. PMID:25664323

Why are hematopoietic stem cells so 'sexy'? on a search for developmental explanation.

PubMed

Ratajczak, M Z

2017-08-01

Evidence has accumulated that normal human and murine hematopoietic stem cells express several functional pituitary and gonadal sex hormones, and that, in fact, some sex hormones, such as androgens, have been employed for many years to stimulate hematopoiesis in patients with bone marrow aplasia. Interestingly, sex hormone receptors are also expressed by leukemic cell lines and blasts. In this review, I will discuss the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that hematopoietic stem cells are related to subpopulation of migrating primordial germ cells. To support of this notion, the anatomical sites of origin of primitive and definitive hematopoiesis during embryonic development are tightly connected with the migratory route of primordial germ cells: from the proximal epiblast to the extraembryonic endoderm at the bottom of the yolk sac and then back to the embryo proper via the primitive streak to the aorta-gonado-mesonephros (AGM) region on the way to the genital ridges. The migration of these cells overlaps with the emergence of primitive hematopoiesis in the blood islands at the bottom of the yolk sac, and definitive hematopoiesis that occurs in hemogenic endothelium in the embryonic dorsal aorta in AGM region.

Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: an Italian multicenter experience.

PubMed

Faraci, Maura; Zecca, Marco; Pillon, Marta; Rovelli, Attilio; Menconi, Maria Cristina; Ripaldi, Mimmo; Fagioli, Franca; Rabusin, Marco; Ziino, Ottavio; Lanino, Edoardo; Locatelli, Franco; Daikeler, Thomas; Prete, Arcangelo

2014-02-01

Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Clinical presentations of parvovirus B19 infection.

PubMed

Servey, Jessica T; Reamy, Brian V; Hodge, Joshua

2007-02-01

Although most persons with parvovirus B19 infection are asymptomatic or have mild, nonspecific, cold-like symptoms, several clinical conditions have been linked to the virus. Parvovirus B19 usually infects children and causes the classic "slapped-cheek" rash of erythema infectiosum (fifth disease). The virus is highly infectious and spreads mainly through respiratory droplets. By the time the rash appears, the virus is no longer infectious. The virus also may cause acute or persistent arthropathy and papular, purpuric eruptions on the hands and feet ("gloves and socks" syndrome) in adults. Parvovirus B19 infection can trigger an acute cessation of red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis, or congenital anemia. This is even more likely in patients with illnesses that have already shortened the lifespan of erythrocytes (e.g., iron deficiency anemia, human immunodeficiency virus, sickle cell disease, thalassemia, spherocytosis). A clinical diagnosis can be made without laboratory confirmation if erythema infectiosum is present. If laboratory confirmation is needed, serum immunoglobulin M testing is recommended for immunocompetent patients; viral DNA testing is recommended for patients in aplastic crisis and for those who are immunocompromised. Treatment is usually supportive, although some patients may require transfusions or intravenous immune globulin therapy. Most patients recover completely.

[The main etiopathogenic mechanisms of neurocutaneous diseases].

PubMed

Vicente, F J; Gil, P; Vázquez-Doval, F J

1997-09-01

Neurocutaneous syndromes constitute a large and complex group of diseases in which recent medical advances, particularly in the field of molecular biology and genetics, have afforded a deeper understanding of the way in which these diseases originate. In this article, we review the advances concerning pathogenic mechanisms. First, we discuss the malformations disorders of the central nervous system associated with skin disorders, which range from spinal and/or cranial dysraphism with skin lesions to fustrated forms of malformations of the neural tube, such us membranous aplasia cutis. Neurocutaneous vascular disorders can be due to malformational disease, such as in Sturge-Weber syndrome, as well as to autoimmune diseases. The analysis of mutations affecting the capacity for migration and differentiation of melanocyte precursors enables us to gain a better understanding of disorders of the cells of the neural crest, such as piebaldism and Waardenburg's syndrome. Mutations in tumor suppressor genes play an important part in the development of hamartomatous and neoplastic lesions in neurofibromatosis and tuberous sclerosis. Genetic mosaicism, both of the functional and the genomic kind, accounts for the great diversity of phenotypes and the distribution of neurocutaneous diseases. Lastly, neurocutaneous syndromes such as the paracrinopathies form an attractive hypothesis, which is as yet to be confirmed.

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

PubMed

Manukjan, Georgi; Bösing, Hendrik; Schmugge, Markus; Strauß, Gabriele; Schulze, Harald

2017-11-01

Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome. © 2017 John Wiley & Sons Ltd.

Clinical concerns of immunogenicity produced at cellular levels by biopharmaceuticals following their parenteral administration into human body.

PubMed

Tamilvanan, Shunmugaperumal; Raja, Natarajan Livingston; Sa, Biswanath; Basu, Sanat Kumar

2010-08-01

Similar to the low molecular weight traditional drugs, biopharmaceuticals are capable of producing not only therapeutic effects but also side effects provided if the dose of these compounds exceeds certain concentration and/or if the exposure duration of these compounds at subtoxic doses is being lengthened. In addition, a major drawback of biopharmaceuticals is the risk of antibody formation. Following the administration of biopharmaceuticals into human body, the formation of antidrug-antibody (ADA) or neutralizing antibody and other general immune system effects (including allergy, anaphylaxis, or serum sickness) are of clinical concern regarding therapeutic efficacy and patient safety. For example, drug-induced neutralizing antibodies to erythropoietin (EPO) result in pure red cell aplasia, whereas drug-induced acquired anti-factor VIII antibodies worsen the pathology associated with hemophilia. Since most of the already developed or under development biopharmaceuticals are to some extent immunogenic, the regulatory agencies insist to conduct potential ADA formation during the drug development process itself. This review encompasses a short overview on the clinical concerns of immunogenicity produced at cellular levels by growth hormone, interferon-alpha, EPO, factor VIII, and factor IX following their parenteral administration into human body. Clinical concerns related to immunogenicity produced by the biosimilar versions of these drugs are also presented wherever possible.

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

PubMed Central

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Hypervariability of biofilm formation and oxacillin resistance in a Staphylococcus epidermidis strain causing persistent severe infection in an immunocompromised patient.

PubMed

Weisser, Maja; Schoenfelder, Sonja M K; Orasch, Christina; Arber, Caroline; Gratwohl, Alois; Frei, Reno; Eckart, Martin; Flückiger, Ursula; Ziebuhr, Wilma

2010-07-01

We report on a leukemic patient who suffered from a persistent, generalized, and eventually fatal Staphylococcus epidermidis infection during prolonged aplasia. Over a 6-week period, we isolated a genetically and phenotypically unstable S. epidermidis strain related to an epidemic clone associated with hospital infections worldwide. Strikingly, the strain showed a remarkable degree of variability, with evidence of selection and increasing predominance of biofilm-producing and oxacillin-resistant variants over time. Thus, in the early stages of the infection, the strain was found to generate subpopulations which had spontaneously lost the biofilm-mediating ica locus along with the oxacillin resistance-conferring mecA gene. These deletion mutants were obviously outcompeted by the ica- and mecA-positive wild-type genotype, with the selection and predominance of strongly biofilm-forming and oxacillin-resistant variants in the later stages of the infection. Also, a switch from protein- to polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG)-mediated-biofilm production was detected among ica-positive variants in the course of the infection. The data highlight the impact of distinct S. epidermidis clonal lineages as serious nosocomial pathogens that, through the generation and selection of highly pathogenic variants, may critically determine disease progression and outcome.

Decrease in hematopoietic stem cell domains as a delayed effect of x-irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

Although the hematopoietic integrity of locally X-irradiated sites can be restored for a time even after fairly large doses, a secondary aplasia often occurs some months later. To gain further insight into this delayed effect within the framework of the stem cell regulatory domain hypothesis, we characterized the growth kinetics of spleen colony forming units (CFU-S) in WBB6FI-+/+ bone marrow transplanted into WBB6FI-W/WV mice in which one leg had been exposed to 10-30 Gy of X rays 4-5 months previously. Compared to unirradiated contralateral marrow, fewer CFU-S either reached the previously irradiated marrow or were seeded into sites that couldmore » support growth. The initial exponential growth of effectively seeded CFU-S was unchanged, but growth deceleration (inflection point) occurred at a lower level of CFU-S in marrow previously irradiated with 20-30 Gy. This change in the inflection point indicates a radiation dose-dependent decrease consistent with the decrease in bone marrow cellularity. The decrease in effective stem cell domains after 20 Gy was calculated to be about 35%. We interpret these results to reflect the highly localized nature of delayed radiation damage to the marrow microenvironment.« less

Pathogenesis and treatment of leukemia: an Asian perspective.

PubMed

Kwong, Yok-Lam

2012-03-01

Leukemias occur worldwide, but there are important geographic differences in incidences. Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

PubMed

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

PubMed Central

Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T.; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge

2015-01-01

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. PMID:26077718

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

PubMed

Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

2015-06-29

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. © 2015 Aspelund et al.

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fermand, J.P.; Levy, Y.; Gerota, J.

1989-01-01

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15more » and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.« less

CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery.

PubMed

Vesseur, A C; Verbist, B M; Westerlaan, H E; Kloostra, F J J; Admiraal, R J C; van Ravenswaaij-Arts, C M A; Free, R H; Mylanus, E A M

2016-12-01

To provide an overview of anomalies of the temporal bone in CHARGE syndrome relevant to cochlear implantation (CI), anatomical structures of the temporal bone and the respective genotypes were analysed. In this retrospective study, 42 CTs of the temporal bone of 42 patients with CHARGE syndrome were reviewed in consensus by two head-and-neck radiologists and two otological surgeons. Anatomical structures of the temporal bone were evaluated and correlated with genetic data. Abnormalities that might affect CI surgery were seen, such as a vascular structure, a petrosquamosal sinus (13 %), an underdeveloped mastoid (8 %) and an aberrant course of the facial nerve crossing the round window (9 %) and/or the promontory (18 %). The appearance of the inner ear varied widely: in 77 % of patients all semicircular canals were absent and the cochlea varied from normal to hypoplastic. A stenotic cochlear aperture was observed in 37 %. The middle ear was often affected with a stenotic round (14 %) or oval window (71 %). More anomalies were observed in patients with truncating mutations than with non-truncating mutations. Temporal bone findings in CHARGE syndrome vary widely. Vascular variants, aberrant route of the facial nerve, an underdeveloped mastoid, aplasia of the semicircular canals, and stenotic round window may complicate cochlear implantation.

Propagation d'impulsions femtosecondes térawatts dans l'atmosphère et applications

NASA Astrophysics Data System (ADS)

Méjean, G.

2005-11-01

'étend de l'ultraviolet (230 nm) à l'infrarouge (4,5 μm). De même, la propagation dans l'air, sous différentes conditions (pluie, brouillard, turbulence), des faisceaux térawatts femtosecondes a été caractérisée afin de développer des applications atmosphériques. Il nous a ainsi été possible de développer le LIDAR à lumière blanche pour réaliser des mesures préliminaires d'ozone et d'aérosols simultanément. De même, grâce à la propagation fortement non-linéaire du faisceau qui permet de transporter des hautes intensités sur de longue distance, nous avons pu détecter et identifier, à distance, des aérosols biologiques et des cibles solides (LIBS) en induisant in situ des effets non-linéaires. Enfin, nous avons montré que le déclenchement et le guidage de décharges de haute tension par une impulsion laser femtoseconde sous la pluie reste possible avec une efficacité comparable à l'atmosphère sèche. D'autre part, une configuration à double impulsion laser augmente l'efficacité de déclenchement des décharges. Ces résultats nous rapproche de la perspective de déclenchement et guidage de foudre par laser.

Revetements bioactifs a base de chondroitine sulfate et de facteurs de croissance pour applications vasculaires

NASA Astrophysics Data System (ADS)

Lequoy, Pauline

Malgre des avancees technologiques indeniables, l'efficacite des implants biomedicaux est encore limitee par les biomateriaux synthetiques qui les composent, notamment en raison de leur incapacite a generer une reponse biologique adequate. En particulier, la guerison tissulaire autour des implants vasculaires reste problematique. Une etude de la litterature a montre que dans le cas des endoprotheses couvertes (tuyaux polymeriques utilises pour la reparation endovasculaire des anevrismes de l'aorte abdominale), le manque de guerison observe s'explique non seulement par l'inertie des biomateriaux utilises mais aussi par le fait que l'implant est insere dans un vaisseau malade favorisant la mort des cellules par apoptose et presentant une depletion cellulaire marquee. L'hypothese a la base de ce projet est qu'un revetement bioactif pourrait ameliorer la guerison et la colonisation de l'implant par les cellules vasculaires et ainsi favoriser l'attachement de l'implant dans le vaisseau malade afin de prevenir les complications a long terme. Dans ce contexte, deux molecules anti-apoptotiques ont ete selectionnees pour developper le revetement, la chondroitine sulfate (CS), un glycosaminoglycane de la matrice extracellulaire, et le facteur de croissance de l'epiderme (EGF) qui possede egalement un role important dans la guerison tissulaire. L'un des defis de ce projet est de preserver la bioactivite de ces molecules lors de leur immobilisation dans un revetement. Pour etablir une preuve de concept, nous avons demontre qu'un revetement CS+EGF obtenu par greffage covalent permet d'ameliorer significativement la survie des cellules vasculaires humaines (cellules musculaires lisses, CMLV, et fibroblastes) sur les materiaux realistes (PET, ePTFE). Apres avoir transfere ce revetement sur des implants commerciaux en ePTFE, des tests in vivo ont demontre une amelioration de la guerison grâce au revetement bioactif, cependant la guerison n'a pas ete totale dans la cavite

Presented at the AGARD Conference on Piloted Simulation Effectiveness, held in Brussels, Belgium on 14-17 October 1991 (L’Efficacite de la Simulation Pilotee)

DTIC Science & Technology

1992-02-01

these following sections will includ descriptions of the flight results have validated die simulation study approach im t md mehodolies assocated with the...Consultant and E-xchange Programme and the Aerospace Applications Studies Programme. The results of AGARD work are reported to the member nations and...tasks with ever-increasing levels of fidelity is leading to a steady growth in their use for all areas of aviation from new concept studies , through

Polarization studies on zinc in hydrochloric acid solution containing some organic solvents

NASA Astrophysics Data System (ADS)

Mohamed, A. K.

1999-05-01

The corrosion behaviour of zinc metal in some organic solvents was tested electrochemically using galvanometric polarization measurements. The results showed that the studied organic solvents act as mixed type inhibitors. The inhibition was assumed to occur via physical adsorption of the inhibitor molecules fitting a Temkin's isotherm. The inhibition eficiency of the solvents increase in the order: glycerol>ethylene glycol>DMSO>dioxane. This order is not affected by the variation in temperature in the range 35-55 circC. The increase in temperature was found to increase the corrosion in absence and in presence of inhibitors. Some thermodynamic parameters for adsorption were also computed and discussed. Le comportement de corrosion du zinc métallique dans certains solvants organiques a été testé électrochimiquement en utilisant les mesures de polarisation galvanométrique. Les résultats ont montré que les solvants organiques étudiés agissent comme des inhibiteurs de type mixte. L'inhibition semble se produire par l'adsorption physique des molécules inhibitrices selon une isotherme de Temkin. L'efficacité d'inhibition des solvants augmente dans l'ordre suivant : glycérol>éthylène glycol>DMSO>dioxane. Cet ordre n'est pas affecté par une variation de température dans l'intervalle compris entre 35 et 55 circC. La corrosion augmente avec la température, en absence ou en présence d'inhibiteurs. Certains paramètres thermodynamiques d'adsorption ont été calculés et discutés.

Sequence variants in ESR1 and OXTR are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

PubMed

Brucker, Sara Yvonne; Frank, Liliane; Eisenbeis, Simone; Henes, Melanie; Wallwiener, Diethelm; Riess, Olaf; van Eijck, Barbara; Schöller, Dorit; Bonin, Michael; Rall, Kristin Katharina

2017-11-01

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature. DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations). In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease. The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica.

Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.

PubMed

Powis, Zöe; Hart, Alexa; Cherny, Sara; Petrik, Igor; Palmaer, Erika; Tang, Sha; Jones, Carolyn

2017-06-02

Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient. Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava. DES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.

A Phase 2 Study of Concurrent Fludarabine and Rituximab for the Treatment of Marginal Zone Lymphomas

PubMed Central

Brown, Jennifer R; Friedberg, Jonathan W.; Feng, Yang; Scofield, Sarah; Phillips, Kimberly; Cin, Paola Dal; Joyce, Robin; Takvorian, Ronald W; Fisher, David C; Fisher, Richard I; Liesveld, Jane; Marquis, Diana; Neuberg, Donna; Freedman, Arnold S

2009-01-01

SUMMARY The marginal zone lymphomas are a recently defined group of related diseases likely arising from a common cell of origin, the marginal zone B cell. Data on therapy for subtypes other than gastric MALT has been largely limited to retrospective case series. We therefore undertook this prospective phase 2 study of fludarabine and rituximab for the treatment of marginal zone lymphomas. 26 patients were enrolled, 14 with nodal MZL, 8 with MALT lymphomas and 4 with splenic MZL; 81% were receiving initial systemic therapy. Only 58% (95% CI 37–77%) of patients completed the planned six cycles, due to significant hematologic, infectious and allergic toxicity. Four late toxic deaths occurred due to infections (15% (95% CI 4.3–35%), two related to delayed bone marrow aplasia and two related to MDS. Nonetheless, the ORR was 85% (95% CI 65–96%), with 54% CRs. The progression-free survival at 3.1 years of follow-up is 79.5% (95% CI, 63–96%). We conclude that although concurrent fludarabine and rituximab given at this dose and schedule is a highly effective regimen in the treatment of marginal zone lymphomas, the significant hematologic and infectious toxicity observed both during and after therapy is prohibitive in this patient population, emphasizing the need to study marginal zone lymphomas as a separate entity. PMID:19344412

A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.

PubMed

Marcadier, Julien L; Mears, Alan J; Woods, Elizabeth A; Fisher, Jamie; Airheart, Cory; Qin, Wen; Beaulieu, Chandree L; Dyment, David A; Innes, A Micheil; Curry, Cynthia J

2016-01-01

PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder. © 2015 Wiley Periodicals, Inc.

A novel homozygous Arg222Trp missense mutation in WNT7A in two sisters with severe Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Kantaputra, Piranit N; Mundlos, Stefan; Sripathomsawat, Warissara

2010-11-01

Al-Awadi/Raas-Rothschild/Schinzel phocomelia (AARRS) syndrome, a rare autosomal recessive disorder, comprises malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. Mutations in WNT7A have been reported as cause of the syndrome. We report on two sisters in a Thai family with short and malformed long bones, absent fibulae, flexion contracture of digits, and a/hypoplastic nails. Fusion between severely malformed femora and slender tibiae has never been reported in patients with WNT7A mutations. Lower limbs were more severely malformed than the upper ones and the pelvis was also severely affected. Multiple fusions of long bones and of the femoral heads to the acetabula were evident. A novel homozygous missense mutation in coding exon 4 of the WNT7A was detected in both affected daughters (c.664C > T) leading to an amino acid exchange from arginine to tryptophan (p.Arg222Trp; R222W). The phenotype is likely to result from an abnormality of all three signaling centers in the developing limb resulting in ventralization with a loss of dorsal structures (aplasia/hypoplasia of nails) a loss of anterior-posterior identity (single distal bones in lower limb without polarity) and an outgrowth defect resulting in distal truncations. © 2010 Wiley-Liss, Inc.

Intrapartum diagnostic of Roberts syndrome - case presentation.

PubMed

Socolov, Răzvan Vladimir; Andreescu, Nicoleta Ioana; Haliciu, Ana Maria; Gorduza, Eusebiu Vlad; Dumitrache, Florentin; Balan, Raluca Anca; Puiu, Maria; Dobrescu, Mihaela Amelia; Socolov, Demetra Gabriela

2015-01-01

Roberts syndrome is a rare disease, with multiple limb and skeletal abnormalities (called "pseudothalidomide disease"). There are only around 150 cases described in literature. We present a case of Roberts syndrome, diagnosed in moment of delivery, after a pregnancy without prenatal follow-up. The stillborn baby was naturally delivered by a 17-year-old primiparous woman at 38 weeks of amenorrhea. The pregnancy was not followed due to socioeconomic and family situation, and no prenatal ultrasound was performed. The male baby has 2650 g and presented several morphological abnormalities and tight double umbilical abdominal loop. The macroscopic evaluation showed: dolichocephaly, hypoplastic inferior maxilla with micrognathia, antimongoloid palpebral slant, pterygium colli, abnormal and lower implanted ears, superior limbs phocomelia, syndactyly at lower left limb and tetradactyly in all limbs, bilateral cryptorchidism, pancreatic aplasia. Roberts syndrome is a rare genetic disease with recessive autosomal transmission generated by mutations in ESCO2 gene, located on chromosome 8. The disease should be easy to diagnose by antenatal ultrasound examination, but in our case, the lack of prenatal follow-up determined the diagnostic at term. We believe consider this case is an argument towards introducing ultrasound-screening compulsory to all pregnancies. To identify a possible genetic mutation, further investigations of the parents are in progress, but classically the disease has a recessive autosomal transmission.

The devil is in the details: retention of recipient group A type 5 years after a successful allogeneic bone marrow transplant from a group O donor.

PubMed

Cooling, Laura L W; Herrst, Michelle; Hugan, Sherri L

2018-01-01

ABO-incompatible (ABOi) hematopoietic stem cell transplants (HSCTs) can present challenges in the blood bank. During transplantation, patients receive components that are ABO-compatible with both the donor graft and recipient; this practice can strain group O red blood cell (RBC) inventories.1 In addition, there are risks for acute hemolysis at the time of infusion and in the early post-transplant period.1,2 In ABO major-incompatible bone marrow HSCTs, which contain significant quantities of donor RBCs that are ABOi with recipient plasma, it is common to perform a RBC depletion of the bone marrow in an effort to minimize hemolysis at the time of infusion.2 Furthermore, patients with high-titer ABO antibodies may undergo a prophylactic, pre-transplant plasma exchange to further reduce the risk of acute hemolysis, delayed RBC engraftment, and pure RBC aplasia.2-4 ABO minor-incompatible HSCTs, in which donor plasma is ABOi with the recipient, have less risk for hemolysis at the time of infusion but can result in transient hemolysis approximately 10-21 days post-transplant, especially in patients undergoing nonmyeloablative HSCT and/or patients who have not received methotrexate for graft-versus-host-disease (GVHD) prophylaxis.1-4 In these patients, viable donor B-lymphocytes in the graft may expand and produce ABO antibodies capable of hemolyzing patient RBCs.

RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6.

PubMed

Szenker-Ravi, Emmanuelle; Altunoglu, Umut; Leushacke, Marc; Bosso-Lefèvre, Célia; Khatoo, Muznah; Thi Tran, Hong; Naert, Thomas; Noelanders, Rivka; Hajamohideen, Amin; Beneteau, Claire; de Sousa, Sergio B; Karaman, Birsen; Latypova, Xenia; Başaran, Seher; Yücel, Esra Börklü; Tan, Thong Teck; Vlaeminck, Lena; Nayak, Shalini S; Shukla, Anju; Girisha, Katta Mohan; Le Caignec, Cédric; Soshnikova, Natalia; Uyguner, Zehra Oya; Vleminckx, Kris; Barker, Nick; Kayserili, Hülya; Reversade, Bruno

2018-05-01

The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling 1-3 . Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes. Moreover, endogenous depletion or addition of exogenous RSPO2 or RSPO3 in triple-knockout Lgr4/5/6 cells could still affect WNT responsiveness. Instead, we found that the concurrent deletion of rnf43 and znrf3 in Xenopus embryos was sufficient to trigger the outgrowth of supernumerary limbs. Our results establish that RSPO2, without the LGR4/5/6 receptors, serves as a direct antagonistic ligand to RNF43 and ZNRF3, which together constitute a master switch that governs limb specification. These findings have direct implications for regenerative medicine and WNT-associated cancers.

Development of an anti-EPO antibody detection kit based on lab-on-a-chip and bridging antibody technologies.

PubMed

Oh, Jin-Gyo; Seong, Jihyun; Han, Sunmi; Heo, Tae-Hwe

2018-05-17

Immunogenicity is a major concern in the use of biological drugs. In particular, antibody-mediated pure red cell aplasia (PRCA) is a rare condition that is caused by administration of recombinant erythropoietin. There are numerous assay platforms for detect EPO anti-drug antibody (ADA), and most have appropriate assay sensitivity, but in need of improvement in terms of assay turnaround time and user accessibility. Here, the new method was developed based on lab-on-a-chip technology and bridging ELISA. The FREND™ Cartridge is equipped with a microfluidic lateral flow channel, enabling easy, fast and accurate immunoassays with small sample volumes. Biotinylated EPO was immobilized on the avidin-coated solid phase of the test zone in the FREND™ cartridge. Initially, ADA in the serum sample binds to the detector conjugate (EPO-HRP-anti HRP antibody-FL bead) in the conjugation zone, and it flows into the test zone prepared with capture complex (avidin-biotinylated EPO). Unbound detector complexes are captured in the reference zone. The FREND™ system detects and quantifies the fluorescence signals in each zone and then calculates the concentration of EPO ADA in the sample. The FREND™ EPO ADA kit may be useful in local clinics as a rapid method for monitoring patients administered recombinant erythropoietin. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Occlusal characteristics and prevalence of associated dental anomalies in the primary dentition.

PubMed

Lochib, Seema; Indushekar, K R; Saraf, Bhavna Gupta; Sheoran, Neha; Sardana, Divesh

2015-06-01

Morphological variations in primary dentition are of great concern to a pediatric dentist as it may pose clinical problems like dental caries, delayed exfoliation and also anomalies in the permanent dentition, such as impaction of successors, supernumerary teeth, permanent double teeth or aplasia of teeth. The present study was conducted to investigate the presence of dental anomalies in the primary dentition of 1000 schoolchildren in the 3-5 year-old age group in Faridabad. One-thousand schoolchildren were examined using Type III examination (WHO, 1997) for primary molar relationship, occlusal characteristics, primate spaces, physiological spaces and other anomalies of teeth, including number and morphology. The prevalence of physiological spaces in maxillary and mandibular arches was 50.9% and 46.7%, respectively, whereas primate spaces were found in 61.7% of the children in the maxillary arch and 27.9% in the mandibular arch. The prevalence of unilateral anterior and posterior cross-bite was 0.1% and 0.8%, respectively, in the present study. The prevalence of hypodontia in the primary dentition was found to be 0.4% and the prevalence of fusion and gemination in the present study was 0.5%. Double teeth (fusion and gemination) and hypodontia were the most common dental anomalies found in the primary dentition in the present study. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

PubMed

Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

2008-07-01

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

Radiation-induced hematopoietic myelosuppression and genotoxicity get significantly countered by active principles of Podophyllum hexandrum: A study in strain 'A' mice.

PubMed

Verma, Savita; Gupta, Manju Lata

2015-01-01

To investigate the protective role of a novel formulation, prepared by a combination of three active principles isolated from Podophyllum hexandrum (G-002M), against radiation- mediated hematopoietic suppression and cytogenetic aberrations in lethally irradiated mice. G-002M, a combination of podophyllotoxin, podophyllotoxin-β-D glucoside and rutin, was administered intramuscularly in mice (- 1 h) to radiation (9 Gy) exposure. The animals were autopsied at different time intervals for further studies. Loss of bone marrow progenitor cells, altered myeloid/erythroid ratio, serum erythropoietin and pancytopenia in irradiated mice was found significantly (p < 0.001) ameliorated in G-002M pre-administered mice within 30 d. Bcl-2 (B-cell lymphoma 2) and BAX (Bcl-2-associated X) protein expression was also positively (p < 0.001) countered in these mice. Chromosomal aberrations in 30 d were found remarkably (p < 0.001) reduced in marrow of G-002M pretreated mice. Accelerated antioxidants, reduced DNA damage, stimulated lymphocyte proliferation and minimal cellular atrophy in spleen were some of the other key features observed in G-002M administered mice. Reduction in hematopoietic aplasia and chromosomal aberrations, besides, early recovery in bone marrow and spleen of G-002M pretreated mice, could be attributed to its free radical scavenging, DNA protecting and apoptotic proteins modulating ability against radiation.

Mayer-Rokitansky-Kuster-Hauser Syndrome: Embryology, Genetics and Clinical and Surgical Treatment

PubMed Central

Sturlese, Emanuele; Retto, Giovanni; Retto, Annalisa; De Dominici, Rosanna; Puzzolo, Domenico

2013-01-01

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a pathological condition characterized by primary amenorrhea and infertility and by congenital aplasia of the uterus and of the upper vagina. The development of secondary sexual characters is normal as well as that the karyotype (46,XX). Etiologically, this syndrome may be caused by the lack of development of the Müllerian ducts between the fifth and the sixth weeks of gestation. To explain this condition, it has been suggested that in patients with MRKH syndrome, there is a very strong hyperincretion of Müllerian-inhibiting factor (MIF), which would provoke the lack of development of the Müllerian ducts from primitive structures (as what normally occurs in male phenotype). These alterations are commonly associated with renal agenesis or ectopia. Specific mutations of several genes such as WT1, PAX2, HOXA7-HOXA13, PBX1, and WNT4 involved in the earliest stages of embryonic development could play a key role in the etiopathogenesis of this syndrome. Besides, it seems that the other two genes, TCF2 (HNF1B) and LHX1, are involved in the determinism of this pathology. Currently, the most widely nonsurgical used techniques include the “Frank's dilators method,” while the surgical ones most commonly used are those developed by McIndoe, Williams, Vecchietti, Davydov, and Baldwin. PMID:23431465

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene

PubMed Central

Sonmez, Fatma Mujgan; Uctepe, Eyyup; Gunduz, Mehmet; Gormez, Zeliha; Erpolat, Seval; Oznur, Murat; Sagiroglu, Mahmut Samil; Demirci, Huseyin; Gunduz, Esra

2016-01-01

Summary Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better. PMID:27672547

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene.

PubMed

Sonmez, Fatma Mujgan; Uctepe, Eyyup; Gunduz, Mehmet; Gormez, Zeliha; Erpolat, Seval; Oznur, Murat; Sagiroglu, Mahmut Samil; Demirci, Huseyin; Gunduz, Esra

2016-08-01

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

Dissecting the transcriptional phenotype of ribosomal protein deficiency: implications for Diamond-Blackfan Anemia

PubMed Central

Aspesi, Anna; Pavesi, Elisa; Robotti, Elisa; Crescitelli, Rossella; Boria, Ilenia; Avondo, Federica; Moniz, Hélène; Da Costa, Lydie; Mohandas, Narla; Roncaglia, Paola; Ramenghi, Ugo; Ronchi, Antonella; Gustincich, Stefano; Merlin, Simone; Marengo, Emilio; Ellis, Steven R.; Follenzi, Antonia; Santoro, Claudio; Dianzani, Irma

2014-01-01

Defects in genes encoding ribosomal proteins cause Diamond Blackfan Anemia (DBA), a red cell aplasia often associated with physical abnormalities. Other bone marrow failure syndromes have been attributed to defects in ribosomal components but the link between erythropoiesis and the ribosome remains to be fully defined. Several lines of evidence suggest that defects in ribosome synthesis lead to “ribosomal stress” with p53 activation and either cell cycle arrest or induction of apoptosis. Pathways independent of p53 have also been proposed to play a role in DBA pathogenesis. We took an unbiased approach to identify p53-independent pathways activated by defects in ribosome synthesis by analyzing global gene expression in various cellular models of DBA. Ranking-Principal Component Analysis (Ranking-PCA) was applied to the identified datasets to determine whether there are common sets of genes whose expression is altered in these different cellular models. We observed consistent changes in the expression of genes involved in cellular amino acid metabolic process, negative regulation of cell proliferation and cell redox homeostasis. These data indicate that cells respond to defects in ribosome synthesis by changing the level of expression of a limited subset of genes involved in critical cellular processes. Moreover, our data support a role for p53-independent pathways in the pathophysiology of DBA. PMID:24835311

Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran.

PubMed

Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat; Monavari, Seyed Hamidreza

2017-03-01

Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.

Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran

PubMed Central

Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat

2017-01-01

Background Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. Methods This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. Results The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. Conclusion In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures. PMID:28401102

Loss of heterozygosity at 7p in Wilms' tumour development

PubMed Central

Powlesland, R M; Charles, A K; Malik, K T A; Reynolds, P A; Pires, S; Boavida, M; Brown, K W

2000-01-01

Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaign PMID:10646884

Odontoma: retrospective study and confocal laser scanning microscope analysis of 52 cases.

PubMed

Crincoli, V; Scivetti, M; Di Bisceglie, M B; Lucchese, A; Favia, G

2007-01-01

The aim of this study was to perform a retrospective analysis of 52 cases of odontoma treated at the Department of Dentistry and Surgery, University of Bari, in the period 1971-2005. The odontogenic tumors were diagnosed as complex or compound odontoma following histological analysis and clinical radiological examination, and applying the 2005 WHO classification. The data analysis was conducted by considering the following factors: gender, age, site of the lesion, association with impacted teeth, aplasia, presence of supernumerary teeth as well as preoperative diagnosis by panoramic and periapical radiographs. Biopsy tissue samples were conventionally processed for histopathologic paraffin embedding and then were observed by optical microscopy and subsequently by confocal laser scanning microscopy (CLSM) in autofluorescence. Thirty specimens (57.6%) were from females and 22 (42.3%) were from males patients. The patients' age ranged from 5 to 75 years. Fifty-one percent of the specimens were excised from the mandible. In the maxilla, the most common location for odontomas was the anterior region. Most odontomas were associated with impacted teeth and only in one case there was an odontoma instead of a permanent tooth. Odontomas are considered hamartomatous malformations whose diagnosis is generally formulated by routinary radiographic examination. The CLSM analysis could help in diagnosis and histopathological analysis showing well-defined follicular area entrapped in hard tissues and pointing out ghost cells, otherwise not identifiable by traditional microscopy.

dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure.

PubMed

Dos Santos, Reinaldo Sousa; Daures, Mathilde; Philippi, Anne; Romero, Sophie; Marselli, Lorella; Marchetti, Piero; Senée, Valérie; Bacq, Delphine; Besse, Céline; Baz, Baz; Marroquí, Laura; Ivanoff, Sarah; Masliah-Planchon, Julien; Nicolino, Marc; Soulier, Jean; Socié, Gérard; Eizirik, Decio L; Gautier, Jean-François; Julier, Cécile

2017-04-01

We describe a new syndrome characterized by early-onset diabetes associated with bone marrow failure, affecting mostly the erythrocytic lineage. Using whole-exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase ( DUT ) gene (National Center for Biotechnology Information Gene ID 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, whereas none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation. This replicated observation probability was highly significant, thus confirming the role of this DUT mutation in this syndrome. DUT is a key enzyme for maintaining DNA integrity by preventing misincorporation of uracil into DNA, which results in DNA toxicity and cell death. We showed that DUT silencing in human and rat pancreatic β-cells results in apoptosis via the intrinsic cell death pathway. Our findings support the importance of tight control of DNA metabolism for β-cell integrity and warrant close metabolic monitoring of patients treated by drugs affecting dUTP balance. © 2017 by the American Diabetes Association.

