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Sample records for temporal bone myeloid

  1. Temporal bone imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemmerling, Marc [Algemeen Ziekenhuis Sint-Lucas, Gent (Belgium). Dept. of Radiology; Foer, Bert de (ed.) [Sint-Augustinus Ziekenhuis, Wilrijk (Belgium). Dept. of Radiology

    2015-04-01

    Complete overview of imaging of normal and diseased temporal bone. Straightforward structure to facilitate learning. Detailed consideration of newer imaging techniques, including the hot topic of diffusion-weighted imaging. Includes a chapter on anatomy that will be of great help to the novice interpreter of imaging findings. Excellent illustrations throughout. This book provides a complete overview of imaging of normal and diseased temporal bone. After description of indications for imaging and the cross-sectional imaging anatomy of the area, subsequent chapters address the various diseases and conditions that affect the temporal bone and are likely to be encountered regularly in clinical practice. The classic imaging methods are described and discussed in detail, and individual chapters are included on newer techniques such as functional imaging and diffusion-weighted imaging. There is also a strong focus on postoperative imaging. Throughout, imaging findings are documented with the aid of numerous informative, high-quality illustrations. Temporal Bone Imaging, with its straightforward structure based essentially on topography, will prove of immense value in daily practice.

  2. Aneurysmal bone cyst of temporal bone.

    Science.gov (United States)

    Ansari, Sajid; Ahmad, Kaleem; Gupta, Mukesh Kumar; Rauniyar, Raj Kumar

    2013-09-07

    Aneurysmal bone cysts (ABC) are benign neoplasms frequently occurring in the long tubular bones. It is very rare in temporal bone. We report a case of ABC of the left temporal bone in an 8-year-old Asian boy who presented clinically with swelling over the left temporal region for 5 months. CT and MRI features were suggestive of ABC. Surgical resection was performed and on follow-up the patient was doing well. CT and MRI are the imaging modalities for proper evaluation of ABC, aiding to diagnosis and helpful in treatment planning.

  3. Ivory Osteoma Of Temporal Bone

    Directory of Open Access Journals (Sweden)

    Ravi Meher

    2006-03-01

    Full Text Available Osteomas are slow growing bony tumors common in fronto-ethmoid regions and rare in temporal bone. These are usually asymptomatic and require treatment mainly for cosmetic reasons. We describe a case of temporal bone osteoma in a female.

  4. Treatment of Temporal Bone Fractures.

    Science.gov (United States)

    Diaz, Rodney C; Cervenka, Brian; Brodie, Hilary A

    2016-10-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted.

  5. Treatment of Temporal Bone Fractures

    Science.gov (United States)

    Diaz, Rodney C.; Cervenka, Brian; Brodie, Hilary A.

    2016-01-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted. PMID:27648399

  6. Osteoradionecrosis of the temporal bone

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    Fujimori, Masato; Koyama, Yukiko; Enomoto, Fuyuki; Ichikawa, Ginichiro [Juntendo Univ., Tokyo (Japan). School of Medicine

    2002-08-01

    We report a case of temporal bone necrosis that emerged after radiotherapy for epipharyngeal carcinoma performed 13 years ago. The patient was a 51-year-old male. His major complaint was left facial swelling. The patient underwent chemotherapy and radiotherapy (Co 60, 6120 rad), as the treatment of that period, for epipharyngeal carcinoma from September 30, 1986 to January 31, 1987. He also underwent lobectomy of the left temporal lobe in brain surgery for left temporal lobe necrosis in August, 1989. After that operation, we saw constriction in his left external acoustic meatus and continued the follow-up. On October 22, 1999 he felt a left facial swelling. We found skin defects and ulcer formation in the front part of his left ear. Although we administered an antiseptic and antibiotic to the diseased area, his condition did not improve. He was hospitalized for the purpose of undergoing medical treatment on January 6, 2000. We found extensive skin necrosis and defects in his left auricular area. The corrupted temporal bone reached the zygomatic, the bone department external acoustic meatus and the mastoid process was exposing. We performed debridement of the diseased area on January 19, 2000. On February 23, we performed reconstruction by left trapezius muscle flap after debridement once again. One year after the operation, the flap was completely incorporated. (author)

  7. Schneiderian papilloma of the temporal bone

    NARCIS (Netherlands)

    van der Putten, L.; Bloemena, E.; Merkus, P.; Hensen, E.F.

    2013-01-01

    Temporal bone Schneiderian papilloma may present as a primary tumour originating from the middle ear and mastoid process, or an extension from sinonasal disease. Both forms are rare, this being only the 18th case of primary temporal bone Schneiderian papilloma described to date. Although the current

  8. Giant osteoblastoma of temporal bone: case report

    Directory of Open Access Journals (Sweden)

    FIGUEIREDO EBERVAL GADELHA

    1998-01-01

    Full Text Available Benign osteoblastoma is an uncommon bone tumor accounting for approximately 1% of all bone tumors. There are only 35 cases of skull osteoblastoma reported in the literature. We describe the case of a 23 year old male with a giant osteoblastoma of temporal bone submitted to a total removal of the tumor after an effective embolization of all external carotid branches. The authors discuss diagnostic and management aspects of this uncommon skull tumor.

  9. Acute radiographic workup of blunt temporal bone trauma: maxillofacial versus temporal bone CT.

    Science.gov (United States)

    Dempewolf, Ryan; Gubbels, Sam; Hansen, Marlan R

    2009-03-01

    To evaluate the radiographic workup of blunt temporal bone trauma and determine the utility of maxillofacial computed tomography (CT) versus temporal bone CT in identifying carotid canal fractures. Retrospective review. The charts of 227 patients evaluated at a level I trauma center receiving a temporal bone CT for blunt head trauma within 48 hours of admission were reviewed. Acute evaluation findings and complications were noted. Sensitivity, specificity, positive predictive value, and negative predictive (NPV) value were calculated for maxillofacial CT's ability to identify carotid canal fractures compared to temporal bone CT. One hundred forty fractures were found. Physical exam findings of blood in the external auditory canal as the sole finding, and blood in the external auditory canal with associated hemotympanum were significantly associated with absence and presence of fracture respectively. The sensitivity and specificity of maxillofacial CT for identifying carotid canal fractures, when compared to temporal bone CT, were 90.3% and 94.4% respectively (NPV > 95%). Only 6% of all patients either did have or should have had their management changed based on the temporal bone CT findings. All of these changes were regarding further workup for blunt carotid artery injury. A combination of helical computed tomography and physical exam findings can allow for judicious use of temporal bone CTs when no maxillofacial CT is indicated. Temporal bone CTs rarely change acute management. But when they do, it is in regard to the need for further workup of possible vascular injury. Lastly, maxillofacial CTs are adequate for identifying carotid canal fractures.

  10. VSTM-v1, a potential myeloid differentiation antigen that is downregulated in bone marrow cells from myeloid leukemia patients

    OpenAIRE

    Xie, Min; Li, Ting; Li, Ning; Li, Jinlan; Yao, Qiumei; Han, Wenling; Ruan, Guorui

    2015-01-01

    Leukocyte differentiation antigens often represent important markers for the diagnosis, classification, prognosis, and therapeutic targeting of myeloid leukemia. Herein, we report a potential leukocyte differentiation antigen gene VSTM1 (V-set and transmembrane domain-containing 1) that was downregulated in bone marrow cells from leukemia patients and exhibited a higher degree of promoter methylation. The expression level of its predominant encoded product, VSTM1-v1, was positively correlated...

  11. European status on temporal bone training

    DEFF Research Database (Denmark)

    Frithioff, Andreas; Sørensen, Mads Sølvsten; Andersen, Steven Arild Wuyts

    2018-01-01

    laboratory facilities for training seems to be decreasing. Alternatives to traditional training can consist of drilling artificial models made of plaster or plastic but also virtual reality (VR) simulation. Nevertheless, the integration and availability of these alternatives into specialist training programs...... remain unknown. METHODS: We conducted a questionnaire study mapping current status on temporal bone training and included responses from 113 departments from 23 countries throughout Europe. RESULTS: In general, temporal bone training during residency in ORL is organized as in-house training...

  12. Comparison of temporal bone fractures in children and adults.

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    Kang, Ho Min; Kim, Myung Gu; Hong, Seok Min; Lee, Ho Yun; Kim, Tae Hyun; Yeo, Seung Geun

    2013-05-01

    Contrary to our expectation, that the clinical characteristics of temporal bone fracture would differ in children and adults, we found that the two groups were similar. Most studies of temporal bone fractures have been performed in adults. To our knowledge, no study has investigated differences in temporal bone fractures in children and adults. We therefore investigated differences in temporal bone fractures in adults and children by examining the manifestations and clinical symptoms of temporal bone fractures in pediatric patients. The demographic and clinical characteristics were assessed in 32 children and 186 adults with temporal bone fractures. All patients underwent computed tomography of the temporal bone. Causes of fracture, gender distribution, manifestations of temporal bone fracture, and clinical symptoms were similar in adults and children (p > 0.05 each). Petrous fracture, ear fullness, dizziness, and tinnitus were significantly more frequent in adults than in children (p < 0.05 each).

  13. 3D Printed Pediatric Temporal Bone: A Novel Training Model.

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    Longfield, Evan A; Brickman, Todd M; Jeyakumar, Anita

    2015-06-01

    Temporal bone dissection is a fundamental element of otologic training. Cadaveric temporal bones (CTB) are the gold standard surgical training model; however, many institutions do not have ready access to them and their cost can be significant: $300 to $500. Furthermore, pediatric cadaveric temporal bones are not readily available. Our objective is to develop a pediatric temporal bone model. Temporal bone model. Tertiary Children's Hospital. Pediatric patient model. We describe the novel use of a 3D printer for the generation of a plaster training model from a pediatric high- resolution CT temporal bone scan of a normal pediatric temporal bone. Three models were produced and were evaluated. The models utilized multiple colors (white for bone, yellow for the facial nerve) and were of high quality. Two models were drilled as a proof of concept and found to be an acceptable facsimile of the patient's anatomy, rendering all necessary surgical landmarks accurately. The only negative comments pertaining to the 3D printed temporal bone as a training model were the lack of variation in hardness between cortical and cancellous bone, noting a tactile variation from cadaveric temporal bones. Our novel pediatric 3D temporal bone training model is a viable, low-cost training option for previously inaccessible pediatric temporal bone training. Our hope is that, as 3D printers become commonplace, these models could be rapidly reproduced, allowing for trainees to print models of patients before performing surgery on the living patient.

  14. Establishing a temporal bone laboratory: considerations for ENT specialist training.

    LENUS (Irish Health Repository)

    Fennessy, B G

    2012-02-01

    Cadaveric temporal bone dissection in a temporal bone laboratory is a vital component in training safe, competent otorhinolaryngologists. Recent controversies pertaining to organ retention have resulted in a more limited supply of temporal bones. Consequently, current trainees are dissecting far fewer bones than their consultants. We discuss the establishment of a temporal bone laboratory in the Department of Anatomy in the University College Cork, from the timely preparation and preservation of the tissue to its disposal. Comparisons are drawn between our experience and that of the United States training schemes. The temporal bone laboratory in Cork is the only one in existence in Ireland. The exposure and experience obtained by registrars rotating through Cork, has resulted in noticeable improvements in their operative abilities. The temporal bone laboratory remains a core component to training. It is hoped that this article may facilitate other units overcoming obstacles to establish a temporal bone laboratory.

  15. CT of temporal bone - IV. inner ear

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    Kwon, Jae Yoon; Sung, Kyu Bo; Youn, Eun Kyoung; Park, Youn Kyeung; Lee, Young Uk [Koryo general Hospital, Seoul (Korea, Republic of)

    1990-07-15

    Temporal bone CT was done in 697 patients from April 1985 to October 1989. The abnormal findings were seen in 453 patients, which were chronic otitis media in 355 patients, fracture in 49 patients and congenital anomaly in 44 patients, etc. The abnormal findings of inner ear were observed on 46 patients. The results were summarized as follows : 1. The incidence of inner ear involvement by chronic otitis media was 7.3% (26/355 : labyrinthine fistula in 17 patients, labyrinthitis ossificans in 9 patients). Labyrinthine fistula was most commonly located on lateral semicircular canal (15/17, 88.2%). 2. Fusion of vestibule with lateral semicircular canal and formation of common cavity was demonstrated incidentally in 5 patients (0.7% of total number of temporal bone CT), and bilateral in 3 patients. 3. The incidence of inner ear anomaly in congenital ear anomaly was 11.4% (5/44). All cases were bilateral and three patients showed associated middle ear anomaly. 4. The incidence of involvement of bony labyrinth in temporal bone fracture was 10.2% (5/49). Labyrinthine fracture was seen all patients of transverse(3) and mixed fracture(1). In longitudinal fracture, labyrinthine fracture was seen in 2.2% (1/45). 5. Others were traumatic labyrinthitis ossificans(1), intracanalicular acoustic neuroma(3) and facial nerve neuroma(1)

  16. Acute myeloid leukaemia with mutated NPM1 presenting with extensive bone marrow necrosis and Charcot-Leyden crystals.

    Science.gov (United States)

    Taylor, Gordon; Ivey, Adam; Milner, Benedict; Grimwade, David; Culligan, Dominic

    2013-09-01

    Here, we report an unusual case of acute myeloid leukaemia with mutated NPM1 presenting with pancytopenia and leukoerythroblastosis, without circulating blasts and bone marrow necrosis with numerous Charcot-Leyden crystals, but no eosinophilia.

  17. [Unifocal eosinophilic granuloma of the temporal bone].

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    Rodríguez Fernández-Freire, A; Porras Alonso, E; Benito Navarro, J R; Rodríguez Pérez, M; Hervás Núñez, M J

    2007-01-01

    We present a case of a twelve year old child with a eosinophilic granuloma of the temporal bone. The eosinophilic granuloma is the most frecuent and most benign form of the histiocytosis of the Langerhans cells. The frecuency of the othological manifestations of this condition varies between 15-60 percent and radiologically, the images are characterized by litho-lesions with sharp edges. The diagnosis is histological and the treatment includes surgical intervention accompanied by inter-lesion corticoid-therapy and/or radiotherapy.

  18. Activation of Myeloid-Derived Suppressor Cells in Bone Marrow

    Science.gov (United States)

    2013-12-01

    osteoclasts bone contains other resident macrophages, especially in the endosteal and periosteal areas (15). These “osteal” macrophages support... periosteal regions, PTH treatment resulted in increased cellularity of relatively cuboidal-shaped bone-lining cells and recruited F4/80+osteal macrophages...1315153111 PNAS Early Edition | 1 of 6 M ED IC A L SC IE N CE S Appendix 2 covered the periosteal lining cells. In contrast, control bones showed

  19. Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment.

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    Denis Evseenko

    Full Text Available Lysophosphatidic acid (LPA is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation. LPA receptors were expressed at significantly higher levels on Common Myeloid Progenitors (CMP than either multipotent Hematopoietic Stem/Progenitor Cells (HSPC or Common Lymphoid Progenitors (CLP suggesting that LPA acts on committed myeloid progenitors. Functional studies demonstrated that LPA enhanced migration, induced cell proliferation and reduced apoptosis of isolated CMP, but had no effect on either HSPC or CLP. Analysis of adult and fetal human bone marrow sections showed that PPAP2A, (the enzyme which degrades LPA was highly expressed in the osteoblastic niche but not in the perivascular regions, whereas Autotaxin (the enzyme that synthesizes LPA was expressed in perivascular regions of the marrow. We propose that a gradient of LPA with the highest levels in peri-sinusoidal regions and lowest near the endosteal zone, regulates the localization, proliferation and differentiation of myeloid progenitors within the bone marrow marrow.

  20. Temporal bone anatomy in Panthera tigris

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    Walsh, Edward J.; Ketten, Darlene R.; Arruda, Julie; Armstrong, Douglas L.; Curro, Thomas; Simmons, Lee G.; Wang, Lily M.; McGee, Joann

    2004-05-01

    Preliminary findings suggest that members of Panthera tigris subspecies may rely on low-frequency acoustic cues when communicating with conspecifics either in the field or in captivity. This view is supported by the observation that individuals are sensitive to tone bursts in the 300-500-Hz range and produce significant acoustic energy in an overlapping frequency band in the case of close encounter roars. Other utterances within the vocal repertoire of tigers also contain, and are often dominated by, low frequency acoustic energy that can extend into the infrasonic range. Efforts to determine temporal bone correlates of P. tigris bioacoustical features were recently initiated using computerized tomography to assess key aspects of middle and inner ear morphology from a small set of adult Siberian tigers (P. tigris altaica) and one neonate. Obvious peripheral auditory specializations were not observed and structures comprising the auditory periphery were consistent with the anatomical character of felids generally. Although cochlear dimensions appeared to be adultlike, or nearly so, in the case of the neonate, other temporal bone features were grossly immature. The relationship between acoustic sensitivity, the spectral character of a subset of close encounter calls and cochlear dimensions will be considered.

  1. Radiation injury to the temporal bone

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    Guida, R.A.; Finn, D.G.; Buchalter, I.H.; Brookler, K.H.; Kimmelman, C.P. (New York Eye and Ear Infirmary/New York Medical College (USA))

    1990-01-01

    Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditory canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.

  2. Chondrosarcoma of the temporal bone: a case report

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    Park, Man Soo; Lee, Sang Youl; Chung, Jae Gul; Lee, Deok Hee; Jung, Seung Mun; Ryu, Dae Sik [Kang Nung Hospital, Ulsan Univ. Kangnung (Korea, Republic of)

    2001-07-01

    Chondrosarcoma of the temporal bone is a rare lesion. Clinically it has been confused with chordoma, glomus jugulare tumor and meningioma, among other conditions, and due to its anatomic location, cranial nerve palsy is frequently observed. We report a case involving a 50-year-old woman with chondrosarcoma of the temporal bone.

  3. Primary temporal bone secretory meningioma presenting as chronic otitis media.

    NARCIS (Netherlands)

    Marcelissen, T.A.; Bondt, R.B.J de; Lammens, M.M.Y.; Manni, J.J.

    2008-01-01

    We report an extremely rare case of a secretory meningioma primarily involving the temporal bone. A 56-year old female patient presented to us with a history of a chronic otitis media and unilateral hearing loss. Diagnostic investigations revealed a tumor arising from the temporal bone without signs

  4. Role of mastoid pneumatization in temporal bone fractures.

    Science.gov (United States)

    Ilea, A; Butnaru, A; Sfrângeu, S A; Hedeşiu, M; Dudescu, C M; Berce, P; Chezan, H; Hurubeanu, L; Trombiţaş, V E; Câmpian, R S; Albu, S

    2014-07-01

    The mastoid portion of the temporal bone has multiple functional roles in the organism, including regulation of pressure in the middle ear and protection of the inner ear. We investigated whether mastoid pneumatization plays a role in the protection of vital structures in the temporal bone during direct lateral trauma. The study was performed on 20 human temporal bones isolated from cadavers. In the study group formed by 10 temporal bone samples, mastoid cells were removed and the resulting neocavities were filled. The mastoids were maintained intact in the control group. All samples were impacted at the same speed and kinetic energy. The resultant temporal bone fractures were evaluated by CT. Temporal squama fractures were 2.88 times more frequent, and mastoid fractures were 2.76 times more frequent in the study group. Facial nerve canal fractures were 6 times more frequent in the study group and involved all the segments of the facial nerve. Carotid canal fractures and jugular foramen fractures were 2.33 and 2.5 times, respectively, more frequent in the study group. The mastoid portion of the temporal bone plays a role in the absorption and dispersion of kinetic energy during direct lateral trauma to the temporal bone, reducing the incidence of fracture in the setting of direct trauma. © 2014 by American Journal of Neuroradiology.