Cochlear Implantation in Patients With CHARGE Syndrome.

PubMed

Rah, Yoon Chan; Lee, Ji Young; Suh, Myung-Whan; Park, Moo Kyun; Lee, Jun Ho; Chang, Sun O; Oh, Seung-Ha

2016-11-01

To determine the optimal surgical approach for cochlear implantation (CI) preoperatively based on the spatial relation of a displaced facial nerve (FN) and middle ear structures and to analyze clinical outcomes of CHARGE syndrome. Facial nerve displacement and associated deviation of inner ear structures were analyzed in 13 patients (17 ears) with CHARGE syndrome who underwent CI. Surgical accessibility through the facial recess was assessed based on anatomical landmarks. Postoperative speech performance and associated clinical characteristics were analyzed. The most consistently identified ear anomalies were semicircular canal aplasia (100%), ossicular anomaly (100%), and vestibular hypoplasia (88%). Facial nerve displacement was found in 77% of cases (anteroinferior: 47%, anterior: 24%, inferior: 6%). The width of available surgical space around facial recess was significantly greater in cases of facial recess approach (2.85 ± 0.9 mm) than those of alternative approach (0.12 ± 0.29 mm, P = .02). Postoperatively, 53% achieved better than category 4 on the categories of auditory perception (CAP) scale. The CAP category was significantly correlated with internal auditory canal diameter (P = .025) and did not differ according to the applied surgical approach. Preoperative determination of surgical accessibility through facial recess would be useful for safe surgical approach, and successful hearing rehabilitation was achievable by applying appropriate surgical approaches. © The Author(s) 2016.

Variable expressivity of the phenotype in two families with brachydactyly type E, craniofacial dysmorphism, short stature and delayed bone age caused by novel heterozygous mutations in the PTHLH gene.

PubMed

Jamsheer, Aleksander; Sowińska-Seidler, Anna; Olech, Ewelina M; Socha, Magdalena; Kozłowski, Kazimierz; Pyrkosz, Antoni; Trzeciak, Tomasz; Materna-Kiryluk, Anna; Latos-Bieleńska, Anna

2016-05-01

Brachydactyly refers to shortening of digits due to hypoplasia or aplasia of bones forming the hands and/or feet. Isolated brachydactyly type E (BDE), which is characterized by shortened metacarpals and/or metatarsals, results in a small proportion of patients from HOXD13 or PTHLH mutations, although in the majority of cases molecular lesion remains unknown. BDE, like other brachydactylies, shows clinical heterogeneity with highly variable intrafamilial and interindividual expressivity. In this study, we investigated two Polish cases (one familial and one sporadic) presenting with BDE and additional symptoms due to novel PTHLH mutations. Apart from BDE, the affected family showed short stature, mild craniofacial dysmorphism and delayed bone age. Sanger sequencing of PTHLH revealed a novel heterozygous frameshift mutation c.258delC(p.N87Tfs*18) in two affected individuals and one relative manifesting mild brachydactyly. The sporadic patient, in addition to BDE, presented with craniofacial dysmorphism, normal stature and bone age, and was demonstrated to carry a de novo heterozygous c.166C>T(p.R56*) mutation. Our paper reports on the two novel truncating PTHLH variants, resulting in variable combination of BDE and other symptoms. Data shown here expand the knowledge on the phenotypic presentation of PTHLH mutations, highlighting significant clinical variability and incomplete penetrance of the PTHLH-related symptoms.

Müllerian Agenesis in Cat Eye Syndrome and 22q11 Chromosome Abnormalities: A Case Report and Literature Review.

PubMed

AlSubaihin, Abdulmajeed; VanderMeulen, John; Harris, Kate; Duck, John; McCready, Elizabeth

2018-04-01

Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. Müllerian agenesis has been reported as a rare finding associated with chromosomal aberrations of the 22q11 chromosomal region including at least 1 individual with cat eye syndrome (CES) and 10 individuals with deletions or duplications of the 22q11.2 region. However, a potential link between 22q11 abnormalities and uterine malformations has been difficult to adequately ascertain because of the limited case reports in the literature. We report a second case of Müllerian agenesis in a girl with CES. A 16-year-old girl presented with bilateral colobomata, primary amenorrhea, and absence of the uterus and upper vagina on pelvic magnetic resonance imaging. Microarray analysis showed tetrasomy of the pericentromeric region of chromosome 22 diagnostic of CES. Müllerian aplasia/hypoplasia might represent a rare feature in CES and should be considered in the investigation of young girls with this syndrome. An increasing number of cases with 22q11 chromosome abnormalities and Müllerian agenesis further highlights the possibility of a gene within the 22q11 region that might mediate normal Müllerian development in girls. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract

PubMed Central

THAM, CHING S.; CHAKRAVARTHI, SRIKUMAR; HALEAGRAHARA, NAGARAJA; DE ALWIS, RANJIT

2013-01-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis. PMID:23403524

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract.

PubMed

Tham, Ching S; Chakravarthi, Srikumar; Haleagrahara, Nagaraja; DE Alwis, Ranjit

2013-02-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis.

Non-Lethal Weapons Effectiveness Assessment Development and Verification Study (Etude d’evaluation, de developpement et de verification de l’efficacite des armes non letales)

DTIC Science & Technology

2009-10-01

will guarantee a solid base for the future. The content of this publication has been reproduced directly from material supplied by RTO or the...intensity threat involving a local population wanting to break into the camp to steal material and food supplies ; and • A higher intensity threat...combatant evacuation opeations, distribute emergency supplies , and evacuate/ relocate refugees and displaced persons. Specified NLW-relevant tasks are

Driving Skills Training for Older Adults: An Assessment of DriveSharp.

PubMed

Johnston, Katherine A; Borkenhagen, David; Scialfa, Charles T

2015-12-01

RÉSUMÉ Les procédures de formation cognitive informatique visent à augmenter la sécurité en améliorant les compétences relatives à la conduite, comme la vitesse-de-traitement et le Useful Field of View. L'étude actuelle a évalué l'efficacité du DriveSharp dans la formation des conducteurs âgés dans un cadre de classe réaliste. Les participants (n = 24) ont assisté à 10 heures de cours de DriveSharp pendant 5 semaines. Les séances pré- et post-test ont evalués améliorations sur un essai dynamique de la perception du risque, Trails A et Trails B. Un groupe de contrôle (n = 18) a terminé seulement les séances pré- et post-test. En classe, les temps de formation étaient plus bas que prévus. L'amélioration des participants aux jeux ont stabilisée après la première évaluation, et le groupe de DriveSharp n'a pas démontré une amélioration significative des performances sur les tests, par rapport au groupe de contrôle. Parmi plusieurs questions relatives à la facilité d'utilisation, les plus problématiques étaient le malentendudes objectifs de la tâche et la différence entre la formation et l'évaluation. Il y a plusieurs implications pour ceux qui utilisent DriveSharp pour améliorer la sécurité des conducteurs âgés.

Validation de la version française du Questionnaire de Bournemouth

PubMed Central

Martel, Johanne; Dugas, Claude; Lafond, D.; Descarreaux, M.

2009-01-01

Les auto questionnaires font partie intégrante de l’évaluation des patients ayant des douleurs cervicales. Le Questionnaire de Bournemouth intègre la réalité biopsychosociale dans l’évaluation des douleurs cervicales et sa version anglais (QBc-a) est validée et présente des propriétés psychométriques de modérées à excellentes. L’objectif de cette étude est de traduire et valider une version française de ce questionnaire. La traduction et l’adaptation a été complétée en utilisant la méthode de traduction contre-traduction qui a permis d’obtenir un consensus entre les deux versions. L’étude de validation impliquait 68 sujets (âge moyen 41 ans) qui participaient à un essai clinique randomisé concernant l’efficacité des thérapies manuelles pour les douleurs cervicales. Le protocole expérimental permettait d’obtenir des données pour évaluer la validité conceptuelle, la validité conceptuelle longitudinale, la fidélité test-retest et la sensibilité au changement. Les données de validité conceptuelle (r = 0,67 et 0,61 et 0,42 respectivement pour la validité conceptuelle pré, post traitement et longitudinale), de fidélité test-retest (r = 0,97) et de sensibilité au changement (taille de l’effet = 0,56 et réponse moyenne normalisée = 0,61) sont adéquates pour suggérer une utilisation de cet auto questionnaire pour la gestion des patients ayant des douleurs cervicales.

Radiorésistance liée à l'hypoxie : de la cellule à l'homme

NASA Astrophysics Data System (ADS)

Guichard, M.; Stern, S.; Lartigau, E.

1998-04-01

Most experimental tumours contain experimental hypoxic cells located either far from the vessels or close to collaped vessels. The radioresistance of these cellscan be reduced by different treatments and, the best one will depend on the proportion of cells in the two categories of hypoxia. In patients, hypoxic areas have been detected in most solid tumours. The outcome of hypoxia during the course of an accelerated radiotherapy treatment is in progresse as well as the efficacy of carbogen (95% O2 5% CO2) to improve radiotherapy. We participate to the development of predictive assays of the tumour response to an irradiation. La plupart des tumeurs expérimentales renferment des cellules hypoxiques clonogènes situées soit à une certaine distance des vaisseaux soit au contact de vaisseaux collabés. La radiorésistance de ces cellules peut être réduite par différents procédés ; le meilleur traitement dépend de la proportion de celles dans les deux catégories d'hypoxie. Chez l'homme, des zones hypoxiques ont été mises en évidence dans la plupart des tumeurs solides. Le devenir de l'hypoxie au cours d'une radiothérapie accélérée ainsi que l'efficacité du carbogène (95 % O2- 5 % CO2) pour améliorer la radiothérapie sont en cours d'étude. Nous participons également au développement de teste prédicitifs de la réponse tumorale à une irradiation.

Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-gamma receptor-deficient hosts.

PubMed

Delisle, Jean-Sébastien; Gaboury, Louis; Bélanger, Marie-Pier; Tassé, Eliane; Yagita, Hideo; Perreault, Claude

2008-09-01

The immunopathologic condition known as graft-versus-host disease (GVHD) results from a type I T-cell process. However, a prototypical type I cytokine, interferon-gamma (IFN-gamma), can protect against several manifestations of GVHD in recipients of major histocompatibility complex (MHC)-mismatched hematopoietic cells. We transplanted hematopoietic cells from C3H.SW donors in wild-type (wt) and IFN-gamma-receptor-deficient (IFN-gammaRKO) MHC-matched C57BL/6 recipients. In IFN-gammaRKO recipients, host cells were unresponsive to IFN-gamma, whereas wt donor cells were exposed to exceptionally high levels of IFN-gamma. From an IFN-gamma perspective, we could therefore evaluate the impact of a loss-of-function on host cells and gain-of-function on donor cells. We found that lack of IFN-gammaR prevented up-regulation of MHC proteins on host cells but did not mitigate damage to most target organs. Two salient phenotypes in IFN-gammaRKO recipients involved donor cells: lymphoid hypoplasia and hematopoietic failure. Lymphopenia was due to FasL-induced apoptosis and decreased cell proliferation. Bone marrow aplasia resulted from a decreased proliferation of hematopoietic stem/progenitor cells that was associated with down-regulation of 2 genes negatively regulated by IFN-gamma: Ccnd1 and Myc. We conclude that IFN-gamma produced by alloreactive T cells may entail a severe graft-versus-graft reaction and could be responsible for cytopenias that are frequently observed in subjects with GVHD.

Clinico-serologic co-relation in bi-directional ABO incompatible hemopoietic stem cell transplantation.

PubMed

Basu, Sabita; Dhar, Supriya; Mishra, Deepak; Chandy, Mammen

2015-01-01

The ABO blood group system is of prime significance in red cell transfusion and organ transplantation. However, ABO compatibility is not critical in allogenic hemopoietic stem cell transplantation (HSCT) and approximately 40-50% of hemopoietic stem cell transplants are ABO incompatible. This incompatibility may be major, minor or bi-directional. Though there are descriptions of transfusion practice and protocols in ABO incompatible HSCT, there are considerable variations and transfusion support in these patients can be very challenging. The immunohematologic observations in two cases of bi-directional ABO incompatible HSCT have been described, and clinico-serologic correlation has been attempted. In both cases, peripheral blood stem cell harvests were obtained using the Cobe spectra cell separator. Immunohematologic assessments in the donor and recipient were done as a part of pre HSCT evaluation. Both the standard tube technique and column agglutination method (Ortho Biovue Micro Bead System) was used. Antibody screen was done by column agglutination method using three cell panel (Surgiscreen cells). Isoagglutinin titration was done by the master dilution method and standard validated techniques were used. The pattern of laboratory findings in the two cases was different and so were the clinical outcomes. Although there was early engraftment in the first case, the second case developed pure red cell aplasia and this was well-reflected in the immunohematologic assessments. Immunohematologic assessment correlated well with the clinical picture and could be used to predict clinical outcome and onset of complications in ABO incompatible HSCT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailo, P.; Nobili, F.

The possible hazands to the fetus and embryo of diagnostic radiologic procedures during pregnancy are reviewed. In addition, 190 cases of congenital maiformations, observed at the authors' cliric between 1950 and l980, were examined in attempts to detect the possible etiologic role of prenatal irradiation in their development. The median age of the mothers was between 28 and 30 yr. Only 23% of the mothers reported having undergone radiodiagnostic tests during pregnancy. Among this group there were 8 infants with deformed feet, 5 with hydrocephalus, 4 with ancephalus, 3 with spina bifida, 3 with hare lip, 3 with penile hypospadias,more » 2 with umbilical hernia, 2 with cleft palate, and 1 each of aplasia of the cranial vault, myelomeningocele, polydactylism, syndactylism, congenital cardiopathy, and imperforate anus. An analysis of the time of irradiation during gestation in relation to the period of fetal development of the structures involved did not implicate radiation in formation of these anomalies, since all of the irradiated mothers received this treatment between the 4th and 9th months of gestation. Consanguinity, syphilis, and Rh incompatibility were present in many of these cases and may have accounted for some of these deformities. It is concluded that diagnostic radiology carried out after the 1st 3 months of pregnancy according to standard procedures are not harmful to the fetus or the mother. (H.H.D.)« less

Noncontrast Magnetic Resonance Lymphography.

PubMed

Arrivé, Lionel; Derhy, Sarah; El Mouhadi, Sanaâ; Monnier-Cholley, Laurence; Menu, Yves; Becker, Corinne

2016-01-01

Different imaging techniques have been used for the investigation of the lymphatic channels and lymph glands. Noncontrast magnetic resonance (MR) lymphography has significant advantages in comparison with other imaging modalities. Noncontrast MR lymphography uses very heavily T2-weighted fast spin echo sequences which obtain a nearly complete signal loss in tissue background and specific display of lymphatic vessels with a long T2 relaxation time. The raw data can be processed with different algorithms such as maximum intensity projection algorithm to obtain an anatomic representation. Standard T2-weighted MR images easily demonstrate the location of edema. It appears as subcutaneous infiltration of soft tissue with a classical honeycomb pattern. True collection around the muscular area may be demonstrated in case of severe lymphedema. Lymph nodes may be normal in size, number, and signal intensity; in other cases, lymph nodes may be smaller in size or number of lymph nodes may be restricted. MR lymphography allows a classification of lymphedema in aplasia (no collecting vessels demonstrated); hypoplasia (a small number of lymphatic vessels), and numerical hyperplasia or hyperplasia (with an increased number of lymphatic vessels of greater and abnormal diameter). Noncontrast MR lymphography is a unique noninvasive imaging modality for the diagnosis of lymphedema. It can be used for positive diagnosis, differential diagnosis, and specific evaluation of lymphedema severity. It may also be used for follow-up evaluation after treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systematic Review of Nontumor Pediatric Auditory Brainstem Implant Outcomes.

PubMed

Noij, Kimberley S; Kozin, Elliott D; Sethi, Rosh; Shah, Parth V; Kaplan, Alyson B; Herrmann, Barbara; Remenschneider, Aaron; Lee, Daniel J

2015-11-01

The auditory brainstem implant (ABI) was initially developed for patients with deafness as a result of neurofibromatosis type 2. ABI indications have recently extended to children with congenital deafness who are not cochlear implant candidates. Few multi-institutional outcome data exist. Herein, we aim to provide a systematic review of outcomes following implantation of the ABI in pediatric patients with nontumor diagnosis, with a focus on audiometric outcomes. PubMed, Embase, and Cochrane. A systematic review of literature was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations. Variables assessed included age at implantation, diagnosis, medical history, cochlear implant history, radiographic findings, ABI device implanted, surgical approach, complications, side effects, and auditory outcomes. The initial search identified 304 articles; 21 met inclusion criteria for a total of 162 children. The majority of these patients had cochlear nerve aplasia (63.6%, 103 of 162). Cerebrospinal fluid leak occurred in up to 8.5% of cases. Audiometric outcomes improved over time. After 5 years, almost 50% of patients reached Categories of Auditory Performance scores >4; however, patients with nonauditory disabilities did not demonstrate a similar increase in scores. ABI surgery is a reasonable option for the habilitation of deaf children who are not cochlear implant candidates. Although improvement in Categories of Auditory Performance scores was seen across studies, pediatric ABI users with nonauditory disabilities have inferior audiometric outcomes. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

PubMed

Racacho, Lemuel; Byrnes, Ashley M; MacDonald, Heather; Dranse, Helen J; Nikkel, Sarah M; Allanson, Judith; Rosser, Elisabeth; Underhill, T Michael; Bulman, Dennis E

2015-12-01

Brachydactyly type A1 is an autosomal dominant disorder primarily characterized by hypoplasia/aplasia of the middle phalanges of digits 2-5. Human and mouse genetic perturbations in the BMP-SMAD signaling pathway have been associated with many brachymesophalangies, including BDA1, as causative mutations in IHH and GDF5 have been previously identified. GDF5 interacts directly as the preferred ligand for the BMP type-1 receptor BMPR1B and is important for both chondrogenesis and digit formation. We report pathogenic variants in BMPR1B that are associated with complex BDA1. A c.975A>C (p.(Lys325Asn)) was identified in the first patient displaying absent middle phalanges and shortened distal phalanges of the toes in addition to the significant shortening of middle phalanges in digits 2, 3 and 5 of the hands. The second patient displayed a combination of brachydactyly and arachnodactyly. The sequencing of BMPR1B in this individual revealed a novel c.447-1G>A at a canonical acceptor splice site of exon 8, which is predicted to create a novel acceptor site, thus leading to a translational reading frameshift. Both mutations are most likely to act in a dominant-negative manner, similar to the effects observed in BMPR1B mutations that cause BDA2. These findings demonstrate that BMPR1B is another gene involved with the pathogenesis of BDA1 and illustrates the continuum of phenotypes between BDA1 and BDA2.

The right vertebral artery originating from the right occipital artery and the absence of the transverse foramen: a rare anatomical variation.

PubMed

Öner, Zülal; Öner, Serkan; Kahraman, Ayşegül Sağır

2017-12-01

Variations in the origin of the vertebral artery (VA) is a congenital anomaly that occurs during embryological development. Multiple variations related to VA origin have been reported in the literature. Abnormal VA origin is usually determined as incidental findings during angiographic or postmortem anatomical studies. Although most of the cases are asymptomatic, in patients with VA anomaly symptoms such as dizziness have been described. The anomalous variation in the origin of the right VA is rare and separated into three categories: (1) originating from the aorta, (2) originating from the carotid arteries, (3) duplicated origin. In this case, we aimed to present the right VA originating from the right occipital artery and concomitant anomalies of the transverse foramen that have not been reported previously according to our knowledge in literature. In a 32-year-old female patient referred to our hospital because of dizziness, the right VA was not observed on magnetic resonance imaging and computed tomography angiography (CTA) examination was performed. CTA showed hypoplasia of the right transverse foramen at the levels of the C1, C5 and C6 vertebrae and aplasia of the right transverse foramen at the levels of the C2, C3 and C4 vertebrae. The right VA originating from the right occipital artery continues to its normal course by entering the cranium through the foramen magnum at the level of the atlantooccipital junction.

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

PubMed

Deal, Cheri; Hasselmann, Caroline; Pfäffle, Roland W; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Shavrikova, Elena P; Cutler, Gordon B; Blum, Werner F

2013-01-01

Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management. Copyright © 2013 S. Karger AG, Basel.

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

PubMed

Meester, Josephina A N; Sukalo, Maja; Schröder, Kim C; Schanze, Denny; Baynam, Gareth; Borck, Guntram; Bramswig, Nuria C; Duman, Duygu; Gilbert-Dussardier, Brigitte; Holder-Espinasse, Muriel; Itin, Peter; Johnson, Diana S; Joss, Shelagh; Koillinen, Hannele; McKenzie, Fiona; Morton, Jenny; Nelle, Heike; Reardon, Willie; Roll, Claudia; Salih, Mustafa A; Savarirayan, Ravi; Scurr, Ingrid; Splitt, Miranda; Thompson, Elizabeth; Titheradge, Hannah; Travers, Colm P; Van Maldergem, Lionel; Whiteford, Margo; Wieczorek, Dagmar; Vandeweyer, Geert; Trembath, Richard; Van Laer, Lut; Loeys, Bart L; Zenker, Martin; Southgate, Laura; Wuyts, Wim

2018-06-20

Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts is currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pediatric cochlear implants: additional disabilities prevalence, risk factors, and effect on language outcomes.

PubMed

Birman, Catherine S; Elliott, Elizabeth J; Gibson, William P R

2012-10-01

To determine the prevalence of additional disabilities in a pediatric cochlear population, to identify medical and radiologic conditions associated with additional disabilities, and to identify the effect of additional disabilities on speech perception and language at 12 months postoperatively. Retrospective case review. Tertiary referral center and cochlear implant program. Records were reviewed for children 0 to 16 years old inclusive, who had cochlear implant-related operations over a 12-month period. Diagnostic and rehabilitative. Additional disabilities prevalence; medical history and radiologic abnormalities; and the effect on Categories of Auditory Performance (CAP) score at 12 months postoperatively. Eighty-eight children having 96 operations were identified. The overall prevalence of additional disabilities (including developmental delay, cerebral palsy, visual impairment, autism and attention deficit disorder) was 33%. The main conditions associated with additional disabilities were syndromes and chromosomal abnormalities (87%), jaundice (86%), prematurity (62%), cytomegalovirus (60%), and inner ear abnormalities including cochlea nerve hypoplasia or aplasia (75%) and semicircular canal anomalies (56%). At 12 months postoperatively, almost all (96%) of the children without additional disabilities had a CAP score of 5 or greater (speech), compared with 52% of children with additional disabilities. Children with developmental delay had a median CAP score of 4, at 12 months compared with 6 for those without developmental delay. Additional disabilities are prevalent in approximately a third of pediatric cochlear implant patients. Additional disabilities significantly affect the outcomes of cochlear implants.

Emerging biological therapies to treat acute lymphoblastic leukemia.

PubMed

Huguet, Françoise; Tavitian, Suzanne

2017-03-01

Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered: Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented. Rituximab, a naked anti-CD20 MoAb, improves the results of chemotherapy in Philadelphia chromosome-negative BCP-ALL. Inotuzumab ozogamicin, an anti-CD22 immunotoxin, yields complete remission (CR) rates of 80% in R/R patients and in elderly newly diagnosed patients. Blinatumomab, a bispecific anti-CD19 and anti-CD3 agent redirects effector T cells towards B leukemic cells, is approved in R/R patients (40% CR, duration 6 months) and under investigation in MRD+ CR patients (80% negativation). Autologous anti-CD19 CAR-T cells undergo proliferation and persistence in the recipient. In limited series, they salvage more than 80% of advanced patients. Cytokine-release syndrome, encephalopathy and B-cell aplasia are shared, to varying extents, by blinatumomab and CAR-T cells. Expert opinion: Despite technological, ethical and clinical issues, biological therapies are currently changing the paradigm of treatment in BCP-ALL, and seem promised to dramatic developments.

Radiation damage aspects of the chernobyl accident

NASA Astrophysics Data System (ADS)

Parmentier, N.; Nenot, J. C.

During the night of 25 to 26 April 1986, the most severe nuclear accident occurred at the Chernobyl power station, about 150km north of Kiev, in the Ukraine. It resulted in the irradiation of 237 workers at dose levels justifying medical care. The most severe cases (115) were hospitalized in Moscow, with 20 patients with doses higher than 6 Gy. In most cases, the treatment was classical, based on transfusion of red cells and platelets, and heavy supportive therapy. For 19 patients with severe aplasia, transplantations of bone marrow (13) or foetal liver (6) were decided. Of these patients only one survived, which justifies the statement from U.S.S.R. physicians: after an accident the indications of grafting are limited and its risks may not justify its use. Most of the complications were related to radiation burns which involved 56 victims and resulted in fatal outcomes in at least 19 patients. The population was evacuated from a 30 km zone around the site; based on direct measurements and calculations, the collective dose was evaluated at 1.6 × 10 4 man Sv, with an individual average lower than 250 mSv. The European part of U.S.S.R. with 75 million persons is supposed to have received a collective dose likely to increase the natural mortality by less than 0.1%. The numbers with cancer in the Northern Hemisphere might increase by 0.004% over the next 50 years.

Congenital or torsion-induced absence of Fallopian tubes. Two case reports.

PubMed

Paternoster, D M; Costantini, W; Uglietti, A; Vasile, C; Bocconi, L

1998-05-01

Unilateral absence of a uterine tube is an extremely rare finding, for which there are two possible etiopathogenic causes: in some cases it is due to haemorrhage filling of the cavity and its reabsorption as a result of asymptomatic torsion of the uterine tube during adult life, in pediatric age or even during intrauterine life; alternatively, the absence may be congenital, associated with developmental alterations of the mesonephric and paramesonephric ducts. The article presents two cases of fallopian tube absence: a congenital monolateral absence and a tubal torsion during pregnancy. The symptomatology of the torsion of the fallopian tube in pregnancy can be milder than in the classic description with peritoneal reaction and severe clinical alteration. The main risk factors for tubal torsion are: adhesions and inflammatory processes, ovarian cysts, usually of dermoid type, menstrual period, pregnancy, abnormal long mesosalpinx and/or mesovarium, pelvic congestion induced by constipation and disturbed venous blood flow from the adnexa. A congenital defect of the mesonephric duct is followed by a homolateral defect of the paramesonephric duct. The resulting anomaly is characterized by the absence of the uterine tube, uterus-tube angle, kidney and ureter. Partial or total unilateral defects of a paramesonephric duct are more common than aplasia of both ducts. Some authors have suggested that an inadequate blood supply during the descent into the pelvis of the caudal part of the paramesonephric duct might feasibly lead to incomplete tube development.

DiGeorge Syndrome: a not so rare disease.

PubMed

Fomin, Angela B F; Pastorino, Antonio Carlos; Kim, Chong Ae; Pereira, C A; Carneiro-Sampaio, Magda; Abe-Jacob, Cristina Miuki

2010-01-01

The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. Of 14 patients (8m - 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n = 12), facial abnormalities (n = 11), hypocalcemia (n = 5) and low lymphocyte count (n=2). The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up.

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

PubMed Central

Porter, David L.; Hwang, Wei-Ting; Frey, Noelle V.; Lacey, Simon F.; Shaw, Pamela A.; Loren, Alison W.; Bagg, Adam; Marcucci, Katherine T.; Shen, Angela; Gonzalez, Vanessa; Ambrose, David; Grupp, Stephan A.; Chew, Anne; Zheng, Zhaohui; Milone, Michael C.; Levine, Bruce L.; Melenhorst, Jan J.; June, Carl H.

2018-01-01

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL. PMID:26333935

Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

PubMed Central

Henig, Israel; Zuckerman, Tsila

2014-01-01

Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient. PMID:25386344

Meier-Gorlin syndrome: growth and secondary sexual development of a microcephalic primordial dwarfism disorder.

PubMed

de Munnik, Sonja A; Otten, Barto J; Schoots, Jeroen; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Borm, George F; Clayton-Smith, Jill; Deal, Cheri L; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Sluiter, A Erik; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2012-11-01

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth. Copyright © 2012 Wiley Periodicals, Inc.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Le pôle de métrologie de SOLEIL

NASA Astrophysics Data System (ADS)

Idir, M.; Brochet, S.; Delmotte, A.; Lagarde, B.; Mercere, P.; Moreno, T.; Polack, F.; Thomasset, M.

2006-12-01

Le Pôle de METROLOGIE de SOLEIL a pour objet de créer sur le synchrotron SOLEIL, une plateforme constituée : - une ligne de lumière utilisant le rayonnement synchrotron (métrologie dite à la longueur d'onde) - d'un laboratoire de métrologie associé (métrologie dite ll classique gg ) Ces deux types de Métrologie sont l'une et l'autre indispensables pour soutenir l'activité de recherche instrumentale en optique X et X-UV. Ce projet de pôle de METROLOGIE ne répondra pas seulement aux besoins des groupes chargés de l'équipement du synchrotron SOLEIL en optiques et détecteurs mais aussi pour préparer, tester et mettre au point les postes expérimentaux, ce qui concerne déjà une large communauté d'utilisateurs. Il sera aussi largement ouvert, dès sa mise en service, à l'ensemble de la communauté scientifique concernée par l'instrumentation X et XUV en Ile de France, en France, voire même en Europe si la demande continue de croître plus vite que l'offre dans ce domaine. Ligne de lumière Métrologie à la longueur d'onde La ligne de lumière sera équipée de plusieurs stations permettant de mesurer, dans la plus grande partie du spectre couvert par le synchrotron, les paramètres photométriques qui caractérisent les éléments optiques, tels que : la réflectivité de surfaces, l'efficacité de diffraction des réseaux, la diffusion des surfaces ou l'efficacité des détecteurs X et X-UV et la calibration absolue. Cette installation pourra servir également à développer des instruments et des diagnostics nécessaires à la caractérisation des faisceaux de rayons X (intensité, taille, degré de cohérence, polarisation etc.) Métrologie Classique La métrologie des surfaces optiques est devenue une nécessité critique pour les laboratoires et les industries qui utilisent les photons X et X-UV (synchrotrons, centres laser, etc. .). En effet, les progrès de calcul et de conception des systèmes optiques pour ces longueurs d'onde (optiques

Evaluation d’une grille de supervision des laboratoires des leishmanioses cutanées au Maroc

PubMed Central

El Mansouri, Bouchra; Amarir, Fatima; Hajli, Yamina; Fellah, Hajiba; Sebti, Faiza; Delouane, Bouchra; Sadak, Abderrahim; Adlaoui, El Bachir; Rhajaoui, Mohammed

2017-01-01

Introduction Afin d’évaluer une grille de contrôle standardisée de laboratoire de diagnostic des leishmanioses, comme nouveau outil de supervision. Méthodes Un essai pilote a été pratiqué sur sept laboratoires provinciaux, appartenant à quatre provinces au Maroc, en suivant l’évolution de leurs performances tous les deux ans, entre l’année 2006 et 2014. Cette étude détaille la situation des laboratoires provinciaux avant et après la mise en œuvre de la grille de supervision. Au total vingt et une grille sont analysées. Résultats En 2006, les résultats ont montré clairement une insuffisance des performances des laboratoires: besoin en formation (41.6%), personnel pratiquant le prélèvement cutané (25%), pénurie en matériels et réactifs (65%), gestions documentaire et local non conformes (85%). Différentes actions correctives ont été menées par le Laboratoire National de Référence des Leishmanioses (LNRL) durant la période d’étude. En 2014, le LNRL a enregistré une nette amélioration des performances des laboratoires. Les besoins en matière de formation, qualité du prélèvement, dotation en matériels et réactifs ont été comblés et une coordination efficace s’est établie entre le LNRL et les laboratoires provinciaux. Conclusion Ceci montre l'efficacité de la grille comme outil de supervision de grande qualité, et comme pierre angulaire de tout progrès qui doit être obtenu dans les programmes de lutte contre les leishmanioses. PMID:29187922

Nécrolyse épidermique liée à l'application cutanée d'une solution d'hydroxyde de potassium

PubMed Central

Korsaga-Somé, Nina; Tapsoba, Patrice; Ouédraogo, Muriel Sidnoma; Ilboudo, Léopold Baowendsom; Barro-Traoré, Fatou; Niamba, Pascal; Traoré, Adama

2015-01-01

Dans nos régions, une solution d'hydroxyde de potassium est régulièrement utilisée en application sur la peau comme traitement traditionnel dans le but de traiter un prurit ou une éruption cutanée. Dans notre pratique quotidienne, nous observons de plus en plus de réactions cutanées à ce type de traitement. Nous rapportons un cas de nécrolyse épidermique généralisée suite à l'application d'une solution concentrée d'hydroxyde de potassium. Il s'agissait d'une patiente de 51 ans, séropositive au VIH2, et au virus de l'hépatite virale C, mais non éligible au traitement antirétroviral. Elle était hospitalisée pour des décollements épidermiques nécrolytiques quasi-généralisés survenue le lendemain de l'application une solution de concentré de potasse sur tout le tégument. Cette solution avait été appliquée dans le but de traiter une éruption micropapuleuse prurigineuse généralisée (exanthème maculo-papuleux) survenue suite à a prise de cotrimoxazole. La réépidermisation était totale sans séquelle après un mois de suivi. Le diagnostic nécrolyse épidermique toxique ou syndrome de Lyell qui met souvent en jeu le pronostic vital avait été écarté devant la conservation de l'état général, l'absence d'atteinte muqueuse et la rapide cicatrisation. Certains traitements traditionnels ont fait la preuve au cours du temps de leur efficacité, mais un mésusage peut être à l'origine d'effets secondaires graves. PMID:26587148

Élimination du bore du silicium par plasma inductif sous champ électrique

NASA Astrophysics Data System (ADS)

Combes, R.; Morvan, D.; Picard, G.; Amouroux, J.