  5. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  6. Building a virtual reality temporal bone dissection simulator.

    Science.gov (United States)

    Kuppersmith, R B; Johnston, R; Moreau, D; Loftin, R B; Jenkins, H

    1997-01-01

    The temporal bone is one of seven bones that comprise the human skull, and has an intimate relationship with many vital structures. Anatomically, its three-dimensional relationships make it one of the most challenging areas for surgeons to understand and master. In addition, the temporal bone contains minute structures that are among the most sophisticated and delicate in the human body. These structures include the cochlea and vestibular organs, which are responsible for hearing and balance; the middle ear, including the ossicles, which conduct acoustic energy to the cochlea; and the facial nerve, which is responsible for controlling the muscles of facial expression, and contributes to the sensation of taste. Additionally, the temporal bone forms a major portion of the skull base, and has intimate relationships to vital structures including the carotid artery, jugular vein, cerebral cortex, brainstem, and cranial nerves. Surgical procedures performed on the temporal bone include: procedures to eradicate chronic and acute infections; procedures to remove malignant and benign tumors within the temporal bone, from the skull base, or from the posterior cranial fossa; procedures to restore the hearing mechanism; procedures to eliminate balance disorders; and procedures to correct congenital anomalies. For surgeons-in-training, and even surgeons-in-practice, mastery of the anatomy of the temporal bone and the many complex approaches necessary to treat patients takes years of focused endeavor. This is typically accomplished through the dissection of human cadaver temporal bones, which are scarce, and require a dedicated laboratory facility. Efforts are currently underway to develop a realistic simulator for temporal bone procedures. Users immersed in the simulator will interact with a three-dimensional temporal bone, derived from patient-specific data, using a haptic interface to simulate traditional surgical procedures. Feedback from experts in otologic surgery will be

  7. Temporal Bone Fracture Causing Superior Semicircular Canal Dehiscence

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    Kevin A. Peng

    2014-01-01

    Full Text Available Importance. Superior semicircular canal dehiscence (SCD is a third window lesion of the inner ear causing symptoms of vertigo, autophony, tinnitus, and hearing loss. A “two-hit” hypothesis has traditionally been proposed, whereby thinly developed bone overlying the superior canal is disrupted by a sudden change in intracranial pressure. Although the symptoms of SCD may be precipitated by head injury, no previous reports have described a temporal bone fracture directly causing SCD. Observations. Two patients sustained temporal bone fractures after closed head trauma, and developed unilateral otologic symptoms consistent with SCD. In each instance, computed tomography imaging revealed fractures extending through the bony roof of the superior semicircular canal. Conclusions and Relevance. Temporal bone fractures, which are largely treated nonoperatively, have not previously been reported to cause SCD. As it is a potentially treatable entity, SCD resulting from temporal bone fracture must be recognized as a possibility and diagnosed promptly if present.

  8. Cadaveric Temporal Bone Dissection: Is It Obsolete Today?

    Directory of Open Access Journals (Sweden)

    Naik, Sulabha M.

    2014-01-01

    Full Text Available Introduction Traditionally, surgical training in otology, is imparted by dissecting harvested human cadaveric temporal bones. However, maintenance of a cadaveric temporal bone laboratory is expensive and carries risk of exposure to infection. In recent times, other modalities of training are gaining ground and are likely to eventually replace cadaveric temporal bone dissection altogether. Objectives Other alternative methods of training are emerging. New technology like simulation and virtual reality as high-fidelity, safer alternatives, are making rapid strides as teaching tools. Other options are the use of animal temporal bones as teaching tools. The advantages of these are compared. Data Synthesis None of these modalities can replicate the innumerable anatomical variations which are a characteristic feature of the human temporal bone. A novice surgeon not only needs exposure to surgical anatomy and it's variations but also needs to develop hand-eye coordination skills to gain expertise. Conclusion Deliberate practice on human cadaveric temporal bones only, will confer both mastery in anatomy and surgical technique. The human cadaveric temporal bone is ideal simulator for training in otology.

  9. Temporal bone dissection practice using a chicken egg.

    Science.gov (United States)

    Meléndez García, José Manuel; Araujo Da Costa, Ana Sofía; Rivera Schmitz, Teresa; Chiesa Estomba, Carlos Miguel; Hamdan Zavarce, Miriam Ileana

    2014-07-01

    Temporal bone drilling practice constitutes an essential stage in training for the surgical approach to this complex anatomic structure. To facilitate adaptation and surgical skills in otologic surgery, we recall the easy cost-effective practice of drilling a chicken egg. The resident in training must master the use of the surgical microscope, the burr, and fine drilling instruments used in dissection. Animal models, plastic temporal bones, prototyped temporal bones, and virtual reality temporal bones have all been used. This article describes a method of training residents' otologic skills by drilling a chicken egg. We used basic support materials found in a typical temporal bone dissection laboratory, with a surgical microscope, a desk, and a drilling system. Practice includes drilling and dissection of the eggshell, preserving the natural eggshell membrane. Learning temporal bone drilling on an egg, using basic materials, allows the surgeon to simulate surgery on a physical model using the same instrumentation that is used in surgery, obviating the need for laboratory conditions required for cadaveric dissection. Simulation is emerging as a mandatory component of surgical training. The egg is an excellent cost-effective model for drilling and dissection training and helps in improving surgical skills, enables learning of fine motor skills, and allows repeated practice. Although this method of training does help one control a drill and manual instrumentation, it does not help with temporal bone anatomy knowledge.

  10. [Acute myeloid leukemia with bone marrow erythroblastosis: about one case illustrating the new WHO classification (2008)].

    Science.gov (United States)

    Vincenot, Anne; Abarah, Wajed; Frayfer, Jamilé; Mahfouz, Imad; Andre-Kerneis, Elisabeth

    2011-01-01

    We reported here a case of acute myeloid leukaemia (AML) in a 28-year-old male patient, which diagnosis is discussed according to the different classifications. This case focused on some new criteria and changes in the new WHO classification (2008) of AML, especially when erythroid precursors represent over 50% of bone marrow nucleated cells. It also pointed on some gene mutations (NPM1, CEPBA, FLT3, WT1…) and their prognostic features in AML with a normal karyotype, leading to individualize two new provisional entities in the WHO classification of tumours of hematopoietic and lymphoid tissues 2008.

  11. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance spe....... In conclusion, the non-invasive MRS method may be a useful and reliable in vivo examination for expansion of haemopoiesis and a correspondent reduction of fat tissue in bone marrow after priming with recombinant human haemopoietic growth factors.......Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance...... (day 0), day 5 and day 12. Spectroscopic examinations were performed with the stimulated echo acquisition mode (STEAM) method on a 1.5 T clinical whole-body imaging unit. A cubic volume of interest (VOI) was selected in the bone marrow of the left iliac bone. The patients responded with a rise in blood...

  12. BASIC PRINCIPLES OF THE PYRAMIDS TEMPORAL BONE RADIOGRAPHY

    Directory of Open Access Journals (Sweden)

    Mirko Krstić

    2007-10-01

    Full Text Available This paper shows the possibilities and advantages of certain methods of temporal bone radiography in diagnosing pathological conditions and diseases of temporal bones, with description of basic techniques of radiological examinations: Mayer’s axial view of the pyramids, the Stenvers view of the pyramids, the Arcelini view of the pyramids, comparative pyramid radiography by Hass, comparative pyramid radiography by Gras-hey, comparative pyramid radiography in submentovertical projection and comparative pyramid radiography in verticosubmental projection.

  13. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  14. Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia.

    Science.gov (United States)

    Percival, Mary-Elizabeth; Lai, Catherine; Estey, Elihu; Hourigan, Christopher S

    2017-07-01

    The diagnosis of acute myeloid leukemia (AML) can be made based on peripheral blood or bone marrow blasts. In this review, we will discuss the role of bone marrow evaluation and peripheral blood monitoring in the diagnosis, management, and follow up of AML patients. For patients with circulating blasts, it is reasonable to perform the necessary studies needed for diagnosis and risk stratification, including multiparametric flow cytometry, cytogenetics, and molecular analysis, on a peripheral blood specimen. The day 14 marrow is used to document hypocellularity in response to induction chemotherapy, but it is unclear if that assessment is necessary as it often does not affect immediate management. Currently, response assessments performed at count recovery for evaluation of remission and measurable residual disease rely on bone marrow sampling. For monitoring of relapse, peripheral blood evaluation may be adequate, but the sensitivity of bone marrow testing is in some cases superior. While bone marrow evaluation can certainly be avoided in particular situations, this cumbersome and uncomfortable procedure currently remains the de facto standard for response assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Myeloid Neoplasms.

    Science.gov (United States)

    Subtil, Antonio

    2017-09-01

    The classification of myeloid neoplasms has undergone major changes and currently relies heavily on genetic abnormalities. Cutaneous manifestations of myeloid neoplasms may be the presenting sign of underlying bone marrow disease. Dermal infiltration by neoplastic cells may occur in otherwise normal skin or in sites of cutaneous inflammation. Leukemia cutis occasionally precedes evidence of blood and/or bone marrow involvement (aleukemic leukemia cutis). Copyright © 2017 Elsevier Inc. All rights reserved.

  16. High Acute Myeloid Leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow

    NARCIS (Netherlands)

    Weidenaar, Alida C.; ter Elst, Arja; Koopmans-Klein, Gineke; Rosati, Stefano; den Dunnen, Wilfred F. A.; Meeuwsen-de Boer, Tiny; Kamps, Willem A.; Vellenga, Edo; de Bont, Eveline S. J. M.

    Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the

  17. A Bone-Thickness Map as a Guide for Bone-Anchored Port Implantation Surgery in the Temporal Bone

    Directory of Open Access Journals (Sweden)

    Jérémie Guignard

    2013-11-01

    Full Text Available The bone-anchored port (BAP is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10 with conventional surgery without assistance (n = 5 in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone.

  18. CT-scanning of ancient Greenlandic Inuit temporal bones

    DEFF Research Database (Denmark)

    Homøe, P; Lynnerup, N; Videbaek, H

    1992-01-01

    Additional morphological evidence of former infectious middle ear disease (IMED) was found by CT-scanning in 5 of 6 Greenlandic Inuit crania strongly suspected for former IMED due to earlier examination revealing either bilateral hypocellularity or asymmetry of the pneumatized area of the temporal...... as a congenital malformation or an infection in infanthood. CT-scan confirms and even adds to the results of conventional X-ray of temporal bones making hypotheses of paleopathology more reliable. The findings also support the environmental theory of pneumatization of the air cell system in the temporal bones....

  19. CT-scanning of ancient Greenlandic Inuit temporal bones

    Energy Technology Data Exchange (ETDEWEB)

    Homoe, P. (Copenhagen Univ. (Denmark). Lab. of Biological Anthropology and Dept. of Otolaryngology, Head and Neck Surgery); Lynnerup, N. (Copenhagen Univ., Lab. of Biological Anthropology and Univ. Inst. of Ferensic Medicine, Copenhagen (Denmark)); Videbaek, H. (Hvidovre Univ. Hospital, Copenhagen (Denmark). Dept. of Radiology)

    1992-01-01

    Additional morphological evidence of former infectious middle ear disease (IMED) was found by CT-scanning in 5 of 6 Greenlandic Inuit crania strongly suspected for former IMED due to earlier examination revealing either bilateral hypocellularity or asymmetry of the pneumatized area of the temporal bones. The CT-scans showed sclerosing and obliteration of the air cells and even destruction of the cellular septae, and a high degree of irregularity of the cells. Sclerosing of the surrounding bone tissue was also found. The findings in one cranium were dubious and could both be regarded as a congenital malformation or an infection in infanthood. CT-scan confirms and even adds to the results of conventional X-ray of temporal bones making hypotheses of paleopathology more reliable. The findings also support the environmental theory of pneumatization of the air cell system in the temporal bones. (13 refs., 10 figs.).

  20. Evidence of Osteoclastic Activity in the Human Temporal Bone.

    Science.gov (United States)

    Kamakura, Takefumi; Nadol, Joseph B

    2017-12-09

    Bone remodeling within the otic capsule has been reported to be inhibited especially at or near the cochlea, except under some pathological conditions such as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur. Microcavitations found in periosteal and endosteal layers of human temporal bone specimens without otosclerosis, Paget's disease, or inflammation as reported in the current study are consistent with osteoclastic bone resorption. Thirty-three temporal bones from 33 patients were prepared for light microscopy and classified into 4 groups: histologically proven dehiscence of the superior semicircular canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older and with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic locations in the temporal bone in all 4 groups, but not in the cochlea or vestibule. Microcavitation within the temporal bone is likely due to osteoclastic activity, and it is seen in both young and old patients, patients with and without otosclerosis, and in cases with SSCD. © 2017 S. Karger AG, Basel.

  1. Massive Cerebrospinal Fluid Leak of the Temporal Bone

    Directory of Open Access Journals (Sweden)

    Giannicola Iannella

    2016-01-01

    Full Text Available Cerebrospinal fluid (CSF leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS with subsequent radiation treatment and second operation with total VS resection.

  2. Cockayne syndrome--an audiologic and temporal bone analysis.

    Science.gov (United States)

    Shemen, L J; Mitchell, D P; Farkashidy, J

    1984-04-01

    Cockayne's syndrome is a triad of dwarfism, retinal atrophy, and deafness. Over thirty cases have been presented in the literature. We have examined and audiometrically tested three patients (ages 13 to 17) with confirmed Cockayne's syndrome and have analyzed the temporal bones of another who died at age 24. To our knowledge this is the first reported temporal bone analysis of a patient with Cockayne's syndrome. Audiograms revealed bilateral symmetric sensorineural hearing loss that was greatest in the high frequencies. Temporal bone examinations revealed inner and outer hair cell losses in the basal turn of the cochlea with corresponding neuron losses in the spiral ganglion. We have found that the clinical and histopathologic features resemble those of presbycusis and conclude that this corresponds well with the generalized, rapid, premature aging process characteristic of this disease.

  3. Temporal bone CT measurement for pediatric cochlear implantation

    Energy Technology Data Exchange (ETDEWEB)

    Naito, Yasushi; Honjo, Iwao; Takahashi, Haruo; Fujiki, Nobuya; Miura, Makoto; Hiroshiba, Shinya [Kyoto Univ. (Japan). Faculty of Medicine

    1995-06-01

    High-resolution computed tomographic (CT) images were analyzed to determine the normal course of skull and temporal bone development. CT images of 146 ears from 81 Japanese children of varying ages were included in this study. The growth of the skull and the temporal bone was rapid during the first 5 years of life followed by gradual but steady development until the age of 15. The period of rapid growth lasted 1 to 2 years longer than that previously reported in American children. Head growth after surgery should be taken into account for successful pediatric cochlear implant surgery. (author).

  4. Osteomyelitis of the Temporal Bone: Terminology, Diagnosis, and Management

    Science.gov (United States)

    Prasad, Sampath Chandra; Prasad, Kishore Chandra; Kumar, Abhijit; Thada, Nikhil Dinaker; Rao, Pallavi; Chalasani, Satyanarayana

    2014-01-01

    Objectives To review the terminology, clinical features, and management of temporal bone osteomyelitis. Design and Setting Prospective study in a tertiary care center from 2001 to 2008. Participants Twenty patients visiting the outpatient department diagnosed with osteomyelitis of the temporal bone. Main Outcome Measures The age, sex, clinical features, cultured organisms, surgical interventions, and classification were analyzed. Results Of the 20 cases, 2 (10%) were diagnosed as acute otitis media. Eighteen (90%) had chronic otitis media. Nineteen (95%) were classified as medial temporal bone osteomyelitis and one (5%) as lateral temporal osteomyelitis. The most common clinical features were ear discharge (100%), pain (83%), and granulations (100%). Facial nerve palsy was seen in seven cases (35%) and parotid involvement in one case. Ten patients (56%) had diabetes mellitus. The organisms isolated were Pseudomonas aeruginosa (80%) and Staphylococcus aureus (13.33%). Histopathology revealed chronic inflammation in 20 patients (100%) and osteomyelitic bony changes in 14 (70%). Surgical debridement was the most preferred modality of treatment (87%). Conclusion A new classification of temporal bone osteomyelitis has been proposed. Bacterial cultures must be performed in all patients. Antibiotic therapy is the treatment of choice. Surgical intervention is necessary in the presence of severe pain, complications, refractory cases, or the presence of bony sequestra on radiology. PMID:25302143

  5. Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy

    DEFF Research Database (Denmark)

    Jensen, K E; Hansen, P B; Larsen, V A

    1994-01-01

    Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance...... absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)/l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light......-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64...

  6. Cost effective use of audiograms after pediatric temporal bone fractures.

    Science.gov (United States)

    Frisenda, Julia L; Schroeder, James W; Ryan, Maura E; Valika, Taher S; Billings, Kathleen R

    2015-11-01

    To identify the relationship of pediatric temporal fractures to the incidence and type of hearing loss present. To analyze the timing and utility of audiometric testing in children with temporal bone fractures. Retrospective case series of 50 pediatric patients with temporal bone fractures who were treated at an urban, tertiary care children's hospital from 2008 to 2014. A statistical analysis of predictors of hearing loss after temporal bone fracture was performed. Fifty-three fractures (69.7%) in 50 patients involved the petrous portion of the temporal bone. The mean age of patients was 7.13 years, and 39 (73.6%) were male. A fall was the most common mechanism of injury in 28 (52.8%) patients, followed by crush injury (n=14, 26.2%), and vehicular trauma (n=10, 18.9%). All otic capsule violating fractures were associated with a sensorineural hearing loss (n=4, 7.5%, p=0.002). Three of four otic capsule sparing fractures were associated with ossicular dislocation, with a corresponding mixed or conductive hearing loss on follow up audiometric testing. The majority of otic capsule sparing fracture patients (n=19/43, 44.2%) who had follow up audiograms had normal hearing, and those with otic capsule violating fractures were statistically more likely to have persistent hearing loss than those with otic capsule sparing fractures (p=0.01). Patients with otic capsule violating fractures or those with ossicular disruption are at higher risk for persistent hearing loss. Cost-saving may be accrued by selecting only those patients at high risk for persistent hearing loss for audiometric testing after temporal bone fractures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

    Directory of Open Access Journals (Sweden)

    F Cappello

    2009-06-01

    Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

  8. A Novel Temporal Bone Simulation Model Using 3D Printing Techniques.

    Science.gov (United States)

    Mowry, Sarah E; Jammal, Hachem; Myer, Charles; Solares, Clementino Arturo; Weinberger, Paul

    2015-09-01

    An inexpensive temporal bone model for use in a temporal bone dissection laboratory setting can be made using a commercially available, consumer-grade 3D printer. Several models for a simulated temporal bone have been described but use commercial-grade printers and materials to produce these models. The goal of this project was to produce a plastic simulated temporal bone on an inexpensive 3D printer that recreates the visual and haptic experience associated with drilling a human temporal bone. Images from a high-resolution CT of a normal temporal bone were converted into stereolithography files via commercially available software, with image conversion and print settings adjusted to achieve optimal print quality. The temporal bone model was printed using acrylonitrile butadiene styrene (ABS) plastic filament on a MakerBot 2x 3D printer. Simulated temporal bones were drilled by seven expert temporal bone surgeons, assessing the fidelity of the model as compared with a human cadaveric temporal bone. Using a four-point scale, the simulated bones were assessed for haptic experience and recreation of the temporal bone anatomy. The created model was felt to be an accurate representation of a human temporal bone. All raters felt strongly this would be a good training model for junior residents or to simulate difficult surgical anatomy. Material cost for each model was $1.92. A realistic, inexpensive, and easily reproducible temporal bone model can be created on a consumer-grade desktop 3D printer.

  9. Craniofacial and temporal bone CT findings in cleidocranial dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Guido E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departamento de Imagenes, Santiago (Chile); Caruso, Paul A.; Curtin, Hugh D. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Jyung, Robert W. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Otology, Boston, MA (United States); Troulis, Maria J. [Massachusetts General Hospital and Harvard Medical School, Department of Oral and Maxillofacial Surgery, Boston, MA (United States)

    2008-08-15

    Cleidocranial dysplasia (CCD) is a multistructural polyostotic genetic disorder that results from mutation of the CBFA1 gene. Hearing loss is a frequent finding in CCD. We describe the CT craniofacial findings in CCD and provide a comprehensive discussion of the CT temporal bone findings in these patients. (orig.)

  10. Temporal Bone Pneumatization in Cystic Fibrosis: A Correlation With Genotype?

    NARCIS (Netherlands)

    Berkhout, Maaike C.; van Rooden, Cornelis J.; Aalbers, Ralph C.; El Bouazzaoui, Lahssan H.; Fokkens, Wytske J.; Rijntjes, Evert; Heijerman, Harry G. M.

    2014-01-01

    Objectives/Hypothesis: Paranasal sinus pneumatization in patients with cystic fibrosis (CF) is less extensive compared to the general population and seems to be correlated to CF genotype. Interestingly, in CF patients temporal bone pneumatization (TBP) is more extensive compared to the general

  11. Squamous cell carcinoma of the temporal bone: results and management.

    NARCIS (Netherlands)

    Kunst, H.P.M.; Lavieille, J.P.; Marres, H.A.M.

    2008-01-01

    OBJECTIVE: Evaluation of the management and survival of patients treated for temporal bone squamous cell carcinoma. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary care, academic referral center. PATIENTS: Twenty-eight patients underwent primary treatment for squamous cell carcinoma of the

  12. Papercraft temporal bone in the first step of anatomy education.

    Science.gov (United States)

    Hiraumi, Harukazu; Sato, Hiroaki; Ito, Juichi

    2017-06-01

    (1) To compare temporal bone anatomy comprehension taught to speech therapy students with or without a papercraft model. (2) To explore the effect of papercraft simulation on the understanding of surgical approaches in first-year residents. (1) One-hundred and ten speech therapy students were divided into three classes. The first class was taught with a lecture only. The students in the second class were given a lecture and a papercraft modeling task without instruction. The third class modeled a papercraft with instruction after the lecture. The students were tested on their understanding of temporal bone anatomy. (2) A questionnaire on the understanding of surgical approaches was completed by 10 residents before and after the papercraft modeling. The papercraft models were cut with scissors to simulate surgical approaches. (1) The average scores were 4.4/8 for the first class, 4.3/8 for the second class, and 6.3/8 for the third class. The third class had significantly better results than the other classes (panatomy using a papercraft temporal bone model is effective in the first step of learning temporal bone anatomy and surgical approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Temporal bone dissection simulator for training pediatric otolaryngology surgeons

    Science.gov (United States)

    Tabrizi, Pooneh R.; Sang, Hongqiang; Talari, Hadi F.; Preciado, Diego; Monfaredi, Reza; Reilly, Brian; Arikatla, Sreekanth; Enquobahrie, Andinet; Cleary, Kevin

    2017-03-01

    Cochlear implantation is the standard of care for infants born with severe hearing loss. Current guidelines approve the surgical placement of implants as early as 12 months of age. Implantation at a younger age poses a greater surgical challenge since the underdeveloped mastoid tip, along with thin calvarial bone, creates less room for surgical navigation and can result in increased surgical risk. We have been developing a temporal bone dissection simulator based on actual clinical cases for training otolaryngology fellows in this delicate procedure. The simulator system is based on pre-procedure CT (Computed Tomography) images from pediatric infant cases (<12 months old) at our hospital. The simulator includes: (1) simulation engine to provide the virtual reality of the temporal bone surgery environment, (2) a newly developed haptic interface for holding the surgical drill, (3) an Oculus Rift to provide a microscopic-like view of the temporal bone surgery, and (4) user interface to interact with the simulator through the Oculus Rift and the haptic device. To evaluate the system, we have collected 10 representative CT data sets and segmented the key structures: cochlea, round window, facial nerve, and ossicles. The simulator will present these key structures to the user and warn the user if needed by continuously calculating the distances between the tip of surgical drill and the key structures.

  14. Temporal bone trauma and complications: computed tomography findings

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Ana Maria Doffemond; Gaiotti, Juliana Oggioni; Couto, Caroline Laurita Batista; Gomes, Natalia Delage; Diniz, Renata Lopes Furletti Caldeira; Motta, Emilia Guerra Pinto Coelho, E-mail: anadoffemond@yahoo.com.br [Hospital Mater Dei, Belo Horizonte, MG (Brazil). Unit of Radiology and Imaging Diagnosis

    2013-03-15

    Most temporal bone fractures result from high-energy blunt head trauma, and are frequently related to other skull fractures or to polytrauma. Fractures and displacements of ossicular chain in the middle ear represent some of the main complications of temporal bone injury, and hence they will be more deeply approached in the present article. Other types of injuries include labyrinthine fractures, dural fistula, facial nerve paralysis and extension into the carotid canal. Computed tomography plays a fundamental role in the initial evaluation of polytrauma patients, as it can help to identify important structural injuries that may lead to severe complications such as sensorineural hearing loss, conductive hearing loss, dizziness and balance dysfunction, perilymphatic fistulas, facial nerve paralysis, vascular injury and others. (author)

  15. Constructive real time feedback for a temporal bone simulator.

    Science.gov (United States)

    Zhou, Yun; Bailey, James; Ioannou, Ioanna; Wijewickrema, Sudanthi; Kennedy, Gregor; O'Leary, Stephen

    2013-01-01

    As demands on surgical training efficiency increase, there is a stronger need for computer assisted surgical training systems. The ability to provide automated performance feedback and assessment is a critical aspect of such systems. The development of feedback and assessment models will allow the use of surgical simulators as self-guided training systems that act like expert trainers and guide trainees towards improved performance. This paper presents an approach based on Random Forest models to analyse data recorded during surgery using a virtual reality temporal bone simulator and generate meaningful automated real-time performance feedback. The training dataset consisted of 27 temporal bone simulation runs composed of 16 expert runs provided by 7 different experts and 11 trainee runs provided by 6 trainees. We demonstrate how Random Forest models can be used to predict surgical expertise and deliver feedback that improves trainees' surgical technique. We illustrate the potential of the approach through a feasibility study.

  16. A metastatic glomus jugulare tumor. A temporal bone report

    Energy Technology Data Exchange (ETDEWEB)

    El Fiky, F.M.; Paparella, M.M.

    1984-01-01

    The clinicopathologic findings in the temporal bone of a patient with a highly malignant metastasizing glomus jugulare tumor are reported. The patient exhibited all the symptoms of primary malignant tumors of the ear, including facial paralysis, otorrhea, pain, hearing loss, tinnitus, dizziness, and vertigo. He was treated with cobalt irradiation followed by radium implant in the ear canal for a residual tumor; then a left-sided radical mastoidectomy was performed.

  17. Melanotic progonoma of temporal and occipital bones: A case report.

    Science.gov (United States)

    Bellarbi, S; Harmouch, A; El Ochi, M R; Fikri, M; Arkha, Y; Sefiani, S

    2013-06-01

    Melanotic progonoma is a rare tumor that primarily affects the maxilla of infants during the first year of life. Involvement in the skull is rare and can mimick other benign or malignant tumors affecting the infant's skull. The authors report a case of melanotic progonoma of right occipital and temporal bones in a 7-months' girl and discuss the histological features, immunohistochemistry study, differential diagnosis and management of this tumor. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Bilateral congenital cholesteatoma of the temporal bone in Crouzon syndrome

    Directory of Open Access Journals (Sweden)

    Đerić Dragoslava

    2015-01-01

    Full Text Available Introduction. Crouzon syndrome is an autosomal dominant genetic disease characterized by bicoronal craniosynostosis, exorbitism with hypertelorism, and maxillary hypoplasia with mandibular prognathism. Case Outline. We present the first reported case of Crouzon syndrome associated with a bilateral congenital cholesteatoma of the temporal bone and discuss about the potential pathogenesis. Conclusion. Early diagnosis and management are crucial to prevent complications and an otologist should be an integral part of the multidisciplinary team.

  19. Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells

    Science.gov (United States)

    Saito, Toshiki I.; Fujisaki, Joji; Carlson, Alicia L.; Lin, Charles P.; Sykes, Megan

    2014-01-01

    Objective In recipients of allogeneic hematopoietic stem cell transplantation to treat hematologic malignancies, we have unexpectedly observed anti-tumor effects in association with donor cell rejection in both mice and humans. Host-type CD8 T cells were shown to be required for these anti-tumor effects in the murine model. Since sustained host CD8 T cell activation was observed in the murine bone marrow following the disappearance of donor chimerism in the peripheral blood, we hypothesized that donor antigen presentation in the bone marrow might be prolonged. Materials and Methods To assess this hypothesis, we established mixed chimerism with green fluorescence protein (GFP)-positive allogeneic bone marrow cells, induced rejection of the donor cells by giving recipient leukocyte infusions (RLI), and utilized in vivo microscopy to follow GFP-positive cells. Results After peripheral donor leukocytes disappeared, GFP persisted within host myeloid cells surrounding the blood vessels in the bone marrow, suggesting that the host myeloid cells captured donor-derived GFP protein. Conclusions Since the host-versus-graft reaction promotes the induction of anti-tumor responses in this model, this retention of donor-derived protein may play a role in the efficacy of RLI as an anti-tumor therapy. PMID:20167247

  20. Surgical timing for facial paralysis after temporal bone trauma.

    Science.gov (United States)

    Xu, Peng; Jin, Aiyan; Dai, Baoqiang; Li, Ruijie; Li, Yefeng

    To explore surgical timing of facial paralysis after temporal bone trauma. The clinical data of the patients with facial paralysis after temporal bone trauma who underwent subtotal facial nerve decompression were retrospectively collected, and 80 cases followed-up for one year were enrolled in the study. They were divided into different subgroups according to the age, onset, and interval between facial paralysis and surgery, and the outcomes of facial nerve between different subgroups were compared. The number of patients who achieved good recovery of HB Grade I or II was 52 of 80 (65.0%). 43 of 66 cases (65.2%) in the younger group had good recovery of facial nerve in contrast to 9 of 14 cases (64.3%) in the elderly group, without significant difference (p>0.05). 9 of 13 cases (69.2%) in the delayed onset group had good recovery, while 43 of 67 cases (64.2%) in the immediate onset group had good recovery, without significant difference (p>0.05). The good recovery rate of the 6months group (P0.05). This study demonstrated that the good recovery rate of facial paralysis after temporal bone trauma was uncorrelated with age and onset. It was better to perform surgical decompression within 3months after facial paralysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Classification of temporal bone pneumatization based on sigmoid sinus using computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Han, S.-J. [Department of Otorhinolaryngology, National Health Insurance Corporation Ilsan Hospital, Seoul (Korea, Republic of); Song, M.H. [Department of Otorhinolaryngology, Yonsei University College of Medicine, Kang-nam Gu, Do-gok Dong, 146-92, Seoul, Republic of Korea 135-720 (Korea, Republic of); Kim, J. [Department of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, W.-S. [Department of Otorhinolaryngology, Yonsei University College of Medicine, Kang-nam Gu, Do-gok Dong, 146-92, Seoul, Republic of Korea 135-720 (Korea, Republic of); Lee, H.-K. [Department of Otorhinolaryngology, Yonsei University College of Medicine, Kang-nam Gu, Do-gok Dong, 146-92, Seoul, Republic of Korea 135-720 (Korea, Republic of)], E-mail: hoki@yuhs.ac

    2007-11-15

    Aim: To analyse several reference structures using axial computed tomography (CT) imaging of the temporal bone, which may reflect pneumatization of the entire temporal bone by statistical correlation to the actual volume of the temporal bone measured using three-dimensional reconstruction. Materials and methods: One hundred and sixteen temporal bones were studied, comprising 48 with normal findings and 68 sides showing chronic otitis media or temporal bone fracture. After measuring the volume of temporal bone air cells by the volume rendering technique using three-dimensional reconstruction images, classification of temporal bone pneumatization was performed using various reference structures on axial images to determine whether significant differences in the volume of temporal bone air cells could be found between the groups. Results: When the sigmoid sinus at the level of the malleoincudal complex was used in the classification, there were statistically significant differences between the groups that correlated with the entire volume of the temporal bone. Grouping based on the labyrinth and the ascending carotid artery showed insignificant differences in volume. Furthermore, there was no significant correlation between the cross-sectional area of the antrum and the entire volume of the temporal bone. Conclusion: The degree of pneumatization of temporal bone can be estimated easily by the evaluation of the air cells around the sigmoid sinus on axial CT images.

  2. Temporal bone chondroblastoma with secondary aneurysmal bone cyst presenting as an intracranial mass with clinical seizure activity.

    Science.gov (United States)

    Stapleton, Christopher J; Walcott, Brian P; Linskey, Katy R; Kahle, Kristopher T; Nahed, Brian V; Asaad, Wael F

    2011-06-01

    Chondroblastomas are rare tumors that characteristically arise from the epiphyseal cartilage of long bones of the immature skeleton. Intracranial involvement is uncommon, though the squamous portion of the temporal bone is preferentially affected due to its cartilaginous origin. Patients with temporal bone chondroblastomas classically present with otologic symptoms, while primary neurological complaints are rare. In this report, we describe a 33 year-old man with a chondroblastoma of the temporal bone and an associated aneurysmal bone cyst constituting a large intracranial mass lesion who presented with new-onset seizure activity. We review issues relevant to the pathology and treatment of these lesions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Aneurysmal Bone Cyst of the Temporal Bone Presenting with Headache and Partial Facial Palsy

    Science.gov (United States)

    Kletke, Stephanie N.; Popovic, Snezana; Algird, Almunder; Alobaid, Abdullah; Reddy, Kesava K. V.

    2015-01-01

    Background Aneurysmal bone cysts (ABCs) are benign bony lesions that rarely affect the skull base. Very few cases of temporal bone ABCs have been reported. We describe the first case of a temporal bone ABC that was thought to be consistent with a meningioma based on preoperative magnetic resonance imaging (MRI) findings. Clinical Presentation An otherwise healthy 23-year-old woman presented with a pulsatile noise in her left ear and a 4-week history of throbbing headache with nausea. There was no associated emesis, visual or auditory changes, or other neurologic features. Neurologic examination revealed a left lower motor neuron facial paresis. Computed tomography and MRI studies demonstrated a large lesion in the left middle cranial fossa skull base with erosion of the petrous temporal bone. Based on the presence of a “dural tail” on preoperative contrast-enhanced T1-weighted imaging, the lesion was interpreted to likely be consistent with a meningioma. An orbitozygomatic approach was utilized for surgical excision. Histopathologic evaluation was consistent with an ABC. Conclusion Postoperatively the patient had improvement in the lower motor neuron facial paresis. It is important to consider ABC in the differential diagnosis of intracranial lesions accompanied by the dural tail sign on MRI. PMID:26251800

  4. Mixed reality temporal bone surgical dissector: mechanical design.

    Science.gov (United States)

    Hochman, Jordan Brent; Sepehri, Nariman; Rampersad, Vivek; Kraut, Jay; Khazraee, Milad; Pisa, Justyn; Unger, Bertram

    2014-08-08

    The Development of a Novel Mixed Reality (MR) Simulation. An evolving training environment emphasizes the importance of simulation. Current haptic temporal bone simulators have difficulty representing realistic contact forces and while 3D printed models convincingly represent vibrational properties of bone, they cannot reproduce soft tissue. This paper introduces a mixed reality model, where the effective elements of both simulations are combined; haptic rendering of soft tissue directly interacts with a printed bone model. This paper addresses one aspect in a series of challenges, specifically the mechanical merger of a haptic device with an otic drill. This further necessitates gravity cancelation of the work assembly gripper mechanism. In this system, the haptic end-effector is replaced by a high-speed drill and the virtual contact forces need to be repositioned to the drill tip from the mid wand. Previous publications detail generation of both the requisite printed and haptic simulations. Custom software was developed to reposition the haptic interaction point to the drill tip. A custom fitting, to hold the otic drill, was developed and its weight was offset using the haptic device. The robustness of the system to disturbances and its stable performance during drilling were tested. The experiments were performed on a mixed reality model consisting of two drillable rapid-prototyped layers separated by a free-space. Within the free-space, a linear virtual force model is applied to simulate drill contact with soft tissue. Testing illustrated the effectiveness of gravity cancellation. Additionally, the system exhibited excellent performance given random inputs and during the drill's passage between real and virtual components of the model. No issues with registration at model boundaries were encountered. These tests provide a proof of concept for the initial stages in the development of a novel mixed-reality temporal bone simulator.

  5. Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in ptpn2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Florian Wiede

    Full Text Available Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2 have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2(ex2-/ex2- mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2(-/- mice (BALB/c-129SJ generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2(ex2-/ex2- mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2(-/- (BALB/c mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea evident in Ptpn2(-/- (BALB/c mice were not detected in Ptpn2(ex2-/ex2- mice. At 14 days of age, bone development was delayed in Ptpn2(-/- (BALB/c mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2(ex2-/ex2- mice. Ptpn2(ex2-/ex2- mice had defects in erythropoiesis and B cell development as evident in Ptpn2(-/- (BALB/c mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2(-/- (BALB/c mice. Moreover, thymic atrophy, another feature of Ptpn2(-/- (BALB/c mice, was delayed in Ptpn2(ex2-/ex2- mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2(-/- (BALB/c mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2(ex2-/ex2- mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent.