1993-05-01

We analyzed purification mechanisms of silicon by inductive plasma with a fluoride slag. The aim is to study boron elimination from doped electronic grade silicon in function of the nature of the slag to obtain a photovoltaic grade silicon. The steady began with the calculation and the comparison of the stability diagram of boron compounds in presence of CaF2, BaF2 and MgF2. This study led us to conclude that BaF2 is the better slag for silicon purification. This has been confirmed by experience. In a second time, we made purifications under electric bias to enhance slag efficiency. We noticed that BaF2 is more sensitive to electric bias than other slags. Nous avons analysé le mécanisme de purification du silicium sous plasma inductif en présence d'un laitier fluoré. L'objectif principal est d'étudier l'élimination du bore du silicium électronique dopé en fonction de la nature du fluorure pour obtenir un silicium de qualité photovoltaïque. L'étude a commencé par l'établissement et la comparaison de diagrammes des composés du bore en présence de CaF2, de MgF2 et de BaF2. Nous avons déduit de cette première étude que BaF2 est le meilleur laitier pour la purification du silicium. Ceci a été corroboré par l'expérience. Nous avons ensuite opéré en présence d'un champ électrique dans le but d'améliorer encore l'efficacité des laitiers. Nous avons constaté que BaF2 est plus sensible au champ électrique que les deux autres laitiers utilisés.

Évaluation des caractéristiques mécaniques du polissoir en polyuréthanne utilisé comme porte abrasifs durant le processus du polissage du verre optique

NASA Astrophysics Data System (ADS)

Aliouane, T.; Bouzid, D.; Belkhir, N.; Bouzid, S.; Herold, V.

2005-05-01

La fabrication des composants en verre optique nécessite des moyens de grande précision dans les procédés de finition vue l'importance accordée à leur qualité.
Durant le processus de polissage des verres optiques, le polissoir est un élément clé et a un impact direct sur les performances des composants optiques, non seulement il est utilisé comme support de grains abrasifs mais il doit posséder la fonction de transmission de la pression aux grains. La connaissance de ses propriétés, essentiellement mécanique, est impérative afin d'obtenir un état de surface optimal des composants optiques destinés à remplir des fonctions très précises dans des appareils optiques très performants.
Dans cette étude, nous avons constaté que les propriétés des polissoirs en polyuréthanne tel que la dureté, le module d'élasticité et la densité varient au cours du polissage. Ce changement a des effets sur l'état de surface de verre optique, causé par le changement microstructural de la surface du polissoir (distribution et dimensions des pores) et par conséquent sur la quantité des abrasifs (en oxyde de cérium) insérée dans les pores, ce qui influe sur la quantité de verre enlevée et sur l'état de surface du composant.
Sur la base des résultats obtenus, il a été prouvé que le polissoir subit des modifications très importantes ce qui influe considérablement sur son efficacité de polissage.

PubMed

Black, Amanda; Guilbert, Edith; Costescu, Dustin; Dunn, Sheila; Fisher, William; Kives, Sari; Mirosh, Melissa; Norman, Wendy V; Pymar, Helen; Reid, Robert; Roy, Geneviève; Varto, Hannah; Waddington, Ashley; Wagner, Marie-Soleil; Whelan, Anne Marie

2017-04-01

Mettre à la disposition des fournisseurs de soins des lignes directrices concernant le recours à des méthodes contraceptives pour prévenir la grossesse et la promotion d'une sexualité saine. Efficacité globale des méthodes contraceptives citées : évaluation de l'innocuité, des effets indésirables et de la baisse du taux de grossesse; effet des méthodes contraceptives citées sur la santé sexuelle et le bien-être général; disponibilité des méthodes contraceptives citées au Canada. RéSULTATS: Des recherches ont été effectuées dans MEDLINE et la base de données Cochrane afin d'en tirer les articles en anglais publiés entre janvier 1994 et décembre 2015 traitant de sujets liés à la contraception, à la sexualité et à la santé sexuelle, dans le but de mettre à jour le consensus canadien sur la contraception paru de février à avril 2004. Nous avons également passé en revue les publications pertinentes du gouvernement canadien, ainsi que les déclarations de principes issues d'organisations compétentes vouées à la santé et à la planification familiale. La qualité des résultats a été évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs. Les recommandations quant à la pratique sont classées en fonction de la méthode décrite dans le rapport du Groupe. DéCLARATIONS SOMMAIRES: RECOMMANDATIONS. Copyright © 2017. Published by Elsevier Inc.

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

PubMed

Rowley, S D; Piantadosi, S; Marcellus, D C; Jones, R J; Davidson, N E; Davis, J M; Kennedy, J; Wiley, J M; Wingard, J R; Yeager, A M

1991-03-01

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

MCM5: a new actor in the link between DNA replication and Meier-Gorlin syndrome.

PubMed

Vetro, Annalisa; Savasta, Salvatore; Russo Raucci, Annalisa; Cerqua, Cristina; Sartori, Geppo; Limongelli, Ivan; Forlino, Antonella; Maruelli, Silvia; Perucca, Paola; Vergani, Debora; Mazzini, Giuliano; Mattevi, Andrea; Stivala, Lucia Anna; Salviati, Leonardo; Zuffardi, Orsetta

2017-05-01

Meier-Gorlin syndrome (MGORS) is a rare disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recessive mutations in ORC1, ORC4, ORC6, CDT1, CDC6, and CDC45, encoding members of the pre-replication (pre-RC) and pre-initiation (pre-IC) complexes, and heterozygous mutations in GMNN, a regulator of cell-cycle progression and DNA replication, have already been associated with this condition. We performed whole-exome sequencing (WES) in a patient with a clinical diagnosis of MGORS and identified biallelic variants in MCM5. This gene encodes a subunit of the replicative helicase complex, which represents a component of the pre-RC. Both variants, a missense substitution within a conserved domain critical for the helicase activity, and a single base deletion causing a frameshift and a premature stop codon, were predicted to be detrimental for the MCM5 function. Although variants of MCM5 have never been reported in specific human diseases, defect of this gene in zebrafish causes a phenotype of growth restriction overlapping the one associated with orc1 depletion. Complementation experiments in yeast showed that the plasmid carrying the missense variant was unable to rescue the lethal phenotype caused by mcm5 deletion. Moreover cell-cycle progression was delayed in patient's cells, as already shown for mutations in the ORC1 gene. Altogether our findings support the role of MCM5 as a novel gene involved in MGORS, further emphasizing that this condition is caused by impaired DNA replication.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.

PubMed

Becknell, Brian; Mohamed, Ahmad Z; Li, Birong; Wilhide, Michael E; Ingraham, Susan E

2015-01-01

Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse

PubMed Central

Becknell, Brian; Mohamed, Ahmad Z.; Li, Birong; Wilhide, Michael E.; Ingraham, Susan E.

2015-01-01

Purpose Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Methods Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Results Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. Conclusions CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice. PMID:26401845

[Favorable Outcome of Hepatosplenic Candidiasis in a Patient with Acute Leukemia].

PubMed

Čolović, Nataša; Arsenijević, Valentina Arsić; Suvajdžić, Nada; Djunić, Irena; Tomin, Dragica

2015-01-01

Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy "3+7" regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2 x 170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (FI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy.Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for"probable HSC" and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved.

SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome.

PubMed

Gervasini, Cristina; Grati, Francesca Romana; Lalatta, Faustina; Tabano, Silvia; Gentilin, Barbara; Colapietro, Patrizia; De Toffol, Simona; Frontino, Giada; Motta, Francesca; Maitz, Silvia; Bernardini, Laura; Dallapiccola, Bruno; Fedele, Luigi; Larizza, Lidia; Miozzo, Monica

2010-10-01

The Mayer-Rokitansky-Küster-Hauser syndrome is defined as congenital aplasia of müllerian ducts derived structures in females with a normal female chromosomal and gonadal sex. Most cases with Mayer-Rokitansky-Küster-Hauser syndrome are sporadic, although familial cases have been reported. The genetic basis of Mayer-Rokitansky-Küster-Hauser syndrome is largely unknown and seems heterogeneous, and a small number of cases were found to have mutations in the WNT4 gene. The aim of this study was to identify possible recurrent submicroscopic imbalances in a cohort of familial and sporadic cases with Mayer-Rokitansky-Küster-Hauser syndrome. Multiplex ligation-dependent probe amplification was used to screen the subtelomeric sequences of all chromosomes in 30 patients with Mayer-Rokitansky-Küster-Hauser syndrome (sporadic, n = 27 and familial, n = 3). Segregation analysis and pyrosequencing were applied to validate the MLPA results in the informative family. Partial duplication of the Xpter pseudoautosomal region 1 containing the short stature homeobox (SHOX) gene was detected in five patients with Mayer-Rokitansky-Küster-Hauser syndrome (familial, n = 3 and sporadic, n = 2) and not in 53 healthy controls. The duplications were not overlapping, and SHOX was never entirely duplicated. Haplotyping in the informative family revealed that SHOX gene duplication was inherited from the unaffected father and was absent in two healthy sisters. Partial duplication of SHOX gene is found in some cases with both familial and sporadic Mayer-Rokitansky-Küster-Hauser type I syndrome.

Fenestrations and Various Duplications of the Posterior Communicating Artery in the Prenatal and Postnatal Periods.

PubMed

Trandafilović, Milena; Vasović, Ljiljana; Vlajković, Slobodan; Đorđević, Gordana; Stojanović, Borisav; Mladenović, Marija

2016-07-01

The 2 paired arteries-the posterior communicating arteries (PCoAs) and the precommunicating parts of the posterior cerebral arteries-form the so-called posterior segment of the cerebral arterial circle on the base of the brain. A number of (ab)normal morphologic features were described in the literature (e.g., unusual kinking, or extreme elongations, hypoplasia, duplications, fenestrations, the infundibular widening, or aplasia of the PCoA in the prenatal and/or postnatal periods). The aim of this study was to analyze an incidence of various fenestrations and duplications of the PCoA, and describe their general features and their association with other vascular abnormalities. The research was performed on the brains of 200 human fetuses and 377 adult cadavers of both genders and different ages using microdissection and macrodissection methods. There were 0.34% cases with PCoA fenestrations and 3.12% cases with various PCoA duplications. Their morphologic features were described and compared with the similar PCoA abnormalities recorded in the scientific literature. There was no association between the PCoA and either duplication or aneurysm in adult cases. After thorough examination, the fenestrations and duplications of the PCoA are distinguished as 2 special forms of vascular abnormalities, and the PCoA duplications are characterized as partial and total. Furthermore, whereas the low incidence of a fenestration of the PCoA suggests it to be a sufficiently rare phenomenon, the duplications of the PCoA trunk are fairly frequent, especially concerning its terminal segment. Copyright © 2016 Elsevier Inc. All rights reserved.

Variations in magnetic resonance venographic anatomy of the dorsal dural venous sinus system in 51 dogs.

PubMed

Fenn, Joe; Lam, Richard; Kenny, Patrick J

2013-01-01

Variations in intracranial dural venous sinus anatomy have been widely reported in humans, but there have been no studies reporting this in dogs. The purpose of this retrospective study was to describe variations in magnetic resonance (MR) venographic anatomy of the dorsal dural venous sinus system in a sample population of dogs with structurally normal brains. Medical records were searched for dogs with complete phase contrast, intracranial MR venograms and a diagnosis of idiopathic epilepsy. Magnetic resonance venograms were retrieved for each dog and characteristics of the dorsal dural sinuses, symmetry of the transverse sinuses and other anatomic variations were recorded. A total of 51 dogs were included. Transverse sinus asymmetry was present in 58.8% of the dogs, with transverse sinus hypoplasia seen in 39.2%, and aplasia in 23.5% of dogs. For 70.6% of dogs, at least one anatomic variation in the dorsal sagittal sinus was observed, including deviation from the midline (33.3%) and collateral branches from either the dorsal sagittal sinus or dorsal cerebral veins (54.9%). In 5 dogs (9.8%) a vessel was also identified running from the proximal transverse sinus to the distal sigmoid sinus, in a similar location to the occipital sinus previously reported in children. Findings from this study indicated that, as in humans, anatomic variations are common in the intracranial dural venous sinus system of dogs. These anatomic variations should be taken into consideration for surgical planning or diagnosis of cerebrovascular disease. © 2013 Veterinary Radiology & Ultrasound.

Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes.

PubMed

Kalejaiye, Adedoyin; Giri, Neelam; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Adams, Charleen D; Rosenberg, Philip S; Kim, H Jeffrey; Alter, Blanche P

2016-12-01

The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss. Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Hearing loss was measured by pure tone audiometry and otologic abnormalities by otomicroscopy. Patients included 33 with FA, 37 with DC, 32 with DBA, and nine with SDS. Hearing loss was most frequent in patients with FA (45%) and DBA (14%). The most common type of hearing loss in FA was conductive (65%). Absent or hypoplastic radius, noted in 21% of the patients with FA, was associated with hearing loss in all cases. Otomicroscopy was abnormal in 66% of patients with FA. Characteristic ear abnormalities included small tympanic membrane (66%), malformed malleus (57%), aberrant tympanic bony island (48%), narrow external auditory canal (EAC) (32%), and abnormal course of chorda tympani (34%). Ear malformations were almost always associated with hearing loss. Hearing loss was rare in patients with DC and SDS. FA is the major IBMFS with associated hearing loss, which is most commonly conductive. Radial hypoplasia or aplasia and characteristic congenital ear malformations are associated with hearing loss in patients with FA. Recognition of these syndrome-specific abnormalities should lead to earlier management of hearing loss. © 2016 Wiley Periodicals, Inc.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

PubMed

Lucidi, Cynthia de A; de Rezende, Christian L E; Jutkowitz, L Ari; Scott, Michael A

2017-09-01

Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4 th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis. © 2017 American Society for Veterinary Clinical Pathology.

Gene expression profile of patients with Mayer-Rokitansky-Küster-Hauser syndrome: new insights into the potential role of developmental pathways.

PubMed

Nodale, Cristina; Ceccarelli, Simona; Giuliano, Mariateresa; Cammarota, Marcella; D'Amici, Sirio; Vescarelli, Enrica; Maffucci, Diana; Bellati, Filippo; Panici, Pierluigi Benedetti; Romano, Ferdinando; Angeloni, Antonio; Marchese, Cinzia

2014-01-01

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.

Gene Expression Profile of Patients with Mayer-Rokitansky-Küster-Hauser Syndrome: New Insights into the Potential Role of Developmental Pathways

PubMed Central

Giuliano, Mariateresa; Cammarota, Marcella; D’Amici, Sirio; Vescarelli, Enrica; Maffucci, Diana; Bellati, Filippo; Panici, Pierluigi Benedetti; Romano, Ferdinando; Angeloni, Antonio; Marchese, Cinzia

2014-01-01

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS. PMID:24608967

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML)

PubMed Central

Ravandi, Farhad; Gojo, Ivana; Patnaik, Mrinal M.; Minden, Mark D.; Kantarjian, Hagop; Johnson-Levonas, Amy O.; Fancourt, Craig; Lam, Raymond; Jones, Mary Beth; Knox, Clayton D.; Rose, Shelonitda; Patel, Payal Shah; Tibes, Raoul

2017-01-01

Objective Evaluate safety/tolerability/efficacy of MK-8242 in subjects with refractory/recurrent AML. Methods MK-8242 was dosed p.o. QD (30–250 mg) or BID (120–250 mg) for 7on/7off in 28-day cycle. Dosing was modified to 7on/14off, in 21-day cycle (210 or 300 mg BID). Results 26 subjects enrolled (24 evaluable for response); 5/26 discontinued due to AEs. There were 7 deaths; 1 (fungal pneumonia due to marrow aplasia) possibly drug-related. With the 7on/7off regimen, 2 subjects had DLTs in the 250 mg BID group (both bone marrow failure and prolonged cytopenia). With the 7on/14off, no DLTs were observed in 210 mg BID or 300 mg BID (doses >300 mg not tested). Best responses were: 1/24 PR (11 weeks;120 mg QD, 7on/7off); 1/24 CRi (2 weeks;210 mg BID, 7on/14off); 1/24 morphologic leukemia-free state (4 weeks; 250 mg BID, 7on/7off). PK on Day7 at 210 mg BID revealed AUC0-12hr 8.7 μM*hr, Cmax 1.5 μM (n=5, Tmax, 2–6 hr), T1/2 7.9 hr, CLss/F 28.8 L/hr, and Vss/F 317 L. Conclusions The 7on/14off regimen showed a more favorable safety profile; no MTD was established. Efficacy was seen using both regimens providing impetus for further study of HDM2 inhibitors in subjects with AML. PMID:27544076

Al-Awadi-Raas-Rothschild syndrome with dental anomalies and a novel WNT7A mutation.

PubMed

Kantaputra, Piranit Nik; Kapoor, Seema; Verma, Prashant; Kaewgahya, Massupa; Kawasaki, Katsushige; Ohazama, Atsushi; Ketudat Cairns, James R

2017-12-01

Al-Awadi-Raas-Rothschild syndrome (AARRS; OMIM 276820) is a very rare autosomal recessive limb malformation syndrome caused by WNT7A mutations. AARRS is characterized by various degrees of limb aplasia and hypoplasia. Normal intelligence and malformations of urogenital system are frequent findings. Complete loss of WNT7A function has been shown to cause AARRS, however, its partial loss leads to the milder malformation, Fuhrmann syndrome. An Indian boy affected with AARRS is reported. A novel homozygous base substitution mutation c.550A > C (p.Asn184Asp) is identified in the patient. Parents were heterozygous for the mutation. In addition to the typical features of AARRS, the patient had agenesis of the mandibular left deciduous lateral incisor. The heterozygous parents had microdontia of the maxillary left permanent third molar and taurodontism (enlarged dental pulp chamber at the expense of root) in a number of their permanent molars. Whole exome sequencing of the patient and his parents ruled out mutations in 11 known hypodontia-associated genes including WNT10A, MSX1, EDA, EDAR, EDARADD, PAX9, AXIN2, GREM2, NEMO, KRT17, and TFAP2B. In situ hybridization during tooth development showed Wnt7a expression in wild-type tooth epithelium at E14.5. All lines of evidence suggest that WNT7A has important role in tooth development and its mutation may lead to tooth agenesis, microdontia, and taurodontism. Oral examination of patients with AARRS and Fuhrmann syndromes is highly recommended. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

European consensus on the medical management of acute radiation syndrome and analysis of the radiation accidents in Belgium and Senegal.

PubMed

Gourmelon, Patrick; Benderitter, Marc; Bertho, Jean Marc; Huet, Christelle; Gorin, Norbert Claude; De Revel, Patrick

2010-06-01

A European consensus concerning the medical management of mass radiation exposure was obtained in 2005 during a conference held by the European Group for Blood and Bone Marrow Transplantation, the Institute of Radioprotection and Nuclear Safety, and the University of Ulm. At the conference, a two-step triage strategy to deal with large masses of radiation-exposed patients was designed. The first step of this strategy concerns the first 48 h and involves scoring the patients exclusively on the basis of their clinical symptoms and biological data. This allows the non-irradiated bystanders and outpatient candidates to be identified. The remaining patients are hospitalized and diagnosis is confirmed after the first 48-h period according to the METREPOL (Medical Treatment Protocols for radiation accident victims) scale. This grades the patients according to the severity of their symptoms. It was also agreed that in the case of acute radiation syndrome (ARS), emergency hematopoietic stem cell (HSC) transplantation is not necessary. Instead, cytokines that promote hematological reconstruction should be administered as early as possible for 14-21 d. Crucial tests for determining whether the patient has residual hematopoiesis are physical dose reconstructions combined with daily blood count analyses. It was agreed that HSC transplantation should only be considered if severe aplasia persists after cytokine treatment. Two recent cases of accidental radiation exposure that were managed successfully by following the European consensus with modification are reviewed here. Thus, a European standard for the evaluation and treatment of ARS victims is now available. This standard may be suitable for application around the world.

Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.

PubMed

Wang, RuNan; Yoshida, Kenichi; Toki, Tsutomu; Sawada, Takafumi; Uechi, Tamayo; Okuno, Yusuke; Sato-Otsubo, Aiko; Kudo, Kazuko; Kamimaki, Isamu; Kanezaki, Rika; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Terui, Kiminori; Sato, Tomohiko; Iribe, Yuji; Ohga, Shouichi; Kuramitsu, Madoka; Hamaguchi, Isao; Ohara, Akira; Hara, Junichi; Goi, Kumiko; Matsubara, Kousaku; Koike, Kenichi; Ishiguro, Akira; Okamoto, Yasuhiro; Watanabe, Kenichiro; Kanno, Hitoshi; Kojima, Seiji; Miyano, Satoru; Kenmochi, Naoya; Ogawa, Seishi; Ito, Etsuro

2015-03-01

Diamond-Blackfan anaemia is a congenital bone marrow failure syndrome that is characterized by red blood cell aplasia. The disease has been associated with mutations or large deletions in 11 ribosomal protein genes including RPS7, RPS10, RPS17, RPS19, RPS24, RPS26, RPS29, RPL5, RPL11, RPL26 and RPL35A as well as GATA1 in more than 50% of patients. However, the molecular aetiology of many Diamond-Blackfan anaemia cases remains to be uncovered. To identify new mutations responsible for Diamond-Blackfan anaemia, we performed whole-exome sequencing analysis of 48 patients with no documented mutations/deletions involving known Diamond-Blackfan anaemia genes except for RPS7, RPL26, RPS29 and GATA1. Here, we identified a de novo splicing error mutation in RPL27 and frameshift deletion in RPS27 in sporadic patients with Diamond-Blackfan anaemia. In vitro knockdown of gene expression disturbed pre-ribosomal RNA processing. Zebrafish models of rpl27 and rps27 mutations showed impairments of erythrocyte production and tail and/or brain development. Additional novel mutations were found in eight patients, including RPL3L, RPL6, RPL7L1T, RPL8, RPL13, RPL14, RPL18A and RPL31. In conclusion, we identified novel germline mutations of two ribosomal protein genes responsible for Diamond-Blackfan anaemia, further confirming the concept that mutations in ribosomal protein genes lead to Diamond-Blackfan anaemia. © 2014 John Wiley & Sons Ltd.

[Developmental abnormalities and nevi of the scalp].

PubMed

Behle, V; Hamm, H

2014-12-01

Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor.

[Contribution of pelvic echography to the diagnosis of malformations of the utero-vaginal tract].

PubMed

Ellart, D; Houze de l'Aulnoit, H; Corette, L; Delcroix, M; Brabant, G

1990-01-01

Pelvic ultrasound has become very important in the diagnostic planning of utero-vaginal malformations. Having studies 93 congenital malformations of the utero-vaginal tract, the authors used ultrasound investigations as a first or second line of approach. They are able to describe the way ultrasound can be used for each type of malformation. Ultrasound is undeniably reliable for diagnosing bilateral incomplete aplasia of the uterus; so avoiding the need for laparoscopy. When failure of the uterus to develop on one side occurs it is possible to look for a closed or canalized rudimentary uterine nodule to confirm the diagnosis of a pseudo-unicorn uterus. The diagnosis by ultrasound of a bifid uterus shows up by the appearance of a "V" shape on the bladder. An intra-uterine septum can be diagnosed according to how serious the embryological abnormality is on ultrasound. Similarly the difference between a bicornuate uterus that is really just arcuate or partially septate cannot always be made with ultrasound because the embryological defect is a relatively minor one. Ultrasound examination is able to give a lot of information in diagnosing and calculating how much of the menstrual fluid is held back either on one side or completely. Its value is less when the two sides of the uterus communicate with one another. Although this way of examining patients may make it possible quite often to avoid carrying out hysterosalpingogram and laparoscopy, its greatest value is found when all methods of diagnosis are combined and interpreted in the context of a clinical situation.

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

PubMed

Taniguchi, Kan; Matsuura, Kimio; Matsuoka, Takanori; Nakatani, Hajime; Nakano, Takumi; Furuya, Yasuo; Sugimoto, Takeki; Kobayashi, Michiya; Araki, Keijiro

2005-06-01

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab.

PubMed

Hamaki, T; Kami, M; Kusumi, E; Ueyama, J; Miyakoshi, S; Morinaga, S; Mutou, Y

2001-12-01

A 53-year-old man who had a history of fluminant hepatitis caused by precore mutant hepatitis B virus (HBV) was admitted to our hospital for the treatment of relapsed non-Hodgkin's lymphoma in July 2000. At admission, serum levels of aspartate aminotransferase and alanine aminotransferase were normal, but he tested positive for HBs antigen. The titer was 64-fold by radioimmunoassay. We initiated lamivudine at a daily dose of 75 mg to prevent HBV proliferation during chemotherapy. By September 2000, he had received six courses of rituximab at 375 mg/m(2) and four courses of fludarabine and mitoxantrone. No hepatic damage was observed from the initiation of treatment until March 2001. At present, four months after the completion of chemotherapy, he continues lamivudine, and the titer of HBs antigen is low at 4-fold. Rituximab is usually associated with mild toxicity, usually limited to infusion periods. The drug is not generally associated with increased incidence of opportunistic infections. However, some case reports have been recently published on severe viral infections following administration of rituximab. These include fluminant hepatitis caused by HBV, pure red cell aplasia due to parvovirus B19 and fatal varicella-zoster infection. While it remains unknown whether rituximab can be safely administered in patients with chronic HBV infection, this case report suggested that prophylactic administration of lamivudine is beneficial for suppressing reactivation of HBV during chemotherapy including rituximab. Rituximab should be used cautiously for patients with HBV infection, but prophylactic administration of lamivudine may be beneficial for preventing reactivation of HBV. Copyright 2001 Wiley-Liss, Inc.

Comparison of facial features of DiGeorge syndrome (DGS) due to deletion 10p13-10pter with DGS due to 22q11 deletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goodship, J.; Lynch, S.; Brown, J.

1994-09-01

DiGeorge syndrome (DGS) is a congenital anomaly consisting of cardiac defects, aplasia or hypoplasia of the thymus and parathroid glands, and dysmorphic facial features. The majority of DGS cases have a submicroscopic deletion within chromosome 22q11. However there have been a number of reports of DGS in association with other chromosomal abnormalities including four cases with chromosome 10p deletions. We describe a further 10p deletion case and suggest that the facial features in children with DGS due to deletions of 10p are different from those associated with chromosome 22 deletions. The propositus was born at 39 weeks gestation to unrelatedmore » caucasian parents, birth weight 2580g (10th centile) and was noted to be dysmorphic and cyanosed shortly after birth. The main dysmorphic facial features were a broad nasal bridge with very short palpebral fissures. Echocardiography revealed a large subsortic VSD and overriding aorta. She had a low ionised calcium and low parathroid hormone level. T cell subsets and PHA response were normal. Abdominal ultrasound showed duplex kidneys and on further investigation she was found to have reflux and raised plasma creatinine. She had an anteriorly placed anus. Her karyotype was 46,XX,-10,+der(10)t(3;10)(p23;p13)mat. The dysmorphic facial features in this baby are strikingly similar to those noted by Bridgeman and Butler in child with DGS as the result of a 10p deletion and distinct from the face seen in children with DiGeorge syndrome resulting from interstitial chromosome 22 deletions.« less

DiGeorge Syndrome: a not so rare disease

PubMed Central

Fomin, Angela BF; Pastorino, Antonio Carlos; Kim, Chong Ae; Pereira, Alexandre C; Carneiro‐Sampaio, Magda; Abe Jacob, Cristina Miuki

2010-01-01

INTRODUCTION: The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. OBJECTIVES: To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. METHODS: Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. RESULTS: Of 14 patients (8m – 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n  =  12), facial abnormalities (n  =  11), hypocalcemia (n  =  5) and low lymphocyte count (n = 2). CONCLUSION: The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up. PMID:21049214

Current Results and Future Research Priorities in Late Effects after Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease and Thalassemia: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Stem Cell Transplantation.

PubMed

Shenoy, Shalini; Angelucci, Emanuele; Arnold, Staci D; Baker, K Scott; Bhatia, Monica; Bresters, Dorine; Dietz, Andrew C; De La Fuente, Josu; Duncan, Christine; Gaziev, Javid; King, Allison A; Pulsipher, Michael A; Smith, Angela R; Walters, Mark C

2017-04-01

Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease and thalassemia major. A disease-free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low-risk disease or treatment-related risk factors. Alternate donor HCT and HCT in adults is performed infrequently because of a higher risk profile. Transplant-specific risks include conditioning regimen-related toxicity, graft-versus-host disease, graft rejection with marrow aplasia or disease recurrence, and infections associated with immunosuppression and delayed immune reconstitution. The magnitude of risk depends on patient age, clinical status of the underlying disease (eg, organ injury from vasculopathy and iron overload), donor source, and intensity of the conditioning regimen. These risks are commonly monitored and reported in the short term. Documenting very late outcomes is important, but these data are rarely reported because of challenges imposed by patient drop-out and insufficient resources. This report summarizes long-term follow-up results after HCT for hemoglobin disorders, identifies gaps in knowledge, and discusses opportunities for future investigations. This consensus summary will be followed by a second article detailing comprehensive long-term follow-up recommendations to aid in maintaining health in these individuals and identifying late complication risks that could facilitate interventions to improve outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Diagnosis and clinical characteristics of congenital anosmia: case series report.

PubMed

Qu, Qiuyi; Liu, Jianfeng; Ni, Daofeng; Zhang, Qiuhang; Yang, Dazhang; Wang, Naya; Wu, Xueyan; Han, Honglei

2010-12-01

congenital anosmia is extremely rare and tends to present late. We report on a series of patients with congenital anosmia to analyze its clinical characteristics and present illustrative cases. retrospective chart review. tertiary care centre. thirty-five patients with congenital anosmia were reviewed. A thorough medical history taking, physical examination, and nasal endoscopy were performed in all patients. T&T olfactory testing (n = 33), olfactory event-related potentials (OERPs) (n = 33), and sinonasal computed tomography (CT) (n = 35) were carried out. Magnetic resonance images (MRIs) of the olfactory pathway (n = 34) were available. Serum sex hormones were tested (n = 33). physical examination, olfactory testing, MRI of the olfactory pathway, and serum sex hormones. twenty cases were isolated congenital anosmia (ICA). Fifteen cases were congenital anosmia with other anomalies, including 12 cases with Kallmann syndrome (KS), two with CHARGE syndrome, and one with hypoplasia of the nasal cavity and nasal sinus. T&T olfactory testing indicated anosmia (n = 33). No OERP was obtained (n = 33). CT scans indicated three abnormal patients, including two with unilateral choanal atresia and one with hypoplasia of the nasal cavity and sinus. MRI demonstrated aplasia or hypoplasia of the olfactory bulbs, tracts, and olfactory sulci (n = 34). Serum sex hormones were low in 12 patients with KS. early diagnosis of congenital anosmia on the basis of olfactory symptoms is difficult. MRI of the olfactory pathway plays an important role in anatomic location. ICA is the most common congenital anosmia. KS is the primary presentation of congenital anosmia with other anomalies.

Epstein-Barr virus nuclear antigen-2 detection and typing in immunocompromised children correlated with lymphoproliferative disorder biopsy findings.

PubMed

Mendes, Thiago Marques; Oliveira, Léa Campos de; Yamamoto, Lídia; Del Negro, Gilda Maria Barbaro; Okay, Thelma Suely

2008-06-01

Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, plays a significant role as a cofactor in the process of tumorigenesis, and has consistently been associated with a variety of malignancies especially in immunocompromised patients. Forty-four children and adolescents (21 liver transplant patients, 7 heart transplant, 5 AIDS, 3 autoimmune hepatitis, 2 nephritic syndromes, 2 medullar aplasia, 2 primary immunodeficiency disorder patients, 1 thrombocytopenic purpura and 1 systemic lupus erythematosus) presenting with chronic active EBV infection (VCA-IgM persistently positive; VCA-IgG > 20 AU/mL and positive IgG _ EBNA) had peripheral blood samples obtained during clinically characterized EBV reactivation episodes. DNA samples were amplified in order to detect and type EBV on the basis of the EBNA-2 sequence (EBNA2 protein is essential for EBV-driven immortalization of B lymphocytes). Although we have found a predominance of type 1 EBNA-2 virus (33/44; 75%), 10 patients (22.73%) carried type 2 EBNA-2, and one liver transplant patient (2.27%) a mixture of the two types, the higher proportion of type 2 EBV, as well as the finding of one patient bearing the two types is in agreement with other reports held on lymphoproliferative disorder (LPD) patients, which analyzed tumor biopsies. We conclude that EBNA-2 detection and typing can be performed in peripheral blood samples, and the high prevalence of type 2 in our casuistic indicates that this population is actually at risk of developing LPD, and should be monitored.

Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina in a child exposed to misoprostol during pregnancy.

PubMed

Rosa, Rafael Fabiano Machado; Travi, Giovanni M; Valiatti, Fabiana; Zen, Paulo Ricardo Gazzola; Pinto, Louise Lapagesse; Kiss, Andrea; Graziadio, Carla; Paskulin, Giorgio Adriano

2007-06-01

Poland syndrome has been attributed to a process of vascular disruption, and exposure to misoprostol at 6-8 weeks of gestation has been shown to produce defects attributed to vascular disruption. Herein we report the first case of a patient with Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina, whose mother used misoprostol during pregnancy. A White boy of 1 year and 7 months of age, whose mother used misoprostol during the second month of pregnancy, presented with bilateral epicanthal folds, aplasia of the sternocostal head of the pectoralis major muscle with a hypoplastic nipple on the right side, and asymmetry between the upper limbs. The results of an angiotomographic study showed the presence of an aberrant right subclavian artery. Ultrasonographic evaluation showed turbulence and a high peak in the diastolic velocity in both carotid arteries, suggesting stenosis. Ophthalmologic assessment disclosed an intense bilateral tortuosity of the retinal blood vessels, with arterialnarrowing and rarefaction of the retinal pigment epithelium. This case suggests that the mechanism of vascular disruption of misoprostol could be related to the aberrant subclavian artery and the observed Poland syndrome. His retinal findings are different from those in cases described thus far in the literature, and this pattern of anomaly has never been associated with a gestational exposure to misoprostol. The possibility of a relationship of the aberrant right subclavian artery and the pattern of blood flow verified in the carotid arteries with the eye fundus abnormalities could be causally related or simply coincidental.

The Modified Rambo Transcanal Approach for Cochlear Implantation in CHARGE Syndrome.

PubMed

Wick, Cameron C; Moore, Amy M; Killeen, Daniel E; Isaacson, Brandon

2017-10-01

CHARGE syndrome is associated with a variety of temporal bone anomalies and deafness. The lack of surgical landmarks and facial nerve irregularities make cochlear implantation in this population a challenging endeavor. This study aims to describe a safe and efficacious transcanal approach for cochlear implantation that obviates the need to perform a mastoidectomy and facial recess. Three children with profound hearing loss secondary to CHARGE syndrome. Transcanal cochlear implantation with closure of the ear canal via a modified Rambo meatoplasty. Retrospective chart review of temporal bone anomalies associated with CHARGE syndrome, technical nuances of this transcanal approach, and cochlear implant outcomes. The mean patient age was 2.5 years (range 1.5-3.8 yr). Two were male and two were left ears. All patients had a hypoplastic mastoid, semicircular canal aplasia, and had some degree of cochlear dysplasia. A full cochlear implant insertion was achieved in all cases, even in the presence of grossly abnormal middle ear and facial nerve anatomy. There were no intraoperative or postoperative complications. The mean follow-up was 12.4 months (range, 3.9-25.2 mo). All three patients use their device daily. Their guardians report improved vocalization and environmental awareness. The modified Rambo transcanal approach provides a safe corridor for cochlear implantation in patients with CHARGE syndrome. This approach minimizes the anatomical variations associated with the syndrome and may reduce the risk of electrode extrusion. Implant outcomes in this patient population remain highly variable based on the patient's global cognitive capacity.

A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia.

PubMed

Perl, Alexander E; Kasner, Margaret T; Tsai, Donald E; Vogl, Dan T; Loren, Alison W; Schuster, Stephen J; Porter, David L; Stadtmauer, Edward A; Goldstein, Steven C; Frey, Noelle V; Nasta, Sunita D; Hexner, Elizabeth O; Dierov, Jamil K; Swider, Cezary R; Bagg, Adam; Gewirtz, Alan M; Carroll, Martin; Luger, Selina M

2009-11-01

Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents. We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML. Twenty-nine subjects received sirolimus and MEC across five dose levels. Dose-limiting toxicities were irreversible marrow aplasia and multiorgan failure. The maximum tolerated dose (MTD) of sirolimus was determined to be a 12 mg loading dose on day 1 followed by 4 mg/d on days 2 to 7, concurrent with MEC chemotherapy. Complete or partial remissions occurred in 6 (22%) of the 27 subjects who completed chemotherapy, including 3 (25%) of the 12 subjects treated at the MTD. At the MTD, measured rapamycin trough levels were within the therapeutic range for solid organ transplantation. However, direct measurement of the mTOR target p70 S6 kinase phosphorylation in marrow blasts from these subjects only showed definite target inhibition in one of five evaluable samples. Sirolimus and MEC is an active and feasible regimen. However, as administered in this study, the synergy between MEC and sirolimus was not confirmed. Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response.

Combined Administration of Recombinant Human Megakaryocyte Growth and Development Factor and Granulocyte Colony-Stimulating Factor Enhances Multilineage Hematopoietic Reconstitution in Nonhuman Primates after Radiation-Induced Marrow Aplasia

DTIC Science & Technology

1996-05-01

dose would yield an equivalent or better biological activity. Neupogen ® ( Filgrastim ), r-metHuG-CSF, was produced in E. coli as a...recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoi- etic recovery after otherwise lethal total body

Language, etayage et interactions therapeutiques: Actes du 5eme colloque d'orthophonie/logopedie (Language, Scaffolding and Therepeutic Interactions: Proceedings of the 5th Colloquium on Speech Therapy and Speech Pathology) (Neuchatel, Switzerland, September 25-26, 1998).

ERIC Educational Resources Information Center

Sovilla, J. Buttet, Ed.; de Weck, G., Ed.

1998-01-01

These articles on scaffolding in language and speech pathology/therapy are included in this issue: "Strategies d'etayage avec des enfants disphasiques: sont-elles specifiques?" ("Scaffolding Strategies for Dysphasic Children: Are They Specific?") (Genevieve de Weck); "Comparaison des strategies discursives d'etayage dans un conte et un recit…

Pure Red Cell Aplasia After Chemotherapy for Hodgkin’s Lymphoma: In Vitro Evidence for T Cell Mediated Suppression of Erythropoiesis and Response to Sequential Cyclosporin and Erythropoietin

DTIC Science & Technology

1994-01-01

serologies revealed no evidence of recent or active parvovirus , hepatitis A, B, C, or Immunophenotyping studies on peripheral blood lym- Epstein-Barr...impair erythropoietin production in humans [27-291 and Norbert Frickhofer for the B 19 parvovirus studies and in mice [301. As was documented

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

PubMed Central

de Munnik, Sonja A; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Clayton-Smith, Jill; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Schoots, Jeroen; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

2012-01-01

Meier–Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype–phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months–47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42% predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype–phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. PMID:22333897

Vascular Variations Associated with Intracranial Aneurysms.

PubMed

Orakdogen, Metin; Emon, Selin Tural; Somay, Hakan; Engin, Taner; Is, Merih; Hakan, Tayfun

2017-01-01

To investigate the vascular variations in patients with intracranial aneurysm in circle of Willis. We used the data on 128 consecutive intracranial aneurysm cases. Cerebral angiography images were analyzed retrospectively. Arteries were grouped as anterior cerebral arterial system (ACS), posterior cerebral arterial system (PCS) and middle cerebral arterial system (MCS) for grouping vascular variations. Lateralization, being single/multiple, gender; and also any connection with accompanying aneurysms" number, localization, dimension, whether bleeding/incidental aneurysm has been inspected. Variations were demonstrated in 57.8% of the cases. The most common variation was A1 variation (34.4%). The rate of variations was 36.7%, 24.2% and 10.2% respectively in ACS, PCS and MCS. MCS variations were significantly higher in males. Anterior communicating artery (ACoA) aneurysm observance rates were significantly higher and posterior communicating artery (PCoA) aneurysm and middle cerebral artery (MCA) aneurysm observance rates were significantly lower when compared to "no ACS variation detected" cases. In "PCS variation detected" cases, PCoA aneurysm observance rates and coexistence of multiple variations were significantly higher. The rate of vascular variations in patients with aneurysms was 57.8%. Arterial hypoplasia and aplasia were the most common variations. ACS was the most common region that variations were located in; they were mostly detected on the right side. Coexistence of ACoA aneurysm was higher than PCoA and MCA aneurysms. In the PCS variations group, PCoA aneurysms were the most common aneurysms that accompanying the variation and multiple variations were more common than in the other two groups. The variations in MCS were most common in males.

Anatomical Variability of the Posterior Communicating Artery.

PubMed

Gunnal, Sandhya Arvind; Farooqui, Mujibuddin S; Wabale, Rajendra N

2018-01-01

Although posterior communicating artery (PCoA) is a smaller branch of the internal carotid artery, it gives the main contribution in the formation of circle of Willis (CW) by communicating with the internal carotid arterial system and the vertebro-basilar arterial system. The size of PCoA varies frequently. The present work aims to study the PCoA regarding its morphology, morphometry, and symmetry. This study was conducted on 170 human cadaveric brains. Brains were dissected carefully and delicately to expose all components of CW, especially PCoA. Morphological variations of PCoA were noted along with its morphometry and symmetry. Morphological variations of PCoA were aplasia (3.52%), hypoplasia (25.29%), fenestration (0.58%), and persistent fetal pattern (16.47%). In the present study, we found the five different types of terminations of PCoA. Type I termination was the most common type, seen in 92.94% of cases, Type II termination was seen in 1.17%, Type III and Type IV terminations both were seen in 0.58%, and Type V was seen in 1.17%. The mean length of PCoA was 15.9 mm and 15.3 mm on the right and left sides, respectively. The mean diameter of PCoA was 2.1 mm and 1.9 mm on the right and left sides, respectively. Symmetry of PCoA was seen in 65.29% and asymmetric PCoA was seen in 34.70% of cases. The present study provides the complete description of PCoA regarding its morphology, symmetry, and morphometry. Awareness of these anatomical variations is important in neurovascular procedures.

Anatomical Variability of the Posterior Communicating Artery

PubMed Central

Gunnal, Sandhya Arvind; Farooqui, Mujibuddin S.; Wabale, Rajendra N.

2018-01-01

Objective: Although posterior communicating artery (PCoA) is a smaller branch of the internal carotid artery, it gives the main contribution in the formation of circle of Willis (CW) by communicating with the internal carotid arterial system and the vertebro-basilar arterial system. The size of PCoA varies frequently. The present work aims to study the PCoA regarding its morphology, morphometry, and symmetry. Materials and Methods: This study was conducted on 170 human cadaveric brains. Brains were dissected carefully and delicately to expose all components of CW, especially PCoA. Morphological variations of PCoA were noted along with its morphometry and symmetry. Results: Morphological variations of PCoA were aplasia (3.52%), hypoplasia (25.29%), fenestration (0.58%), and persistent fetal pattern (16.47%). In the present study, we found the five different types of terminations of PCoA. Type I termination was the most common type, seen in 92.94% of cases, Type II termination was seen in 1.17%, Type III and Type IV terminations both were seen in 0.58%, and Type V was seen in 1.17%. The mean length of PCoA was 15.9 mm and 15.3 mm on the right and left sides, respectively. The mean diameter of PCoA was 2.1 mm and 1.9 mm on the right and left sides, respectively. Symmetry of PCoA was seen in 65.29% and asymmetric PCoA was seen in 34.70% of cases. Conclusion: The present study provides the complete description of PCoA regarding its morphology, symmetry, and morphometry. Awareness of these anatomical variations is important in neurovascular procedures. PMID:29682035

High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy.

PubMed

Ridola, Vita; Grill, Jacques; Doz, Francois; Gentet, Jean-Claude; Frappaz, Didier; Raquin, Marie-Anne; Habrand, Jean-Louis; Sainte-Rose, Christian; Valteau-Couanet, Dominique; Kalifa, Chantal

2007-07-01

The objective of the current study was to determine the outcome of children with local recurrence or progression of medulloblastoma in patients who received high-dose chemotherapy (HDC) and posterior fossa (PF) irradiation. HDC consisted in busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by autologous stem cells transplantation (ASCT). PF radiotherapy was delivered at doses from 50 grays (Gy) to 55 Gy on Day +70 after ASCT. Twenty-seven patients developed local recurrence of an initially completely resected medulloblastoma. Twelve patients had local residual disease after surgery and were enrolled into the salvage protocol at the time of local disease progression under conventional chemotherapy. Acute toxicity consisted mainly in hepatic veno-occlusive disease (33% of patients) and bone marrow aplasia. Two toxic deaths (5%) from infections were reported. The 5-year overall survival rate after this salvage treatment (OS(5y)) for the 39 children who were treated was 68.8% (95% confidence interval [95% CI], 53-81.2%). In the group of patients who were treated for local recurrence, the OS(5y) was 77.2% (95% CI, 58.3-89.1%). Patients with local residual disease who were treated at the time of disease progression had an OS(5y) after salvage treatment of only 50% (95% CI, 25.4-74.6%; P = .09). The treatment strategy that was used in this study had manageable immediate toxicity and resulted in a high overall survival rate in the setting of young children with medulloblastoma who developed local recurrence or disease progression. Copyright (c) 2007 American Cancer Society.

ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs

PubMed Central

Syrjä, Pernilla; Arumilli, Meharji; Järvinen, Anna-Kaisa; Rajamäki, Minna

2017-01-01

Acute respiratory distress syndrome (ARDS) is the leading cause of death in critical care medicine. The syndrome is typified by an exaggerated inflammatory response within the lungs. ARDS has been reported in many species, including dogs. We have previously reported a fatal familial juvenile respiratory disease accompanied by occasional unilateral renal aplasia and hydrocephalus, in Dalmatian dogs. The condition with a suggested recessive mode of inheritance resembles acute exacerbation of usual interstitial pneumonia in man. We combined SNP-based homozygosity mapping of two ARDS-affected Dalmatian dogs and whole genome sequencing of one affected dog to identify a case-specific homozygous nonsense variant, c.31C>T; p.R11* in the ANLN gene. Subsequent analysis of the variant in a total cohort of 188 Dalmatians, including seven cases, indicated complete segregation of the variant with the disease and confirmed an autosomal recessive mode of inheritance. Low carrier frequency of 1.7% was observed in a population cohort. The early nonsense variant results in a nearly complete truncation of the ANLN protein and immunohistochemical analysis of the affected lung tissue demonstrated the lack of the membranous and cytoplasmic staining of ANLN protein in the metaplastic bronchial epithelium. The ANLN gene encodes an anillin actin binding protein with a suggested regulatory role in the integrity of intercellular junctions. Our study suggests that defective ANLN results in abnormal cellular organization of the bronchiolar epithelium, which in turn predisposes to acute respiratory distress. ANLN has been previously linked to a dominant focal segmental glomerulosclerosis in human without pulmonary defects. However, the lack of similar renal manifestations in the affected Dalmatians suggest a novel ANLN-related pulmonary function and disease association. PMID:28222102

Radiological characteristics of the knee joint in nail patella syndrome.

PubMed

Tigchelaar, S; Rooy, J de; Hannink, G; Koëter, S; van Kampen, A; Bongers, E

2016-04-01

Nail patella syndrome (NPS) is a skeletal dysplasia with patellofemoral dysfunction as a key symptom. We present the first in-depth radiological evaluation of the knee in a large series of NPS patients and describe the typical malformations. Conventional radiological examination of 95 skeletally mature patients with NPS was performed. Patellar morphology was classified according to the Wiberg classification as modified by Baumgartl and Ficat criteria, and trochlear shape was classified according to the Dejour classification. Patellar aplasia was present in 4/90 (4%), and patellar hypoplasia in 77/90 (86%) of patients. The prevailing patellar shapes were type III, type IV and Hunter's cap. No patellar shape genotype-phenotype association could be found. The malformations of the distal femur comprised shortening of the lateral femoral condyle in 46 out of 84 patients (55%), with a prominent anterior surface of the lateral femoral condyle in 47 out of 84 patients (56%) and a flat anterior surface of the medial femoral condyle in 78 out of 85 patients (92%). The trochlea was type A1 according to the Dejour classification in 79 out of 85 patients (93%). An easily recognisable characteristic quartet of malformations consisting of patellar aplasiaor hypoplasia and the malformations of the distal femur was found in 22 out of 81 patients (27%), with the majority displaying at least three malformations. The distinct malformations of the knee in nail patella syndrome are easily recognisable on conventional radiographs and lead to the correct interpretation of the aberrant morphology which is essential in the treatment of these patellofemoral disorders. ©2016 The British Editorial Society of Bone & Joint Surgery.

Evaluation of radiography as a screening method for detection and characterisation of congenital vertebral malformations in dogs.

PubMed

Brocal, Josep; De Decker, Steven; José-López, Roberto; Guevar, Julien; Ortega, Maria; Parkin, Tim; Ter Haar, Gert; Gutierrez-Quintana, Rodrigo

2018-05-19

Congenital vertebral malformations (CVM) are common in brachycephalic 'screw-tailed' dogs; they can be associated with neurological deficits and a genetic predisposition has been suggested. The purpose of this study was to evaluate radiography as a screening method for congenital thoracic vertebral malformations in brachycephalic 'screw-tailed' dogs by comparing it with CT. Forty-nine dogs that had both radiographic and CT evaluations of the thoracic vertebral column were included. Three observers retrospectively reviewed the images independently to detect CVMs. When identified, they were classified according to a previously published radiographic classification scheme. A CT consensus was then reached. All observers identified significantly more affected vertebrae when evaluating orthogonal radiographic views compared with lateral views alone; and more affected vertebrae with the CT consensus compared with orthogonal radiographic views. Given the high number of CVMs per dog, the number of dogs classified as being CVM free was not significantly different between CT and radiography. Significantly more midline closure defects were also identified with CT compared with radiography. Malformations classified as symmetrical or ventral hypoplasias on radiography were frequently classified as ventral and medial aplasias on CT images. Our results support that CT is better than radiography for the classification of CVMs and this will be important when further evidence of which are the most clinically relevant CVMs is identified. These findings are of particular importance for designing screening schemes of CVMs that could help selective breeding programmes based on phenotype and future studies. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Development of Auditory Perception in Children Following Auditory Brainstem Implantation

PubMed Central

Colletti, Liliana; Shannon, Robert V.; Colletti, Vittorio

2014-01-01

Auditory brainstem implants (ABI) can provide useful auditory perception and language development in deaf children who are not able to use a cochlear implant (CI). We prospectively followed-up a consecutive group of 64 deaf children up to 12 years following ABI implantation. The etiology of deafness in these children was: cochlear nerve aplasia in 49, auditory neuropathy in 1, cochlear malformations in 8, bilateral cochlear post-meningitic ossification in 3, NF2 in 2, and bilateral cochlear fractures due to a head injury in 1. Thirty five children had other congenital non-auditory disabilities. Twenty two children had previous CIs with no benefit. Fifty eight children were fitted with the Cochlear 24 ABI device and six with the MedEl ABI device and all children followed the same rehabilitation program. Auditory perceptual abilities were evaluated on the Categories of Auditory Performance (CAP) scale. No child was lost to follow-up and there were no exclusions from the study. All children showed significant improvement in auditory perception with implant experience. Seven children (11%) were able to achieve the highest score on the CAP test; they were able to converse on the telephone within 3 years of implantation. Twenty children (31.3%) achieved open set speech recognition (CAP score of 5 or greater) and 30 (46.9%) achieved a CAP level of 4 or greater. Of the 29 children without non-auditory disabilities, 18 (62%) achieved a CAP score of 5 or greater with the ABI. All children showed continued improvements in auditory skills over time. The long-term results of ABI implantation reveal significant auditory benefit in most children, and open set auditory recognition in many. PMID:25377987

Selective Insulin-like Growth Factor Resistance Associated with Heart Hemorrhages and Poor Prognosis in a Novel Preclinical Model of the Hematopoietic Acute Radiation Syndrome.

PubMed

Kenchegowda, Doreswamy; Legesse, Betre; Hritzo, Bernadette; Olsen, Cara; Aghdam, Saeed; Kaur, Amandeep; Culp, William; Derrien-Colemyn, Alexandrine; Severson, Grant; Moroni, Maria

2018-05-29

Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features. Gottingen and Sinclair minipigs were exposed to ionizing radiation at hematopoietic doses. The smaller Gottingen minipig strain was more sensitive to radiation; differences in IGF-1 levels were minimal, suggesting that increased sensitivity could depend on weak response to the hormone. Radiation caused IGF-1 selective resistance by inhibiting the anti-inflammatory anti-oxidative stress IRS/PI3K/Akt but not the pro-inflammatory MAPK kinase pathway, shifting IGF-1 signaling towards a pro-oxidant, pro-inflammatory environment. Selective IGF-1 resistance associated with hemorrhages in the heart, poor prognosis, increase in C-reactive protein and NADPH oxidase 2, uncoupling of endothelial nitric oxide synthase, inhibition of nitric oxide (NO) synthesis and imbalance between the vasodilator NO and the vasoconstrictor endothelin-1 molecules. Selective IGF-1 resistance is a novel mechanism of radiation injury, associated with a vicious cycle amplifying reactive oxygen species-induced damage, inflammation and endothelial dysfunction. In the presence of thrombocytopenia, selective inhibition of IGF-1 cardioprotective function may contribute to the development of hemostatic disorders. This finding may be particularly relevant for individuals with low IGF-1 activity, such as the elderly or those with cardiometabolic dysfunctions.

Sequential Oral Hydroxyurea and Intravenous Cytosine Arabinoside in Refractory Childhood Acute Leukemia: A Pediatric Oncology Group Phase I Study

PubMed Central

Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

2015-01-01

Summary At concentrations >0.1 mM, Hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU, 1200 mg/m2 was followed 2 hours later by ara-C, 250-3100 mg/m2 intravenously in 15 minutes. The combination was given on days 1,2,3 and 8,9,10. Thirty-three children (26 ALL, 7 ANLL) were treated; 29 received at least one full course. All patients developed grade 4 cytopenias. Other grade 3-4 toxicities included: hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9) and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1-3 months). 20/26 patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range 0.21-0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism. PMID:18458568

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

PubMed

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial.

PubMed

Adotevi, O; Godet, Y; Galaine, J; Lakkis, Z; Idirene, I; Certoux, J M; Jary, M; Loyon, R; Laheurte, C; Kim, S; Dormoy, A; Pouthier, F; Barisien, C; Fein, F; Tiberghien, P; Pivot, X; Valmary-Degano, S; Ferrand, C; Morel, P; Delabrousse, E; Borg, C

2018-01-01

Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3.10 6 , 8.10 6 and 12.10 6 NK cells/kg) following by a high-dose interleukin-2 (IL-2). Cetuximab was administered intravenously every week for 7 weeks. Nine patients with liver metastases of colorectal or pancreatic cancers were included, three per dose level. Hepatic artery injection was successfully performed in all patients with no report of dose-limiting toxicity. Two patients had febrile aplasia requiring a short-term antibiotherapy. Grade 3/4 anemia and thrombopenia were also observed related to the chemotherapy. Objective clinical responses were documented in 3 patients and among them 2 occurred in patients injected with cell products harboring two KIR ligand mismatches and one in a patient with one KIR ligand mismatch. Immune monitoring revealed that most patients presented an increase but transient of IL-15 and IL-7 cytokines levels one week after chemotherapy. Furthermore, a high expansion of FoxP3 + regulatory T cells and PD-1 + T cells was observed in all patients, related to IL-2 administration. Our results demonstrated that combining allogeneic NK cells transfer via intra-hepatic artery, cetuximab and a high-dose IL-2 is feasible, well tolerated and may result in clinical responses.

The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs.

PubMed

Fiocchi, E H; Cowgill, L D; Brown, D C; Markovich, J E; Tucker, S; Labato, M A; Callan, M B

2017-03-01

Darbepoetin alfa (darbepoetin) is an erythropoiesis-stimulating agent used for the treatment of anemia secondary to chronic kidney disease (CKD) in dogs, but reports describing response are lacking. To evaluate the effectiveness of darbepoetin in dogs with anemia secondary to CKD, dosing protocols, and adverse events. Thirty-three client-owned dogs with naturally occurring CKD, including 26 with comorbidities. Multi-institutional retrospective study. The median starting dosage and highest dosage of darbepoetin administered were 0.5 and 0.8 μg/kg SC once weekly, respectively. Response to treatment was defined as achieving a packed cell volume (PCV) ≥30% or an increase in PCV ≥10%. Twenty-eight of 33 dogs (85%) achieved a PCV ≥30% and 22 of 33 (67%) dogs achieved an increase in PCV ≥10%. Median time to achieve a PCV ≥30% was 29 days. A higher starting dosage was associated with achieving an increase in PCV ≥10% (P = .01). No dog sustained a response at a dosing interval >q21d. Potential adverse events included increased blood pressure requiring treatment (n = 12), seizures (n = 5), vomiting (n = 3), diarrhea (n = 3), and possible pure red cell aplasia (PRCA) (n = 2). Darbepoetin, when combined with treatment of comorbidities, is an effective treatment for anemia secondary to CKD in dogs. A dosing interval >q21d was ineffective at maintaining a response to treatment. PRCA was a possible adverse event in 2 of 33 dogs (6%). Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Split-Hand/Split-Foot Malformation Is Caused by Mutations in the p63 Gene on 3q27

PubMed Central

Ianakiev, Peter; Kilpatrick, Michael W.; Toudjarska, Iva; Basel, Donald; Beighton, Peter; Tsipouras, Petros

2000-01-01

Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac). Results of recent studies have shown that, in heterozygous Dac embryos, the central segment of the apical ectodermal ridge (AER) degenerates, leaving the anterior and posterior segments intact; this finding suggests that localized failure of ridge maintenance activity is the fundamental developmental defect in Dac and, by inference, in SHFM. Results of gene-targeting studies have demonstrated that p63, a homologue of the cell-cycle regulator TP53, plays a critically important role in regulation of the formation and differentiation of the AER. Two missense mutations, 724A→G, which predicts amino acid substitution K194E, and 982T→C, which predicts amino acid substitution R280C, were identified in exons 5 and 7, respectively, of the p63 gene in two families with SHFM. Two additional mutations (279R→H and 304R→Q) were identified in families with EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome. All four mutations are found in exons that fall within the DNA-binding domain of p63. The two amino acids mutated in the families with SHFM appear to be primarily involved in maintenance of the overall structure of the domain, in contrast to the p63 mutations responsible for EEC syndrome, which reside in amino acid residues that directly interact with the DNA. PMID:10839977

[Clinical and biological manifestations in primary parvovirus B19 infection in immunocompetent adult: a retrospective study of 26 cases].

PubMed

Parra, D; Mekki, Y; Durieu, I; Broussolle, C; Sève, P

2014-05-01

Parvovirus B19 causes erythema infectiosum in children, transient aplastic anemia in patients with hemoglobinopathies, pur red cell aplasia in immunocompromised persons and hydrops fetalis in pregnancy. The spectrum of clinical and biological manifestations in immunocompetent adult continues to grow up. We report on a case series of 26 patients with primary parvovirus B19 infection in immunocompetent adults. This is a retrospective study over the period 2000 to 2010 in two departments of internal medecine. The diagnostic was clinical, serological or molecular. There was a female predominance (sex-ratio 3.33/1). Median patient age at diagnostic was 38.8 years (range: 18-68). The predominant symptoms were fever (65%), peripheral and symmetrical polyarthralgia (62%) and skin rash (58%). Two patients had neurological manifestations (sixth cranial nerve palsy, distal paresthesia) and one patient had myocarditis. Abnormal laboratory values included increased acute phase reactants (73%), thrombocytopenia (43%), lymphopenia (38%) and elevated liver enzymes (37%). Antinuclear (19%), anti-DNA (28%) and anti-phospholipids antibodies (14%), and hypocomplementemia (32%) were observed. False reaction with anti-CMV and anti-EBV IgM positivity was documented in 27% of cases. Two patients had persistent parvovirus B19 infection. The diversity of the clinical manifestations of parvovirus B19 infection may be misleading for the clinician. However, the diagnosis should be suspected in immunocompetent adults to limit the risk of transmission to the patients who could develop a severe infection such as pregnant women or immunocompromised patients. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Parvovirus B19.

PubMed

Landry, Marie Louise

2016-06-01

Primary parvovirus B19 infection is an infrequent, but serious and treatable, cause of chronic anemia in immunocompromised hosts. Many compromised hosts have preexisting antibody to B19 and are not at risk. However, upon primary infection, some patients may be able to mount a sufficient immune response to terminate active parvovirus B19 infection of erythroid precursors. The most common consequence of B19 infection in the compromised host is pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia. Anemia persists until neutralizing antibody is either produced by the host or passively administered. Parvovirus B19 should be suspected in compromised hosts with unexplained or severe anemia and reticulocytopenia, or when bone-marrow examination shows either giant pronormoblasts or absence of red-cell precursors. Diagnosis is established by detection of B19 DNA in serum in the absence of IgG antibody to B19. In some cases, IgG antibody is detected but is not neutralizing. Anti-B19 IgM may or may not be present. Therapy includes any or all of the following: red-cell transfusion, adjustment in medications to restore or improve the patient's immune system, and administration of intravenous immunoglobulin (IVIG). Following treatment, patients should be closely monitored, especially if immunosuppression is unchanged or increased. Should hematocrit trend downward and parvovirus DNA trend upward, the therapeutic options above should be revisited. In a few instances, monthly maintenance IVIG may be indicated. Caregivers should be aware that B19 variants, though rarely encountered, can be missed or under-quantitated by some real-time polymerase-chain reaction methods.

Safety of preoperative erythropoietin in surgical calvarial remodeling: an 8-year retrospective review and analysis.

PubMed

Naran, Sanjay; Cladis, Franklyn; Fearon, Jeffrey; Bradley, James; Michelotti, Brett; Cooper, Gregory; Cray, James; Katchikian, Hurig; Grunwaldt, Lorelei; Pollack, Ian F; Losee, Joseph

2012-08-01

Calvarial remodeling is typically associated with significant blood loss. Although preoperative erythropoiesis-stimulating agents have proven to significantly decrease the need for blood transfusions, recent data in adults have raised concerns that elevating hemoglobin levels greater than 12.5 g/dl may increase the risk of thrombotic events. This study was designed to assess the risks of erythropoietin in the pediatric population. Records were retrospectively reviewed from 2000 to 2008 at three major metropolitan children's hospitals of all children undergoing calvarial remodeling after receiving preoperative erythropoietin. Demographic and perioperative outcome data were reviewed, including transfusion reactions, pressure ulcer secondary to prolonged positioning, pneumonia, infection, deep vein thrombosis, cerebrovascular accident, pulmonary embolism, sagittal sinus thrombosis, pure red cell aplasia, and myocardial infarction. A total of 369 patients met the inclusion criteria (mean age, 0.86±1.1 years). On average, three preoperative doses of erythropoietin were administered (600 U/kg). Iron was also supplemented. No complications associated with dosing were noted, there were no thrombotic events identified, and no other major complications were seen (i.e., death or blindness). Thirty-one patients (8.40 percent) experienced one or more postoperative complications. There was no significant correlation between hemoglobin levels greater than 12.5 g/dl and the occurrence of any noted complication. With zero thrombotic postoperative complications, the authors estimate the risk of a thrombotic event in the pediatric population to be less than 0.81 percent (95 percent confidence). These data suggest that preoperative administration of erythropoietin in children undergoing calvarial remodeling does not appear to increase the incidence of thrombotic events or other significant complications. Therapeutic, IV.

Risk factors for central line-associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study.

PubMed

Viana Taveira, Michelle Ribeiro; Lima, Luciana Santana; de Araújo, Cláudia Corrêa; de Mello, Maria Júlia Gonçalves

2017-02-01

Totally implantable venous access ports (TIVAPs) are used for prolonged central venous access, allowing the infusion of chemotherapy and other fluids and improving the quality of life of children with cancer. TIVAPs were developed to reduce the infection rates associated with central venous catheters; however, infectious events remain common and have not been fully investigated in pediatric oncology patients. A retrospective cohort was formed to investigate risk factors for central line-associated bloodstream infection (CLABSI) in pediatric cancer patients. Sociodemographic, clinical, and TIVAP insertion-related variables were evaluated, with the endpoint being the first CLABSI. A Kaplan-Meier analysis was performed to determine CLABSI-free catheter survival. Overall, 188 children were evaluated over 77,541 catheter days, with 94 being diagnosed with CLABSI (50%). Although coagulase-negative staphylococci were the pathogens most commonly isolated, Gram-negative microorganisms (46.8%) were also prevalent. In the multivariate analysis, factors that increased the risk for CLABSI were TIVAP insertion prior to chemotherapy (risk ratio [RR] = 1.56; P < 0.01), white blood cell count less than 1,000 mm -3 on the day of implantation (RR = 1.64; P < 0.01), and chronic malnutrition (RR = 1.41; P < 0.05). Median time without CLABSI following TIVAP insertion was 74.5 days. Risk factors for CLABSI in pediatric cancer patients with a TIVAP may be related to the severity of the child's condition at catheter insertion. Insertion of the catheter before chemotherapy and unfavorable conditions such as malnutrition and bone marrow aplasia can increase the risk of CLABSI. Protocols must be revised and surveillance increased over the first 10 weeks of treatment. © 2016 Wiley Periodicals, Inc.

19q13.32 microdeletion syndrome: three new cases.

PubMed

Castillo, Angela; Kramer, Nancy; Schwartz, Charles E; Miles, Judith H; DuPont, Barbara R; Rosenfeld, Jill A; Graham, John M

2014-01-01

A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 microdeletion syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2-3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 microdeletion syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20-23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, and ZNF541. These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.

PubMed

Choo, Daniel I; Tawfik, Kareem O; Martin, Donna M; Raphael, Yehoash

2017-12-01

The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries. © 2017 Wiley Periodicals, Inc.

Sodium orthovanadate (vanadate), a potent mitigator of radiation-induced damage to the hematopoietic system in mice

PubMed Central

Wang, Bing; Tanaka, Kaoru; Morita, Akinori; Ninomiya, Yasuharu; Maruyama, Kouichi; Fujita, Kazuko; Hosoi, Yoshio; Nenoi, Mitsuru

2013-01-01

Previous in vitro and in vivo studies have shown that sodium orthovanadate (vanadate), an inorganic vanadium compound, could effectively suppress radiation-induced p53-mediated apoptosis via both transcription-dependent and transcription-independent pathways. As a potent radiation protector administered at a dose of 20 mg/kg body weight (20 mg/kg) prior to total body irradiation (TBI) by intra-peritoneal (ip) injection, it completely protected mice from hematopoietic syndrome and partially from gastrointestinal syndrome. In the present study, radiation mitigation effects from vanadate were investigated by ip injection of vanadate after TBI in mice. Results showed that a single administration of vanadate at a dose of 20 mg/kg markedly improved the 30-day survival rate and the peripheral blood hemogram, relieved bone marrow aplasia and decreased occurrence of the bone marrow micronucleated erythrocytes in the surviving animals. The dose reduction factor was 1.2 when a single dose of 20 mg/kg was administered 15 min after TBI in mice using the 30-day survival test as the endpoint. Results also showed that either doubling the vanadate dose (40 mg/kg) in a single administration or continuing the vanadate treatment (after a single administration at 20 mg/kg) from the following day at a dose of 5 mg/kg per day for 4 consecutive days further significantly improved the efficacy for rescuing bone marrow failure in the 30-day survival test. Taken together, these findings indicate that vanadate would be a potent mitigator suppressing the acute lethality (hematopoietic syndrome) and minimizing the detrimental effects (anhematopoiesis and delayed genotoxic effects) induced by TBI in mice. PMID:23349341

Genetic evidence for heterogeneity in the etiology of CBAVD: Haplotype analysis in families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerem, B.; Rave-Harel, N.; Goshen, R.