  6. A Retrospective Review of Temporal Bone Imaging With Respect to Bone-Anchored Hearing Aid Placement.

    Science.gov (United States)

    Baker, Aaron R; Fanelli, David G; Kanekar, Sangam; Isildak, Huseyin

    2017-01-01

    Current bone-anchored hearing aid (BAHA) guidelines recommend placement of the titanium implant 5 to 7 cm posterior to the ear canal. Previous studies show that bone conducted hearing is maximized the closer the transducer is to the cochlea. We aim to investigate the position of the sigmoid sinus with respect to BAHA implants to determine whether they may be safely placed closer to the ear canal in patients with chronic ear disease, enhancing the amplification available to the patient. We performed a retrospective review of high-resolution temporal bone computed tomographies (CTs), comparing multiple measurements between ears with chronic ear disease and normal controls. Images were obtained at a single academic medical center. Eighty patients (160 ears) with temporal bone CTs performed between 2006 and 2009 were measured. Patients with chronic ear disease were identified by international statistical classification of diseases and related health problems, revision 9 code and confirmation by review of the imaging. Measurements were made on axial CT slices from a point 1 cm posterior to the sigmoid sinus to the posterior margin of the external canal. The squamous temporal bone thickness was also measured at this point. Forty-seven patients (55 ears) had chronic ear disease. Distance from the posterior canal was significantly different between normal and diseased ears (36.3 mm versus 33.5 mm, p hearing aids may be safely placed closer to the external canal than the current recommendations. This could allow for better transduction as well as sound localization in BAHA patients.

  7. [Computed tomography of the temporal bone in diagnosis of chronic exudative otitis media].

    Science.gov (United States)

    Zelikovich, E I

    2005-01-01

    Computed tomography (CT) of the temporal bone was made in 37 patients aged 2 to 55 years with chronic exudative otitis media (CEOM). In 21 of them the pathology was bilateral. The analysis of 58 CT images has identified CT signs of chronic exudative otitis media. They include partial (17 temporary bones) or complete (38 temporal bones) block of the bone opening of the auditory tube, pneumatic defects of the tympanic cavity (58 temporal bones), pneumatic defects of the mastoid process and antrum (47 temporal bones), pathologic retraction of the tympanic membrane. The examination of the temporal bone detected both CT-signs of CEOM and other causes of hearing disorders in 14 patients (26 temporal bones) with CEOM symptoms and inadequately high hypoacusis. Among these causes were malformation of the auditory ossicula (n=5), malformation of the labynthine window (n=2), malformation of the middle and internal ear (n=4), a wide aqueduct of the vestibule, labyrinthine anomaly of Mondini's type (n=1), cochlear hypoplasia (n=4), stenosis of the internal acoustic meatuses (n=2). Sclerotic fibrous dysplasia was suggested in 2 temporal bones (by CT data). CT was repeated after surgical treatment of 10 patients (14 temporal bones) and visual assessment of tympanostomy results was made.

  8. Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling

    2015-01-01

    (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells...... with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity...... and also immunoregulation and regenerative processes. Better understanding and characterization of myeloid cell heterogeneity is essential for future development of treatments controlling inflammation and inducing neuroprotection and neuroregeneration in diseased CNS. Here, we describe and compare three...

  9. Multi-material 3D Models for Temporal Bone Surgical Simulation.

    Science.gov (United States)

    Rose, Austin S; Kimbell, Julia S; Webster, Caroline E; Harrysson, Ola L A; Formeister, Eric J; Buchman, Craig A

    2015-07-01

    A simulated, multicolor, multi-material temporal bone model can be created using 3-dimensional (3D) printing that will prove both safe and beneficial in training for actual temporal bone surgical cases. As the process of additive manufacturing, or 3D printing, has become more practical and affordable, a number of applications for the technology in the field of Otolaryngology-Head and Neck Surgery have been considered. One area of promise is temporal bone surgical simulation. Three-dimensional representations of human temporal bones were created from temporal bone computed tomography (CT) scans using biomedical image processing software. Multi-material models were then printed and dissected in a temporal bone laboratory by attending and resident otolaryngologists. A 5-point Likert scale was used to grade the models for their anatomical accuracy and suitability as a simulation of cadaveric and operative temporal bone drilling. The models produced for this study demonstrate significant anatomic detail and a likeness to human cadaver specimens for drilling and dissection. Simulated temporal bones created by this process have potential benefit in surgical training, preoperative simulation for challenging otologic cases, and the standardized testing of temporal bone surgical skills. © The Author(s) 2015.

  10. Myeloid Precursors in the Bone Marrow of Mice after a 30-Day Space Mission on a Bion-M1 Biosatellite.

    Science.gov (United States)

    Sotnezova, E V; Markina, E A; Andreeva, E R; Buravkova, L B

    2017-02-01

    The content of myeloid stem CFU in bone marrow karyocytes from the tibial bone of C57Bl/6 mice was evaluated after a 30-day Bion-M1 pace flight/ground control experiment and subsequent 7-day recovery period. After the space flight, we observed a significant decrease in the number of erythroid progenitors in the bone marrow, including common myeloid precursor - granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte CFU. After 7-day readaptation, CFU level in flight animals did not recover completely. In the ground control, the count of erythroid burst-forming units was higher than in vivarium animals. Comparison of the changes observed in fight and ground experiments demonstrated effects associated space flight factors and manifesting in suppression of the bone marrow erythropoiesis.

  11. Study of a temporal bone of Homo heildelbergensis.

    Science.gov (United States)

    Urquiza, Rafael; Botella, Miguel; Ciges, Miguel

    2005-05-01

    The characteristic features of the Hh specimen conformed to those of other Pleistocene human fossils, indicating strong cranial structures and a heavy mandible. The mastoid was large and suggested a powerful sternocleidomastoid muscle. The inner ear and tympanic cavities were similar in size and orientation, suggesting that their functions were probably similar. Our observations suggest that the left ear of this Hh specimen was healthy. The large canaliculo-fenestral angle confirms that this ancestor was bipedal. It also strongly suggests that Hh individuals were predisposed to develop certain pathologies of the labyrinth capsule associated with bipedalism, in particular otosclerosis. We studied a temporal bone of Homo heidelbergensis (Hh) in order to investigate the clinical and physiological implications of certain morphological features, especially those associated with the evolutionary reorganization of the inner ear. The bone, found in a breach of a cave near MAáaga in southern Spain, together with Middle Upper Pleistocene faunal remains, is >300000 years old. Four analytical methods were employed. A 3D high-resolution surface laser scan was used for anatomical measurements. For the sectional analysis of the middle and inner ears of Hh we used high-resolution CT, simultaneously studying a normal temporal bone from Homo sapiens sapiens (Hss). To study the middle and inner ear spaces we used 3D reconstruction CT preceded by an intra-bone air shielding technique. To examine the tympanic cavities and measure the canaliculo fenestral angle, we used a special minimally invasive endoscopic procedure. The surface, sectional and 3D CT examinations showed that the Hh specimen was generally more robust and larger than the Hss specimen. It had a large glenoid fossa. The external meatus was wide and deep. The middle ear, and especially the mastoid, was large and widely pneumatized. There were no appreciable differences in the position and size of the labyrinthine spaces

  12. The Rates and Clinical Characteristics of Pneumolabyrinth in Temporal Bone Fracture.

    Science.gov (United States)

    Choi, Hyo Geun; Lee, Hyo-Jeong; Lee, Joong Seob; Kim, Dong Hyun; Hong, Sung Kwang; Park, Bumjung; Kim, Si Whan; Kim, Ja Hee; Kim, Hyung-Jong

    2015-07-01

    Pneumolabyrinth is a rare inner ear clinical manifestation. To date, only about 50 cases have been reported—all as case reports. Consequently, the rate and clinical characteristics of pneumolabyrinth have not been evaluated. Of the 38, 568 patients who visited our emergency department for head trauma, 466 underwent temporal bone computed tomography (CT). One hundred seventy-five patients had temporal bone fracture (13 bilateral temporal bone fractures; 188 ears with temporal bone fractures), and 14 patients had pneumolabyrinth (15 ears with pneumolabyrinth; 1 bilateral case). A retrospective review of their medical records and radiologic findings was performed. Temporal bone fractures were classified by two different systems: the traditional classification and an otic capsule-based classification. Pneumolabyrinth occurred in 8.0% of all temporal bone fractures, 4.0% of longitudinal temporal bone fractures, 16.1% of transverse or mixed temporal bone fractures, and 48.4% of otic capsule-violating temporal bone fractures. In all cases, pneumolabyrinth was found on CT, which was performed within 3 days, but not on follow-up CT performed 5 days or longer after head trauma. All patients complained of hearing loss and dizziness. Hearing in most patients (83.3%) did not improve, whereas dizziness improved in 91.7% of patients. Air was located only in the vestibule or semicircular canal in 53.3% and in the vestibular or semicircular canal and cochlea in 46.6% of ears with pneumolabyrinth. The initial hearing threshold and recovery rate using pure-tone audiometry were not different according to the air location in the inner ear. Pneumolabyrinth was more common than expected; we believe that the timing of evaluation affects its rarity. Pneumolabyrinth was detected in nearly 50% of patients with otic capsule-violating temporal bone fractures when CT scanning was performed early after trauma.

  13. Differential intracochlear sound pressure measurements in normal human temporal bones.

    Science.gov (United States)

    Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S; Merchant, Saumil N; Ravicz, Michael E; Rosowski, John J

    2009-03-01

    We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. The technique we employ, which exploits microscale fiberoptic pressure sensors, enables the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. In our results, the sound pressure in scala vestibuli (P (SV)) was much greater than scala tympani pressure (P (ST)), except for very low and high frequencies where P (ST) significantly affected the input to the cochlea. The differential pressure (P (SV) - P (ST)) is a superior measure of ossicular transduction of sound compared to P (SV) alone: (P (SV)-P (ST)) was reduced by 30 to 50 dB when the ossicular chain was disarticulated, whereas P (SV) was not reduced as much. The middle ear gain P (SV)/P (EC) and the differential pressure normalized to ear canal pressure (P (SV) - P (ST))/P (EC) were generally bandpass in frequency dependence. At frequencies above 1 kHz, the group delay in the middle ear gain is about 83 micros, over twice that of the gerbil. Concurrent measurements of stapes velocity produced estimates of cochlear input impedance, the differential impedance across the partition, and round window impedance. The differential impedance was generally resistive, while the round window impedance was consistent with compliance in conjunction with distributed inertia and damping. Our technique of measuring differential pressure can be used to study inner ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round window stimulation and bone conduction)--situations that cannot be completely quantified by measurements of stapes velocity or scala vestibuli pressure by themselves.

  14. Facial nerve paralysis associated with temporal bone masses.

    Science.gov (United States)

    Nishijima, Hironobu; Kondo, Kenji; Kagoya, Ryoji; Iwamura, Hitoshi; Yasuhara, Kazuo; Yamasoba, Tatsuya

    2017-10-01

    To investigate the clinical and electrophysiological features of facial nerve paralysis (FNP) due to benign temporal bone masses (TBMs) and elucidate its differences as compared with Bell's palsy. FNP assessed by the House-Brackmann (HB) grading system and by electroneurography (ENoG) were compared retrospectively. We reviewed 914 patient records and identified 31 patients with FNP due to benign TBMs. Moderate FNP (HB Grades II-IV) was dominant for facial nerve schwannoma (FNS) (n=15), whereas severe FNP (Grades V and VI) was dominant for cholesteatomas (n=8) and hemangiomas (n=3). The average ENoG value was 19.8% for FNS, 15.6% for cholesteatoma, and 0% for hemangioma. Analysis of the correlation between HB grade and ENoG value for FNP due to TBMs and Bell's palsy revealed that given the same ENoG value, the corresponding HB grade was better for FNS, followed by cholesteatoma, and worst in Bell's palsy. Facial nerve damage caused by benign TBMs could depend on the underlying pathology. Facial movement and ENoG values did not correlate when comparing TBMs and Bell's palsy. When the HB grade is found to be unexpectedly better than the ENoG value, TBMs should be included in the differential diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    of leukaemic cells increased to > 90% and the pH dropped to about 6.5. The fraction of NITP+ cells increased to > 80% in bone marrow and to about 40% in blood. The fraction of BrdUrd+ cells was unchanged in blood, but decreased in bone marrow both for normal cells (from about 20% to 5%), and for leukaemic...

  16. Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling

    2015-01-01

    (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells......Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system...... with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity...

  17. Distinct clonal anomalies involving in acute myeloid leukemia at diagnosis and after bone marrow transplantation : Distinct RUNX1 anomalies in AML

    OpenAIRE

    Braekeleer, Etienne; Douet-Guilbert, Nathalie; Basinko, Audrey; Bris, Marie-Josée; Morel, Frédéric; Berthou, Christian; Férec, Claude; Braekeleer, Marc

    2010-01-01

    Distinct clonal anomalies involving RUNX1 in acute myeloid leukemia at diagnosis and after bone marrow transplantation phone: +33-2-98016476 (Braekeleer, Marc) (Braekeleer, Marc) Faculte de Medecine et des Sciences de la Sante, Universite de Brest - Brest - FRANCE (Braekeleer, Etienne) Institut National de la Sante et de la Recherche Medicale (INSERM) - U613 - Brest - FRANCE (Braekeleer, Etienne) Hopital Morvan, Service de Cytogenetique, Cyto...

  18. Three-dimensional CT imaging with a helical scan on temporal bone

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Honghan; Hiraishi, Kumiko; Uesugi, Yasuo; Sakakura, Atsushi; Yoshikawa, Shuji; Shimizu, Takaya; Sueyoshi, Kozo; Narabayashi, Isamu [Osaka Medical Coll., Takatsuki (Japan)

    1996-06-01

    To evaluate the usefulness of three-dimensional (3D) CT on the lesions of temporal bone, we studied 19 patients with disorders on the region of temporal bone by high speed helical CT. The results showed that 8 patients with congenital hearing disorder had deficiency of the auditory ossicles, 2 patients with chronic otitis media had deformity and shortness of the auditory ossicles, 4 patients with trauma had fracture of the temporal bone (1 patient was complicated by doubtful fracture of the incus), 5 patients (4 patients with acquired hearing disorder and 1 patient with otorrhea) had space-occupying lesions. 3-D helical CT could detect abnormal findings on all the patients and it was an important examination for the temporal bone. (author)

  19. Links Between Surgical Landmarks of the Temporal Bone and Cochlear Implant Approaches

    Directory of Open Access Journals (Sweden)

    Gabriel Lostun

    2015-12-01

    Full Text Available Objective: We aimed to underline the surgical importance of the distances between the landmarks of the temporal bone, important for quantifying the benefits and disadvantages of two different cochlear implant techniques.

  20. Osteoradionecrosis of sphenoid and temporal bones in a patient with maxillary sinus carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Inokuchi, T.; Sano, K.; Kaminogo, M. (Nagasaki Univ. School of Dentistry (Japan))

    1990-09-01

    A case of radionecrosis of sphenoid and temporal bones is reported. The patient received a combination of surgery, radiotherapy, and chemotherapy for his left maxillary sinus carcinoma. After the combined therapy, necrosis accompanying inflammation developed in the maxillary and temporal regions. Excision of the necrotic tissues was done, and the left ascending ramus of the mandible was resected because of persistent tumor mass at the left infratemporal fossa. Although the excision wound of the maxilla healed by epithelialization, an area of nonvital bone remained exposed in the temporal region, where progressive osteonecrosis with infection led to breakdown of the skin. The necrotic bones of the zygomatic arch and the sphenotemporal sutural region became visible through the skin defect, and computerized tomography scan revealed bone necrosis involving the inferolateral area and the base of the skull. Excision of the necrotic bone and reconstruction with sternocleidomastoid myocutaneous flap were performed.

  1. Inflammatory Pseudotumor of the Temporal Bone: Three Cases and a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Huiqin Tian

    2013-01-01

    Full Text Available Inflammatory pseudotumor (IP is a clinically aggressive but histologically benign condition of unknown cause. Its appearance in the temporal bone is uncommon. We present clinical, radiological, and histopathologic findings of three cases originating in the temporal bone. In the first case, a simultaneous IP of the temporal bone and parotid gland was found with histopathologic confirmation. In the second case, an enlarged cervical node, which was also believed to be related to IP, was observed accompanied with the temporal lesion. While the third case presented with chronic suppurative otitis media. Two of them were treated by surgery alone with complete resolve of the diseases. Another one underwent tympanomastoidectomy in combination with oral steroids, radiation, and chemotherapy, but the IP still recurred. A comprehensive review of the literature on clinical features of the temporal pseudotumor was conducted.

  2. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    . Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  3. Anatomia do osso temporal de ovelhas sob aspectos didáticos Lambs' temporal bone anatomy under didactic aspects

    Directory of Open Access Journals (Sweden)

    André Gurr

    2011-02-01

    Full Text Available É difícil encontrar ossos temporais humanos para o ensino de cirurgia otológica. Ossos temporais de ovelhas podem representar uma possível alternativa. MATERIAIS E MÉTODOS: Os ossos temporais de ovelhas foram dissecados em um programa convencional de dissecação de osso temporal no laboratório. Incluímos mastoidectomia, abordagens endaurais, mas também analisamos a aparência externa, o meato acústico externo e o hipotímpano. Algumas etapas são diferentes das preparações de ossos humanos. Os resultados morfométricos foram comparados à anatomia conhecida de humanos para verificar se o osso temporal de ovelhas seria utilizável para o ensino de cirurgia otológica. RESULTADOS: O osso temporal de ovelhas parece menor do que o humano. Encontramos uma área bolhosa se estendendo ao hipotímpano abaixo do meato acústico externo. A membrana timpânica é muito semelhante à humana. O meato acústico externo é menor e mais curto. A cadeia ossicular exibe analogias para com a humana. DISCUSSÃO: Esse estudo mostra que especificamente o ouvido médio, a membrana timpânica e o conduto auditivo externo são morfologicamente semelhantes às suas contrapartidas encontradas nos ossos temporais humanos. A ovelha parece ser um modelo viável para o ensino da anatomia do ouvido. A menor escala de algumas estruturas, especialmente dos componentes externos do osso temporal representa uma desvantagem. CONCLUSÕES: A ovelha parece representar uma alternativa viável no ensino de cirurgia otológica.Human temporal bones in teaching ear surgery are rare. The lamb's temporal bone might be a possible alternative. MATERIAL AND METHODS: Temporal bones of the lamb were dissected with a typical temporal bone lab drilling program. We included a mastoidectomy, endaural approaches, but also analyzed the outer appearance, the external ear canal and the hypotympanon. Some steps differed from preparation done in humans. The morphometric results were compared to

  4. Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cells generated in vitro from murine bone marrow.