1994-09-01

Male infertility due to congenital aplasia of the vas deference (CBAVD) is present in almost all CF male patients. It is also found in 1-2% of infertile otherwise healthy males. Several studies have found that about 10% of males with CBAVD carry 2 CF mutations, 40% carry one mutation and 50% have no mutations. These results indicate that in some males CBAVD is caused by two mutated CF alleles. However, in cases of males with one or no identified CF mutations, the association between CBAVD and CF is unclear. We therefore performed, in addition to CF mutation analysis, an extendedmore » haplotype analysis in 7 families of CBAVD males (2 had 2 brothers with CBAVD). Our results show that in 6 of the families, the infertile males inherited different CF alleles than their fertile brothers. However, in 2 families, in which no CF mutations were as of yet identified, different results were found. In one family, 2 infertile brothers differed in their haplotypes: both inherited from their mother the same CF allele, while from their father they inherited different alleles. Furthermore, their fertile brother inherited the same CF alleles as one of his fertile brothers. In another family, 2 brothers, one with CBAVD and the other fertile, inherited the same 2 CFTR alleles. These results provide genetic evidence for heterogeneity in the etiology of CBAVD. In some families the CBAVD is caused by 2 CF mutations, in others it is caused by other mechanism(s): heterozygosity for a CF mutation influenced by different threshold levels, mutations in other gene(s), or interaction between the two.« less

Genomewide Linkage Scan for Split–Hand/Foot Malformation with Long-Bone Deficiency in a Large Arab Family Identifies Two Novel Susceptibility Loci on Chromosomes 1q42.2-q43 and 6q14.1

PubMed Central

Naveed, Mohammed; Nath, Swapan K.; Gaines, Mathew; Al-Ali, Mahmoud T.; Al-Khaja, Najib; Hutchings, David; Golla, Jeffrey; Deutsch, Samuel; Bottani, Armand; Antonarakis, Stylianos E.; Ratnamala, Uppala; Radhakrishna, Uppala

2007-01-01

Split–hand/foot malformation with long-bone deficiency (SHFLD) is a rare, severe limb deformity characterized by tibia aplasia with or without split-hand/split-foot deformity. Identification of genetic susceptibility loci for SHFLD has been unsuccessful because of its rare incidence, variable phenotypic expression and associated anomalies, and uncertain inheritance pattern. SHFLD is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has also been postulated. We conducted a genomewide linkage analysis, using a 10K SNP array in a large consanguineous family (UR078) from the United Arab Emirates (UAE) who had disease transmission consistent with an autosomal dominant inheritance pattern. The study identified two novel SHFLD susceptibility loci at 1q42.2-q43 (nonparametric linkage [NPL] 9.8, P=.000065) and 6q14.1 (NPL 7.12, P=.000897). These results were also supported by multipoint parametric linkage analysis. Maximum multipoint LOD scores of 3.20 and 3.78 were detected for genomic locations 1q42.2-43 and 6q14.1, respectively, with the use of an autosomal dominant mode of inheritance with reduced penetrance. Haplotype analysis with informative crossovers enabled mapping of the SHFLD loci to a region of ∼18.38 cM (8.4 Mb) between single-nucleotide polymorphisms rs1124110 and rs535043 on 1q42.2-q43 and to a region of ∼1.96 cM (4.1 Mb) between rs623155 and rs1547251 on 6q14.1. The study identified two novel loci for the SHFLD phenotype in this UAE family. PMID:17160898

Maternal vitamin B12 deficiency affects spermatogenesis at the embryonic and immature stages in rats.

PubMed

Watanabe, Toshiaki; Ebara, Shuhei; Kimura, Sachiko; Maeda, Kunihiko; Watanabe, Yoshitaka; Watanabe, Hiroshi; Kasai, Shigenobu; Nakano, Yoshihisa

2007-03-01

To evaluate the role of cobalamin (Cbl) on spermatogenesis, the effect of dietary vitamin B(12) deficiency on early spermatogenesis was histologically investigated in male fetuses and newborns in the first filial generation (F(1) males) of rats. There was no difference in the number of gonocytes and supporting cells of Sertoli in the gonad in male fetuses on day 16 of gestation and in the testes in F(1) males at 0 days of age between vitamin B(12)-deficient (VB12-D) and vitamin B(12)-supplemented (VB12-S) groups. However, at 21 days of age, a decreased number of spermatogonia and no spermatocytes were observed in the VB12-D group. Numerous TUNEL positive cells were located among spermatocytes of the spermatogenic epithelium. The ultrastructural features examined using transmission electron microscopy were considered to be indicative of apoptosis. The incidence of seminiferous tubules having apoptotic cells was 51.5% in the VB12-D group. At 60 days of age, aplasia of the spermatids and spermatozoa was detected in the VB12-D group. In the connective tissue between the seminiferous tubules, many interstitial Leydig cells and blood vessels were observed in the VB12-D group, as compared with the VB12-S group. These changes produced by vitamin B(12) deficiency can be reversed by providing a VB12-S diet after weaning at 21 days of age. From these findings, such a vitamin B(12) deficiency during gestation and lactation could affect the germ cells and especially damage spermatocytes in F(1) male rats, which indicates that Cbl may be an essential constituent in the meiosis of spermatogenesis.

[Bone marrow transplantation in aplastic anemia. Experience at a Mexican institution. Bone marrow transplantation group of the Salvador Zubirán National Institute of Nutrition].

PubMed

León-Rodríguez, E; Sosa Sánchez, R; Gómez, E; Ochoa Sosa, C

1993-01-01

During the period of May 1986 through February 1991, nine allogeneic bone marrow transplants (BMT) on eight severe aplastic anemia (SAA) patients were performed at the Instituto Nacional de la Nutrición Salvador Zubirán in Mexico City. Mean age at BMT was 18 years (age interval 12-30); seven were men; all patients had a clinical history of multiple blood transfusions; six individuals were infected at the time of the transplant. The conditioning regimens were: cyclophosphamide (Cy) in three patients; Cy+ total nodal radiation in five; and total nodal radiation only in the second transplant of one patient. Graft versus host disease (GVHD) prophylaxis was attempted with methotrexate plus cyclosporin A (CsA) in six patients, methylprednisolone plus CsA in two, and prednisone + CsA in the patient retransplanted. All procedures were carried out under single reverse isolation without gut decontamination. Seven of the nine procedures grafted (two cases died on days +8 and +25 due to infection). In the surviving, the median time for reaching > 1.0 white blood cells x 10(9)/L was 22 days (time interval 11-31); > 0.5 neutrophils x 10(9)/L in 27 days (time interval 15-42) and the same lapse to reach > 50 platelets x 10(9)/L. Length of hospital stay was 42 days (time interval 15-61). Acute GVHD was seen in one of the seven patients surviving the period of bone marrow aplasia (14%). Of six long term survivors (including one patient with a second transplant) chronic GVHD was present in four (67%): chronic GVHD was fatal in one individual but was well controlled in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Seven Strategies for Improving the Quality and Efficiency of the Education System. Notes, Comments... No. 192 = Sept strategies visant a ameliorer la qualite et l'efficacite du systeme d'education.

ERIC Educational Resources Information Center

Schiefelbein, Ernesto

Seven strategies for improving the quality and efficiency of educational system in Latin American are delineated within the context of background information on the coverage and efficiency of school systems from 1970 to 1980, technical and institutional limitations to educational progress, and an estimate of the impact of the strategies.…

Les campagnes de dépistage du VIH, une stratégie efficace pour l’accès universel à la prévention et au traitement ? L’expérience du Burkina Faso

PubMed Central

Somé, J.F.; Desclaux, A.; Ky-Zerbo, O.; Lougué, M.; Kéré, S.; Obermeyer, C.; Simaga, F.

2014-01-01

Objectifs l’augmentation du taux de personnes qui connaissent leur statut VIH est un impératif, notamment en Afrique subsaharienne, ce qui impose d’évaluer les stratégies utilisées pour accroître la fréquentation des services de dépistage. Cet article vise à faire le bilan de la pertinence, de la faisabilité et de l’efficacité des campagnes nationales de dépistagemenées entre 2006 et 2010 au Burkina Faso. Méthodologie une analyse de toutes les données de fréquentation du conseil dépistage sur cette période a été faite, couplée à des entretiens avec les principaux acteurs intervenant dans le dépistage. Résultats les résultats montrent que les huit campagnes de dépistage organisées sur la période ont permis à 487 727 personnes de faire leur test VIH. Ce nombre représente 50 % du nombre total de personnes ayant fait leur test et contribue à hauteur de 24,6 % au dépistage des personnes séropositives identifiées au cours de cette période. Les campagnes ont touché des populations difficiles à atteindre (en particulier les jeunes), à un coût moindre. Conclusions cette stratégie est donc pertinente pour identifier les personnes VIH+. Son intérêt pour la prévention, important selon les soignants et au vu des populations jeunes qui y participent, devrait être mesuré par des études complémentaires. Les campagnes sont efficaces et coût-efficaces même dans un pays de niveau de prévalence faible. Ces résultats soulignent l’intérêt de la synergie entre les associations et les services de santé dans l’offre de services de conseil et dépistage. PMID:24681563

Mise à jour sur l’utilisation clinique de la buprénorphine

PubMed Central

Ducharme, Simon; Fraser, Ronald; Gill, Kathryn

2012-01-01

Résumé Objectif Examiner les données scientifiques actuelles sur la buprénorphine-naloxone pour le traitement des troubles liés aux opioïdes, en insistant sur le contexte des soins primaires. Qualité des données On a fait une recension dans MEDLINE et la base de données Cochrane des synthèses critiques. Les données probantes sont surtout de niveau I. Message principal La buprénorphine est un agoniste partiel des récepteurs μ des opioïdes et un antagoniste des récepteurs κ des opioïdes ayant une longue demi-vie et un potentiel moins grand que la méthadone d’entraîner un usage abusif. Pour une désintoxication, la buprénorphine est au moins équivalente à la méthadone et supérieure à la clonidine. Comme thérapie de substitution, la buprénorphine est clairement supérieure au placebo. La méthadone comporte de légers avantages en ce qui a trait à la rétention en thérapie, mais une approche par étape en utilisant initialement la buprénorphine-naloxone est aussi efficace. Il est possible, sécuritaire et efficace de recourir à la buprénorphine en milieu de soins primaires. On peut obtenir l’autorisation de prescrire de la buprénorphine après avoir suivi une formation en ligne. Conclusion La buprénorphine est un agent sécuritaire et efficace pour la désintoxication en cas de dépendance aux opioïdes. Elle peut servir d’agent de première intention dans les programmes de thérapie de substitution, en raison de son potentiel plus faible d’usage abusif en comparaison d’autres opioïdes. Son efficacité en milieux de soins primaires en fait un outil thérapeutique utile pour les médecins de famille.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Descartes, M.; Longshore, J.W.; Crawford, E.

We report an infant with double trisomy 48,XXX,+18, who also displayed features of Roberts syndrome. All previously published cases with similar double trisomy have presented with features of trisomy 18 syndrome. The chromosome analysis done at birth revealed the double trisomy; parental chromosomes were normal. The proband presented with microbrachycephaly, unilateral cleft lip and palate, choanal atresia, midfacial capillary hemanioma, thin nares, shallow orbits, malformed ears, sparse hair, hypomelia of the upper limbs, rocker-bottom feet, auricular septal defect and agenesis of the corpus callosum. Characteristic features of Roberts syndrome included hypomelia, midfacial defects, and severe growth deficiency. Among the manymore » different features reported in the literature for patients with trisomy 18 syndrome, the most consistent were growth deficiency, clenched fingers and congenital heart defects (e.g. VSD, ASD, PDA). Although some of our patient`s features such as cleft lip and cleft palate, low-set malformed ears, ASD, defects of the corpus callosum, choanal atresia, radial aplasia could also be seen in trisomy 18 syndrome (in 10-50% of the cases), her phenotype was more typical of Roberts syndrome because of symmetrical hypomelia and midfacial defects. Our patient`s chromosomes did not show premature separation of centromeric heterochromatin, a feature reported to occur in approximately one-half of individuals with Roberts syndrome. Sporadic aneuploidy involving different chromosomes has been found in lymphocyte cultures from some Roberts syndrome patients and is considered by some authors as a mitotic mutant. This aneuploidy is most likely to be chromosome gain. The simultaneous occurrence of trisomy X and 18 is extremely rare with only 11 cases having been reported in the literature. Our patient is unique since she has the double trisomy in addition to the characteristic features of Roberts syndrome.« less

Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varekamp, A.E.; de Vries, A.J.; Zurcher, C.

1987-10-01

The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose ratemore » (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy.« less

Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population.

PubMed

Casey, Jillian P; McGettigan, Paul A; Healy, Fiona; Hogg, Claire; Reynolds, Alison; Kennedy, Breandan N; Ennis, Sean; Slattery, Dubhfeasa; Lynch, Sally A

2015-02-01

We present a study of five children from three unrelated Irish Traveller families presenting with primary ciliary dyskinesia (PCD). As previously characterized disorders in the Irish Traveller population are caused by common homozygous mutations, we hypothesised that all three PCD families shared the same recessive mutation. However, exome sequencing showed that there was no pathogenic homozygous mutation common to all families. This finding was supported by histology, which showed that each family has a different type of ciliary defect; transposition defect (family A), nude epithelium (family B) and absence of inner and outer dynein arms (family C). Therefore, each family was analysed independently using homozygosity mapping and exome sequencing. The affected siblings in family A share a novel 1 bp duplication in RSPH4A (NM_001161664.1:c.166dup; p.Arg56Profs*11), a radial-spoke head protein involved in ciliary movement. In family B, we identified three candidate genes (CCNO, KCNN3 and CDKN1C), with a 5-bp duplication in CCNO (NM_021147.3:c.258_262dup; p.Gln88Argfs*8) being the most likely cause of ciliary aplasia. This is the first study to implicate CCNO, a DNA repair gene reported to be involved in multiciliogenesis, in PCD. In family C, we identified a ∼3.5-kb deletion in DYX1C1, a neuronal migration gene previously associated with PCD. This is the first report of a disorder in the relatively small Irish Traveller population to be caused by >1 disease gene. Our study identified at least three different PCD genes in the Irish Traveller population, highlighting that one cannot always assume genetic homogeneity, even in small consanguineous populations.

Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation

PubMed Central

Gregory, L. C.; Humayun, K. N.; Turton, J. P. G.; McCabe, M. J.; Rhodes, S. J.

2015-01-01

Background: LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies. Objective/Hypothesis: To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients. Method: We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants. Results: We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype. Conclusion: We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life. PMID:25871839

Efficacy and safety of rituximab for systemic lupus erythematosus-associated immune cytopenias: A multicenter retrospective cohort study of 71 adults.

PubMed

Serris, Alexandra; Amoura, Zahir; Canouï-Poitrine, Florence; Terrier, Benjamin; Hachulla, Eric; Costedoat-Chalumeau, Nathalie; Papo, Thomas; Lambotte, Olivier; Saadoun, David; Hié, Miguel; Blanche, Philippe; Lioger, Bertrand; Gottenberg, Jacques-Eric; Godeau, Bertrand; Michel, Marc

2018-03-01

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias. © 2017 Wiley Periodicals, Inc.

Allopurinol might improve response to azathioprine and 6-mercaptopurine by correcting an unfavorable metabolite ratio.

PubMed

Gardiner, Sharon J; Gearry, Richard B; Burt, Michael J; Chalmers-Watson, Teresa; Chapman, Bruce A; Ross, Alison G; Stedman, Catherine A M; Huelsen, Alexander; Barclay, Murray L

2011-01-01

Allopurinol potentiates azathioprine and 6-mercaptopurine (6-MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6-TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response. Sixteen individuals were identified who were taking azathioprine or 6-MP, and were commenced on allopurinol to improve a high 6-MMPN:TGN ratio. Metabolite concentrations were compared before and after commencing allopurinol, and markers of disease control were compared. The addition of 100-300 mg allopurinol daily and thiopurine dose reduction (17-50% of the original dose) resulted in a reduction of the median (and range) 6-MMPN concentration, from 11,643 (3,365-27,832) to 221 (55-844) pmol/8×10(8) red blood cells (RBC; P=0.0005), increased 6-TGN from 162 (125-300) to 332 (135-923) pmol/8×10(8) RBC (P=0.0005), and reduced the 6-MMPN:6-TGN ratio from 63 (12-199) to 1 (0.1-4.5) (P=0.0005). There was a significant reduction in steroid dose requirements at 12 months (P=0.04) and trends for improvement in other markers of disease control. One patient developed red cell aplasia that resolved upon stopping azathioprine and allopurinol. In those with a high 6-MMPN:6-TGN ratio (>20), response to thiopurine treatment might be improved by the addition of allopurinol, together with a reduced thiopurine dose and close hematological monitoring. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review.

PubMed

Singh, Vijay K; Newman, Victoria L; Seed, Thomas M

2015-01-01

One of the greatest national security threats to the United States is the detonation of an improvised nuclear device or a radiological dispersal device in a heavily populated area. As such, this type of security threat is considered to be of relatively low risk, but one that would have an extraordinary high impact on health and well-being of the US citizenry. Psychological counseling and medical assessments would be necessary for all those significantly impacted by the nuclear/radiological event. Direct medical interventions would be necessary for all those individuals who had received substantial radiation exposures (e.g., >1 Gy). Although no drugs or products have yet been specifically approved by the United States Food and Drug Administration (US FDA) to treat the effects of acute radiation syndrome (ARS), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and pegylated G-CSF have been used off label for treating radiation accident victims. Recent threats of terrorist attacks using nuclear or radiologic devices makes it imperative that the medical community have up-to-date information and a clear understanding of treatment protocols using therapeutically effective recombinant growth factors and cytokines such as G-CSF and GM-CSF for patients exposed to injurious doses of ionizing radiation. Based on limited human studies with underlying biology, we see that the recombinants, G-CSF and GM-CSF appear to have modest, but significant medicinal value in treating radiation accident victims. In the near future, the US FDA may approve G-CSF and GM-CSF as ‘Emergency Use Authorization’ (EUA) for managing radiation-induced aplasia, an ARS-related pathology. In this article, we review the status of growth factors for the treatment of radiological/nuclear accident victims.

Medical management of the acute radiation syndrome.

PubMed

López, Mario; Martín, Margarita

2011-07-13

The acute radiation syndrome (ARS) occurs after whole-body or significant partial-body irradiation (typically at a dose of >1 Gy). ARS can involve the hematopoietic, cutaneous, gastrointestinal and the neurovascular organ systems either individually or in combination. There is a correlation between the severity of clinical signs and symptoms of ARS and radiation dose. Radiation induced multi-organ failure (MOF) describes the progressive dysfunction of two or more organ systems over time. Radiation combined injury (RCI) is defined as radiation injury combined with blunt or penetrating trauma, burns, blast, or infection. The classic syndromes are: hematopoietic (doses >2-3 Gy), gastrointestinal (doses 5-12 Gy) and cerebrovascular syndrome (doses 10-20 Gy). There is no possibility to survive after doses >10-12 Gy. The Phases of ARS are-prodromal: 0-2 days from exposure, latent: 2-20 days, and manifest illness: 21-60 days from exposure. Granulocyte-colony stimulating factor (G-CSF) at a dose of 5 μg/kg body weight per day subcutaneously has been recommended as treatment of neutropenia, and antibiotics, antiviral and antifungal agents for prevention or treatment of infections. If taken within the first hours of contamination, stable iodine in the form of nonradioactive potassium iodide (KI) saturates iodine binding sites within the thyroid and inhibits incorporation of radioiodines into the gland. Finally, if severe aplasia persists under cytokines for more than 14 days, the possibility of a hematopoietic stem cell (HSC) transplantation should be evaluated. This review will focus on the clinical aspects of the ARS, using the European triage system (METREPOL) to evaluate the severity of radiation injury, and scoring groups of patients for the general and specific management of the syndrome.

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells

PubMed Central

Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

2013-01-01

Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×106 cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective “off the shelf” therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia. PMID:23823334

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells.

PubMed

Gaberman, Elena; Pinzur, Lena; Levdansky, Lilia; Tsirlin, Maria; Netzer, Nir; Aberman, Zami; Gorodetsky, Raphael

2013-01-01

Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×10(6) cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective "off the shelf" therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia.

Sequential oral hydroxyurea and intravenous cytosine arabinoside in refractory childhood acute leukemia: a pediatric oncology group phase 1 study.

PubMed

Dubowy, Ronald; Graham, Michael; Hakami, Nasrollah; Kletzel, Morris; Mahoney, Donald; Newman, Edward; Ravindranath, Yaddanapudi; Camitta, Bruce

2008-05-01

At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.

Mutations in XLF/NHEJ1/Cernunnos gene results in downregulation of telomerase genes expression and telomere shortening.

PubMed

Carrillo, Jaime; Calvete, Oriol; Pintado-Berninches, Laura; Manguan-García, Cristina; Sevilla Navarro, Julian; Arias-Salgado, Elena G; Sastre, Leandro; Guenechea, Guillermo; López Granados, Eduardo; de Villartay, Jean-Pierre; Revy, Patrick; Benitez, Javier; Perona, Rosario

2017-05-15

NHEJ1-patients develop severe progressive lymphocytopenia and premature aging of hematopoietic stem cells (HSCs) at a young age. Here we show a patient with a homozygous-NHEJ1 mutation identified by whole exome-sequencing that developed severe pancytopenia and bone marrow aplasia correlating with the presence of short telomeres. The mutation resulted in a truncated protein. In an attempt to identify the mechanism behind the short telomere phenotype found in the NHEJ1-patient we downregulated NHEJ1 expression in 293T and CD34+cells. This downregulation resulted in reduced telomerase activity and decreased expression of several telomerase/shelterin genes. Interestingly, cell lines derived from two other NHEJ1-deficient patients with different mutations also showed increased p21 expression, inhibition in expression of several telomerase complex genes and shortened telomeres. Decrease in expression of telomerase/shelterin genes did not occur when we inhibited expression of other NHEJ genes mutated in SCID patients: DNA-PK, Artemis or LigaseIV. Because premature aging of HSCs is observed only in NHEJ1 patients, we propose that is the result of senescence induced by decreased expression of telomerase/shelterin genes that lead to an inhibition of telomerase activity. Previous reports failed to find this connection because of the use of patient´s cells immortalized by TERT expression or recombined telomeres by ALT pathway. In summary, defective regulation of telomere biology together with defective V(D)J recombination can negatively impact on the evolution of the disease in these patients. Identification of telomere shortening is important since it may open new therapeutic interventions for these patients by treatments aimed to recover the expression of telomerase genes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Meta-analysis and systematic review of the number of non-syndromic congenitally missing permanent teeth per affected individual and its influencing factors

PubMed Central

Rakhshan, Hamid

2016-01-01

Summary Background and purpose: Dental aplasia (or hypodontia) is a frequent and challenging anomaly and thus of interest to many dental fields. Although the number of missing teeth (NMT) in each person is a major clinical determinant of treatment need, there is no meta-analysis on this subject. Therefore, we aimed to investigate the relevant literature, including epidemiological studies and research on dental/orthodontic patients. Methods: Among 50 reports, the effects of ethnicities, regions, sample sizes/types, subjects’ minimum ages, journals’ scientific credit, publication year, and gender composition of samples on the number of missing permanent teeth (except the third molars) per person were statistically analysed (α = 0.05, 0.025, 0.01). Limitations: The inclusion of small studies and second-hand information might reduce the reliability. Nevertheless, these strategies increased the meta-sample size and favoured the generalisability. Moreover, data weighting was carried out to account for the effect of study sizes/precisions. Results: The NMT per affected person was 1.675 [95% confidence interval (CI) = 1.621–1.728], 1.987 (95% CI = 1.949–2.024), and 1.893 (95% CI = 1.864–1.923), in randomly selected subjects, dental/orthodontic patients, and both groups combined, respectively. The effects of ethnicities (P > 0.9), continents (P > 0.3), and time (adjusting for the population type, P = 0.7) were not significant. Dental/orthodontic patients exhibited a significantly greater NMT compared to randomly selected subjects (P < 0.012). Larger samples (P = 0.000) and enrolling younger individuals (P = 0.000) might inflate the observed NMT per person. Conclusions: Time, ethnic backgrounds, and continents seem unlikely influencing factors. Subjects younger than 13 years should be excluded. Larger samples should be investigated by more observers. PMID:25840586

The reliability and validity of qualitative scores for the Controlled Oral Word Association Test.

PubMed

Ross, Thomas P; Calhoun, Emily; Cox, Tara; Wenner, Carolyn; Kono, Whitney; Pleasant, Morgan

2007-05-01

The reliability and validity of two qualitative scoring systems for the Controlled Oral Word Association Test [Benton, A. L., Hamsher, de S. K., & Sivan, A. B. (1983). Multilingual aplasia examination (2nd ed.). Iowa City, IA: AJA Associates] were examined in 108 healthy young adults. The scoring systems developed by Troyer et al. [Troyer, A. K., Moscovich, M., & Winocur, G. (1997). Clustering and switching as two components of verbal fluency: Evidence from younger and older healthy adults. Neuropsychology, 11, 138-146] and by Abwender et al. [Abwender, D. A., Swan, J. G., Bowerman, J. T., & Connolly, S. W. (2001a). Qualitative analysis of verbal fluency output: Review and comparison of several scoring methods. Assessment, 8, 323-336] each demonstrated excellent interrater reliability (all indices at or above r(icc)=.9). Consistent with previous research [e.g., Ross, T. P. (2003). The reliability of cluster and switch scores for the COWAT. Archives of Clinical Psychology, 18, 153-164), test-retest reliability coefficients (N=53; M interval 44.6 days) for the qualitative scores were modest to poor (r(icc)=.6 to .4 range). Correlations among COWAT scores, measures of executive functioning, verbal learning, working memory, and vocabulary were examined. The idea that qualitative scores represent distinct executive functions such as cognitive flexibility or strategy utilization was not supported. We offer the interpretation that COWAT performance may require the ability to retrieve words in a non-routine manner while suppressing habitual responses and associated processing interference, presumably due to a spread of activation across semantic or lexical networks. This interpretation, though speculative at present, implies that clustering and switching on the COWAT may not be entirely deliberate, but rather an artifact of a passive (i.e., state-dependent) process. Ideas for future research, most noticeably experimental studies using cognitive methods (e.g., priming), are

[Diagnosis for human parvovirus B19-polyarthritis: usefulness of empty particle B19.ELISA and B19-DNA.PCR].

PubMed

Hatakeyama, Y; Ishii, K; Murai, C; Sugamura, K; Mitomo, N; Saitoh, T; Rikimaru, Y; Okazaki, T; Sasaki, T

1998-10-01

To evaluate the usefulness of new ELISA for human parvovirus B19 (B19) antibodies and PCR for the diagnosis of acute onset of B19 polyarthritis. We evaluated the reproducibility and sensitivity on the detection of anti-B19 antibody by ELISA using recombinant VP-1 and VP-2 (empty particle), and then studied for the prevalence of IgM and IgG B19 antibody in 125 samples for anti-B19 tests. The random study on anti-B19 antibody assay as well as PCR for B19-DNA was also performed in 130 cases with acute onset of arthritis excluding those with known origins, 224 with rheumatoid arthritis and 149 with other categories. The results by using B19-empty particle ELISA were reproducible and showed the assay was a sensitive way for clinical use. IgM anti-B19 antibodies were positive not only in all samples from erythema infectiosum, but also often in those from hemolytic anemia, pure red cell aplasia, fetal hydrops, hepatic injury, fever of unknown origin. Among 130 with acute onset of arthritis, 21 showed positive tests for IgM anti-B19 antibody and/or B19 DNA. On the other hand, 4 among 224 patients with rheumatoid arthritis were positive for IgM anti-B19 antibody, but all of 149 in control group were negative for IgM anti-B19 antibodies and for B19 DNA. Anti-B19 ELISA using B19-empty particle which has been introduced as a routine test system, is a useful tool for the diagnosis of acute onset of B19 arthritis. An additional examination using PCR for B19 DNA may contribute for understanding persistent B19 polyarthritis or reactivation of B19 infection.

Recurrent high level parvovirus B19/genotype 2 viremia in a renal transplant recipient analyzed by real-time PCR for simultaneous detection of genotypes 1 to 3.

PubMed

Liefeldt, Lutz; Plentz, Annelie; Klempa, Boris; Kershaw, Olivia; Endres, Anne-Sophie; Raab, Ulla; Neumayer, Hans-H; Meisel, Helga; Modrow, Susanne

2005-01-01

Organ transplant recipients infected with parvovirus B19 frequently develop persistent viremia associated with chronic anemia and pure red cell aplasia. In this study, a male renal transplant recipient who had been infected with parvovirus B19/genotype 2 after renal transplantation at the age of 34 years is described. The patient was repeatedly treated with high dose intravenous immunoglobulin (IVIG) that resulted in the resolvement of symptoms but not in virus eradication. During an observation period of 33 months after transplantation three phases associated with high parvovirus B19 viremia were observed. Both the first and the second viremic phases were combined with severe anemia. Parvovirus B19 specific IgM-antibodies were initially detected at the beginning of the second phase in continually rising concentrations. Initially eradication of the virus by immunoglobulin therapy was reported after the first viremic phase [Liefeldt et al. (2002): Nephrol Dial Transplant 17:1840-1842]. Retrospectively this statement has to be corrected. It was based on the use of a qualitative PCR assay specific for parvovirus B19 genotype 1 associated with reduced sensitivity for detection of genotype 2. After sequence analysis of the viral DNA and adjustment of a real-time PCR assay (TaqMan) for quantitative detection of all three B19 virus genotypes analysis of consecutive serum samples allowed the demonstration of long lasting phases with reduced viral loads following IVIG-treatment. These results demonstrate that IVIG treatment of parvovirus B19-triggered anemia in transplant recipients offers an opportunity to resolve symptoms, but does not guarantee eradication of the virus. Since reactivation of parvovirus B19 infection can result in high virus load associated with the recurrence of symptoms repeated screening for viral DNA is recommended using the TaqMan system established for quantitative detection of all three genotypes of parvovirus B19. Copyright 2005 Wiley-Liss, Inc.

Endothelin-A-receptor antagonism with atrasentan exhibits limited activity on the KU-19-19 bladder cancer cell line in a mouse model.

PubMed

Herrmann, Edwin; Tiemann, Arne; Eltze, Elke; Bolenz, Christian; Bremer, Christoph; Persigehl, Thorsten; Hertle, Lothar; Wülfing, Christian

2009-10-01

The endothelin axis consists of endothelin-1 (ET-1) and its two receptors, ET(A)- and ET(B)-receptor (ET(A)-R and ET(B)-R). In several tumor entities, the ET(A)-R plays a significant role as a drug target. In our study, we investigated whether inhibition of ET(A)-R with atrasentan leads to an antitumor effect in urinary bladder carcinoma as well. Twenty nude mice with thymic aplasia were subcutaneously administered 2 x 10(6) KU-19-19 bladder cancer cells in the right flank. Starting on the 22nd day after the injection, ten animals were treated with atrasentan (2.5 mg/kg BW intraperitoneally), and another ten animals were treated with placebo. During treatment, absolute tumor growth and relative growth rate over time were determined. After the end of treatment, the mitosis and necrosis rates, microvessel density, and receptor density in the tumor tissue were analyzed by immunohistochemistry. In addition, the expression intensities of ET-1, ET(A)-R, and ET(B)-R were evaluated semiquantitatively and compared between the groups. No significant differences between the active-treatment and placebo groups were detected, either with respect to absolute tumor growth (P = 0.333) or mitosis rate (P = 0.217). In the analysis of the necrosis rate and receptor density for ET(A)-R, a trend toward higher values in the active-treatment group (mean necrosis rate = 63.67%, receptor density: 1.417) than in the placebo group (mean necrosis rate = 46.25%, receptor density: 1.270) was found; however, neither difference was statistically significant (P = 0.08 and 0.219, respectively). ET(A)-R blockade with atrasentan in a bladder cancer xenograft model shows no significant antitumor effect.

Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic hemochromatosis and in inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fillet, G.; Beguin, Y.; Baldelli, L.

1989-08-01

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated frommore » the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.« less

Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for Hereditary Junctional Epidermolysis Bullosa in Sheep

PubMed Central

Suárez-Vega, Aroa; Gutiérrez-Gil, Beatriz; Benavides, Julio; Perez, Valentín; Tosser-Klopp, Gwenola; Klopp, Christophe; Keennel, Stephen J.; Arranz, Juan José

2015-01-01

In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mutation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genodermatosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa (JEB) has been detected in two commercial flocks. The JEB locus was mapped to Ovis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein. A functional analysis of this deletion revealed decreased levels of mRNA in JEB skin samples and the absence of integrin β4 labeling in immunohistochemical assays. Genotyping of c.4412_4415del showed perfect concordance with the recessive mode of the disease phenotype. Selection against this causal mutation will now be used to solve the problem of JEB in flocks of Churra sheep. Furthermore, the identification of the ITGB4 mutation means that affected sheep can be used as a large mammal animal model for the human form of epidermolysis bullosa with aplasia cutis. Our approach evidences that RNA-seq offers cost-effective alternative to identify variants in the species in which high resolution exome-sequencing is not straightforward. PMID:25955497

Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia

PubMed Central

Barrett, David; Aplenc, Richard; Porter, David L.; Rheingold, Susan R.; Teachey, David T.; Chew, Anne; Hauck, Bernd; Wright, J. Fraser; Milone, Michael C.; Levine, Bruce L.; June, Carl H.

2014-01-01

Summary Chimeric antigen receptor–modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre–B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×106 to 1.2×107 CTL019 cells per kilogram of body weight. In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce anti-leukemic efficacy. Complete remission was observed in both patients and is ongoing in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen receptor–modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL. PMID:23527958

A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.

PubMed

Bluteau, Olivier; Sebert, Marie; Leblanc, Thierry; Peffault de Latour, Régis; Quentin, Samuel; Lainey, Elodie; Hernandez, Lucie; Dalle, Jean-Hugues; Sicre de Fontbrune, Flore; Lengline, Etienne; Itzykson, Raphael; Clappier, Emmanuelle; Boissel, Nicolas; Vasquez, Nadia; Da Costa, Mélanie; Masliah-Planchon, Julien; Cuccuini, Wendy; Raimbault, Anna; De Jaegere, Louis; Adès, Lionel; Fenaux, Pierre; Maury, Sébastien; Schmitt, Claudine; Muller, Marc; Domenech, Carine; Blin, Nicolas; Bruno, Bénédicte; Pellier, Isabelle; Hunault, Mathilde; Blanche, Stéphane; Petit, Arnaud; Leverger, Guy; Michel, Gérard; Bertrand, Yves; Baruchel, André; Socié, Gérard; Soulier, Jean

2018-02-15

Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders ( GATA2 , RUNX1 ), telomeropathies ( TERC , TERT , RTEL1 ), ribosome disorders ( SBDS , DNAJC21 , RPL5 ), and DNA repair deficiency ( LIG4 ). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling. © 2018 by The American Society of Hematology.

Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

PubMed Central

Martinel Lamas, Diego J.; Carabajal, Eliana; Prestifilippo, Juan P.; Rossi, Luis; Elverdin, Juan C.; Merani, Susana; Bergoc, Rosa M.; Rivera, Elena S.; Medina, Vanina A.