    Directory of Open Access Journals (Sweden)

    Júlia Kurkó

    Full Text Available Myeloid-derived suppressor cells (MDSCs are innate immune cells capable of suppressing T-cell responses. We previously reported the presence of MDSCs with a granulocytic phenotype in the synovial fluid (SF of mice with proteoglycan (PG-induced arthritis (PGIA, a T cell-dependent autoimmune model of rheumatoid arthritis (RA. However, the limited amount of SF-MDSCs precluded investigations into their therapeutic potential. The goals of this study were to develop an in vitro method for generating MDSCs similar to those found in SF and to reveal the therapeutic effect of such cells in PGIA.Murine bone marrow (BM cells were cultured for 3 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF, interleukin-6 (IL-6, and granulocyte colony-stimulating factor (G-CSF. The phenotype of cultured cells was analyzed using flow cytometry, microscopy, and biochemical methods. The suppressor activity of BM-MDSCs was tested upon co-culture with activated T cells. To investigate the therapeutic potential of BM-MDSCs, the cells were injected into SCID mice at the early stage of adoptively transferred PGIA, and their effects on the clinical course of arthritis and PG-specific immune responses were determined.BM cells cultured in the presence of GM-CSF, IL-6, and G-CSF became enriched in MDSC-like cells that showed greater phenotypic heterogeneity than MDSCs present in SF. BM-MDSCs profoundly inhibited both antigen-specific and polyclonal T-cell proliferation primarily via production of nitric oxide. Injection of BM-MDSCs into mice with PGIA ameliorated arthritis and reduced PG-specific T-cell responses and serum antibody levels.Our in vitro enrichment strategy provides a SF-like, but controlled microenvironment for converting BM myeloid precursors into MDSCs that potently suppress both T-cell responses and the progression of arthritis in a mouse model of RA. Our results also suggest that enrichment of BM in MDSCs could improve the

  5. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34(+) bone marrow cells, following gamma irradiation in cynomolgus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [CEA, DSV, Serv Immunovirol, Inst Maladies Emergentes et Therapies Innovantes, Fontenay Aux Roses (France); Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [Univ Paris 11, UMR E01, Orsay (France); Negre, D.; Cosset, F. [Univ Lyon, UCB Lyon 1, IFR 128, F-69007 Lyon (France); Negre, D.; Cosset, F. [INSERM, U758, F-69007 Lyon (France); Negre, D.; Cosset, F.L. [Ecole NormaleSuper Lyon, F-69007 Lyon (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Lab Radiobiol, F-78352 Jouy En Josas (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Etude Genome, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Radiobiol Lab, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Etude Genome, F-78352 Jouy En Josas (France)

    2008-07-01

    Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myelo-ablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34{sup +} bone marrow cells following gamma irradiation in cynomolgus macaques. The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% {+-} 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudo-typed and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% {+-} 10%). A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producing eGFP were detected as early as three days after transplantation,and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion: The transplantation of CD34{sup +} bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T-and B-lymphocyte, thrombocyte and red blood cell compartments. (authors)

  6. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Auregan Gwenaelle

    2008-06-01

    Full Text Available Abstract Background Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. Results The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%. A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.

  7. A computerized tomography study of the morphological interrelationship between the temporal bones and the craniofacial complex

    Science.gov (United States)

    Costa, Helder Nunes; Slavicek, Rudolf; Sato, Sadao

    2012-01-01

    The hypothesis that the temporal bones are at the center of the dynamics of the craniofacial complex, directly influencing facial morphology, has been put forward long ago. This study examines the role of the spatial positioning of temporal bones (frontal and sagittal inclination) in terms of influencing overall facial morphology. Several 3D linear, angular and orthogonal measurements obtained through computerized analysis of virtual models of 163 modern human skulls reconstructed from cone-beam computed tomography images were analyzed and correlated. Additionally, the sample was divided into two subgroups based on the median value of temporal bone sagittal inclination [anterior rotation group (n = 82); posterior rotation group (n = 81)], and differences between groups evaluated. Correlation coefficients showed that sagittal inclination of the temporal bone was significantly (P < 0.01) related to midline flexion, transversal width and anterior–posterior length of the basicranium, to the anterior–posterior positioning of the mandible and maxilla, and posterior midfacial height. Frontal inclination of the temporal bone was significantly related (P < 0.01) to basicranium anterior–posterior and transversal dimensions, and to posterior midfacial height. In comparison with the posterior rotation group, the anterior rotation group presented a less flexed and anterior–posteriorly longer cranial base, a narrower skull, porion and the articular eminence located more superiorly and posteriorly, a shorter posterior midfacial height, the palatal plane rotated clockwise, a more retrognathic maxilla and mandible, and the upper posterior occlusal plane more inclined and posteriorly located. The results suggest that differences in craniofacial morphology are highly integrated with differences in the positional relationship of the temporal bones. The sagittal inclination of the temporal bone seems to have a greater impact on the 3D morphology of the craniofacial complex than

  8. TEMPORAL MODELING OF DNA DEGRADATION IN BONE REMAINS

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    Andrei Stefan

    2012-06-01

    Full Text Available The aim of this study is to follow the changes that occur, in time, at DNA level and to establish an efficient and reliable protocol for ancestral DNA extraction from bones found in archaeological sites. To test whether the protocol is efficient and capable of yielding good quality DNA, extraction was first performed on fresh bones. The material consists of fresh pig (Sus scrofa and cow (Bos taurus bones that were grounded by using a drill operating at low speed. The bone powder was then incubated in lysis buffer in the presence of proteinase K. DNA isolation and purification were done by using the phenol:chloroform protocol and DNA was precipitated with absolute ethanol stored at -20oC. The extractions were carried out once every month for a total of four extractions

  9. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-09-06

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

    Science.gov (United States)

    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.

  11. Transparent model of temporal bone and vestibulocochlear organ made by 3D printing.

    Science.gov (United States)

    Suzuki, Ryoji; Taniguchi, Naoto; Uchida, Fujio; Ishizawa, Akimitsu; Kanatsu, Yoshinori; Zhou, Ming; Funakoshi, Kodai; Akashi, Hideo; Abe, Hiroshi

    2018-01-01

    The vestibulocochlear organ is composed of tiny complex structures embedded in the petrous part of the temporal bone. Landmarks on the temporal bone surface provide the only orientation guide for dissection, but these need to be removed during the course of dissection, making it difficult to grasp the underlying three-dimensional structures, especially for beginners during gross anatomy classes. We report herein an attempt to produce a transparent three-dimensional-printed model of the human ear. En bloc samples of the temporal bone from donated cadavers were subjected to computed tomography (CT) scanning, and on the basis of the data, the surface temporal bone was reconstructed with transparent resin and the vestibulocochlear organ with white resin to create a 1:1.5 scale model. The carotid canal was stuffed with red cotton, and the sigmoid sinus and internal jugular vein were filled with blue clay. In the inner ear, the internal acoustic meatus, cochlea, and semicircular canals were well reconstructed in detail with white resin. The three-dimensional relationships of the semicircular canals, spiral turns of the cochlea, and internal acoustic meatus were well recognizable from every direction through the transparent surface resin. The anterior semicircular canal was obvious immediately beneath the arcuate eminence, and the topographical relationships of the vestibulocochlear organ and adjacent great vessels were easily discernible. We consider that this transparent temporal bone model will be a very useful aid for better understanding of the gross anatomy of the vestibulocochlear organ.

  12. Temporal Bone Osteomyelitis: The Relationship with Malignant Otitis Externa, the Diagnostic Dilemma, and Changing Trends

    Directory of Open Access Journals (Sweden)

    Jia-Cheng Chen

    2014-01-01

    Full Text Available Fifty-five patients hospitalized for osteomyelitis of the temporal bone between 1990 and 2011 were divided into two study groups: group 1 was patients collected from 1990 to 2001 and group 2 was composed of patients between 2002 and 2011. Clinical diagnostic criteria and epidemiologic data were analyzed to illustrate the altering features of osteomyelitis of the temporal bone. Group 1 patients were characterized by high prevalence of diabetes and more commonly suffered from otalgia, otitis externa and granulation tissue in the external auditory canal and higher positive culture for Pseudomonas aeruginosa. Noticeable changing trends were found between both groups, including declining prevalence of diabetes, fewer patients complaining of pain or presenting with otitis externa, and canal granulation, and increased variety of pathogens in group 2. We should highlight the index of clinical suspicion for osteomyelitis of the temporal bone, even in nondiabetic or immunocompetent patients. Painless otorrhea patients were also at risk of osteomyelitis of the temporal bone, especially patients with previous otologic operation. Increased multiplicity of pathogens amplified the difficulty of diagnosis for osteomyelitis of the temporal bone.

  13. Evaluation of a haptics-based virtual reality temporal bone simulator for anatomy and surgery training.

    Science.gov (United States)

    Fang, Te-Yung; Wang, Pa-Chun; Liu, Chih-Hsien; Su, Mu-Chun; Yeh, Shih-Ching

    2014-02-01

    Virtual reality simulation training may improve knowledge of anatomy and surgical skills. We evaluated a 3-dimensional, haptic, virtual reality temporal bone simulator for dissection training. The subjects were 7 otolaryngology residents (3 training sessions each) and 7 medical students (1 training session each). The virtual reality temporal bone simulation station included a computer with software that was linked to a force-feedback hand stylus, and the system recorded performance and collisions with vital anatomic structures. Subjects performed virtual reality dissections and completed questionnaires after the training sessions. Residents and students had favorable responses to most questions of the technology acceptance model (TAM) questionnaire. The average TAM scores were above neutral for residents and medical students in all domains, and the average TAM score for residents was significantly higher for the usefulness domain and lower for the playful domain than students. The average satisfaction questionnaire for residents showed that residents had greater overall satisfaction with cadaver temporal bone dissection training than training with the virtual reality simulator or plastic temporal bone. For medical students, the average comprehension score was significantly increased from before to after training for all anatomic structures. Medical students had significantly more collisions with the dura than residents. The residents had similar mean performance scores after the first and third training sessions for all dissection procedures. The virtual reality temporal bone simulator provided satisfactory training for otolaryngology residents and medical students. Copyright © 2013. Published by Elsevier Ireland Ltd.

  14. Temporal bone changes in patients with Goldenhar syndrome with special emphasis on inner ear abnormalities.

    Science.gov (United States)

    Hennersdorf, Florian; Friese, Natascha; Löwenheim, Hubert; Tropitzsch, Anke; Ernemann, Ulrike; Bisdas, Sotirios

    2014-06-01

    Goldenhar syndrome is a developmental disorder presenting with orofacial and vertebral anomalies, which are also accompanied by abnormalities in other organs. We examined temporal bone changes with special emphasis on inner ear abnormalities in these patients. A retrospective review of 7 new cases in addition to a previously published series of 14 cases with clinically diagnosed Goldenhar syndrome was carried out to search for inner ear anomalies. In addition, temporal bone imaging studies from the literature were summarized and compared with our results. Departments of Neuroradiology and Otorhinolaryngology at a university hospital. In addition to the previous series of 14 patients, 7 new patients with Goldenhar syndrome were identified. Patients underwent otologic examination, audiometric studies, and high-resolution computed tomography (CT) or magnetic resonance imaging (MRI) of the temporal bone. Temporal bone changes and specifically inner ear malformations. Nineteen of 21 patients showed changes of the external and middle ear correlating with the literature. Seven of 21 patients showed inner ear abnormalities constituting one-third of all patients. These ranged from mild such as vestibular enlargement to severe defects such as cochlear hypoplasia and common cavity. Inner ear abnormalities were present in one-third of patients. Although in some cases, these might not be of clinical significance, some patients show severe defects of the inner ear requiring more complex hearing loss therapy. Therefore, imaging of the temporal bone structures is important in the care of these patients.

  15. Temporal bone surgery causes reduced nitric oxide synthase activity in the ipsilateral guinea pig hippocampus.

    Science.gov (United States)

    Zheng, Y; Smith, P F; Darlington, C L

    1999-01-08

    There is a lack of data on the neurochemical basis for the interaction between the vestibular system and the hippocampus. The aim of the present study was to determine levels of nitric oxide synthase (NOS) activity in the ipsilateral and contralateral hippocampi at 10 h following unilateral deafferentation of the peripheral vestibular nerve (UVD) in guinea pig, using a radio-enzymatic technique. The levels of NOS activity were similar in the contralateral hippocampus following either a sham temporal bone operation or the UVD. However, NOS activity was significantly lower in the ipsilateral hippocampus following both the UVD and the sham temporal bone surgery (P<0.05 for both comparisons). These results suggest that even sham temporal bone surgery results in a reduction in NOS activity in the ipsilateral hippocampus.

  16. Bilateral Facial Paralysis Caused by Bilateral Temporal Bone Fracture: A Case Report and a Literature Review

    Directory of Open Access Journals (Sweden)

    Sultan Şevik Eliçora

    2015-01-01

    Full Text Available Bilateral facial paralysis caused by bilateral temporal bone fracture is a rare clinical entity, with seven cases reported in the literature to date. In this paper, we describe a 40-year-old male patient with bilateral facial paralysis and hearing loss that developed after an occupational accident. On physical examination, House-Brackmann (HB facial paralysis of grade 6 was observed on the right side and HB grade 5 paralysis on the left. Upon temporal bone computed tomography (CT examination, a fracture line exhibiting transverse progression was observed in both petrous temporal bones. Our patient underwent transmastoid facial decompression surgery of the right ear. The patient refused a left-side operation. Such patients require extensive monitoring in intensive care units because the presence of multiple injuries means that facial functions are often very difficult to evaluate. Therefore, delays may ensue in both diagnosis and treatment of bilateral facial paralysis.

  17. Diagnostic Challenges in a Case of IgG4-RD Affecting the Temporal Bone.

    Science.gov (United States)

    Vuncannon, Jackson Ross; Panella, Nicholas John; Magliocca, Kelly R; Mattox, Douglas E

    2017-03-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described fibroinflammatory condition with a characteristic histology. While IgG4-RD can affect a great variety of anatomical sites, it has been seldom described in the temporal bone. Herein, a case IgG4-RD occurring in the temporal bone of a 35-year-old woman is reported. This case of IgG4-RD of the temporal bone proved a uniquely challenging diagnosis due to slightly atypical histology falling outside of "highly suggestive" criteria. We suggest that IgG4-RD remains a challenging diagnosis to reach despite increased awareness of the condition. We further suggest that clinicopathologic correlation remain the cornerstone of diagnosis as the spectrum of presentations of this newly described disease may be wider than previously anticipated.

  18. A novel etiology for pneumolabyrinth after temporal bone fracture without otic capsule involvement.

    Science.gov (United States)

    Muelleman, Thomas J; Bhalla, Vidur; Staecker, Hinrich

    2017-01-01

    Pneumolabyrinth has been considered an indicator of otic capsule involvement in temporal bone fractures. We present a novel theory for the etiology of pneumolabyrinth in a trauma patient without an otic capsule fracture: passage of intrathecal air into the labyrinth. Our patient experienced transient bilateral pneumolabyrinth after head trauma due to a motor vehicle collision. The patient was noted to have extensive pneumocephalus and a unilateral temporal bone fracture that spared the otic capsule. Initial computed tomography (CT) scans demonstrated air in the cochlea and both internal auditory canals. A high-resolution CT scan 6 hours later showed resolution of this air. Pneumolabyrinth may not be a sensitive indicator of otic capsule involvement in temporal bone fractures. In addition to middle ear sources, air in the labyrinth can also plausibly originate intrathecally, especially in the setting of pneumocephalus.

  19. Spatial and temporal variations of the callus mechanical properties during bone transport

    Energy Technology Data Exchange (ETDEWEB)

    Mora-Macias, J.; Reina-Romo, E.; Pajares, A.; Miranda, P.; Dominguez, J.

    2016-07-01

    Nanoindentation allows obtaining the elastic modulus and the hardness of materials point by point. This technique has been used to assess the mechanical propeties of the callus during fracture healing. However, as fas as the authors know, the evaluation of mechanical properties by this technique of the distraction and the docking-site calluses generated during bone transport have not been reported yet. Therefore, the aim of this work is using nanoindentation to assess the spatial and temporal variation of the elastic modulus of the woven bone generated during bone transport. Nanoindentation measurements were carried out using 6 samples from sheep sacrificed at different stages of the bone transport experiments. The results obtained show an important heterogeneity of the elastic modulus of the woven bone without spatial trends. In the case of temporal variation, a clear increase of the mean elastic modulus with time after surgery was observed (from 7±2GPa 35 days after surgery to 14±2GPa 525 days after surgery in the distraction callus and a similar increase in the docking site callus). Comparison with the evolution of the elastic modulus in the woven bone generated during fracture healing shows that mechanical properties increase slower in the case of the woven bone generated during bone transport. (Author)

  20. A case of chronic myeloid leukemia with features of essential thrombocythemia in peripheral blood and bone marrow

    OpenAIRE

    Byun, Young Jae; Park, Byeong-Bae; Lee, Eun Sung; Choi, Kyung Soo; Lee, Dae Sung

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by overproduction of myeloid white blood cells. Philadelphia chromosome is an essential finding for CML diagnosis. Generally, a clinical diagnosis of essential thrombocythemia (ET) can be established from isolated marked thrombocytosis in peripheral blood. However, Philadelphia chromosome-positivity or bcr/abl rearrangement with isolated thrombocytosis should be diagnosed as CML, not ET, according to World Health Or...

  1. Virtual temporal bone: an interactive 3-dimensional learning aid for cranial base surgery

    OpenAIRE

    Kockro, R A; Hwang, P Y

    2009-01-01

    OBJECTIVE: We have developed an interactive virtual model of the temporal bone for the training and teaching of cranial base surgery. METHODS: The virtual model was based on the tomographic data of the Visible Human Project. The male Visible Human's computed tomographic data were volumetrically reconstructed as virtual bone tissue, and the individual photographic slices provided the basis for segmentation of the middle and inner ear structures, cranial nerves, vessels, and brainstem. These st...

  2. Statistical model estimating the occurrence of otitis media from temporal bone pneumatization

    DEFF Research Database (Denmark)

    Homøe, P; Lynnerup, N; Rasmussen, N

    1994-01-01

    In order to investigate the relationship between the pneumatization of temporal bones and the occurrence of otitis media in Greenlandic Inuit, 36 Greenlandic Inuit were examined by radiography of the temporal bones. The pneumatized cell area was measured planimetrically. All subjects answered...... a questionnaire on infectious middle ear disease (IMED), and an objective otologic examination was performed. Nine persons of 34 (26%) reported IMED in childhood, and there was IMED reported in all pneumatized areas below 400 mm2. Based on bilateral area measures, a polychotomous logistic regression model...

  3. Displasia fibrosa do osso temporal: relato de dois casos Fibrous dysplasia of the temporal bone: report of two cases

    Directory of Open Access Journals (Sweden)

    Roberto Claudio B. Oliveira

    2004-10-01

    Full Text Available A displasia fibrosa do osso temporal é uma doença de etiologia ainda controversa, manifestando-se principalmente por estenose progressiva do conduto auditivo externo e pela perda condutiva da audição. Outras manifestações incluem abaulamento na região temporal ou retroauricular, otorréia, otalgia e disacusia sensório-neural. A incidência é maior no sexo masculino e acomete principalmente a raça branca. O exame radiológico característico demonstra um aspecto de "vidro-fosco" homogêneo envolvido por uma concha de tecido cortical denso, embora existam outros padrões radiológicos desta enfermidade. O exame microscópico demonstra um trabeculado ósseo semelhante aos caracteres chineses. Este estudo relata dois casos de displasia fibrosa do osso temporal que se destacam, pois ultrapassaram o osso temporal, acometendo a região zigomática, sendo que no segundo caso houve também comprometimento do osso esfenóide e o pterigóide. Os pacientes foram submetidos à mastoidectomia radical modificada e tiveram boa evolução.Fibrous dysplasia of the temporal bone (FDTB is a disorder which etiology is still controversial. Its main clinical feature is a progressive narrowing of the external auditory canal following by conductive hearing loss. Temporal or retroauricular enlargement, ear discharge, otalgia, and sensorineural hearing loss are additional findings. Women and Caucasians are more affected. The prominent finding is a homogeneous radiodense "grounded glass" like image shell surrounded by dense cortical tissue. However, other radiological patterns of this disease may be displayed. Microscopically, a trabecular of bone in "Chinese letter" configuration is found. The two cases of FDTB herein reported are particularly special for a far beyond temporal commitment reaching the zygomatic area in the first case and sphenoid and pterygoid bones in the second one. This infrequent clinical feature with unusual radiological findings made these

  4. Validation of exposure visualization and audible distance emission for navigated temporal bone drilling in phantoms.

    Directory of Open Access Journals (Sweden)

    Eduard H J Voormolen

    Full Text Available BACKGROUND: A neuronavigation interface with extended function as compared with current systems was developed to aid during temporal bone surgery. The interface, named EVADE, updates the prior anatomical image and visualizes the bone drilling process virtually in real-time without need for intra-operative imaging. Furthermore, EVADE continuously calculates the distance from the drill tip to segmented temporal bone critical structures (e.g. the sigmoid sinus and facial nerve and produces audiovisual warnings if the surgeon drills in too close vicinity. The aim of this study was to evaluate the accuracy and surgical utility of EVADE in physical phantoms. METHODOLOGY/PRINCIPAL FINDINGS: We performed 228 measurements assessing the position accuracy of tracking a navigated drill in the operating theatre. A mean target registration error of 1.33±0.61 mm with a maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal bone phantoms, once using EVADE, and once using a standard neuronavigation interface. While using standard neuronavigation the surgeons damaged three modeled temporal bone critical structures. No structure was hit by surgeons utilizing EVADE. Surgeons felt better orientated and thought they had improved tumor exposure with EVADE. Furthermore, we compared the distances between surface meshes of the virtual drill cavities created by EVADE to actual drill cavities: average maximum errors of 2.54±0.49 mm and -2.70±0.48 mm were found. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that EVADE gives accurate feedback which reduces risks of harming modeled critical structures compared to a standard neuronavigation interface during temporal bone phantom drilling.

  5. Facial nerve problems and hearing loss in patients with temporal bone fractures: demographic data.

    Science.gov (United States)

    Yetiser, Sertac; Hidir, Yusuf; Gonul, Engin

    2008-12-01

    The incidence of temporal bone fractures have increased in recent decades together with the increasing traffic and population. The aim of this study is to evaluate the cause, treatment methods, radiologic, and intraoperative findings in patients with temporal bone fractures. Thirty-five patients with temporal bone fracture who have been followed between 1992 and 2006 were retrospectively reviewed. Computerized tomography and audiometric tests were obtained. Electrophysiological evaluation of the facial nerve in patients with traumatic facial paralysis was carried by serial electromyogram (EMG). House-Brackmann grading system was used to evaluate the function of the facial nerve. Twenty-three patients underwent operation for facial paralysis or hearing loss. Results of medical and surgical therapy were documented. Traffic crash was the most common cause (54%). Eighteen (51.4%) of patients had conductive hearing loss, 6 (17.14%) of the patients had sensorineural hearing loss, and 11 (31.42%) had normal hearing. Transient or persistent facial paralysis was detected in 24 of 35 patients (68.57%). Nineteen patients underwent partial or total facial decompression. Preoperative EMG of the majority of the operated patients revealed total axonal degeneration. The most common affected area of the facial nerve by trauma was the vertical segment (31.58%). House-Brackmann 1 and 2 grade was achieved in majority of the patients. Fourteen ossicular abnormalities were detected in 10 patients, and the abnormality was usually related to the incus. More than 10 dB air-bone gap closure was achieved in six of eight patients (75%). Traffic crashes continue to be the main cause of temporal bone fractures. Facial paralysis caused by temporal bone trauma can be satisfactorily treated by decompression. EMG, clinical grading, and onset of the paralysis are important guides for the surgery. Restoration of the hearing can be achieved in majority of patients.

  6. Testicular myeloid sarcoma: case report

    Directory of Open Access Journals (Sweden)

    Luzia Beatriz Ribeiro Zago

    2013-01-01

    Full Text Available Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started.

  7. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  8. Recurrence of a t(8;21-Positive Acute Myeloid Leukemia in the Form of a Granulocytic Sarcoma Involving Cranial Bones: A Diagnostic and Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Ambra Di Veroli

    2013-01-01

    Full Text Available Granulocytic sarcoma (GS is a rare extramedullary solid tumor defined as an accumulation of myeloblasts or immature myeloid cells. It can cooccur with or precede the acute myeloid leukemia (AML as well as following treated AML. The incidence of GS in AML patients is 3–8% but it significantly rises in M2 FAB subtype AML. This variety of AML harbors t(8;21 in up to 20–25% of cases (especially in children and black ones of African origin and, at a molecular level, it is characterized by the generation of a fusion gene known as RUNX1-RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence, the t(8;21 and the relative transcript represent the most common cytogenetic and molecular abnormalities in GS. FLT3-ITD mutation was rarely described in AML patients presenting with GS. FLT3 ITD is generally strongly associated with poor prognosis in AML, and is rarely reported in patients with t(8;21. GS presentation is extremely variable depending on organs involved; in general, cranial bones and sinus are very rarely affected sites. We report a rare case of GS occurring as a recurrence of a previously treated t(8;21, FLT3-ITD positive AML, involving mastoid bones and paravertebral tissues.

  9. Effect of temporal bone resection on temporomandibular joint function: a quality of life study.

    Science.gov (United States)

    de Casso, Carmen; Kwhaja, Sadie; Davies, Stephen; Al-Ani, Ziad; Saeed, Shakeel R; Homer, Jarrod J

    2010-01-01

    Temporal bone resection for carcinoma may affect quality of life (QOL) and result in temporomandibular joint (TMJ) disorders. The aims of this study were to 1) assess TMJ function after temporal bone resection, and 2) assess the impact of TMJ dysfunction on QOL. Chart and patient review and QOL study. Tertiary referral center (Manchester Royal Infirmary). Thirty patients who had undergone temporal bone resection were identified. Thirteen patients were alive and were included in the study. All patients were submitted to a clinical examination to identify TMJ disorders and determine facial nerve function, and they all answered the University of Washington QOL (UW-QOL) questionnaire (version 4). Eight patients had TMJ disorders with reduced mobility in either direction and/or significant pain. Main factors affecting QOL were pain (P = 0.001), appearance (P = 0.001), and anxiety (P = 0.000). Neither facial nerve palsy nor TMJ disorders affected QOL. The responses to the UW-QOL questionnaire showed that 69 percent of our patients had a good QOL. A total of 61.53 percent of our patients had TMJ dysfunction presenting as restriction of jaw mobility with or without pain. TMJ dysfunction is present in a significant number of patients after temporal bone resection, resulting in longstanding problems, which should be addressed accordingly. Poor QOL results from ongoing pain and psycho-social disturbance.

  10. la dysplasie fibreuse du rocher fibrous dysplasia of the temporal bone

    African Journals Online (AJOL)

    9. 4- Nager GT, Kennedy DW, and Kopstein E. Fibrous dysplasia: a re- view of the disease and its manifestations in the temporal bone. Ann. OtolRhinolLaryngol 1982;92(Suppl.): 1–52. 5- Papadakis CE, Skoulakis CE, Propakapis EP, et al.

  11. Incidental internal carotid artery calcifications on temporal bone CT in children

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Bernadette; Jones, Blaise [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Blackham, Aaron [University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2007-02-15

    Incidental internal carotid artery (ICA) calcifications are occasionally noted on CT images of the brain and temporal bone. In adults, incidental calcifications have been correlated with increased incidence of hypercholesterolemia, cardiac disease, diabetes and carotid stenosis. To determine the incidence of incidental calcifications of the carotid siphon on temporal bone CT in children. We retrospectively reviewed 24 months of consecutive temporal bone CT examinations in children aged 18 years and younger. CT examinations on 663 patients were reviewed and the presence or absence of ICA calcifications was ranked as absent, questionable or definitive. In patients in whom definitive calcifications were identified, hospital charts were reviewed for evidence of diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia and chronic renal disease as potential causes of early atherosclerosis. Of the 663 patients, 25% had definitive calcifications within the wall of the ICA: 6% of children younger than 2 years and 28% of children 12-19 years of age. Incidentally noted ICA calcifications are a common finding on temporal bone CT in children, most likely a physiologic response to turbulent flow at natural bends in the artery rather than secondary to underlying disease predisposing to early atherosclerotic calcification. (orig.)

  12. Pneumatization of the Temporal Bones in a Greenlandic Inuit Anthropological Material

    DEFF Research Database (Denmark)

    Homøe, P; Lynnerup, N

    1991-01-01

    The degree of pneumatization of the temporal bones correlates with exposure during childhood and adolescence to infectious middle ear diseases (IMED), both acute and chronic. The pneumatized area as seen on cranial X-rays can be measured. This was applied to an anthropological material in order...

  13. Creation of a 3D printed temporal bone model from clinical CT data.

    Science.gov (United States)

    Cohen, Joss; Reyes, Samuel A

    2015-01-01

    Generate and describe the process of creating a 3D printed, rapid prototype temporal bone model from clinical quality CT images. We describe a technique to create an accurate, alterable, and reproducible rapid prototype temporal bone model using freely available software to segment clinical CT data and generate three different 3D models composed of ABS plastic. Each model was evaluated based on the appearance and size of anatomical structures and response to surgical drilling. Mastoid air cells had retained scaffolding material in the initial versions. This required modifying the model to allow drainage of the scaffolding material. External auditory canal dimensions were similar to those measured from the clinical data. Malleus, incus, oval window, round window, promontory, horizontal semicircular canal, and mastoid segment of the facial nerve canal were identified in all models. The stapes was only partially formed in two models and absent in the third. Qualitative feel of the ABS plastic was softer than bone. The pate produced by drilling was similar to bone dust when appropriate irrigation was used. We present a rapid prototype temporal bone model made based on clinical CT data using 3D printing technology. The model can be made quickly and inexpensively enough to have potential applications for educational training. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. High grade hemangioendothelioma of the temporal bone in a child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Lim; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Lee, Hee Jeong; Park, Hyun Jin; Byun, Jae Young [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.

  15. Systems-based identification of temporal processing pathways during bone cell mechanotransduction.

    Directory of Open Access Journals (Sweden)

    Leah E Worton

    Full Text Available Bone has long been established to be a highly mechanosensitive tissue. When subjected to mechanical loading, bone exhibits profoundly different anabolic responses depending on the temporal pattern in which the stimulus is applied. This phenomenon has been termed temporal processing, and involves complex signal amplification mechanisms that are largely unidentified. In this study, our goal was to characterize transcriptomic perturbations arising from the insertion of intermittent rest periods (a temporal variation with profound effects on bone anabolism in osteoblastic cells subjected to fluid flow, and assess the utility of these perturbations to identify signaling pathways that are differentially activated by this temporal variation. At the level of the genome, we found that the common and differential alterations in gene expression arising from the two flow conditions were distributionally distinct, with the differential alterations characterized by many small changes in a large number of genes. Using bioinformatics analysis, we identified distinct up- and down-regulation transcriptomic signatures associated with the insertion of rest intervals, and found that the up-regulation signature was significantly associated with MAPK signaling. Confirming the involvement of the MAPK pathway, we found that the insertion of rest intervals significantly elevated flow-induced p-ERK1/2 levels by enabling a second spike in activity that was not observed in response to continuous flow. Collectively, these studies are the first to characterize distinct transcriptomic perturbations in bone cells subjected to continuous and intermittent stimulation, and directly demonstrate the utility of systems-based transcriptomic analysis to identify novel acute signaling pathways underlying temporal processing in bone cells.

  16. Successful Function-Preserving Therapy for Chondroblastoma of the Temporal Bone Involving the Temporomandibular Joint

    Directory of Open Access Journals (Sweden)

    Junkichi Yokoyama

    2011-02-01

    Full Text Available We present a case involving a late diagnosis of chondroblastoma of the temporal skull base involving the temporomandibular joint (TMJ. Following an initial misdiagnosis and unsuccessful treatment over a period of 5 years, the patient was referred to our department for further evaluation and possible surgical intervention for occlusal abnormalities, trismus, clicking of the TMJ, and hearing impairment. Based on preoperative immunochemical studies showing positive reaction of multinucleated giant cells for S-100 protein, the final diagnosis was chondroblastoma. The surgical approach – postauricular incision and total parotidectomy, with complete removal of the temporal bone, including the TMJ via the extended middle fossa – was successful in preserving facial nerves and diminishing clinical manifestations. This study highlights a misdiagnosed case in an effort to underline the importance of medical examinations and accurate differential diagnosis in cases involving any tumor mass in the temporal bone.

  17. Unbiased Stereologic Estimation of the Spatial Distribution of Paget’s Disease in the Human Temporal Bone

    DEFF Research Database (Denmark)

    Bloch, Sune Land; Sørensen, Mads Sølvsten

    2014-01-01

    remodeling around the inner ear space and to compare it with that of otosclerosis in a contemporary context of temporal bone dynamics. MATERIALS AND METHODS: From the temporal bone collection of Massachusetts Eye and Ear Infirmary, 15 of 29 temporal bones with Paget's disease were selected to obtain......BACKGROUND: It has been suggested that Paget's disease of bone and otosclerosis may share a myxoviral etiology. However, the association between virus infection and pathologic bone remodeling is still controversial. The aim of this study was to estimate the spatial distribution of pagetic bone...... is similar to the normal distribution of perilabyrinthine bone remodeling but entirely different from the spatial location of otosclerosis, which are focal and centripetally distributed around the inner ear space. CONCLUSION: In Paget's disease, the antiresorptive barrier around the inner ear space becomes...

  18. Large capillary hemangioma of the temporal bone with a dural tail sign: A case report

    KAUST Repository

    YANG, GUANG

    2014-05-13

    The present study reports a rare case of large capillary hemangioma of the temporal bone with a dural tail sign. A 57-year-old female presented with pulsatile tinnitus and episodic vertigo associated with a ten-year history of an intermittent faint headache. Magnetic resonance imaging revealed a mass in the right petrous bone, which was hypointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images, and showed a dural tail sign following gadolinium administration. Pre-operatively, this tumor was believed to be a meningioma. During surgery, the vascular tumor was removed by a modified pterional approach. A histopathological examination indicated that the tumor was a capillary hemangioma. Although intraosseous capillary hemangiomas are rare, they most frequently affect the temporal bone. Hemangiomas of the temporal bone may mimic other more common basal tumors. The diagnosis is most often made during surgical resection. The dural tail sign is not specific for meningioma, as it also occurs in other intracranial or extracranial tumors. The treatment of intratemporal hemangiomas is complete surgical excision, with radiotherapy used for unresectable lesions. To the best of our knowledge, the present study is the fourth case of intraosseous intracranial capillary hemangioma, but the largest intratemporal hemangioma to be reported in the literature to date.

  19. Case analysis of temporal bone lesions with facial paralysis as main manifestation and literature review.

    Science.gov (United States)

    Chen, Wen-Jing; Ye, Jing-Ying; Li, Xin; Xu, Jia; Yi, Hai-Jin

    2017-08-23

    This study aims to discuss clinical characteristics, image manifestation and treatment methods of temporal bone lesions with facial paralysis as the main manifestation for deepening the understanding of such type of lesions and reducing erroneous and missed diagnosis. The clinical data of 16 patients with temporal bone lesions and facial paralysis as main manifestation, who were diagnosed and treated from 2009 to 2016, were retrospectively analyzed. Among these patients, six patients had congenital petrous bone cholesteatoma (PBC), nine patients had facial nerve schwannoma, and one patient had facial nerve hemangioma. All the patients had an experience of long-term erroneous diagnosis. The lesions were completely excised by surgery. PBC and primary facial nerve tumors were pathologically confirmed. Facial-hypoglossal nerve anastomosis was performed on two patients. HB grade VI was recovered to HB grade V in one patient. The anastomosis failed due to severe facial nerve fibrosis in one patient. Hence, HB remained at grade VI. Postoperative recovery was good for all patients. No lesion recurrence was observed after 1-6 years of follow-up. For the patients with progressive or complete facial paralysis, imaging examination should be perfected in a timely manner. Furthermore, PBC, primary facial nerve tumors and other temporal bone space-occupying lesions should be eliminated. Lesions should be timely detected and proper intervention should be conducted, in order to reduce operation difficulty and complications, and increase the opportunity of facial nerve function reconstruction.

  20. Clinical features and radiological evaluation of otic capsule sparing temporal bone fractures.

    Science.gov (United States)

    Song, S W; Jun, B C; Kim, H

    2017-03-01

    To evaluate the clinical and radiological aspects of otic capsule sparing temporal bone fractures. Using medical records, 188 temporal bones of 173 patients with otic capsule sparing temporal bone fractures were evaluated. Otoscopic findings and symptoms, facial paralysis, and hearing loss were assessed. Using regional analysis, 7 fractures were classified as type I, 85 as type II, 169 as type III and 114 as type IV. Fourteen of the 17 facial paralysis cases improved to House-Brackmann grade II or lower at an average of 57.6 days after the initial evaluation. Thirty-one patients underwent initial and follow-up pure tone audiometry examinations. The air-bone gap closed significantly from 27.2 dB at an average of 21.8 days post-trauma to 19.6 dB at an average of 79.9 days post-trauma, without the need for surgical intervention. Initial conservative treatment for facial paralysis or conductive hearing loss is possible in otic capsule sparing fracture cases after careful evaluation of the patient.

  1. Semicircular canal dehiscence: Frequency and distribution on temporal bone CT and its relationship with the clinical outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Elmali, Muzaffer, E-mail: muzafel@yahoo.com.tr [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Polat, Ahmet Veysel, E-mail: veyselp@hotmail.com [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Kucuk, Harun, E-mail: hardrmd@yahoo.com [Department of Otorhinolaryngology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Atmaca, Sinan, E-mail: sinanatmaca@yahoo.com [Department of Otorhinolaryngology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Aksoy, Ahmet, E-mail: toxocara47@hotmail.com [Department of Otorhinolaryngology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey)

    2013-10-01

    Purpose: In this study, we aimed to investigate the frequency of SCD and its distribution and relationship with clinical outcomes on thin-section CT of the temporal bone. Materials and methods: Digital temporal bone CT images of 850 consecutive patients (1700 temporal bone CTs, 5100 SCs) who presented with a range of complaints such as vertigo, deafness, ear pain, fullness, and discharge between January 2008 and December 2011 were re-evaluated. Axial and oblique coronal reconstruction images of the temporal bone were made with a reconstruction thickness of 0.5 mm. Additionally, superior SC was evaluated in two perpendicular planes. Results: Out of 850 patients, 70 had completely normal temporal bone CT. Ninety-three patients had at least one SCD. In the temporal bone-based evaluation, 119 (26 bilateral, 67 unilateral) of 1700 temporal bones (7%) showed dehiscence. The SC-based evaluation revealed 125 SCD (2.5%) in 5100 SCs. The total number and rates of SCD were as follows: superior 103 (82.4%), posterior 13 (10.4%), and lateral nine (7.2%). Twenty of the 93 patients with SCD (21.5%) revealed no other findings on their temporal bone CTs. We determined a significant correlation between vestibular complaints, conductive hearing loss and SCD but there was no correlation between mixed, sensorineural hearing loss and SCD. Conclusion: We determined the frequency of SCD in 11% of patients and 7% of temporal bones. With regards to the distribution, the superior SC showed the highest dehiscence rate (82.4%). We found a significant correlation between vestibular symptoms, conductive hearing loss and SCD.