2013-01-01

Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy. PMID:23922686

ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary vitreous

PubMed Central

Prasov, Lev; Masud, Tehmina; Khaliq, Shagufta; Mehdi, S. Qasim; Abid, Aiysha; Oliver, Edward R.; Silva, Eduardo D.; Lewanda, Amy; Brodsky, Michael C.; Borchert, Mark; Kelberman, Daniel; Sowden, Jane C.; Dattani, Mehul T.; Glaser, Tom

2012-01-01

The vertebrate basic helix–loop–helix (bHLH) transcription factor ATOH7 (Math5) is specifically expressed in the embryonic neural retina and is required for the genesis of retinal ganglion cells (RGCs) and optic nerves. In Atoh7 mutant mice, the absence of trophic factors secreted by RGCs prevents the development of the intrinsic retinal vasculature and the regression of fetal blood vessels, causing persistent hyperplasia of the primary vitreous (PHPV). We therefore screened patients with hereditary PHPV, as well as bilateral optic nerve aplasia (ONA) or hypoplasia (ONH), for mutations in ATOH7. We identified a homozygous ATOH7 mutation (N46H) in a large family with an autosomal recessive PHPV disease trait linked to 10q21, and a heterozygous variant (R65G, p.Arg65Gly) in one of five sporadic ONA patients. High-density single-nucleotide polymorphism analysis also revealed a CNTN4 duplication and an OTX2 deletion in the ONA cohort. Functional analysis of ATOH7 bHLH domain substitutions, by electrophoretic mobility shift and luciferase cotransfection assays, revealed that the N46H variant cannot bind DNA or activate transcription, consistent with structural modeling. The N46H variant also failed to rescue RGC development in mouse Atoh7−/− retinal explants. The R65G variant retains all of these activities, similar to wild-type human ATOH7. Our results strongly suggest that autosomal recessive persistent hyperplastic primary vitreous is caused by N46H and is etiologically related to nonsyndromic congenital retinal nonattachment. The R65G allele, however, cannot explain the ONA phenotype. Our study firmly establishes ATOH7 as a retinal disease gene and provides a functional basis to analyze new coding variants. PMID:22645276

Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.

PubMed

Grupp, Stephan A; Kalos, Michael; Barrett, David; Aplenc, Richard; Porter, David L; Rheingold, Susan R; Teachey, David T; Chew, Anne; Hauck, Bernd; Wright, J Fraser; Milone, Michael C; Levine, Bruce L; June, Carl H

2013-04-18

Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre-B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10(6) to 1.2×10(7) CTL019 cells per kilogram of body weight. In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce antileukemic efficacy. Complete remission was observed in both patients and is ongoing in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen receptor-modified T cells are capable of killing even aggressive, treatment-refractory acute leukemia cells in vivo. The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL.

Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for Hereditary Junctional Epidermolysis Bullosa in Sheep.

PubMed

Suárez-Vega, Aroa; Gutiérrez-Gil, Beatriz; Benavides, Julio; Perez, Valentín; Tosser-Klopp, Gwenola; Klopp, Christophe; Keennel, Stephen J; Arranz, Juan José

2015-01-01

In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mutation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genodermatosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa (JEB) has been detected in two commercial flocks. The JEB locus was mapped to Ovis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin β4 protein. A functional analysis of this deletion revealed decreased levels of mRNA in JEB skin samples and the absence of integrin β4 labeling in immunohistochemical assays. Genotyping of c.4412_4415del showed perfect concordance with the recessive mode of the disease phenotype. Selection against this causal mutation will now be used to solve the problem of JEB in flocks of Churra sheep. Furthermore, the identification of the ITGB4 mutation means that affected sheep can be used as a large mammal animal model for the human form of epidermolysis bullosa with aplasia cutis. Our approach evidences that RNA-seq offers cost-effective alternative to identify variants in the species in which high resolution exome-sequencing is not straightforward.

Military Command Team Effectiveness: Model and Instrument for Assessment and Improvement (L’efficacite des Equipes de Commandement Militaires: un Modele et un Instrument Pour L’evaluation et L’amelioration)

DTIC Science & Technology

2005-04-01

influence team performance (e.g., Gender , race, age) (Morgan and Lassiter, 1992). • Leadership – the deliberate attempt to influence team outcomes...members of an organisation to be subject to an implicit socialisation process that brings members’ belief structures, values and goals into line with...Bowers, 1999). • Mix of Demographic Characteristics (e.g., age, gender , ethnicity, and culture). Whether more homogeneity or more heterogeneity is

Mesure Objective De L'attenuation et De L'effet D'occlusion Des Protecteurs Auditifs a Partir Des Potentiels Evoques Stationnaires et Multiples =

NASA Astrophysics Data System (ADS)

Valentin, Olivier

mesurer objectivement l'attenuation des protecteurs auditifs : les resultats obtenus a 500 Hz et 1 kHz demontrent que l'attenuation mesuree a partir des PEASM est relativement equivalente a l'attenuation calculee par la methode REAT, ce qui est en accord avec ce qui etait attendu puisque l'effet de masquage induit par le bruit physiologique aux basses frequences est relativement negligeable a ces frequences. Les resultats du protocole 2 demontrent que les PEASM peuvent etre egalement utilises pour mesurer objectivement l'effet d'occlusion induit par le port de protecteurs auditifs : l'effet d'occlusion mesure a partir des PEASM a 500 Hz est plus eleve que celui calcule par l'intermediaire de la methode subjective au seuil de l'audition, ce qui est en accord avec ce qui etait attendu puisqu'en dessous d'1 kHz, l'effet de masquage induit par le bruit physiologique aux basses frequences est source de biais pour les resultats obtenus par la methode subjective car il y a surestimation des seuils de l'audition en basse frequence lors du port de protecteurs auditifs. Toutefois, les resultats obtenus a 250 Hz sont en contradiction avec les resultats attendus. D'un point de vue scientifique, ce travail de these a permis de realiser deux nouvelles methodes innovantes pour mesurer objectivement l'attenuation et l'effet d'occlusion des protecteurs auditifs intra-auriculaires par electroencephalographie. D'un point de vue sante et securite au travail, les avancees presentees dans cette these pourraient aider a concevoir des protecteurs auditifs plus performants. En effet, si ces deux nouvelles methodes objectives etaient normalisees pour caracteriser les protecteurs auditifs intra-auriculaires, elles pourraient permettre : (i) de mieux apprehender l'efficacite reelle de la protection auditive et (ii) de fournir une mesure de l'inconfort induit par l'occlusion du canal auditif lors du port de protecteurs. Fournir un protecteur auditif dont l'efficacite reelle est adaptee a l

Mise à jour sur le nouveau vaccin 9-valent pour la prévention du virus du papillome humain

PubMed Central

Yang, David Yi; Bracken, Keyna

2016-01-01

Résumé Objectif Informer les médecins de famille quant à l’efficacité, à l’innocuité, aux effets sur la santé publique et à la rentabilité du vaccin 9-valent contre le virus du papillome humain (VPH). Qualité des données Des articles pertinents publiés dans PubMed jusqu’en mai 2015 ont été examinés et analysés. La plupart des données citées sont de niveau I (essais randomisés et contrôlés et méta-analyses) ou de niveau II (études transversales, cas-témoins et épidémiologiques). Des rapports et recommandations du gouvernement sont aussi cités en référence. Message principal Le vaccin 9-valent contre le VPH, qui offre une protection contre les types 6, 11, 16, 18, 31, 33, 45, 52 et 58 du VPH, est sûr et efficace et réduira encore plus l’incidence des infections à VPH, de même que les cas de cancer lié au VPH. Il peut également protéger indirectement les personnes non immunisées par l’entremise du phénomène d’immunité collective. Un programme d’immunisation efficace peut prévenir la plupart des cancers du col de l’utérus. Les analyses montrent que la rentabilité du vaccin 9-valent chez les femmes est comparable à celle du vaccin quadrivalent original contre le VPH (qui protège contre les types 6, 11, 16 et 18 du VPH) en usage à l’heure actuelle. Toutefois, il faut investiguer plus en profondeur l’utilité d’immuniser les garçons avec le vaccin 9-valent contre le VPH. Conclusion en plus d’être sûr, le vaccin 9-valent protège mieux contre le VPH que le vaccin quadrivalent. Une analyse coûtefficacité en favorise l’emploi, du moins chez les adolescentes. Ainsi, les médecins devraient recommander le vaccin 9-valent à leurs patients plutôt que le vaccin quadrivalent contre le VPH.

Matériaux pour la dépollution des gaz d'échappement automobile

NASA Astrophysics Data System (ADS)

Mouaddib-Moral, N.; Gauthier, C.

2002-04-01

Les premières législations antipollution ont été mises en place suite à la détection, aux Etats Unis plus particulièrement en Californie, du smog photochimique et des pluies acides, néfastes pour la faune et la flore. Les estimations de la contribution de l'automobile aux émissions de composés, considérés comme précurseurs de ces phénomènes, ont été suffisantes pour provoquer la mise en place de normes draconiennes en matière d'émissions automobiles. Les matériaux catalytiques ont été évalués en tant que solution possible pour réduire les émissions à l'échappement. En Europe, l'utilisation des catalyseurs trois voies a été généralisée sur les véhicules essence fonctionnant à richesse stoechiométrique à partir de 1993. Une nouvelle génération de catalyseurs appelée piège à oxydes d'azote (NOx) est maintenant nécessaire pour le post-traitement des gaz d'échappement des motorisations à essence fonctionnant en mélange pauvre (combustion en présence d'un excès d'oxygène) pour diminuer la consommation et par conséquent réduire les émissions du CO2 connu pour son impact sur l'effet de serre. La dépollution des moteurs diesel via un catalyseur d'oxydation a été généralisée en Europe depuis 1996. La sévérisation des normes européennes impose pour les moteurs diesel le recours à des matériaux spécifiques pour le traitement des oxydes d'azotes et des particules par l'intermédiaire de filtres à particules dont l'efficacité de filtration est supérieure à 95%, mais doivent subir des régénérations périodiques.

Étude des déterminants individuels de l’adoption du dossier de santé électronique du Québec

PubMed Central

Mezni, H; M-P, Gagnon; Duplantie, J

2016-01-01

Résumé Objectif Selon des études précédentes, les dossiers de santé électroniques peuvent améliorer l’efficacité, la sécurité et la qualité de la prise en charge médicale. Cependant, les prestataires de soins restent réticents quant à son utilisation, ce qui limite son impact sur le système de santé. La présente étude avait pour objectif d’évaluer les perceptions des médecins face au dossier de santé du Québec. Méthodes À partir d’une revue de la littérature sur les facteurs influençant l’adoption des nouvelles technologies de l’information et des communications (NTIC) en général et de la cybersanté en particulier, nous avons élaboré un questionnaire semi-structuré. Au total, 12 médecins utilisateurs potentiels du dossier de santé du Québec (DSQ) ont complété et retourné le questionnaire. Par la suite, nous avons opéré une analyse thématique de contenu, suivie par une théorisation des concepts obtenus. Résultats L’intention d’adopter le DSQ est influencée positivement par l’utilité perçue, la facilité d’utilisation perçue, la démonstrabilité des résultats, la compatibilité du système avec la pratique et l’autoefficacité informatique perçue par les médecins. Inversement, la résistance au changement influence négativement l’adoption du DSQ par les médecins. Conclusion L’identification des déterminants de l’adoption du dossier de santé du Québec est cruciale pour les responsables du secteur de la santé au Québec. Il sera ainsi possible de saisir les attentes des utilisateurs potentiels et d’ajuster les stratégies d’implantation en vue de favoriser une meilleure intégration de cette technologie dans les pratiques médicales. PMID:27867453

Evaluation du niveau de connaissance des patients sur la gestion du traitement par les antis vitamines K dans le service de cardiologie de Ouagadougou

PubMed Central

Samadoulougou, André; Temoua Naibe, Dangwé; Mandi, Germain; Yameogo, Relwendé Aristide; Kabore, Elisé; Millogo, Georges; Yameogo, Nobila Valentin; Kologo, Jonas Koudougou; Thiam/Tall, Anna; Toguyeni, Boubacar Jean Yves; Zabsonre, Patrice

2014-01-01

Introduction Les antivitamines K (AVK), traitement anticoagulant oral le plus largement prescrit, posent un réel problème de santé publique du fait de leur risque iatrogène. L'objectif de cette étude était de préciser le niveau de connaissance des patients sur la gestion de leur traitement par les AVK. Méthodes Il s'est agi d'une enquête transversale descriptive réalisée au CHU-Yalgado Ouédraogo, sur une période de 03 mois : du 1er mars au 31 mai 2012. Un questionnaire a été administré aux patients bénéficiant d'un traitement AVK depuis au moins un mois. Résultats Soixante-dix patients ont été inclus dans l'étude dont 30 hommes. L'âge moyen était de 49 ans ± 16 ans. Les cardiopathies et la maladie thromboembolique veineuse justifiant l'institution du traitement AVK étaient retrouvées respectivement dans 58,6% et 41,4% des cas. Le nom de l'AVK et la raison exacte du traitement étaient connus respectivement dans 91,4% et 67,1% des cas. Plus de la moitié des patients (68,6%) savaient que les AVK rendaient le sang plus fluide. Quarante-six patients (65,7%) citaient l'INR comme examen biologique de surveillance du traitement et seulement 28 patients (40%) connaissaient les valeurs cibles. La majorité des patients ne connaissait pas les risques encourus en cas de surdosage (72,8%) et de sous-dosage (71,4%). Une automédication par anti-inflammatoire non stéroïdien était signalée par 18 patients (25,7%). Les choux (74,3%) et la laitue (62,9%), aliments à consommer avec modération, étaient les plus cités. Conclusion Les connaissances des patients sur la gestion des AVK étaient fragmentaires et insuffisantes pour assurer la sécurité et l'efficacité du traitement. La création d'un programme d'éducation thérapeutique sur les AVK s'avère alors nécessaire. PMID:25870741

Analyse des interactions energetiques entre un arena et son systeme de refrigeration

NASA Astrophysics Data System (ADS)

Seghouani, Lotfi

le systeme de ventilation de l'arena a ete mis en evidence. Mots cles. Arena, Systeme de refrigeration, Consommation d'energie, Efficacite energetique, Conduction au sol, Performance annuelle.

Immune reconstitution in patients with Fanconi anemia after allogeneic bone marrow transplantation.

PubMed

Perlingeiro Beltrame, Miriam; Malvezzi, Mariester; Bonfim, Carmem; Covas, Dimas Tadeu; Orfao, Alberto; Pasquini, Ricardo

2014-07-01

Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions, including hematopoietic stem cell transplantation (HSCT). Successful BM transplantation (BMT) requires reconstitution of normal immunity. In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and natural killer (NK) lymphocytes in 23 patients with Fanconi anemia before and after BMT on days +30, +60, +100, +180, +270 and +360. In parallel, we evaluated the effect of related versus unrelated donor marrow as well as the presence of graft-versus-host disease (GVHD). After transplantation, we found different kinetics of recovery for the distinct major subsets of lymphocytes. NK cells were the first to recover, followed by cytotoxic CD8(+) T cells and B cells, and finally CD4(+) helper T cells. Early lymphocyte recovery was at the expense of memory cells, potentially derived from the graft, whereas recent thymic emigrant (CD31(+) CD45RA(+)) and naive CD4(+) or CD8(+) T cells rose only at 6 months after HSCT, in the presence of immunosuppressive GVHD prophylactic agents. Only slight differences were observed in the early recovery of cytotoxic CD8(+) T cells among those cases receiving a graft from a related donor versus an unrelated donor. Patients with GVHD displayed a markedly delayed recovery of NK cells and B cells as well as of regulatory T cells and both early thymic emigrant and total CD4(+) T cells. Our results support the utility of post-transplant monitoring of a peripheral blood lymphocyte subset for improved follow-up of patients with Fanconi anemia undergoing BMT. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The approval process for biosimilar erythropoiesis-stimulating agents.

PubMed

Wish, Jay B

2014-09-05

A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well. Copyright �

C7 vertebra homeotic transformation in domestic dogs - are Pug dogs breaking mammalian evolutionary constraints?

PubMed

Brocal, J; De Decker, S; José-López, R; Manzanilla, E G; Penderis, J; Stalin, C; Bertram, S; Schoenebeck, J J; Rusbridge, C; Fitzpatrick, N; Gutierrez-Quintana, R

2018-05-14

The number of cervical vertebrae in mammals is almost constant at seven, regardless of their neck length, implying that there is selection against variation in this number. Homebox (Hox) genes are involved in this evolutionary mammalian conservation, and homeotic transformation of cervical into thoracic vertebrae (cervical ribs) is a common phenotypic abnormality when Hox gene expression is altered. This relatively benign phenotypic change can be associated with fatal traits in humans. Mutations in genes upstream of Hox, inbreeding and stressors during organogenesis can also cause cervical ribs. The aim of this study was to describe the prevalence of cervical ribs in a large group of domestic dogs of different breeds, and explore a possible relation with other congenital vertebral malformations (CVMs) in the breed with the highest prevalence of cervical ribs. By phenotyping we hoped to give clues as to the underlying genetic causes. Twenty computed tomography studies from at least two breeds belonging to each of the nine groups recognized by the Federation Cynologique Internationale, including all the brachycephalic 'screw-tailed' breeds that are known to be overrepresented for CVMs, were reviewed. The Pug dog was more affected by cervical ribs than any other breed (46%; P < 0.001), and was selected for further analysis. No association was found between the presence of cervical ribs and vertebral body formation defect, bifid spinous process, caudal articular process hypoplasia/aplasia and an abnormal sacrum, which may infer they have a different aetiopathogenesis. However, Pug dogs with cervical ribs were more likely to have a transitional thoraco-lumbar vertebra (P = 0.041) and a pre-sacral vertebral count of 26 (P < 0.001). Higher C7/T1 dorsal spinous processes ratios were associated with the presence of cervical ribs (P < 0.001), supporting this is a true homeotic transformation. Relaxation of the stabilizing selection has likely occurred, and

Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist

PubMed Central

Levine, Bruce L.

2016-01-01

The field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)-modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T-cell signaling and costimulatory domains that can be used to reprogram a patient’s T cells to specifically target tumor cells. CAR T-cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T-cell therapy-associated toxicities, including cytokine release syndrome, macrophage activation syndrome, and tumor lysis syndrome, have been observed and effectively managed in the clinic. In patients with significant clinical responses, sustained B-cell aplasia has also been observed and is a marker of CAR T-cell persistence that might provide long-term disease control. Education on CAR T-cell therapy efficacy and safety management is critical for clinicians and patients who are considering this novel type of treatment. In the present report, the current landscape of CAR T-cell therapy, the effective management of patients undergoing treatment, and which patients are the most suitable candidates for current trials are discussed. Implications for Practice: The present report describes the current status of chimeric antigen receptor (CAR) T lymphocytes as an immunotherapy for patients with relapsed or refractory B-cell malignancies. CAR T cells targeting CD19, a protein expressed on many B-cell malignancies, typically induce high complete response rates in patients with B-cell leukemia or lymphoma who have very limited therapeutic options. Recent clinical trial results of CD19 CAR T-cell therapies and the management of CAR T-cell-associated adverse events are discussed. The present

Gestion de la douleur chronique par les infirmières des Groupes de médecine de famille

PubMed Central

Bergeron, Dave A; Bourgault, Patricia; Gallagher, Frances

2015-01-01

INTRODUCTION : Des milliers de personnes souffrent actuellement de douleur chronique (DC) pour laquelle la prise en charge s’avère souvent inadéquate. Au Québec, les infirmières qui oeuvrent dans les Groupes de médecine de famille (GMF) jouent un rôle clé dans le suivi des personnes aux prises avec des problèmes de santé chroniques dont la DC. OBJECTIFS : Cette étude a pour objectifs de décrire les activités réalisées par les infirmières œuvrant en GMF en lien avec la gestion de la douleur chez la clientèle souffrant de DC, ainsi que les barrières à ces activités. MÉTHODE : Un dispositif descriptif corrélationnel transversal de type enquête postale a été utilisé. La population accessible à l’étude comprend les infirmières qui figurent sur la liste des membres de l’Ordre des infirmières et infirmiers du Québec travaillant en GMF. L’ensemble des infirmières figurant sur cette liste ayant consenti à être contactées à leur domicile pour des fins de recherche ont été contactées. Un questionnaire postal auto-administré (Pain Management Activities Questionnaire) a été complété par 53 infirmières travaillant en GMF. RÉSULTATS : Les trois activités le plus souvent réalisées par les infirmières sont d’établir une relation thérapeutique avec le client; de discuter avec le médecin de l’efficacité des mesures thérapeutiques et de faire un enseignement personnalisé au client. Les infirmières ont la perception qu’elles rencontrent en moyenne 2,68 personnes par semaine qui souffrent de DC. La méconnaissance des interventions possibles en douleur (71,7%) et la non-disponibilité de l’information sur la gestion de la douleur (52,8%) constituent les principales barrières selon les infirmières sondées. CONCLUSION : Les infirmières au sein des GMF font actuellement peu d’activités en gestion de la DC probablement en raison du manque de reconnaissance de la DC. PMID:25848847

La stimulation magnétique transcrânienne (SMT) dans la recherche fondamentale et clinique en neuroscience

PubMed Central

Valero-Cabré, Antoni; Pascual-Leone, Alvaro; Coubard, Olivier A.

2011-01-01

Introduction Les méthodes de stimulation cérébrale non invasives telles que la Stimulation Magnétique Transcrânienne (SMT) sont largement utilisées pour établir des inférences causales sur les relations entre cerveau et comportement. Des applications cliniques basées sur la SMT ont également été développées pour traiter des affections neurologiques ou psychiatriques comme la dépression, la dystonie, la douleur, les acouphènes ou les séquelles d’accident vasculaire cérébral. État des connaissances La SMT fonctionne en induisant de manière non invasive et de manière focale des courants électriques dans des régions corticales, modulant ainsi leur niveau d’activité de façon variable suivant la fréquence, le nombre d’impulsions, les intervalles et la durée de stimulation utilisés. S’agissant du cortex moteur, on sait par exemple que les patterns d’impulsions de SMT à basse fréquence ou ceux délivrées de manière continue tendent à déprimer l’activité locale, tandis que la SMT à haute fréquence et discontinus tend à la potentialiser. Outre ses effets locaux, la SMT peut aussi avoir des effets à distance sur les régions cérébrales, véhiculés par les connections anatomiques et qui dépendent de l’efficacité et du signe de ces connexions. Perspectives Dans le domaine de la recherche fondamentale et des applications thérapeutiques, l’utilisation efficace de la SMT requiert, cependant, la compréhension approfondie de ses principes opérationnels, de ses risques, de ses potentialités et de ses limites. Dans cet article, nous présentons les principes par lesquels opèrent les méthodes de stimulation cérébrale non invasive, et en particulier la SMT. Conclusion À l’issue de sa lecture, le lecteur sera en mesure de discuter de façon critique les études scientifiques et cliniques utilisant la SMT, ainsi que de concevoir des applications SMT suivant une hypothèse a priori dans le domaine de la recherche en

L'observance thérapeutique dans les dermatoses chroniques: à propos de 200 cas

PubMed Central

Amraoui, Nissrine; Gallouj, Salim; Berraho, Mohamed Amine; Najjari, Chakib; Mernissi, Fatima zohra

2015-01-01

Introduction L'observance thérapeutique est la capacité à prendre correctement son traitement, tel qu'il est prescrit par le médecin. Elle est peu étudiée en dermatologie. Méthodes Le but de notre étude est d’évaluer l'observance chez les patients suivis au service de dermatologie du Centre Hospitalier Universitaire Hassan II de Fès pour une dermatose chronique et de rechercher les facteurs liés à une mauvaise observance à travers une étude incluant 200 patients suivis depuis au moins 6 mois. L’évaluation de l'observance s'est faite essentiellement à l'aide d'un entretien et les facteurs liés à l'observance ont été recherchés par un questionnaire. Résultats 68% de nos patients étaient observant, la mauvaise observance était associée à un niveau socio économique et d’étude bas, à une vie solitaire, à une durée de suivi longue, aux effets secondaires et au coût élevé des traitements, à l'absence d'efficacité, à une faible visibilité des lésions, à une ordonnance complexe, à une explication faible de la maladie, et à des difficultés d'accès à la consultation. Le taux d'observance retrouvé dans notre étude est un taux satisfaisant selon les données de la littérature, notre étude a confirmée certaines facteurs connues et a mis le point sur d'autres facteurs peu étudiés tel un traitement traditionnel associé, la part de chaque forme de traitement dans le respect de l'ordonnance, les dermatoses les plus touchées par les difficulté d'observance a savoir les dermatoses bulleuses et le psoriasis, et l'intérêt du pharmacien. Conclusion Cette analyse de la fréquence de ce phénomène et des facteurs essentiels qui l'influencent permet de cibler la prise en charge à travers une personnalisation de l'entretien médical, une adaptation du suivi au contexte de nos patients et à la nature de notre institution de santé. PMID:26848363

Revetements antireflet-passivation a base de nitrure de silicium PECVD pour cellules solaires triple-jonction III-V/ Ge

NASA Astrophysics Data System (ADS)

Homier, Ram

Dans le contexte environnemental actuel, le photovoltaïque bénéficie de l'augmentation des efforts de recherche dans le domaine des énergies renouvelables. Pour réduire le coût de la production d'électricité par conversion directe de l'énergie lumineuse en électricité, le photovoltaïque concentré est intéressant. Le principe est de concentrer une grande quantité d'énergie lumineuse sur des petites surfaces de cellules solaires multi-jonction à haute efficacité. Lors de la fabrication d'une cellule solaire, il est essentiel d'inclure une méthode pour réduire la réflexion de la lumière à la surface du dispositif. Le design d'un revêtement antireflet (ARC) pour cellules solaires multi-jonction présente des défis à cause de la large bande d'absorption et du besoin d'égaliser le courant produit par chaque sous-cellule. Le nitrure de silicium déposé par PECVD en utilisant des conditions standards est largement utilisé dans l'industrie des cellules solaires à base de silicium. Cependant, ce diélectrique présente de l'absorption dans la plage des courtes longueurs d'onde. Nous proposons l'utilisation du nitrure de silicium déposé par PECVD basse fréquence (LFSiN) optimisé pour avoir un haut indice de réfraction et une faible absorption optique pour l'ARC pour cellules solaires triple-jonction III-V/Ge. Ce matériau peut aussi servir de couche de passivation/encapsulation. Les simulations montrent que l'ARC double couche SiO2/LFSiN peut être très efficace pour réduire les pertes par réflexion dans la plage de longueurs d'onde de la sous-cellule limitante autant pour des cellules solaires triple-jonction limitées par la sous-cellule du haut que pour celles limitées par la sous-cellule du milieu. Nous démontrons aussi que la performance de la structure est robuste par rapport aux fluctuations des paramètres des couches PECVD (épaisseurs, indice de réfraction). Mots-clés : Photovoltaïque concentré (CPV), cellules solaires

The role of HRCT and three-dimensional VR CT findings in patients of congenital atresia combined with microtia.

PubMed

Gao, Ruzhen; Wang, Yun; Fan, Yue; Ai, Xing; Zhang, Xiaona; Xue, Huadan; Chen, Xiaowei; Jin, Zhengyu

2012-12-01

To determine the anatomic differences in patients of atresia by using high-resolution computed tomography (HRCT) and 3D volume rendered (VR) CT. High-resolution computed tomography (HRCT) was performed in 43 atresia patients including 34 unilateral atresia patients (n=34, 26 males, 8 females, mean age 13.82 years, range 8-19 years) and 9 bilateral atresia patients (6 males, 3 females, mean age 13.2 years, range 9-19 years). HRCT and 3D VR findings were compared with those in 43 normal ears of the unilateral atresia patients with normal PTA results (n=34, 26 males, 8 females, mean age 13.82 years, range 8-19 years) and 11 patients with sensorineural hearing loss but with no associated aplasia of the middle and inner ear (n=22, 7 males and 4 females, range 8-20.8 years, median age of 13.4 years) by using the independent one sample T test. On the HRCT images, the angle between the basic line and the tympanic segment of the facial nerve is more acute. And the area of the malleus-incus-joint or the malleus-incus-complex in the diseased ears is smaller than that in the control subjects (P<0.05). The tympanic segment is shorter and the area of the tympanic cavity is smaller in the atresia group, while the diameter of the oval window is also smaller in atresia group than that in the control group (P<0.05). The morphologic differences of the small ossicles and the entire length of the tympanic and mastoid segments can be depicted on a single 3D VR CT image. The facial nerve demonstrates abnormal lateral and anterior displacement in the CAA patients and the area of the Malleus-incus-joint and the tympanic cavity are significantly smaller, and the oval window is much narrower in the control group. HRCT and 3D VR CT provide valuable information about preoperative planning of patients with CAA. Measurements of all the angles and length serve as useful adjunct measurements in determining surgical candidacy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome.

PubMed

Raziel, A; Friedler, S; Gidoni, Y; Ben Ami, I; Strassburger, D; Ron-El, R

2012-01-01

The genital malformations in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

PubMed

Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

PubMed Central

Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

2011-01-01

Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus

Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease.

PubMed

Fishbane, Steven; Singh, Bhupinder; Kumbhat, Seema; Wisemandle, Wayne A; Martin, Nancy E

2018-06-19

This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia. In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment. The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths ( n =5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients ( n =1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia. This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically

Motivational beliefs, cognitive engagement, and achievement in language and mathematics in elementary school children.

PubMed

Metallidou, Panagiota; Vlachou, Anastasia

2007-02-01

metacognitive frameworks and ideas for future research are discussed. Cette étude porte sur les différences contextuelles dans les patrons relationnels entre les diverses composantes motivationnelle, cognitive et métacognitive de l'apprentissage et de la performance auto-régulés dans deux domaines d'étude clé du programme, soit la langue et les mathématiques. Ces différences contextuelles ont été examinées dans un échantillon de 263 d'enfants d'une école primaire grecque (of) en cinquième et sixième année. Les différences sexuelles et les différences d'âge ont été aussi étudiées. Les élèves ont été priés de compléter le «Motivated Strategies for Learning Questionnaire» (Pintrich & De Groot, 1990 ) qui comprend cinq facteurs: (a) l'auto-efficacité, (b) la valeur intrinsèque, (c) un test d'anxiété, (d) l'utilisation d'une stratégie cognitive et (e) les stratégies d'auto-régulation. Ils ont répondu aux énoncés du questionnaire sur une échelle de type Likert à 7 points en termes de leur comportement en classe de langue et en classe de mathématiques séparément. De plus, les enseignants ont été priés d'évaluer chaque résultat de leurs élèves dans la langue grecque et en mathématique sur une échelle allant de 1 à 20 points en comparaison au reste de la classe. Les résultats de l'étude ont indiqué très peu de différences dans les patrons relationnels entre les composantes auto-régulées à l'intérieur et entre les domaines d'étude. En même temps, les résultats ont révélé un caractère contextuel spécifique des composantes auto-regulées. De plus, la présente étude (a) a confirmé le rôle médiateur des stratégies dans la relation motivation-performance, (b) a souligné le rôle différé des stratégies cognitive et régulatoire dans la prédiction de la performance dans les domaines d'étude qui diffèrent dans leurs caractéristiques structurelles du contenu et (c) a souligné le rôle motivationnel clé de l'auto-efficacit

CTEF 2.0 - Assessment and Improvement of Command Team Effectiveness: Verification of Model and Instrument (CTEF 2.0 - Diagnostic et Amelioration de l’Efficacite d’un Team de Commandement: Verification du Modele et de l’Instrument)

DTIC Science & Technology

2010-09-01

what level of detail is needed to build their teams, and they can add more detailed items from the model in order to tap deeper in the performance of...of a project on ‘Command Team Effectiveness’ by Task Group 127 for the RTO Human Factors and Medicine Panel (RTG HFM-127). Published...vérification du modèle et de l’instrument) This Technical Report documents the findings of a project on ‘Command Team Effectiveness’ by Task Group

Nouvelles morphologies de fibres electrofilees de polymere thermosensible =

NASA Astrophysics Data System (ADS)

Sta, Marwa

Ce memoire presente une etude sur la possibilite d'obtenir des membranes a base de polymeres thermosensibles avec differentes morphologies pour des applications d'administration de medicaments. Ces membranes ont ete obtenues par electrofilage du Poly (N vinylcaprolactame) (PNVCL), un polymere thermosensible, soit seul ou en melange avec du Polycaprolactone (PCL), un polymere biodegradable. Les parametres de procede ainsi que les proprietes de la solution a electrofiler ont ete optimises dans le but de creer des fibres de PNVCL lisses, continues et sans perles. Des solutions du melange (PNVCL) / (PCL) ont ete ensuite preparees en suivant quatre methodes differentes de preparation. Ces methodes se basent sur l'emploi de solvants distincts, eau distillee et chloroforme, avec differentes concentrations de polymere, 42wt% et 30wt% respectivement. Ces solutions ont ete electrofilees en utilisant les parametres de procede qui correspondaient aux meilleures conditions pour l'electrofilage du PNVCL. Ensuite, le ketophofene, un medicament hydrophobe, a ete ajoute au PNVCL et au melange PNVCL/PCL avant l'electrofilage afin d'etudier la capacite des fibres de PNVCL et de melanges de retenir le medicament hydrophobe et a en faire sa liberation. Enfin, des fibres noyau-enveloppes ont ete obtenues par electrofilage coaxial, en utilisant une solution aqueuse du melange PNVCL/PCL (42 wt%) pour l'enveloppe et une solution aqueuse du PEG (30 wt%) pour le noyau. Les morphologies des membranes resultantes et de leurs fibres ont ete caracterisees par microscopie electronique a balayage (MEB). La temperature de solution critique inferieure (LCST) de ces fibres, qui est la temperature en dessous de laquelle le polymere est soluble dans l'eau et au-dessus duquel il precipite, a ete evaluee par calorimetrie differentielle a balayage (DSC). L'efficacite d'encapsulation (EE) et la liberation du medicament ont ete evaluees en utilisant la technique de spectrophotometrie UV-visible. Des coupes

Evaluation d'un ecosysteme pastoral sahelien: Apport de la geomatique (Oursi, Burkina Faso)

NASA Astrophysics Data System (ADS)

Kabore, Seraphine Sawadogo

L'objectif principal de cette recherche est la mise au point d'une architecture d'integration de donnees socio-bio-geographiques et de donnees satellitales dans un Systeme d'Information Geographique (SIG) en vue d'une aide a la prise de decisions dans un environnement semi-aride au nord du Burkina Faso. Elle repond a la question fondamentale de l'interpretation des effets des facteurs climatiques et socioeconomiques sur le milieu pastoral. La recherche s'est appuyee sur plusieurs hypotheses de travail: possibilite d'utilisation de modele de simulation, d'approche multicritere et de donnees de teledetection dans un cadre de systeme d'information geographique. L'evolution spatiotemporelle des parametres de productivite du milieu a ete evaluee par approche dynamique selon le modele de Wu et al. (1996) qui modelise les interactions entre le climat, le milieu physique, le vegetal et l'animal pour mieux quantifier la biomasse primaire. A ce modele, quatre parametres ont ete integres par approche floue et multicritere afin de prendre en compte la dimension socioeconomique de la productivite pastorale (apport majeur de la recherche): la sante, l'education, l'agriculture et l'eau. La teledetection (imagerie SPOT) a permis de definir la production primaire a partir de laquelle les simulations ont ete realisees sur 10 annees. Les resultats obtenus montrent une bonne correlation entre biomasse primaire in situ et celle calculee pour les deux modeles, avec toutefois une meilleure efficacite du modele modifie (4 fois plus) dans les zones de forte productivite ou l'on note un taux de surexploitation agricole eleve. A cause de la variabilite spatiale de la production primaire in situ, les erreurs des resultats de simulation (8 a 11%) sont acceptables et montrent la pertinence de l'approche grace a l'utilisation des SIG pour la spatialisation et l'integration des differents parametres des modeles. Les types de production secondaire preconises (production de lait pendant 7 mois ou

Effets des electrons secondaires sur l'ADN

NASA Astrophysics Data System (ADS)

Boudaiffa, Badia

Les interactions des electrons de basse energie (EBE) representent un element important en sciences des radiations, particulierement, les sequences se produisant immediatement apres l'interaction de la radiation ionisante avec le milieu biologique. Il est bien connu que lorsque ces radiations deposent leur energie dans la cellule, elles produisent un grand nombre d'electrons secondaires (4 x 104/MeV), qui sont crees le long de la trace avec des energies cinetiques initiales bien inferieures a 20 eV. Cependant, il n'y a jamais eu de mesures directes demontrant l'interaction de ces electrons de tres basse energie avec l'ADN, du principalement aux difficultes experimentales imposees par la complexite du milieu biologique. Dans notre laboratoire, les dernieres annees ont ete consacrees a l'etude des phenomenes fondamentaux induits par impact des EBE sur differentes molecules simples (e.g., N2, CO, O2, H2O, NO, C2H 4, C6H6, C2H12) et quelques molecules complexes dans leur phase solide. D'autres travaux effectues recemment sur des bases de l'ADN et des oligonucleotides ont montre que les EBE produisent des bris moleculaires sur les biomolecules. Ces travaux nous ont permis d'elaborer des techniques pour mettre en evidence et comprendre les interactions fondamentales des EBE avec des molecules d'interet biologique, afin d'atteindre notre objectif majeur d'etudier l'effet direct de ces particules sur la molecule d'ADN. Les techniques de sciences des surfaces developpees et utilisees dans les etudes precitees peuvent etre etendues et combinees avec des methodes classiques de biologie pour etudier les dommages de l'ADN induits par l'impact des EBE. Nos experiences ont montre l'efficacite des electrons de 3--20 eV a induire des coupures simple et double brins dans l'ADN. Pour des energies inferieures a 15 eV, ces coupures sont induites par la localisation temporaire d'un electron sur une unite moleculaire de l'ADN, ce qui engendre la formation d'un ion negatif transitoire

Les recommandations de prise en charge des complications métaboliques associées aux antipsychotiques de deuxième génération chez les enfants et les adolescents

PubMed Central

Ho, Josephine; Panagiotopoulos, Constadina; McCrindle, Brian; Grisaru, Silviu; Pringsheim, Tamara

2012-01-01

HISTORIQUE : Les antipsychotiques de deuxième génération s’associent souvent à des complications métaboliques. Ces médicaments sont utilisés plus souvent pour le traitement des troubles de santé mentale chez les enfants, ce qui a requis l’élaboration de lignes directrices officielles sur la surveillance de leur innocuité et de leur efficacité. Des lignes directrices ont déjà été élaborées pour surveiller les complications métaboliques et neurologiques. Afin d’aider les praticiens qui effectuent ces interventions de surveillance, une série de recommandations thérapeutiques complémentaires a été élaborée pour les cas où l’on observe des mesures ou des résultats anormaux. OBJECTIF : Créer des recommandations probantes afin de contribuer à la prise en charge des complications métaboliques chez les enfants traités au moyen d’antipsychotiques de deuxième génération. MÉTHODOLOGIE : Les auteurs ont procédé à une analyse systématique des publications sur les complications métaboliques des antipsychotiques de deuxième génération chez les enfants. Les membres du groupe consensuel ont évalué l’information recueillie grâce à l’analyse bibliographique systématique et ont fait appel à un processus de groupe nominal pour parvenir à un consensus à l’égard de recommandations thérapeutiques. Dans la mesure du possible, ils se sont reportés aux lignes directrices existantes sur l’évaluation et le traitement des anomalies métaboliques chez les enfants. RÉSULTATS : Des recommandations probantes sont présentées pour contribuer à la prise en charge des complications métaboliques, y compris la prise de poids, l’augmentation du tour de taille, l’élévation des taux de prolactine, de cholestérol, de triglycérides et de glucose, les épreuves de fonction hépatique anormales et les études thyroïdiennes anormales. CONCLUSION : Il faut recourir à des mesures de surveillance convenables lorsqu’on prescrit

Déshumidification de l'air d'une serre par contact direct à courants croisés avec une solution hygroscopique organique

NASA Astrophysics Data System (ADS)

Chraibi, A.; Jaffrin, A.; Makhlouf, S.; Bentounes, N.