  2. Posttraumatic Temporal Bone Meningocele Presenting as a Cystic Mass in the External Auditory Canal.

    Science.gov (United States)

    Alijani, Babak; Bagheri, Hamid Reza; Chabok, Shahrokh Yousefzadeh; Behzadnia, Hamid; Dehghani, Siavash

    2016-07-01

    Temporal bone meningoencephalic herniation may occur in head trauma. It is a rare condition with potentially dangerous complications. Several different routes for temporal bone meningoencephalocele have been proposed. An11-year-old boy with history of head trauma initially presented with a 9-months history of progressive right-sided hearing loss and facial weakness. The other complaint was formation of a cystic mass in the right external auditory canal. The patient underwent surgery via a mini middle cranial fossa craniotomy associated with a transmastoid approach. Although presenting symptoms can be subtle, early suspicion and confirmatory imaging aid in establishing the diagnosis. The combination of computed tomography and magnetic resonance imaging will help in proper preoperative diagnosis. The operation includes transmastoid, middle cranial fossa repair, or combination of both. The multilayer closure of bony defect is very important to avoid cerebrospinal fluid leak. Clinical manifestations, diagnosis, and surgical approaches for posttraumatic meningoencephaloceles arising in the head and neck region are briefly discussed.

  3. Aspects of temporal bone anatomy and pathology in conjunction with cochlear implant surgery

    Energy Technology Data Exchange (ETDEWEB)

    Stjernholm, Christina [Karolinska Inst., Stockholm (Sweden). Soedersjukhuset

    2003-07-01

    Cochlear implantation is a treatment for patients with severe sensorineural hearing loss/deafness, who get no help from ordinary hearing aids. The cochlear implant is surgically placed under the skin near the ear and a very thin electrode array is introduced into the cochlea of the inner ear, where it stimulates the remaining nerve fibers. The operation is complicated; it is performed with the aid of a microscope, and involves drilling very close to vital vessels and important nerves. High resolution computed tomography (CT) of the temporal bone is a part of the preoperative evaluation preceding cochlear implantation. It is a method for visualizing the bony structures of the middle and inner ear - to diagnose pathology and to describe the anatomy. The first work concerns CT of the temporal bone and cochlear implant surgery in children with CHARGE association. This is a rare condition with multiple congenital abnormalities, sometimes lethal. Children with CHARGE have different combinations of disabilities, of which impairments of vision and hearing, as well as balance problems and facial palsy can lead to developmental delay. There have been few reports of radiological temporal bone changes and none of cochlear implant surgery for this group. The work includes a report of the findings on preoperative CT and at surgery, as well as postimplant results in two children. A review of the latest diagnostic criteria of CHARGE and the temporal bone changes found in international literature is also included. The conclusion was that certain combinations of temporal bone changes in CHARGE are, if not specific, at least extremely rare in other materials. CT can visualize these changes and be used as a diagnostic tool. This is important, since some of the associated disabilities are not so obvious from the start. Early treatment is vital for the child's development. This work also shows that cochlear implantation may help some of these often very isolated children to

  4. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia.

    Science.gov (United States)

    Aljafar, Hadeel M; Alsuhibani, Sari S; Alahmari, Mohammad S; Alzahrani, Musaed A

    2015-10-01

    Otologic manifestations in chronic lymphocytic leukemia (CLL) are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhagic bullae on the posterior segment of tympanic membrane. Left sided facial paralysis developed on the third day of admission. Full recovery of facial paralysis is achieved by 10 days course of corticotherapy. Histological examination of middle ear tissue biopsy showed infiltration by monotonous small lymphoid cells, showing round nuclei, condensed chromatin suggestive of CLL. Although rare, unusual otologic manifestations should raise the suspicion of a temporal bone metastasis as a sign of relapsing CLL.

  5. Neutrophil Extracellular Traps and Fibrin in Otitis Media: Analysis of Human and Chinchilla Temporal Bones.

    Science.gov (United States)

    Schachern, Patricia A; Kwon, Geeyoun; Briles, David E; Ferrieri, Patricia; Juhn, Steven; Cureoglu, Sebahattin; Paparella, Michael M; Tsuprun, Vladimir

    2017-10-01

    Bacterial resistance in acute otitis can result in bacterial persistence and biofilm formation, triggering chronic and recurrent infections. To investigate the middle ear inflammatory response to bacterial infection in human and chinchilla temporal bones. Six chinchillas underwent intrabullar inoculations with 0.5 mL of 106 colony-forming units (CFUs) of Streptococcus pneumoniae, serotype 2. Two days later, we counted bacteria in middle ear effusions postmortem. One ear from each chinchilla was processed in paraffin and sectioned at 5 µm. The opposite ear was embedded in epoxy resin, sectioned at a thickness of 1 µm, and stained with toluidine blue. In addition, we examined human temporal bones from 2 deceased donors with clinical histories of otitis media (1 with acute onset otitis media, 1 with recurrent infection). Temporal bones had been previously removed at autopsy, processed, embedded in celloidin, and cut at a thickness of 20 µm. Sections of temporal bones from both chinchillas and humans were stained with hematoxylin-eosin and immunolabeled with antifibrin and antihistone H4 antibodies. Histopatological and imminohistochemical changes owing to otitis media. Bacterial counts in chinchilla middle ear effusions 2 days after inoculation were approximately 2 logs above initial inoculum counts. Both human and chinchilla middle ear effusions contained bacteria embedded in a fibrous matrix. Some fibers in the matrix showed positive staining with antifibrin antibody, others with antihistone H4 antibody. In acute and recurrent otitis media, fibrin and neutrophil extracellular traps (NETs) are part of the host inflammatory response to bacterial infection. In the early stages of otitis media the host defense system uses fibrin to entrap bacteria, and NETs function to eliminate bacteria. In chronic otitis media, fibrin and NETs appear to persist.

  6. Diagnosis of temporal bone diseases using three-dimensional images with multislice CT

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Yoshihiro; Togami, Taro; Murota, Makiko; Fukunaga, Kotaro; Hino, Ichiro; Sato, Katashi; Ohkawa, Motoomi [Kagawa Medical Univ., Miki (Japan)

    2001-08-01

    We evaluated the usefulness of three-dimensional images with multislice CT in the temporal bone diseases. Fifty-nine cases (26 with medial otitis, 8 choresteatoma, 10 congenital malformation, 3 high jugular bulb, 2 otosclerosis, and 10 others) were included in this study. In the ossicular and inner ear lesions, oblique multiplanar images of the long axis of each ossicle was useful the detection of abnormality. Structural deformity of ossicles and bony labyrinth were clearly delineated by surface rendering images. (author)

  7. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia

    OpenAIRE

    Aljafar, Hadeel M.; Alsuhibani, Sari S.; Alahmari, Mohammad S.; Alzahrani, Musaed A.

    2015-01-01

    Otologic manifestations in chronic lymphocytic leukemia (CLL) are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhag...

  8. Anatomical Relationship of the Middle Cranial Fossa Dura to Surface Landmarks of the Temporal Bone.

    Science.gov (United States)

    Alhussaini, Mohamed A; Mattingly, Jameson K; Cass, Stephen P

    2017-10-01

    The suprameatal crest and temporal line provides a reliable landmark to the middle fossa dura. Surface anatomy of the temporal bone is used to guide mastoid surgery, but studies investigating these landmarks are limited. The aim of this study was to examine the anatomical relationship of the middle fossa dura to the temporal line. Thirty-two fresh hemicephalic temporal bones were prepared by drawing four lines along the mastoid including the suprameatal crest and temporal line (line 2), one line 5 mm superior to line 2 (line 1), and one 5 mm inferior to line 2 (line 3), and at Reid's base line (line 4). Four points were marked along these lines anterior to posterior 3 mm apart. A 1 mm bur was used to drill perpendicular to these points to examine the relationship to the middle fossa dura. The dura was found inferior to line 2 in 6.3% at point 1, 6.3% at point 2, 9.4% at point 3, and 18.8% at point 4. The dura in line 1 was found inferior to point 1 in 52.1%, point 2 in 46.9%, point 3 in 56.3%, and point 4 in 62.5%. Only one specimen (3.1%) had dura lying inferior to line 3. No specimens were inferior line 4 at any point. The dura of the middle fossa lies superior the temporal line in >80% of specimens and at least 5 mm superior in nearly half. This indicates the temporal line or a line slightly inferior to this is reliably inferior the middle fossa dura.

  9. Suture restriction of the temporal bone as a risk factor for acute otitis media in children: cohort study

    Directory of Open Access Journals (Sweden)

    Morin Chantal

    2012-11-01

    Full Text Available Abstract Background Eustachian tube (ET dysfunction plays an important role in the pathogenesis of acute otitis media (AOM. Unfortunately, there is a lack of knowledge about the exact role of the ET’s bony support, the temporal bone, on occurrence of AOM. This study investigates whether severe suture restriction of the temporal bone is a risk factor for development of AOM in young children. Methods Using a prospective cohort design, 64 children aged 6 to 18 months without prior history of AOM were followed during the cold season (September 2009 to April 2010. Temporal bone status (categorized as with or without severe suture restriction was evaluated using palpation and a cranial bone mobility test. Information about potential baseline confounders and risk factors for AOM (gender, age, birth weight, gestational age, use of pacifier, daycare attendance, presence of siblings, low socioeconomic status, breastfeeding ≥ 6 months, parental smoking and history of upper respiratory tract infection were also collected. Occurrence of AOM diagnosed by physicians blinded to temporal bone status was the main outcome. Data were analyzed using hierarchical linear and nonlinear (multilevel models. Results Severe suture restriction of the temporal bone was identified in 23 children (35.9%. At least one AOM episode was diagnosed in 14 (48.3% of the ears associated with temporal bones previously identified as having severe suture restriction and in 28 (28.3% of those without severe suture restriction. Higher risk for AOM was explained by severe suture restriction of the temporal bone (adjusted relative risk (RR, 2.26, 95% CI 1.43 to 2.91, p Conclusions The study results indicate that severe suture restriction of the temporal bone is a risk factor for AOM in young children. Subsequent intervention studies are needed to determine if this mechanical risk factor can be modified in young children.

  10. Temporal aneurysmal bone cyst: cost-effective method to achieve gross total resection.

    Science.gov (United States)

    Sodhi, Harsimrat Bir Singh; Salunke, Pravin; Agrawal, Parimal; Gupta, Kirti

    2016-08-01

    Aneurysmal bone cyst (ABC) is a vascular benign bony expansile lesion. The treatment is gross total resection. Surgery for a skull base aneurysmal bone cyst poses a significant challenge because of its vascularity and the adjacent neurovascular structures. We present the case of a young male with a temporal aneurysmal bone cyst who underwent gross total resection of the lesion. The external carotid artery (ECA) was temporarily clamped to cut off the vascular supply. There was no intraoperative event, and the patient made a good postoperative clinical recovery. This technique was used as an alternative to subselective endovascular embolization of the ECA branches. This case represents a simple yet cost-effective surgical technique to control bleeding for a highly vascular lesion such as ABCs, especially in resource-deficient countries.

  11. Advanced bionics thin lateral and Helix II electrodes: a temporal bone study.

    Science.gov (United States)

    Wright, Charles G; Roland, Peter S; Kuzma, Janusz

    2005-11-01

    This study was performed to evaluate the insertional properties of two cochlear implant electrodes recently developed by Advanced Bionics Corporation. Anatomic study using human cadaveric temporal bones. The electrode prototypes we tested are the Thin Lateral and Helix II arrays, which incorporate features designed to minimize insertional trauma. A total of eight electrodes (4 of each prototype) were evaluated after insertion into freshly fixed temporal bones. The electrodes were inserted by way of standard cochleostomies, and the specimens were subsequently dissected to assess electrode position, insertion depth, and intracochlear trauma. Quantitative data regarding insertion depths and contact distances from the modiolus are presented for all electrodes tested. The mean insertion depths were 368 degrees for the Thin Lateral electrodes, which are designed to approximate the lateral cochlear wall, and 436 degrees for the Helix II electrodes, which occupy a more medial position in the scala tympani. No evidence of insertional trauma was observed with either electrode. The ease of insertion and absence of trauma were confirmed during additional trials in which electrode behavior was directly observed during insertion into previously opened cochleas. Both electrodes performed favorably in our human temporal bone trials, and both arrays appear promising for clinical use, especially in patients with residual hearing in whom atraumatic insertion is an important objective.

  12. Using the petrous part of the temporal bone to estimate fetal age at death.

    Science.gov (United States)

    Nagaoka, Tomohito; Kawakubo, Yoshinori

    2015-03-01

    Little is understood about the age-related changes in the petrous part of the temporal bone in fetal life. The purposes of this study were to examine documented skeletal remains of Japanese fetuses, to measure the length of the petrous part, and to develop diagnostic standards for fetal age-at-death estimation that could be applied to poorly preserved skeletons. The results indicated that it is possible to use a regression equation to estimate age at death directly from the length of the petrous part of the temporal bone. The application of the present method to a different population led to a fetal age-at-death estimation with an error of less than 1 month. We also used the Bayesian estimation, which yielded posterior probabilities of age, conditional on being of a particular length of the petrous part. The reference table of estimated gestational age may provide an easy-to-use indicator of the fetal age at death. In conclusion, measurement of the petrous part of the temporal bone may offer a new methodological basis for forensic and bioarchaeological diagnoses of fetuses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Quantifying temporal bone morphology of great apes and humans: an approach using geometric morphometrics

    Science.gov (United States)

    Lockwood, Charles A; Lynch, John M; Kimbel, William H

    2002-01-01

    The hominid temporal bone offers a complex array of morphology that is linked to several different functional systems. Its frequent preservation in the fossil record gives the temporal bone added significance in the study of human evolution, but its morphology has proven difficult to quantify. In this study we use techniques of 3D geometric morphometrics to quantify differences among humans and great apes and discuss the results in a phylogenetic context. Twenty-three landmarks on the ectocranial surface of the temporal bone provide a high level of anatomical detail. Generalized Procrustes analysis (GPA) is used to register (adjust for position, orientation and scale) landmark data from 405 adults representing Homo, Pan, Gorilla and Pongo. Principal components analysis of residuals from the GPA shows that the major source of variation is between humans and apes. Human characteristics such as a coronally orientated petrous axis, a deep mandibular fossa, a projecting mastoid process, and reduced lateral extension of the tympanic element strongly impact the analysis. In phenetic cluster analyses, gorillas and orangutans group together with respect to chimpanzees, and all apes group together with respect to humans. Thus, the analysis contradicts depictions of African apes as a single morphotype. Gorillas and orangutans lack the extensive preglenoid surface of chimpanzees, and their mastoid processes are less medially inflected. These and other characters shared by gorillas and orangutans are probably primitive for the African hominid clade. PMID:12489757

  14. Inflammation and tumors of the temporal bone; Entzuendungen und Tumoren des Schlaefenbeins

    Energy Technology Data Exchange (ETDEWEB)

    Burian, M. [Universitaetsklinik fuer Hals-, Nasen- und Ohrenkrankheiten, Allgemeines Krankenhaus, Wien (Austria)

    1997-12-01

    The term `inflammation of the middle ear` covers a couple of deseases which range from the acute otitis media to the middle ear cholesteatoma. However, a clear characterization of a certain pathology is essential for any further treatment. Therefore this article presents a short overview about the different types of infections and their clinical manifestation. The tumors of the temporal bone show a great variety in their incidence. Even if tumors like the acoustic neurinoma or the paraganglioma are compareable common, the chondroblastoma of the temporal bone is absolutely rare. In spite of these differences the individual temporal bone neoplasias are shortly mentioned herein. (orig.) [Deutsch] Der Begriff Mittelohrentzuendung umfasst ein weites Spektrum von Krankheiten welches von der akuten Mittelohrentzuendung bis hin zum Cholesteatom reicht. Es soll in diesem Artikel eine kurze Uebersicht ueber die verschiedenen Entzuendungen gegeben werden, wobei vor allem auf eine klare Begriffsdefinition der einzelnen Entzuendungsformen und deren klinisches Erscheinungsbild geachtet wurde. Bei den Tumoren des Schlaefenbeins ist ein grosser Unterschied in der Inzidenz der einzelnen Tumoren gegeben. Waehrend Neubildungen wie das Akustikusneurinom oder das Paragangliom vergleichsweise haeufig im klinischen Alltag zu sehen sind, stellen Veraenderungen wie das Chondroblastom eine Raritaet dar. Trotz dieses Unterschieds im Vorkommen der verschiedenen Tumoren, wurde versucht, einen kurzen Gesamtueberblick ueber die Tumore des Mittel- und Innenohres zu geben. (orig.)

  15. Cone-Beam Computed Tomography: A New Method for Imaging of the Temporal Bone

    Energy Technology Data Exchange (ETDEWEB)

    Peltonen, L.I.; Aarnisalo, A A.; Jero, J. (Dept. of Otorhinolaryngology, Helsinki Univ. Central Hospital, Helsinki (Finland)); Kaeser, Y.; Kortesniemi, M.K.; Robinson, S.; Suomalainen, A. (Dept. of Radiology, Helsinki Univ. Central Hospital, Helsinki (Finland))

    2009-06-15

    Background: Clinical cone-beam computed tomography (CBCT), used in diagnostics of dental and maxillofacial radiology for almost 10 years, allows three-dimensional (3D) imaging of a focused area, with reasonable radiation dose. Purpose: To clarify the applicability of CBCT in imaging of the temporal bone. Material and Methods: We imaged cadaver temporal bones, one non-operated and five postmortem operated, with CBCT to evaluate the accuracy of this method in showing clinically important landmarks and the positions of middle-ear implants. In addition, to clarify the imaging protocols for the best possible result, we conducted a contrast-to-noise ratio (CNR) analysis by imaging a specially built phantom insert with different protocols. Results: For all the temporal bones, image quality was good and of diagnostic value, and the surgical landmarks as well as positions and details of the implants could be accurately observed. Based on measurements conducted with the phantom, the best possible clarity of the images with the machine used (3D Accuitomo; Morita Co., Kyoto (Japan)) was achieved with a tube voltage of 80 kVp and a current of 4 mA. Conclusion: Cone-beam CT is a promising new method for otologic imaging, based on its accuracy and relatively low radiation exposure per investigation

  16. CT diagnosis and differential diagnosis of otodystrophic lesions of the temporal bone

    Energy Technology Data Exchange (ETDEWEB)

    D' Archambeau, O.; Parizel, P.M.; Schepper, A.M. De (Antwerp University Hospital (Belgium). Department of Radiology); Koekelkoren, E.; Van De Heyning, P. (Antwerp University Hospital (Belgium). Department of E.N.T.)