1995-07-01

Greenhouse air can be dehumidified by direct contact with a desicant fluid on a trickle exchanger. The water vapour extraction rate depends on the hygroscopicity of the fluid and on the exchanger efficiency. An organic fluid, the triethylene glycol (TEG) at 90% concentration, has been tested. Cross corrugated cellulosic pads, of the type used in cooling, irrigated with TEG, were placed in a wind channel to dehumidify air at various speeds and temperatures. A semi-analytical model, based on energy and mass conservation, correctly reproduces the water vapor extraction rate and the enthalpy change of both fluids. It is shown that TEG trickling through a ventilated pad of 1 m^2 area and 0.1 m thickness can be used to extract 3 to 5 kg of water vapor per hour in greenhouse climate control applications. Several pads arranged in series can be used to decrease more efficiently the absolute humidity of the air, for other applications like food drying or industrial compressed air. Une technique de déshumidification de l'air des serres consiste à le soumettre au contact d'une solution hygroscopique au sein d'un échangeur ruisselant. Le taux d'extraction de vapeur d'eau dépend à la fois du pouvoir hygroscopique de la solution et de l'efficacité de l'échangeur. Une solution hygroscopique organique, le triéthylène glycol à 90% de concentration, a été expérimentée. Un échangeur ruisselant constitué de parois de cellulose ondulées à corrugations croisées, du type “cooling pad” pour serres agricoles, a été testé pour déshumidifier de l'air dans une soufflerie expérimentale. Un modèle semi-analytique, basé sur les équations de conservation de l'énergie et de masse, permet de rendre compte des échanges et de déduire les paramètres de sortie des deux fluides en contact, à partir des caractéristiques d'entrée. Cette étude permet de chiffrer à environ 3 à 5kg/h la capacité de déshumidification d'un panneau d'un mètre carré et de 10cm d

Synthese de champs sonores adaptative

NASA Astrophysics Data System (ADS)

Gauthier, Philippe-Aubert

montrent l'efficacite des algorithmes et la capacite de l'AWFS a attenuer les erreurs attribuables a des reflexions acoustiques. Le neuvieme chapitre presente des resultats experimentaux d'AWFS. L'objectif etait de valider la methode et d'evaluer les performances de l'AWFS. Un autre algorithme prometteur est aussi teste. Les resultats demontrent la bonne marche de l'AWFS et des algorithmes testes. Autant dans le cas de la reproduction de champs harmoniques que dans le cas de la reproduction de champs a large bande, l'AWFS reduit l'erreur de reproduction de la WFS et les effets indesirables causes par les lieux de reproduction.

Evaluation de la qualite osseuse par les ondes guidees ultrasonores =

NASA Astrophysics Data System (ADS)

Abid, Alexandre

La caracterisation des proprietes mecaniques de l'os cortical est un domaine d'interet pour la recherche orthopedique. En effet, cette caracterisation peut apporter des informations primordiales pour determiner le risque de fracture, la presence de microfractures ou encore depister l'osteoporose. Les deux principales techniques actuelles de caracterisation de ces proprietes sont le Dual-energy X-ray Absorptiometry (DXA) et le Quantitative Computed Tomogaphy (QCT). Ces techniques ne sont pas optimales et presentent certaines limites, ainsi l'efficacite du DXA est questionnee dans le milieu orthopedique tandis que le QCT necessite des niveaux de radiations problematiques pour en faire un outil de depistage. Les ondes guidees ultrasonores sont utilisees depuis de nombreuses annees pour detecter les fissures, la geometrie et les proprietes mecaniques de cylindres, tuyaux et autres structures dans des milieux industriels. De plus, leur utilisation est plus abordable que celle du DXA et n'engendrent pas de radiation ce qui les rendent prometteuses pour detecter les proprietes mecaniques des os. Depuis moins de dix ans, de nombreux laboratoires de recherche tentent de transposer ces techniques au monde medical, en propageant les ondes guidees ultrasonores dans les os. Le travail presente ici a pour but de demontrer le potentiel des ondes guidees ultrasonores pour determiner l'evolution des proprietes mecaniques de l'os cortical. Il commence par une introduction generale sur les ondes guidees ultrasonores et une revue de la litterature des differentes techniques relatives a l'utilisation des ondes guidees ultrasonores sur les os. L'article redige lors de ma maitrise est ensuite presente. L'objectif de cet article est d'exciter et de detecter certains modes des ondes guides presentant une sensibilite a la deterioration des proprietes mecaniques de l'os cortical. Ce travail est realise en modelisant par elements finis la propagation de ces ondes dans deux modeles osseux

Caracterisation thermique de modules de refroidissement pour la photovoltaique concentree

NASA Astrophysics Data System (ADS)

Collin, Louis-Michel

Pour rentabiliser la technologie des cellules solaires, une reduction du cout d'exploitation et de fabrication est necessaire. L'utilisation de materiaux photovoltaiques a un impact appreciable sur le prix final par quantite d'energie produite. Une technologie en developpement consiste a concentrer la lumiere sur les cellules solaires afin de reduire cette quantite de materiaux. Or, concentrer la lumiere augmente la temperature de la cellule et diminue ainsi son efficacite. Il faut donc assurer a la cellule un refroidissement efficace. La charge thermique a evacuer de la cellule passe au travers du recepteur, soit la composante soutenant physiquement la cellule. Le recepteur transmet le flux thermique de la cellule a un systeme de refroidissement. L'ensemble recepteur-systeme de refroidissement se nomme module de refroidissement. Habituellement, la surface du recepteur est plus grande que celle de la cellule. La chaleur se propage donc lateralement dans le recepteur au fur et a mesure qu'elle traverse le recepteur. Une telle propagation de la chaleur fournit une plus grande surface effective, reduisant la resistance thermique apparente des interfaces thermiques et du systeme de refroidissement en aval vers le module de refroidissement. Actuellement, aucune installation ni methode ne semble exister afin de caracteriser les performances thermiques des recepteurs. Ce projet traite d'une nouvelle technique de caracterisation pour definir la diffusion thermique du recepteur a l'interieur d'un module de refroidissement. Des indices de performance sont issus de resistances thermiques mesurees experimentalement sur les modules. Une plateforme de caracterisation est realisee afin de mesurer experimentalement les criteres de performance. Cette plateforme injecte un flux thermique controle sur une zone localisee de la surface superieure du recepteur. L'injection de chaleur remplace le flux thermique normalement fourni par la cellule. Un systeme de refroidissement est installe

Lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse

PubMed Central

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-01-01

Résumé Objectif Présenter aux médecins de famille un résumé clinique pratique des lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse, produites par le National Opioid Use Guideline Group. Qualité des données Pour produire les lignes directrices, les chercheurs ont effectué une synthèse critique de la littérature médicale sur l’efficacité et l’innocuité des opioïdes pour la douleur chronique non cancéreuse et ont rédigé une série de recommandations. Un panel de 49 cliniciens experts de toutes les régions du Canada ont passé en revue l’ébauche et ont atteint un consensus sur 24 recommandations. Message principal Il est recommandé de faire un dépistage du risque de dépendance avant de prescrire des opioïdes. On recommande des opioïdes faibles (codéine et tramadol) pour une douleur de légère à modérée qui n’a pas répondu aux traitements de première intention. On peut essayer l’oxycodone, l’hydromorphone et la morphine chez les patients qui n’ont pas eu de soulagement avec des opioïdes plus faibles. Une faible dose initiale et une lente hausse du titrage sont recommandées, ainsi qu’une étroite surveillance du patient qu’on a d’abord renseigné. Les médecins doivent surveiller l’apparition de complications comme l’apnée du sommeil. La dose optimale est celle qui améliore le fonctionnement ou atténue les cotes d’évaluation de la douleur d’au moins 30 %. Pour la grande majorité des patients, la dose optimale sera bien en deçà de l’équivalent de 200 mg de morphine par jour. On recommande le sevrage progressif pour les patients qui n’ont pas répondu à un essai d’opioïdes adéquat. Conclusion Les opioïdes jouent un rôle important dans la prise en charge de la douleur chronique non cancéreuse, mais il faut en prescrire avec prudence pour limiter les dommages potentiels. Les nouvelles lignes directrices

Vulvovaginite : Dépistage et prise en charge de la trichomonase, de la candidose vulvovaginale et de la vaginose bactérienne.

PubMed

van Schalkwyk, Julie; Yudin, Mark H

2016-12-01

Analyser les données probantes et formuler des recommandations quant au dépistage et à la prise en charge de la candidose vulvovaginale, de la trichomonase et de la vaginose bactérienne. Parmi les issues évaluées, on trouve l'efficacité de l'antibiothérapie, les taux de guérison en ce qui concerne les infections simples et compliquées, et les implications de ces pathologies pendant la grossesse. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE, EMBASE, CINAHL et The Cochrane Library en juin 2013 au moyen d'un vocabulaire contrôlé (p. ex. « vaginitis », « trichomoniasis », « vaginal candidiasis ») et de mots clés (p. ex. « bacterial vaginosis », « yeast », « candidiasis », « trichomonas vaginalis », « trichomoniasis », « vaginitis », « treatment ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n'a été appliquée en matière de date, mais les résultats ont été limités aux documents rédigés en anglais ou en français. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en mai 2014. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques et auprès de sociétés de spécialité médicale nationales et internationales. La qualité des résultats est évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). DéCLARATIONS SOMMAIRES: RECOMMANDATIONS. Copyright © 2016. Published by Elsevier Inc.

Comparison of anchorage reinforcement with temporary anchorage devices or a Herbst appliance during lingual orthodontic protraction of mandibular molars without maxillary counterbalance extraction.

PubMed

Metzner, Rebecca; Schwestka-Polly, Rainer; Helms, Hans-Joachim; Wiechmann, Dirk

2015-06-20

Orthodontic protraction of mandibular molars without maxillary counterbalance extraction in cases of aplasia or extraction requires stable anchorage. Reinforcement may be achieved by using either temporary anchorage devices (TAD) or a fixed, functional appliance. The objective was to compare the clinical effectiveness of both methods by testing the null-hypothesis of no significant difference in velocity of space closure (in mm/month) between them. In addition, we set out to describe the quality of posterior space management and treatment-related factors, such as loss of anchorage (assessed in terms of proportions of gap closure by posterior protraction or anterior retraction), frequencies of incomplete space closure, and potential improvement in the sagittal canine relationship. Twenty-seven subjects (15 male/12 female) with a total of 36 sites treated with a lingual multi-bracket appliance were available for retrospective evaluation of the effects of anchorage reinforcement achieved with either a Herbst appliance (n(subjects) = 15; 7 both-sided/8 single-sided Herbst appliances; n(sites) = 22) or TADs (n(subjects )= 12; 2 both-sided; 10 single-sided; n(sites) = 14). Descriptive analysis was based on measurements using intra-oral photographs which were individually scaled to corresponding plaster casts and taken on insertion of anchorage mechanics (T1), following removal of anchorage mechanics (T2), and at the end of multi-bracket treatment (T3). The null-hypothesis was rejected: The rate of mean molar protraction was significantly faster in the Herbst-reinforced group (0.51 mm/month) than in the TAD group (0.35). While complete space closure by sheer protraction of posterior teeth was achieved in all Herbst-treated cases, space closure in the TAD group was achieved in 76.9% of subjects by sheer protraction of molars, and it was incomplete in 50% of cases (mean gap residues: 1 mm). Whilst there was a deterioration in the canine relationship towards

Conjoined twins: implications for blastogenesis.

PubMed

Machin, G A

1993-01-01

fail to develop (interaction aplasia) because of conflicting migrational pathways or abnormal concentrations of morphogens in and around the neoaxes. 8. Where the cardiovascular system is discordantly expressed in dicephalus and thoracopagus twins, the right heart is more severely malformed, depending on the degree of interaction of the two embryonic septa transversa. 9. The septum transversum provides mesenchymal components to the heawrt and liver; the epithelial components (derived fro the foregut[s]) may vary in number from the number of mesenchymal septa transversa contributing to the liver of the CT embryo.(ABSTRACT TRUNCATED AT 400 WORDS)

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

PubMed

Elias, A D; Ayash, L; Anderson, K C; Hunt, M; Wheeler, C; Schwartz, G; Tepler, I; Mazanet, R; Lynch, C; Pap, S

1992-06-01

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous

Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Xue-Lian; Gu, Xiao-Lei

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles receivedmore » the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future

(90)Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study.

PubMed

Chevallier, Patrice; Eugene, Thomas; Robillard, Nelly; Isnard, Françoise; Nicolini, Franck; Escoffre-Barbe, Martine; Huguet, Françoise; Hunault, Mathilde; Marcais, Antoine; Gaschet, Joelle; Cherel, Michel; Guillaume, Thierry; Delaunay, Jacques; Peterlin, Pierre; Eveillard, Marion; Thomas, Xavier; Ifrah, Norbert; Lapusan, Simona; Bodet-Milin, Caroline; Barbet, Jacques; Faivre-Chauvet, Alain; Ferrer, Ludovic; Bene, Marie C; Le Houerou, Claire; Goldenberg, David M; Wegener, William A; Kraeber-Bodéré, Françoise

2015-03-01

Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study. Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457. Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4). (90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies. Immunomedics and Direction de la Recherche Clinique of Nantes

Sigmoid colon vaginoplasty in children.

PubMed

Ekinci, S; Karnak, I; Ciftci, A O; Senocak, M E; Tanyel, F C; Büyükpamukçu, N

2006-06-01

Vaginal construction is necessary for the patients with aplasia of Mullerian ducts, testicular feminisation and androgen insensitivity syndromes. Many methods of vaginal construction have been described. We report here the outcomes of six adolescent patients who underwent sigmoid colon vaginoplasty with special emphasis on the surgical technique and outcomes. Between 1990 and 2003, six patients underwent sigmoid vaginoplasty after a diagnosis of 5alpha-reductase deficiency (n = 3), testicular feminisation (n = 2) or vaginal atresia (n = 1). The mean age was 16 years (13 to 18). Wide spectrum antibiotics and whole-gut preparation were used in all cases. A 15-20 cm segment of sigmoid colon was pulled through the retrovesical tunnel. The proximal end was closed in two layers in patients with 5alpha-reductase deficiency and with testicular feminisation. A distal anastomosis was carried out to the opening made on the vaginal plate (5alpha-reductase deficiency) or on the tip of the shallow rudimentary vagina (testicular feminisation). The sigmoid segment was interposed between the blind end of the atretic vagina and the perineum in the patient with vaginal atresia. Patients were instructed to perform daily vaginal irrigation. The neovagina was examined and calibrated under anaesthesia. No routine vaginal dilatation was recommended. All but one patient had an uneventful postoperative period and were discharged within 7-8 days. All patients had an excellent cosmetic result with an appropriate vaginal length. One of the patients experienced late stenosis of the introitus which responded to dilatations. Mucus discharge was not a significant problem. The patient with vaginal atresia (Bardet-Biedl syndrome) experienced deep vein thrombosis, renal failure and sepsis, resulting in death. Sigmoid colon vaginoplasty is a special procedure which appears appropriate for the construction of a new vagina in children. A sigmoid colon neovagina meets all necessary criteria after a

Willingness to pay for adverse drug event regulatory actions.

PubMed

Bouvy, Jacoline; Weemers, Just; Schellekens, Huub; Koopmanschap, Marc

2011-11-01

Regulatory requirements for the pharmaceutical industry have become increasingly demanding with respect to the safety and effectiveness of drugs. The objective of this study was to determine the willingness to pay (WTP), of both the Dutch general public and dialysis patients, for regulatory requirements related to reducing the risk of pure red cell aplasia (PRCA) associated with epoetin alpha use. A survey was carried out in April 2009. The Dutch general public (n = 422) was approached through a survey sampling agency. Patients (n = 112) were included through several Dutch dialysis clinics because they are often treated with epoetin alpha and therefore were expected to have a higher WTP than the general public. The survey aimed to determine the WTP for reducing the risk of PRCA in epoetin alpha users from 4.5 to 0 per 10 000 patients per year, based on regulatory actions that have been taken by the European Medicines Agency (EMA). WTP was determined via a payment scale and an open-ended follow-up question. Patients were asked how much extra per year they would be willing to pay for their basic healthcare insurance. We used two censored regression models to test the association between WTP and a set of independent variables: a Tobit model with the stated WTP as the dependent variable and an interval regression model with the interval between the lower and upper bounds of the payment scale as the dependent variable. The patients' mean WTP was significantly higher (€46.52) than that of the general public (€24.40). The Tobit model showed significant associations (α = 0.05) with WTP for dialysis patients, risk perception and respondents' opinions on costs of healthcare. The interval regression model showed significant associations with WTP for the same variables as the Tobit model and for one additional variable (risk aversion). Income did not significantly affect WTP. A scenario with a 10-fold larger risk reduction did not increase WTP significantly

Etude de la flore bactérienne contaminant les téléphones mobiles avant et après la désinfection: comparaison entre les professionnels soignants de l'hôpital militaire d'instruction Mohammed V de Rabat et les témoins

PubMed Central

Uwingabiye, Jean; Moustanfii, Wafaa; Chadli, Meryem; Sekhsokh, Yassine

2015-01-01

Introduction L'objectif de notre travail était évaluer la contamination microbienne des téléphones mobiles utilisés par les personnels soignants des différents services de l'hôpital militaire d'instructions Mohammed V de Rabat et la comparer à celui d'une population témoin et aussi démontrer l'efficacité des solutions hydroalcoolique dans la désinfection de ces téléphones mobiles. Méthodes Il s'agit d'une étude descriptive transversale réalisée sur une période de 9 mois entre septembre 2010 et juin 2011, dans le service de bactériologie de l'hôpital militaire d'Instruction Mohammed V. Résultats L’étude bactériologique a été faite sur 240 téléphones mobiles dont 50% provenaient de personnels de sante. Le taux de contamination bactérienne de tous les téléphones mobiles était de 100%. Les cultures des bactéries isolées au niveau des téléphones mobiles du personnel médical étaient plus polymorphes que celles de la population témoin (p=0,028). Parmi 437 bactéries isolées: 223(51%) provenaient de téléphones de personnels de santé et 214(49%) de téléphones de la population témoin avec une différence qui n’était pas statistiquement significative(p>0,05) sauf pour les isolats de Staphylocoque à coagulase négative et Staphylococcus aureus. Les bactéries isolées étaient représentées par: Staphylocoque à coagulase (57,7%), Staphylococcus aureus (18,1%), Corynebacterium sp (18,8%), Bacillus sp (2,3%) et autres (2,2%). La différence entre la prévalence des bactéries isolées selon les services et les fonctions des personnels de santé n’était pas statistiquement significative (p>0,05). La désinfection des téléphones portables par la solution hydroalcoolique a réduit à 99,5% le nombre des colonies. Conclusion Ce travail montre que les téléphones portables pourraient jouer un rôle dans la transmission des infections nosocomiales et communautaires. Dans le cadre de prévention de ces risques, il faut

Les pyélonephrites aigues de la femme enceinte: place du traitement médical et indications d'un drainage de la voie excrétrice supérieure (y'a-t-il des facteurs prédictifs cliniques, biologiques et radiologiques pour rendre le drainage licite?)

PubMed Central

El Bahri, Abdessamad; Janane, Abdellatif; Chafiki, Jaouad; Arnaud, Tayiri; Ghadouane, Mohammed; Ameur, Ahmed; Abbar, Mohammed

2015-01-01

Les pyélonéphrites aigues gravidiques (PNAg) sont fréquentes et peuvent avoir des conséquences maternelles et fœtales graves. Le but de notre étude était de déterminer les facteurs prédictifs cliniques, biologiques et radiologiques qui permettent de se limiter au traitement médical ou d'associer un drainage de la voie excrétrice supérieure dans la prise en charge des PNAg. Nous rapportons, de façon rétrospective une série de 26 cas dans les services d'Urologie et de Gynécologie de l'Hôpital Militaire d'Instruction Mohamed V de Rabat (Maroc) sur une période allant du 1er Janvier 2010 au 30 Aout 2012. Toutes les patientes avaient une PNAg symptomatique objectivée par l'ECBU et/ou l’échographie rénale. La fréquence de la pyélonéphrite aigue gravidique par rapport aux pyélonéphrites aigues en général a été de 27,95% avec une prédominance chez les primipares de 53,84%. Son pic de fréquence se situe à 73,08% pour les gestantes âgées de 19 à 37 ans ainsi qu'au troisième trimestre (77%) de la grossesse. La triade clinique fièvre, lombalgie, troubles mictionnels et l’échographie rénale sont les éléments importants du diagnostic. L'antibiothérapie probabiliste a été débuté d'emblée et adaptée en fonctions des résultats de l'examen cytobactériologique des urines. Sa durée est de trois à six semaines en fonction de l’évolution clinique. La protéine C réactive est un marqueur de progression de la maladie ou de l'efficacité thérapeutique. Les principaux facteurs prédictifs du drainage de la voie excrétrice supérieure sont: persistance de la symptomatologie clinique, du syndrome infectieux et des anomalies visibles à l’échographie rénale ainsi que l'altération de la fonction rénale. La montée de la sonde JJ est le principal traitement urologique. Le traitement médical repose sur l'antibiothérapie probabiliste qui sera adaptée Ultérieurement en fonction des résultats de l'antibiogramme. Les facteurs pr

Des recommandations probantes pour surveiller l’innocuité des antipsychotiques de deuxième génération chez les enfants et les adolescents

PubMed Central

Pringsheim, Tamara; Panagiotopoulos, Constadina; Davidson, Jana; Ho, Josephine

2012-01-01

HISTORIQUE : Au Canada, l’utilisation d’antipsychotiques, notamment les antipsychotiques de deuxième génération (ADG), a augmenté de façon considérable depuis cinq ans chez les enfants ayant des troubles de santé mentale. Ces médicaments ont le potentiel de causer de graves complications métaboliques et neurologiques lorsqu’on les utilise de manière chronique. OBJECTIF : Synthétiser les données probantes relatives aux effets secondaires métaboliques et neurologiques précis associés à l’usage d’ADG chez les enfants et fournir des recommandations probantes sur la surveillance de ces effets secondaires. MÉTHODOLOGIE : Les auteurs ont procédé à une analyse systématique des essais cliniques contrôlés des ADG auprès d’enfants. Ils ont fait des recommandations à l’égard de la surveillance de l’innocuité des ADG d’après un modèle de classification fondé sur le système GRADE (système de notation de l’évaluation et de l’élaboration des recommandations). Lorsque les données probantes n’étaient pas suffisantes, ils fondaient leurs recommandations sur le consensus et l’avis d’experts. Un groupe consensuel multidisciplinaire a analysé toutes les données probantes pertinentes et est parvenu à un consensus à l’égard des recommandations. RÉSULTATS : Les recommandations probantes portant sur la surveillance de l’innocuité des ADG figurent dans les présentes lignes directrices. Les auteurs indiquent la qualité des recommandations relatives à des examens physiques et tests de laboratoire précis à l’égard de chaque ADG à des moments déterminés. CONCLUSION : De multiples essais aléatoires et contrôlés ont permis d’évaluer l’efficacité de bon nombre des ADG utilisés pour traiter les troubles de santé mentale en pédiatrie. Toutefois, leurs avantages ne sont pas sans risques : on observe à la fois des effets secondaires métaboliques et neurologiques chez les enfants traités au moyen d�

Consensus canadien sur la contraception (3(e) partie de 4) : chapitre 8 - contraception à progestatif seul.

PubMed

Black, Amanda; Guilbert, Edith; Costescu, Dustin; Dunn, Sheila; Fisher, William; Kives, Sari; Mirosh, Melissa; Norman, Wendy V; Pymar, Helen; Reid, Robert; Roy, Geneviève; Varto, Hannah; Waddington, Ashley; Wagner, Marie-Soleil; Whelan, Anne Marie

2016-03-01

Fournir des lignes directrices aux fournisseurs de soins quant à l'utilisation de modes de contraception pour la prévention de la grossesse et quant à la promotion d'une sexualité saine. Orientation des praticiens canadiens en ce qui concerne l'efficacité globale, le mécanisme d'action, les indications, les contre-indications, les avantages n'étant pas liés à la contraception, les effets indésirables, les risques et le protocole de mise en œuvre des modes de contraception abordés; planification familiale dans le contexte de la santé sexuelle et du bien-être général; méthodes de counseling en matière de contraception; et accessibilité et disponibilité des modes de contraception abordés au Canada. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE et The Cochrane Library entre janvier 1994 et janvier 2015 au moyen d'un vocabulaire contrôlé (p. ex. contraception, sexuality, sexual health) et de mots clés (p. ex. contraception, family planning, hormonal contraception, emergency contraception) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre janvier 1994 et janvier 2015. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2015. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé pr

Impact of illegal trade on the quality of epoetin alfa in Thailand.

PubMed

Fotiou, Fotis; Aravind, Suresh; Wang, Ping-Ping; Nerapusee, Osot

2009-02-01

Reports from the World Health Organization have suggested that counterfeit medicines pose a serious problem in developing countries. An investigation of anti-erythropoietin antibody-mediated pure red cell aplasia in Thailand found evidence of drug smuggling, which may have serious safety implications. This study assessed the authenticity and quality of epoetin alfa samples in Thailand. Samples of epoetin alfa-prefilled syringes were collected from the pharmacies at 2 major hospitals (62 samples), 8 retail pharmacies (41 samples), and Thai authorities (30 samples confiscated from smugglers at 2 airports, and 6 samples from a condominium used by smugglers). These samples were tested against the European Union Pharmacopeia specifications for aggregate content in epoetins of <2%. The integrity of epoetin alfa distribution channels, coldchain processes (maintenance at 2 degrees C-8 degrees C), primary and secondary packaging components (eg, batch number, expiration date, appearance, letter size), and company's confidential features (eg, nature of the ink, type and quality of the paper, other covered features) were also investigated. The main outcome measures were protein aggregate content, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting; and isoform distribution, assessed by isoelectric focusing and Western blotting. Epoetin alfa samples obtained from the company's cold-chain and authorized distribution channels met all quality standards, as did all epoetin alfa samples obtained from the hospital pharmacies. However, evidence showed that some samples were being smuggled or sold illegally through certain unauthorized retail pharmacies. The epoetin alfa samples obtained from both airports and the condominium were stored improperly at room temperature. Aggregate levels exceeded the specification of <2% in 11 samples from 2 of the retail pharmacies (range, 1.2%-3.1%), 15 samples from the Dongmuang Airport (range, 2.2%-17.0%), and

Pituitary stalk interruption syndrome presenting as short stature: a case report.

PubMed

Ram, Nanik; Ali, Syed Ahsan; Hussain, Syed Zubair

2014-12-19

Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from Pakistan. A 17-year-old Pakistani young man presented with short stature and underdeveloped secondary sexual characters. His siblings and parents were healthy, with normal height. An examination showed his blood pressure was 90/60 mmHg, and his height, weight, and body mass index were 142 cm, 34.5 kg, and 17.10 kg/m2, respectively. He had no hair growth on his face, axilla, or pubis. His testes were between 1 and 2 mL in size, with a 4 cm-at-stretch micropenis. His lab investigations showed that his thyroid stimulating hormone (TSH) was 8.58 uIU/mL (0.4 to 4.2), his free thyroid hormone level FT4 was 0.46 ng/dL (0.89 to 1.76), his prolactin was 21.1 ng/mL (3.0 to 14.7), and his baseline cortisol was 0.30 ug/dL (4.3 to 22.4). His cortisol level after 60 minutes of cosyntropin injection was 3.5 ug/dL (4.3 to 22.4), his insulin like growth factor IGF-1 was 31.56 ng/mL (247.3 to 481.7), his testosterone level was under 2.5 ng/dL (2 to 800), his follicle stimulating hormone FSH was 0.41 uIU/mL (0.0 to 10.0), and his leutinizing hormone LH was under 0.1 uIU/mL (1.2 to 7.8). His bone age was 10 years according to the Greulich and Pyle method, as shown by X-rays. The results from his pituitary magnetic resonance imaging scan were consistent with pituitary stalk interruption syndrome. We describe a young

Modelisation de photodetecteurs a base de matrices de diodes avalanche monophotoniques pour tomographie d'emission par positrons

NASA Astrophysics Data System (ADS)

Corbeil Therrien, Audrey

quantifier l'impact des parametres du photodetecteur sur la resolution en energie et la resolution en temps et ainsi optimiser les performances de la matrice de PAMP. Par exemple, l'augmentation du ratio de surface active ameliore les performances, mais seulement jusqu'a un certain point. D'autres phenomenes lies a la surface active, comme le bruit thermique, provoquent une degradation du resultat. Le simulateur nous permet de trouver un compromis entre ces deux extremes. Les simulations avec les parametres initiaux demontrent une efficacite de detection de 16,7 %, une resolution en energie de 14,2 % LMH et une resolution en temps de 0.478 ns LMH. Enfin, le simulateur propose, bien qu'il vise une application en TEP, peut etre adapte pour d'autres applications en modifiant la source de photons et en adaptant les objectifs de performances. Mots-cles : Photodetecteurs, photodiodes avalanche monophotoniques, semiconducteurs, tomographie d'emission par positrons, simulations, modelisation, detection monophotonique, scintillateurs, circuit d'etouffement, SPAD, SiPM, Photodiodes avalanche operees en mode Geiger

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.

PubMed

Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L

2015-02-07

(6) CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0-36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. National Institutes of Health Intramural funds and St Baldrick's Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Third-generation CD28/4-1BB chimeric antigen receptor T cells for chemotherapy relapsed or refractory acute lymphoblastic leukaemia: a non-randomised, open-label phase I trial protocol.

PubMed

Tang, Xiao-Yi; Sun, Yao; Zhang, Ang; Hu, Guo-Liang; Cao, Wei; Wang, Dan-Hong; Zhang, Bin; Chen, Hu

2016-12-30

grading system. In addition, patients with grade 3 or 4 neurotoxicities or persistent B-cell aplasia will be treated with dexamethasone (10 mg intravenously every 6 hours) or IgG, respectively. Descriptive and analytical analyses will be performed. Ethical approval for the study was granted on 10 July 2014 (YLJS-2014-7-10). Written informed consent will be taken from all participants. The results of the study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report. NCT02186860. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Lymphangiosarcoma in a 3.5-year-old Bullmastiff bitch with vaginal prolapse, primary lymph node fibrosis and other congenital defects.

PubMed

Williams, J H; Birrell, J; Van Wilpe, E

2005-09-01

Lymphangiosarcoma is an extremely rare tumour in dogs with only 16 cases reported in the literature. Lymphoedema, which may be primary due to defects in the lymphatic system, or secondary to various other pathologies, often precedes malignancy. Of the 16 canine reports, only 1 dog was confirmed as having had prior primary lymphoedema due to aplasia of the popliteal lymph nodes. A case of lymphangiosarcoma is described in a 3.5-year-old purebred, Bullmastiff bitch which presented with vaginal blood 'spotting' for 3 weeks after cessation of oestrus, during which intromission by the male had been unsuccessful. During ovariohysterectomy a large multicystic, proliferative, spongy, fluid-filled, brownish-red mass surrounding the cervix and projecting into the abdominal space was removed with the cervix, and a diagnosis of lymphangiosarcoma made on histological and electron microscopic examination of the tissue. Ultrastructurally, no basement membrane or pericytes were found, only some of the neoplastic endothelial cells were linked by tight junctions while there were gaps between others, and neither micropinocytotic vesicles nor Weibel-Palade bodies occurred in the cells examined. Very few of the endothelial cells lining the many interlinking, tortuous maze of channels, stained slightly positive immunohistochemically for factor VIII-related antigen. The channels were filled mostly with serous fluid, and occasionally mixed leucocytes and some erythrocytes. The endothelium was often associated with underlying blocks of collagenous material, as well as loosely-arranged aggregates of lymphocytes, other mononuclear cells and occasional neutrophils in the connective tissue septae and more prominently perivascularly. The bitch was discharged on antibiotic treatment but returned 2 weeks later with apparent prolapsed vagina which failed to reduce over the next week. Laparotomy revealed the tumour to have spread extensively in the caudal abdomen to involve the broad ligament and

Formation of social and household skills in children with hand defects.

PubMed

Klimon, Nataly; Koryukov, Alexander; Loseva, Nina; Starobina, Elena

2015-08-01

The aim of this study was to consider the peculiarities of forming social and household skills, and the criteria for their evaluation, as well as an assessment of functional capacity, in children with hand defects both before and after surgical treatment and rehabilitation courses using a system of games. We elaborated and implemented a program of social rehabilitation of preschool children with congenital and acquired hand defects for the development of their functional capabilities and the formation of social and household skills after surgical treatment and prosthetics using play therapy methods. As part of this work, 140 preschool children aged 3-7 years underwent social rehabilitation. Most of the children had congenital hand defects-122 children (87 %): 96 children (79 %) with ectrodactylia, adactylia, hypoplasia, aplasia, hand splitting, club hand, or partial gigantism; 26 children (21 %) with congenital syndactylism and constricted bonds and 18 children (13 %) with acquired defects (burn deformity, amputation). 110 children (79 %) had reached the stage of surgical correction; 30 children (21 %) reached the stage of prosthetics. Most of the children participating in the experiment (78 children, 56 %) had defects of fingers on one hand. The program aimed at solving specific rehabilitation tasks: formation and improvement of all possible types of grip under the existing defect including those after surgery and prosthetics; development of tactile sensations in fingers; development of fine motor skills; increase in range of motion in all joints of the damaged hand; development of attention and concentration; formation of social and household skills appropriate to age; and development of the ability to achieve the set task. Analysis of the level of social and household skills of children with hand defects undergoing rehabilitation treatment at the hospital depending on the age prior to medical and social rehabilitation showed that preschool children with

Utilisation de l'essai comete et du biomarqueur gamma-H2AX pour detecter les dommages induits a l'ADN cellulaire par le 5-bromodeoxyuridine post-irradiation

NASA Astrophysics Data System (ADS)

La Madeleine, Carole

le BrdU au niveau cellulaire. Notre hypothese (basee sur des resultats preliminaires effectues dans notre laboratoire) est que l'irradiation de l'ADN cellulaire en presence de BrdU augmentera le nombre de bris simple brin sans toutefois augmenter le nombre de bris double brin. Les resultats presentes dans ce memoire semblent corroborer cette hypothese. Les nouvelles methodes d'analyse, soient l'essai comete et la detection des foci gamma-H2AX remettent en question ce qui a ete dit sur le BrdU au sujet de l'induction des cassures double brin depuis plusieurs annees. L'ensemble de ces nouveaux resultats effectue a l'aide de cellules ayant incorporees du BrdU sont en correlation avec de precedents resultats obtenus dans notre laboratoire sur des oligonucleotides bromes. Ils reaffirment que l'irradiation combinee au BrdU augmente l'induction de bris simple brin mais pas de bris double brin. L'investigation approfondie des mecanismes d'action non elucides du BrdU au niveau cellulaire et son utilisation a des moments strategiques pendant le traitement de radiotherapie pourraient accroitre son efficacite a des fins d'utilisation clinique. Mots cles : 5-bromodeoxyuridine, dimeres interbrins, dommage a l'ADN, essai comete, H2AX, radiosensibilisateur, radiotherapie

Approche à l’égard des nouveaux anticoagulants oraux en pratique familiale

PubMed Central

Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

2014-01-01

Résumé Objectif Traiter des différentes éventualités pouvant survenir durant le suivi clinique et la prise en charge prolongés des patients prenant de nouveaux anticoagulants oraux (NACO). Qualité des données Aux fins de cette révision narrative (non systématique), nous avons effectué une recherche dans la base de données PubMed afin de relever des études cliniques récentes (soit de janvier 2008 à la semaine 32 de 2013) portant sur l’emploi des NACO pour la prévention des AVC dans les cas de fibrillation auriculaire et le traitement de la thromboembolie veineuse aiguë. Nous avons utilisé cette base de données probantes pour répondre à nos questions prédéfinies ayant trait à l’emploi des NACO en pratique générale. Message principal Le dabigatran et le rivaroxaban doivent être pris avec les repas afin de limiter la dyspepsie et de favoriser l’absorption, respectivement. Aucun NACO n’est accompagné de restrictions alimentaires, à l’exception de la consommation modérée d’alcool, et le rivaroxaban et l’apixaban peuvent être écrasés, au besoin. Les antiacides ne semblent pas perturber l’efficacité des NACO. Comme c’est le cas avec la warfarine, les patients traités aux NACO doivent éviter l’emploi prolongé d’anti-inflammatoires non stéroïdiens et d’antiplaquettaires. Chez les patients devant subir une chirurgie, il faut interrompre la prise de NACO de 2 à 5 jours avant l’intervention, en fonction du risque de saignement, et le traitement par le NACO doit être habituellement repris au moins 24 heures après la chirurgie. Il n’est habituellement pas nécessaire d’effectuer un test préopératoire de coagulation. Chez les patients qui développent un saignement, un saignement mineur ne justifie habituellement pas un test de laboratoire ni l’interruption du traitement par le NACO; dans le cas des saignements majeurs, il faut se concentrer sur l’application de mesures localisées visant à endiguer le

[The role of hormone analysis in the nosologic diagnosis and in the control of treatment of congenital primary hypothyroidism].

PubMed

Shilin, D E; Shvora, N M; Pykov, M I; Ibragimova, G V; Krotkov, F F; Riabykh, A V; Ponkratova, T S; Kasatkina, E P

2003-08-01

A total of 125 children and teenagers, aged 1 to 15 (including 74 patients with primary congenital hypothyroidism--CH--and 51 healthy children), were investigated in the city of Moscow for the purpose of elaborating new approaches towards the differentiated diagnostics of CH and of optimizing the assessment of the adequacy of its substitutive hormonal therapy (SHT). The concentrations of the thyrotropic hormone (TTH), free fractions of triiodothyronine and thyroxin (cT3 and cT4), thyreoglobulin (Tg) and of thyreoid peroxidase (hard-phase test-tube method, electro-chemiluminescent reaction, i.e. magnetic microparticles, based on the streptovidin-biotin technology; ruthenium mark at the "Elecsys 1010" analyzer with reagents manufactured by "F. Hoffman--La Rosh Ltd.", Switzerland.) were determined early in the morning on the empty stomach. On the basis of the above mentioned, the thyroid reserve index (TRI = Tg/TG), integral thyroid index (ITI = [cT3 + cT4]/TTG), and the integral of peripheral conversion (IPC = cT3/cT4) were calculated. The thyroid gland (TG) was visualized by the "Acuson-128 XP" ultrasonic device, "Acuson Corp.", USA, with a linear sensor of 10 Mhz, as well as by the "Toshiba-90B" gamma-chamber, Japan, with a low-energy collimator in 24 hours after an oral intake of sodium iodide marked by the iodine 123-isotope with an activity of 50 Mbc and after the cessation of SHT 3 to 5 weeks before. The complex diagnosis revealed 8 variations of primary CH; aplasia and TG dystopia and defects of the synthesis of the sodium-iodine symporter or Tg-concentration were found to belong to the most severe disease types according to hormonal parameters. As for Tg, in 52% of cases it was normal, undeterminable--23% and higher--25%. A simultaneously implemented ultrasonic scanning (USS) ensured a final diagnosis in subgroups, respectively, in all cases, in 25% and in 75% of patients. On the whole, after the two diagnostic stages (Tg + USS/ITR), the indications for

Pharmacothérapie de la dépression chez les aînés

PubMed Central

Frank, Christopher

2014-01-01

ceux qui ont une dépression récurrente ou des symptômes sévères devraient continuer le traitement indéfiniment. La prise en charge de situations particulières comme une dépression profonde ou une dépression avec psychose est discutée, y compris le recours à une thérapie électroconvulsive. Les critères pour demander une consultation en psychiatrie gériatrique sont indiqués; par ailleurs, de nombreux médecins de famille n’ont pas aisément accès à une telle ressource ou à d’autres stratégies cliniques non pharmacologiques. Conclusion L’efficacité de la pharmacothérapie de la dépression n’est pas considérablement influencée par l’âge. L’identification de la dépression, le choix du traitement approprié, le tritrage des médicaments, la surveillance des effets secondaires et la durée suffisante du traitement amélioreront les résultats pour les patients plus âgés.

Etude aerodynamique d'un jet turbulent impactant une paroi concave

NASA Astrophysics Data System (ADS)

LeBlanc, Benoit

Etant donne la demande croissante de temperatures elevees dans des chambres de combustion de systemes de propulsions en aerospatiale (turbomoteurs, moteur a reaction, etc.), l'interet dans le refroidissement par jets impactant s'est vu croitre. Le refroidissement des aubes de turbine permet une augmentation de temperature de combustion, ce qui se traduit en une augmentation de l'efficacite de combustion et donc une meilleure economie de carburant. Le transfert de chaleur dans les au bages est influence par les aspects aerodynamiques du refroidissement a jet, particulierement dans le cas d'ecoulements turbulents. Un manque de comprehension de l'aerodynamique a l'interieur de ces espaces confinees peut mener a des changements de transfert thermique qui sont inattendus, ce qui augmente le risque de fluage. Il est donc d'interet pour l'industrie aerospatiale et l'academie de poursuivre la recherche dans l'aerodynamique des jets turbulents impactant les parois courbes. Les jets impactant les surfaces courbes ont deja fait l'objet de nombreuses etudes. Par contre des conditions oscillatoires observees en laboratoire se sont averees difficiles a reproduire en numerique, puisque les structures d'ecoulements impactants des parois concaves sont fortement dependantes de la turbulence et des effets instationnaires. Une etude experimentale fut realisee a l'institut PPRIME a l'Universite de Poitiers afin d'observer le phenomene d'oscillation dans le jet. Une serie d'essais ont verifie les conditions d'ecoulement laminaires et turbulentes, toutefois le cout des essais experimentaux a seulement permis d'avoir un apercu du phenomene global. Une deuxieme serie d'essais fut realisee numeriquement a l'Universite de Moncton avec l'outil OpenFOAM pour des conditions d'ecoulement laminaire et bidimensionnel. Cette etude a donc comme but de poursuivre l'enquete de l'aerodynamique oscillatoire des jets impactant des parois courbes, mais pour un regime d'ecoulement transitoire, turbulent

Photovaporisation prostatique au laser chez les patients à haut risque hémorragique

PubMed Central

Bouabdallah, Zakaria; Kharbouchi, Amine; Colau, Alexandre; Cariou, Gerard

2013-01-01

Introduction Les patients sous traitement anticoagulant sont à risque élevé de saignement lors de la résection transurétrale de la prostate ou de l'adénomectomie par taille vésicale et ils se voient souvent récuser pour la chirurgie de l'hyperplasie bénigne de la prostate symptomatique. En Utilisant la photovaporisation de la prostate, les patients à haut risque peuvent subir en toute sécurité la chirurgie. Nous avons évalué l'innocuité et l'efficacité de la photovaporisation de la prostate (PVP) chez les patients sous anticoagulants en cours avec les dérivés de la coumarine, l'aspirine ou le clopidogrel, se plaignant de symptômes d'hypertrophie bénigne de la prostate. Méthodes Entre janvier 2009 et mai 2010, 47 hommes sous anticoagulation systémique ont subi une photovaporisation de la prostate. Les données ont été recueillies sur les caractéristiques démographiques, les comorbidités, les complications, la natrémie, l'hémoglobine, le débit urinaire maximal, le résidu post-mictionnel, l'IPSS et les complications. Résultats L'âge moyen était de 78 ans, le volume prostatique moyen était de 44g et le PSA était de 3.4ng/ml. Parmi les 10 patients (21.2%) étaient sous AVK, 27 (57.4%) étaient sous aspirine, 2 (4.2%) étaient sous clopidogrel, un sous fondaparinux et 6 (12.7%) étaient sous 2 anticoagulants ou plus. Le score ASA moyen était de 3. La durée moyenne de fonctionnement de l'appareil était de 38 minutes, l'énergie moyenne utilisée était de 200kJ. La durée moyenne d'hospitalisation était de 2 jours. Les complications survenant dans les 30 jours comprenaient une infection urinaire chez 5 patients (10.6%), une dysurie chez 4 patients et une hémorragie retardée chez 4 autres (8.5%). Un seul de ces patients a nécessité une transfusion sanguine et aucun patient n'a nécessité une réintervention. En 3 mois de suivi un seul patient a nécessité une incision du col vésical pour sclérose du col. Aucune incontinence

Developpement d'un montage simulant l'erosion par la pluie pour l'evaluation des revetements glaciophobes dans le domaine aerospatial

NASA Astrophysics Data System (ADS)

Tremblay, Sarah-Eve

Ce memoire presente le developpement d’un montage simulant l’erosion par la pluie afin d’effectuer l’evaluation de differents revetements glaciophobes dans le domaine aerospatial. Bien que plusieurs revetements presentent une bonne efficacite a reduire l’adherence et/ou l’accumulation de glace, ils ne repondent pas necessairement aux normes de resistance a l’erosion simulee par les gouttes de pluie les frappant a grande vitesse. Il n’existe qu’une installation en Amerique du Nord offrant un service d’essai qui evalue la resistance a l’erosion par la pluie suivant les normes aerospatiales. Etant l’unique institution pouvant faire la certification de peintures utilisees sur les avions en ce qui a trait a l’erosion par la pluie, ce service est donc difficile d’acces et couteux. Le laboratoire international des materiaux antigivre (LIMA) a developpe un essai plus rapide et moins couteux, facilitant ainsi le developpement de revetements glaciophobes devant resister a l’erosion par la pluie. Dans cette etude, le developpement du montage d’erosion par la pluie effectue au laboratoire des materiaux antigivre (LIMA) est presente. En particulier, des essais sur quatre (4) revetements dont la resistance a l’erosion est connue, et sur trois revetements industriels, ont ete effectues afin d’ajuster les differents parametres du montage comme la pression et la temperature de l’eau ainsi que la robustesse du montage. Ensuite, des essais de sensibilite et de reproductibilite des resultats ont egalement ete effectues pour fin de validation du montage et du protocole experimental. Pour ce faire, le montage de type jet d’eau developpe consiste principalement en une pompe a haute pression qui projette un jet d’eau continu passant par les orifices d’un disque tournant. Cette operation permet de generer une goutte de pluie simulee qui est projetee sur un echantillon de revetement statique. L’essai est base sur la norme standard ASTM (Liquid

Beneficial auditory and cognitive effects of auditory brainstem implantation in children.

PubMed

Colletti, Liliana

2007-09-01

This preliminary study demonstrates the development of hearing ability and shows that there is a significant improvement in some cognitive parameters related to selective visual/spatial attention and to fluid or multisensory reasoning, in children fitted with auditory brainstem implantation (ABI). The improvement in cognitive paramenters is due to several factors, among which there is certainly, as demonstrated in the literature on a cochlear implants (CIs), the activation of the auditory sensory canal, which was previously absent. The findings of the present study indicate that children with cochlear or cochlear nerve abnormalities with associated cognitive deficits should not be excluded from ABI implantation. The indications for ABI have been extended over the last 10 years to adults with non-tumoral (NT) cochlear or cochlear nerve abnormalities that cannot benefit from CI. We demonstrated that the ABI with surface electrodes may provide sufficient stimulation of the central auditory system in adults for open set speech recognition. These favourable results motivated us to extend ABI indications to children with profound hearing loss who were not candidates for a CI. This study investigated the performances of young deaf children undergoing ABI, in terms of their auditory perceptual development and their non-verbal cognitive abilities. In our department from 2000 to 2006, 24 children aged 14 months to 16 years received an ABI for different tumour and non-tumour diseases. Two children had NF2 tumours. Eighteen children had bilateral cochlear nerve aplasia. In this group, nine children had associated cochlear malformations, two had unilateral facial nerve agenesia and two had combined microtia, aural atresia and middle ear malformations. Four of these children had previously been fitted elsewhere with a CI with no auditory results. One child had bilateral incomplete cochlear partition (type II); one child, who had previously been fitted unsuccessfully elsewhere

Etude de l’hémogramme dans la drépanocytose homozygote: à propos de 87 patients

PubMed Central

Dahmani, Fatima; Benkirane, Souad; Kouzih, Jaafar; Woumki, Aziz; Mamad, Hassan; Masrar, Azlarab

2016-01-01

thrombocytose. Une leucocytose était observée chez 64.4% des patients et 80.5% ont présenté une neutropénie. Les paramètres de l’hémogramme serviront de base de comparaison lors des crises et permettront d’évaluer l’efficacité de la prise en charge par le clinicien. Les valeurs élevées des globules blancs, plaquettes et CCHM semblent déterminants dans l’expression sévère de la drépanocytose au Maroc. Le profil hématologique du drépanocytaire marocain montre des données semblables à celles rapportées en littérature chez ceux de l’Afrique centrale, avec une leucocytose. Les résultats de notre étude suggèrent que, la drépanocytose est un problème de santé le plus fréquent chez les marocains et que nos résultats sont comparables à ceux décrits dans le syndrome drépanocytaire majeur. PMID:28293356

Managing for sustainability in an arid climate: lessons learned from 20 years of groundwater management in Arizona, USA

NASA Astrophysics Data System (ADS)

Jacobs, Katharine L.; Holway, James M.

Substantial progress has been made within central Arizona in moving towards a more sustainable water future, particularly in transitioning the urban demand from a primarily nonrenewable groundwater-based supply to increasing dependence on the Colorado River, Salt River and effluent. Management efforts include a wide range of regulatory and voluntary programs which have had mixed success. The Department of Water Resources has learned a number of key lessons throughout the years, and this paper attempts to establish the water management context and identify those lessons for the benefit of others who may want to evaluate alternative approaches to groundwater management. Themes to be discussed include evaluating water management approaches in a public policy context, the effectiveness of alternative management approaches and the relative merits of regulatory vs. nonregulatory efforts, and the importance of high-quality data in making management decisions. De nets progrès ont été faits dans le centre de l'Arizona pour aller vers une gestion plus durable de l'eau, en particulier en reportant la demande urbaine d'une alimentation basée sur l'eau souterraine primitivement non renouvelable sur une dépendance croissante des rivières Colorado et Salt et des effluents. Les efforts de gestion portent sur une large gamme de programmes de réglementation et d'actions volontaires qui ont réussi. Le Département des Ressources en Eau a appris un certain nombre de leçons clés au cours des années cet article tente d'établir le contexte de gestion de l'eau et d'identifier ces leçons pour le bénéfice de ceux qui cherchent à évaluer des approches alternatives de gestion de l'eau souterraine. Les thèmes à discuter portent sur l'évaluation des approches de gestion de l'eau dans un contexte de politique publique, l'efficacité d'approches alternatives de gestion et les mérites relatifs d'efforts de réglementation par rapport à une absence de réglementation, et l

Effets de la formation sur la violence conjugale

PubMed Central

Zaher, Eman; Keogh, Kelly; Ratnapalan, Savithiri

2014-01-01

Résumé Objectif Décrire et évaluer l’efficacité de la formation concernant la violence conjugale pour améliorer les connaissances et permettre la reconnaissance et la prise en charge par les médecins des femmes victimes de violence. Sources des données On a fait une recension dans la base de données des révisions systématiques de Cochrane, MEDLINE, PubMed, PsycINFO, ERIC et EMBASE pour trouver des articles publiés entre le 1e janvier 2000 et le 1e novembre 2012. Des recherches manuelles ont complété cette recension pour cerner des articles pertinents à l’aide d’une stratégie de recherche combinant des textes, mots et expressions MeSH. Sélection des études On a choisi des études randomisées contrôlées qui portaient sur des interventions éducatives à l’intention des médecins et fournissaient des données sur les effets des interventions. Synthèse On a inclus 9 études randomisées contrôlées qui décrivaient différentes approches pédagogiques et diverses mesures des résultats. Trois études examinaient les effets d’interventions éducatives pour des médecins en formation postdoctorale et ont constaté une augmentation des connaissances, mais il n’y a eu aucun changement dans le comportement en ce qui a trait à l’identification des victimes de violence conjugale. Six études portaient sur des interventions éducatives pour des médecins en pratique active. Trois d’entre elles utilisaient une approche à multiples facettes pour les médecins, qui combinait une formation ainsi que des interventions de soutien de la part du système pour changer les comportements des médecins, comme une sensibilisation générale accrue à la violence conjugale au moyen de brochures et d’affiches, des aide-mémoire pour rappeler aux médecins comment identifier les victimes, des moyens pour faciliter l’accès des médecins à des services de soutien pour les victimes, la réalisation d’audits et la fourniture de rétroaction. Les

Prise en charge des plaies du périnée en post partum: faut-il prescrire systématiquement un antibiotique?

PubMed Central

Fouelifack, Florent Ymele; Eko, Filbert Eko; Ko’A, Claude Odile Vanessa Ebode; Fouedjio, Jeanne Hortence; Mbu, Robinson Enow

2017-01-01

douleur représentait le principal symptôme à J0 post-partum sans prédominance significative d'un groupe (OR = 0.9; IC = 0.14-7.19; P = 1). Les plaies tuméfiées étaient la deuxième plainte sans variation significative dans les deux groupes (OR = 1.69 ; IC = 0.88-3.24 ; P = 0.13). Aucune variation significative n'a été observée à J0, J2 et J9 entre les 2 protocoles en ce qui concerne les indicateurs étudiés : évolution de la douleur, l'infection, la tuméfaction et le délai de cicatrisation. A J9 la guérison était complète dans les deux groupes et les 2 protocoles s'équivalaient au niveau de l'efficacité et la prévention des infections. Conclusion Au terme de cette étude les deux protocoles étaient équivalents. Nous concluons que pour l'intérêt de l'économie de la santé, il n'est pas utile de prescrire les antibiotiques pour la prise en charge des plaies périnéales. PMID:29564033

Lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse

PubMed Central

Kahan, Meldon; Wilson, Lynn; Mailis-Gagnon, Angela; Srivastava, Anita

2011-01-01

Résumé Objectif Présenter aux médecins de famille un résumé clinique pratique sur la prescription d’opioïdes à des populations particulières en se fondant sur les recommandations faites dans les lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse. Qualité des données Pour produire les lignes directrices, les chercheurs ont effectué une synthèse critique de la littérature médicale en insistant plus précisément sur les études de l’efficacité et de la sécurité des opioïdes dans des populations particulières. Message principal Les médecins de famille peuvent atténuer les risques de surdose, de sédation, d’usage abusif et de dépendance grâce à des stratégies adaptées à l’âge et à l’état de santé des patients. Dans le cas de patients à risque de dépendance, on devrait réserver les opioïdes aux douleurs nociceptives ou neuropathiques bien définies qui n’ont pas répondu aux traitements de première intention. Il faut procéder lentement au titrage des opioïdes, avec des dispensations fréquentes et une étroite surveillance pour dépister tout signe d’usage abusif. Une dépendance aux opioïdes suspectée est prise en charge au moyen d’une thérapie structurée aux opioïdes, d’un traitement à la méthadone ou à la buprénorphine ou encore d’un traitement fondé sur l’abstinence. Les patients souffrant de troubles de l’humeur ou d’anxiété ont tendance à avoir une réponse analgésique atténuée aux opioïdes, sont à risque plus élevé d’usage abusif et prennent souvent des sédatifs qui interagissent défavorablement avec les opioïdes. Il faut prendre des précautions semblables à celles utilisées avec d’autres patients à risque élevé. Il faut faire un sevrage progressif si la douleur du patient demeure sévère même avec un essai adéquat de thérapie aux opioïdes. Chez les personnes âgées, la s

Non-linearite et couplages lumiere-matiere en electrodynamique quantique en circuit

NASA Astrophysics Data System (ADS)

Bourassa, Jerome

écanique lagrangienne et la représentation des modes propres d'oscillation. La grande qualité de la méthode réside dans la description analytique détaillée des paramètres de l'hamiltonien du système en fonction de la géométrie et des caractéristiques électromagnétiques du circuit. Non seulement le formalisme développé réconcilie le modèle quantique avec l'électromagnétisme classique et la théorie des circuits, mais va bien au-delà en formulant d'importantes prédictions sur la nature des interactions et l'influence des fluctuations du vide du résonateur sur la dynamique des qubits supraconducteurs. À l'aide d'exemples numériques réalistes et compatibles avec les technologies actuelles, je montre comment de simples optimisations de conception permettraient d'augmenter grandement l'efficacité et la rapidité d'exécution de calculs quantiques avec l'architecture, en plus d'atteindre des régimes de non-linéarité et de couplage lumière-matière inédits. En permettant de mieux comprendre l'interaction lumière-matière dans les circuits et d'optimiser l'architecture afin d'atteindre de nouveaux régimes de couplages, la méthode d'analyse de circuit développée dans cette thèse permettra de tester et raffiner nos connaissances sur l'électrodynamique quantique et la physique quantique. Mots-clés: Information quantique, électrodynamique quantique, supraconductivité, électromagnétisme, qubit supraconducteur, résonateur non linéaire, couplage ultrafort, effet Kerr.

Prise en charge des troubles de consommation d’opioïdes en première ligne

PubMed Central

Srivastava, Anita; Kahan, Meldon; Nader, Maya

2017-01-01

Résumé Objectif Conseiller les médecins quant aux options thérapeutiques à recommander à des populations précises de patients : approche axée sur l’abstinence, traitement d’entretien par la buprénorphine-naloxone ou traitement d’entretien par la méthadone. Sources d’information Une recherche sur PubMed a été effectuée, et on a relevé dans les publications les données sur l’efficacité, l’innocuité et le profil d’effets indésirables de l’approche axée sur l’abstinence, du traitement par la buprénorphine-naloxone et du traitement par la méthadone. Les études d’observation et interventionnelles ont été incluses. Message principal La méthadone et la buprénorphine-naloxone sont substantiellement plus efficaces que l’approche axée sur l’abstinence. La méthadone présente un taux de rétention plus élevé que la buprénorphine-naloxone, alors que la buprénorphine-naloxone présente un risque plus faible de surdose. Les médecins devraient recommander le traitement par la méthadone ou la buprénorphine-naloxone plutôt que l’approche axée sur l’abstinence, et ce, à tous les groupes de patients (données de niveau I). La méthadone est préférable à la buprénorphine-naloxone chez les patients qui présentent un risque élevé d’abandon, comme les usagers d’opioïdes par injection (données de niveau I). Les jeunes et les femmes enceintes qui font usage d’opioïdes par injection devraient aussi recevoir la méthadone d’abord (données de niveau III). Si la buprénorphine-naloxone est prescrite en premier, il faut faire passer rapidement le patient à la méthadone si les symptômes de sevrage, les fortes envies ou la consommation d’opioïdes persistent malgré une dose optimale de buprénorphine-naloxone (données de niveau II). La buprénorphine-naloxone est recommandée chez les usagers d’opioïdes sur ordonnance par voie orale socialement stables, surtout s’ils ont un emploi ou si leurs

Revetements nanostructures pour la protection des metaux dans les environnements marins

NASA Astrophysics Data System (ADS)

Brassard, Jean-Denis

L'objectif de cette recherche est de verifier qu'un materiau superhydrophobe peut diminuer l'adherence et l'accumulation de la glace tout en conservant de bonnes proprietes anticorrosion. Afin de verifier cette assertion, trois familles de nouveaux revetements micros et nanostructures, identifiees par les lettres A, B, et C, ont ete developpes de facon a pouvoir en determiner l'efficacite glaciophobe en relation avec l'angle de contact particulier a chaque structure obtenue. Les revetements ont tous ete optimises pour que l'angle de contact et l'adherence au substrat soient maximaux. Les trois revetements optimises sont les suivants: Le revetement A a ete developpe pour application sur l'acier galvanise. Les microrugosites creees sont celles de la structure de la couche du zinc electrodepose en surface et les nanorugosites sont celles creees par le film de silicone copolymerise nanostructure. Un temps optimal de 10 min a ete retenu pour l'electrodeposition du zinc, ce dernier maximisant l'angle de contact a 155° lorsqu'enduit d'un film de silicone de 100 nm d'epaisseur. Le revetement B a ete developpe pour application sur un alliage d'aluminium. Les microrugosites creees sont celles de la microstructure granulaire obtenue par gravure de l'aluminium immerge dans un bain de HCl et les nanorugosites sont celles creees d'un meme film nanostructure de silicone copolymerise. La valeur optimale du temps de gravure est de 8 minutes et donne l'angle de contact le plus eleve a 154°, lorsqu'enduit du meme film de silicone de 100 nm d'epaisseur depose sur le revetement A. Le revetement C a ete developpe pour etre applique indifferemment sur tout substrat degraisse d'aluminium ou d'acier. Les microrugosites et les nanorugosites sont celles creees par les agregats de nanoparticules de ZnO rendues hydrophobes melangees au silicone qui sont pulverisees sur une couche d'appret composee de silicone et de polymethylhydrosiloxane. On obtient alors un produit composite rigide ou les

The Dammam aquifer in Bahrain - Hydrochemical characterization and alternatives for management of groundwater quality

NASA Astrophysics Data System (ADS)

Zubari, Waleed K.

orientale. Quatre types de salinisation de l'eau souterraine ont été identifiés : une drainance verticale en provenance d'eaux saumâtres sous-jacentes dans les régions nord-centrales, ouest et est, une intrusion marine dans la région est, une intrusion d'eau de sebkha dans la région sud-ouest, et le retour d'irrigation dans un secteur localisé de la région sud-ouest. Quatre démarches alternatives de gestion de la qualité des eaux souterraines, acceptables par les services chargés de l'eau à Bahreïn, sont discutées et des zones d'action prioritaire sont proposées, selon le type et l'étendue de chacune des sources de salinisation et en fonction des usages de les eaux souterraines dans chaque secteur. L'efficacité des options de gestion proposées pour le contrôle de la dégradation de la qualité de l'aquifère de Damman devrait être ensuite évaluée au moyen d'un modèle de simulation. Resumen El acuífero de Damman, el más importante de Bahrein, se explota para usos agrícolas y domésticos. La sobreexplotación del mismo ha provocado su salinización por cuerpos de agua salada y salobre cercanos. Un estudio hidroquímico identificó las fuentes de salinización y ayudó a dibujar sus áreas de influencia. La calidad del agua subterránea se modifica significativamente en la dirección del flujo, desde el noroeste del país, donde las entradas son laterales y procedentes de Arabia Saudí, hacia el sur y el sudeste. Se han identificado cuatro tipos de salinización: flujo ascendente de agua salobre en las regiones norte-central, este y oeste; intrusión de agua marina en la región este; intrusión de agua salobre al sudoeste y, finalmente, retorno de riego en un área local de la región oeste. Se discuten cuatro alternativas para la gestión del agua y se proponen áreas prioritarias basadas en el tipo y la extensión de cada fuente de salinización y en los usos de agua subterránea en cada zona. La efectividad de las opciones de gestión propuestas

Rainforest Pharmacopeia in Madagascar Provides High Value for Current Local and Prospective Global Uses

PubMed Central

Golden, Christopher D.; Rasolofoniaina, B. J. Rodolph; Anjaranirina, E. J. Gasta; Nicolas, Lilien; Ravaoliny, Laurent; Kremen, Claire

2012-01-01

tropical forests for sustainable use. Botanique de la diversité apporte de la valeur à l’homme par la séquestration du carbone, de l’air et de purification de l’eau, et le provisionnement des aliments sauvages et ethnomedicines. Ici, nous calculons la valeur de ethnomedicines botaniques dans une région de forêt de Madagascar, la zone protégée de Makira, en utilisant une méthode de substitution qui combine les coûts de remplacement et la modélisation des choix. Le bassin versant de Makira peut comprendre environ 0,8% de la diversité botanique mondiale et possède une valeur énorme à la fois dans sa capacité à fournir ethnomedicines botaniques à la population locale et en tant que source de nouveaux médicaments potentiellement pharmaceutiques pour la société dans son ensemble. Environ 241 espèces localement reconnus sont utilisés comme ethnomedicines, y compris 113 espèces d’agricoles ou de mauvaises herbes. Nous assimilé chaque traitement ethnomédicales à la valeur monétaire d’un traitement comparable pharmaceutique ajusté en fonction des préférences personnelles en matière d’efficacité perçue (plutôt que de l’équivalence médicament connu ou supposé). La valeur de l’avantage de ces ethnomedicines botaniques par individu est de $5,40 à 7.90 par année lors de l’utilisation de la valeur des produits pharmaceutiques malgaches fortement subventionnés et de $100,60 à 287,40 lors de l’utilisation de la valeur des produits pharmaceutiques américains. Utilisation de produits pharmaceutiques locales comme des substituts, la valeur par ménage est de $30.24 à 44.30 par an, équivalent à 43–63% du revenu médian des ménages annuelle, ce qui démontre leur importance locale. Utilisation de la valeur des produits pharmaceutiques américaines, le montant est équivalent à 22–63% de la médiane des dépenses annuelles de soins de santé pour les adultes américains de moins de 45 en 2006. Le potentiel de développement de