    The purpose of this study was to assess the diagnostic and differential diagnostic value of high-resolution computed tomography in the evaluation of temporal-bone dystrophies. The study group included 55 patients with osseous abnormalities of the temporal bone in general, and the labyrinthine capsule in particular. In 27 patients the CT scan revealed evidence of otodystrophic lesions. The CT findings in patients with otosclerosis (21 patients), osteogenesis imperfecta (two patients), fibrous dysplasia (one patient). Paget's disease (one patient) and osteoporosis (two patients) are described. The CT scans of 17 patients revealed secondary osseous lesions due to metastasis (five patients), post-inflammatory changes (10 patients) or labyrinthitis ossificans (two patients). Normal variants and congenital mineralization defects were diagnosed in nine patients, Down's syndrome in two. Our results indicate the importance of high-resolution computed tomography as the primary imaging modality in evaluating osseous lesions of the temporal bone and labyrinth. (author). 14 refs.; 13 figs; 2 tabs.

  17. Development of cholesterol granuloma in a temporal bone petrous apex previously containing marrow exposed to air cells.

    Science.gov (United States)

    Selman, Yamil; Wood, John W; Telischi, Fred F; Casiano, Roy R; Angeli, Simon I

    2013-07-01

    There is ongoing debate on the pathogenic mechanisms of cholesterol granuloma formation in the temporal bone. The purpose of this report is to provide evidence in support of the exposed marrow hypothesis in explaining the pathogenesis of petrous apex cholesterol granuloma. Retrospective single case study. The primary outcome evaluated was the diagnosis of a new cholesterol granuloma in a petrous apex that previously demonstrated radiologic evidence of bone marrow exposed to petrous apex air cells. A patient with a unilateral petrous apex cholesterol granuloma develops a new, contralateral cholesterol granuloma in a hyperpneumatized temporal bone petrous apex shown previously to have medullary bone exposed to air cells. This report implicates the medullary-air cell interface in a hyperaerated temporal bone petrous apex in the development and growth of a petrous apex cholesterol granuloma.

  18. Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.

    Science.gov (United States)

    Hussein, K; Stucki-Koch, A; Göhring, G; Kreipe, H; Suttorp, M

    2017-07-01

    Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.

  19. Importance of Stereoscopy in Haptic Training of Novice Temporal Bone Surgery.

    Science.gov (United States)

    Unger, Bertram; Tordon, Bryan; Pisa, Justyn; Hochman, Jordan B

    2016-01-01

    We investigate the effects of stereoscopic simulation on novice trainee surgical performance. 20 first year medical students were randomized into a stereo or non-stereo group. Each participant viewed a 13 minute instructional video and then performed 3 mastoidectomy procedures with an in-house haptic temporal bone simulation, using a 3D-capable display with either active (stereo) or inactive (non-stero) shutter glasses. Following training, participants performed an actual mastoidectomy on a single 3D-printed bone model. The printed models were evaluated by 3 blinded neurotologic surgeons using a 7 point grading system. Two-tailed t-tests showed no significant difference in overall performance (mean score across test categories over all subjects) between stereo (M=3.8, SD=1.1) and non-stereo (M=4.4, SD=1.5) conditions (p=0.163). No significant differences existed in any of the assessed sub-domains. The addition of stereo-vision to haptic training may not affect temporal bone surgical skill acquisition in novice users.

  20. mTOR inhibitor rapamycin induce polymorphonuclear myeloid-derived suppressor cells mobilization and function in protecting against acute graft-versus-host disease after bone marrow transplantation.

    Science.gov (United States)

    Lin, Yu; Wang, Binsheng; Shan, Wei; Tan, Yamin; Feng, Jingjing; Xu, Lin; Wang, Limengmeng; Han, Biqing; Zhang, Mingming; Yu, Jian; Yu, Xiaohong; Huang, He

    2017-11-10

    The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) has been shown to be an effective immunosuppressor in the management of acute graft-versus-host disease (aGVHD) after bone marrow transplantation. Myeloid-derived suppressor cells (MDSCs) also have a protective effect in aGVHD regulation. However, the relationship between RAPA and MDSCs in aGVHD models is unclear. Meanwhile, the effect of RAPA on different subgroups of MDSCs is also less well described. In this study, we demonstrate that in vivo administration of RAPA results in the expansion and functional enhancement of polymorphonuclear MDSCs (PMN-MDSCs) in a murine model of aGVHD. RAPA treatment can enhance the suppressive function of PMN-MDSCs via up-regulation of arginase1 (Arg1) and induced nitric oxide synthase (iNOS) at later time points. Moreover, RAPA can also induce a strong immunosuppressive function in PMN-MDSCs from murine bone marrow in vitro, but has a contrary effect on monocytic MDSCs (M-MDSCs). We found that RAPA-treated PMN-MDSCs can restrain the differentiation of Th1/Th2 cells and promote induction of regulatory T cells in in vitro studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Meningoencephalocele of the temporal bone: pictorial essay on transmastoid extradural-intracranial repair.

    Science.gov (United States)

    Manjila, Sunil; Wick, Cameron C; Cramer, John; Semaan, Maroun T; Bambakidis, Nicholas C; Selman, Warren R; Megerian, Cliff A

    2013-01-01

    A spontaneous meningoencephalocele of the temporal bone may present with effusion in the middle ear, a cerebrospinal fluid leak, hearing loss, or rarely otitic meningitis. Repair of spontaneous encephaloceles in the temporal bone has been performed using transmastoid and transcranial middle fossa approaches or a combination of the two with varied results. The authors present a technical paper on the transmastoid extradural intracranial approach for the management of temporal lobe encephaloceles. Case reports and cadaver dissections are used to provide a pictorial essay on the technique. Advantages and disadvantages compared with alternative surgical approaches are discussed. Traditional transmastoid approaches are less morbid compared with a transcranial repair as they avoid brain retraction. However, in the past, there has been a higher risk of graft failure and hearing loss due to downward graft migration and a potential need for ossicular disarticulation. For the appropriate lesion, the transmastoid extradural intracranial approach lesion offers a stable meningoencephalocele repair without the comorbidity of brain retraction. The authors describe a transmastoid extradural intracranial technique via case reports and cadaver dissections for the repair of spontaneous meningoencephalocele defects larger than 2 cm. This approach provides more support to the graft compared to the conventional transmastoid repair. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The temporal bones from Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain). A phylogenetic approach.

    Science.gov (United States)

    Martínez, I; Arsuaga, J L

    1997-01-01

    Three well-preserved crania and 22 temporal bones were recovered from the Sima de los Huesos Middle Pleistocene site up to and including the 1994 field season. This is the largest sample of hominid temporal bones known from a single Middle Pleistocene site and it offers the chance to characterize the temporal bone morphology of an European Middle Pleistocene population and to study the phylogenetic relationships of the SH sample with other Upper and Middle Pleistocene hominids. We have carried out a cladistic analysis based on nine traits commonly used in phylogenetic analysis of Middle and Late Pleistocene hominids: shape of the temporal squama superior border, articular eminence morphology, contribution of the sphenoid bone to the median glenoid wall, postglenoid process projection, tympanic plate orientation, presence of the styloid process, mastoid process projection, digastric groove morphology and anterior mastoid tubercle. We have found two autapomorphies on the Home erectus temporal bone: strong reduction of the postglenoid process and absence of the styloid process. Modern humans, Neandertals and the Middle Pleistocene fossils from Europe and Africa constitute a clade characterized by a convex superior border of the temporal squama. The European Middle Pleistocene fossils from Sima de los Huesos, Petralona, Steinheim, Bilzingsleben and Castel di Guido share a Neandertal apomorphy: a relatively flat articular eminence. The fossils from Ehringsdorf, La Chaise Suardi and Biache-Saint-Vaast also display another Neandertal derived trait: an anteriorly obliterated digastric groove. Modern humans and the African Middle Pleistocene fossils share a synapomorphy: a sagittally orientated tympanic plate.

  3. Destructive, granulating lesion in the temporal bone after elevated plasma homocysteine

    DEFF Research Database (Denmark)

    Bonding, Per; Skriver, Elisabeth; Helin, Pekka

    2004-01-01

    lesion in the left temporal bone was discovered; repeated histologic examination only showed simple granulation tissue. After 6 months, a part of the bony cochlea was extruded. With approximately 8 months' delay and after the patient had had postoperative lung embolism, plasma homocysteine was found...... to be significantly elevated, a condition known as an independent risk factor for thromboembolic lesions. In the acquired form, it is most often caused by nutritional deficiency of vitamin B cofactors. Accordingly, the patient was treated with folic acid, which rapidly normalized plasma homocysteine. Subsequently...

  4. Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Koschmieder, Steffen; Gelsing, Sandra

    2010-01-01

    of immature myeloid cells, compared with the previously described APL disease induced by PRalpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also...... role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRalpha cells...... were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRalpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRalpha cells contained a slightly higher fraction...

  5. Differential diagnosis between chronic otitis media with and without cholesteatoma by temporal bone CT: focus on bone change and mass effect

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Cheol Kyu; Park, Dong Woo; Seong, Jin Yong; Lee, Kak Soo; Park Choong Ki; Lee, Seung Ro; Hahm, Chang Kok [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2000-01-01

    In order to determine specific differences, we compared the temporal bone CT findings of chronic otitis media (COM) with and without cholesteatoma, focusing on bone change. Between 1997 and 1998, 82 patients (84 cases) underwent temporal bone CT and were shown to have COM, with or without cholesteatoma after mastoidectomy and tympanoplasty. There were 36 cases of COM with cholesteatoma (26 patients, M:F =3D 11:15; age range, 16-61 (mean, 36,2) years), and 58 cases without chlesteatoma (56 patients, M:F =3D 25:31, age range, 15-61 (mean, 36.2) years). The findings of temporal bone CT were analysed at the point of bony changes including erosion and medial displacement of ossicles (malleus, incus, and stapes), erosion or destruction of the scutum, tegmen, facial canal, and lateral semicircular canal, and ballooning of the tympanic cavity and mastoid antrum. In addition, the soft tissue changes seen on temporal bone CT were analyzed at the site of lateral bulging of soft tissue in Prussak's space, perforation of the pars flaccida, tympanic membrane retraction, and tympanosclerosis. We retrospectively compared the findings of temporal bone CT with the surgical findings, and to assess statistical significance, the Chi-square test was used. Bone erosion or destruction was seen in 36.2% of COM cases without cholesteatoma, and in 96.2% of cases with cholesteatoma. Comparing COM with and without cholesteatoma, the erosion of ossicles including the malleus (81%, 24%), incus (88%, 14%), stapes (58%, 10%), scutum (88%, 10%), facial canal (8%, 0%), and lateral semicircular canal (8%, 0%), was more common in COM with cholesteatoma (p-value less than 0.05), with the exception of erosion of the tegmen (8%, 3%). Other bony changes including medial displacement of ossicles (27%, 3%), ballooning of tympanic cavity and mastoid antrum (96%, 16%), and the soft tissue changes including lateral bulging of soft tissue in Prussak's space (58%, 14%) and perforation of the pars

  6. Insertion forces and intracochlear trauma in temporal bone specimens implanted with a straight atraumatic electrode array.

    Science.gov (United States)

    Mirsalehi, Marjan; Rau, Thomas S; Harbach, Lenka; Hügl, Silke; Mohebbi, Saleh; Lenarz, Thomas; Majdani, Omid

    2017-05-01

    The aim of the study was to evaluate insertion forces during manual insertion of a straight atraumatic electrode in human temporal bones, and post-implantation histologic evaluation of the samples to determine whether violation of intracochlear structures is related to insertion forces. In order to minimize intracochlear trauma and preserve residual hearing during cochlear implantation, knowledge of the insertion forces is necessary. Ten fresh frozen human temporal bones were prepared with canal wall down mastoidectomy. All samples were mounted on a one-axis force sensor. Insertion of a 16-mm straight atraumatic electrode was performed from different angles to induce "traumatic" insertion. Histologic evaluation was performed in order to evaluate intracochlear trauma. In 4 of 10 samples, dislocation of the electrode into scala vestibuli was observed. The mean insertion force for all 10 procedures was 0.003 ± 0.005 N. Insertion forces measured around the site of dislocation to scala vestibuli in 3 of 4 samples were significantly higher than insertion forces at the same location of the cochleae measured in samples without trauma (p force during the whole insertion process of the straight atraumatic electrode is lower than reported by other studies using longer electrodes. Based on our study, insertion forces leading to basilar membrane trauma may be lower than the previously reported direct rupture forces.

  7. Self-crimping superelastic nitinol prosthesis and malleostapedotomy: a temporal bone study.

    Science.gov (United States)

    Magliulo, Giuseppe

    2013-02-01

    The aim of this study was to compare the results of application of 2 types of superelastic nitinol prostheses. Temporal bones study with planned data collection. Tertiary referral center. Malleostapedotomy was performed in 15 human temporal bones implanting 3 different prostheses: manually crimping polytetrafluoroethylene (MC-PTFE) piston, nitinol self-crimping polytetrafluoroethylene (SC-PTFE) piston, and a modified nitinol self-crimping polytetrafluoroethylene (mSC-PTFE) piston. The first 2 have a diameter of 0.4 mm and length of 7 mm, whereas the mSC-PTFE piston has a diameter of 0.4 mm but a length of 7.75 mm. We evaluated various parameters of prosthesis attachment-that is, the time for implantation of SC and mSC nitinol loop pistons and the MC platinum loop piston, the quality of attachment of the prostheses to the malleus, their positions with respect to the center of the stapes footplate, and the protrusion of the piston into the vestibule. The mSC-PTFE superelastic nitinol prosthesis showed a statistically significant difference in mean operation time (mSC vs SC, P piston into the vestibule was highly reproducible in all 3 prostheses. Because of its greater length, the mSC-PTFE allows for management of the most varied anatomical conditions. At the same time, its self-crimping nature prevents the risk of distortion of the prosthesis by the crimping process and reduces the operation time in combination with standardized bending of the prosthesis shaft.

  8. Effects of radiation on the temporal bone in patients with head and neck cancer.

    Science.gov (United States)

    Lambert, Elton M; Gunn, G Brandon; Gidley, Paul W

    2016-09-01

    Radiotherapy is a key component in the treatment of many head and neck cancers, and its potential to cause long-term adverse effects has become increasingly recognized. In this review, we describe the short-term and long-term sequelae of radiation-associated changes in and injury to the temporal bone and its related structures. The pathophysiology of radiation-induced injury and its clinical entities, including sensorineural hearing loss, chronic otitis media, osteoradionecrosis, and radiation-associated malignancies, are described. We also discuss radiation dose to the head and neck as it relates to these conditions. An improved understanding of radiation's effects on the temporal bone will enable physicians and researchers to continue efforts to reduce radiotherapy-related sequelae and guide clinicians in diagnosing and treating the various otologic conditions that can arise in patients with head and neck cancer who have received radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1428-1435, 2016. © 2016 Wiley Periodicals, Inc.

  9. Optimal Imaging Parameters for Readout-segmented EPI of the Temporal Bone.

    Science.gov (United States)

    Azuma, Toshiya; Kodama, Takao; Yano, Takanori; Enzaki, Masahiro; Nakamura, Masato; Murata, Katsutoshi

    2015-01-01

    Readout-segmented echo planar imaging (rs-EPI) is a form of multi-shot EPI. rs-EPI is affected less by susceptibility artifacts than single-shot EPI (ss-EPI), which is widely used for diffusion-weighted imaging, so rs-EPI is expected to produce less image distortion. In this study, we compared rs-EPI and conventional ss-EPI of the temporal bone region, which contains abundant amounts of air and frequently exhibits changes in magnetic susceptibility. In addition, we used a phantom to determine the optimum rs-EPI acquisition conditions for clinical use and investigated the clinical utility of rs-EPI in 20 patients (8 men, 12 women, mean age, 54.3 ± 16.7-years-old) with cholesteatoma (mean apparent diffusion coefficient on ss-EPI, 0.88 × 10(-3) ± 0.18 mm(2)/s). The images of the temporal bone region produced using rs-EPI exhibited less distortion than those obtained with ss-EPI (P < 0.05).

  10. Molecular temporal bone pathology: II. Ramsay Hunt syndrome (herpes zoster oticus).

    Science.gov (United States)

    Wackym, P A

    1997-09-01

    In 1907 J. Ramsay Hunt suggested that herpes zoster oticus resulted from a geniculate ganglionitis; however, many contemporary authors believe that this disorder represents a neuritis or polycranial neuropathy. Herpes varicella-zoster viral (VZV) DNA was identified, using the polymerase chain reaction, in archival celloidin-embedded temporal bone sections from two patients who clinically had Ramsay Hunt syndrome (herpes zoster oticus). The presence of VZV was confirmed by sequencing the PCR products. These experiments demonstrated that VZV genomic DNA was present in the geniculate ganglion of the side with facial paralysis and cutaneous recrudescence in both patients and in the clinically unaffected side in patient 1. In addition, patient 2 had a sudden hearing loss and was found to have VZV genomic DNA in sections from the affected side containing the spiral ganglion, Scarpa's ganglion, organ of Corti, and macula of the saccule. No VZV genomic DNA was identified in temporal bone sections from five patients with Bell's palsy and ten patients without evidence of otologic disease. In this study, the histopathology of these two cases yielded complementary information regarding the role of VZV in herpes zoster oticus. These data suggest that in patients with Ramsay Hunt syndrome, latent VZV is located in the geniculate ganglia and may be present in the auditory and vestibular primary afferent ganglia in some patients.

  11. Acoustic effects of a superior semicircular canal dehiscence: a temporal bone study.

    Science.gov (United States)

    Luers, J C; Pazen, D; Meister, H; Lauxmann, M; Eiber, A; Beutner, D; Hüttenbrink, K B

    2015-03-01

    A dehiscence of the superior semicircular canal is said to be responsible for a number of specific and unspecific ear symptoms and possible a conductive hearing loss of up to 40 dB. As in vivo a dehiscence would not be opened against air, but is naturally patched with dura and the brain, it was our aim to investigate the effects of an superior semicircular canal dehiscence on the air conduction hearing in fresh human temporal bones with different boundary conditions. At ten fresh human temporal bones, we investigated the transmission of sound energy through the middle and inner ear using a round window microphone and laser Doppler vibrometer for perilymph motions inside the dehiscence. After baseline measurements, the superior semicircular canal was opened. We investigated the change of the transfer function when the canal is opened against air (pressure equivalent water column), against a water column and when it is patched with a layer of dura. Opening the superior semicircular canal resulted in a loss of sound transmission of maximal 10-15 dB only in frequencies below 1 kHz. When covering the dehiscence with a water column, the conductive hearing component was reduced to 6-8 dB. Placing a dura patch on top of the dehiscence resulted in a normalization of the transfer function. If our experiments are consistent with the conditions in vivo, then superior semicircular canal dehiscence does not lead to an extensive and clinically considerable conductive air conduction component.

  12. [Isolated myeloid sarcoma involving the mediastinum].

    Science.gov (United States)

    Jelić-Puskarić, Biljana; Kardum-Skelin, Ika; Sustercić, Dunja; Pazur, Marina; Vrhovac, Radovan; Radić-Kristo, Delfa; Gredelj-Simec, Njetocka; Kovacević, Dragica Obad; Plasćak, Jasmina; Gasparov, Slavko; Jaksić, Branimir

    2011-09-01

    Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature myeloid cells and most commonly involving the bone, skin, lymph nodes, soft tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in 2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop before or concurrently with AML, or may be the initial manifestation of AML relapse in previously treated patients. Blast transformation of some form of myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as myeloid sarcoma. A major differential diagnostic problem is isolated primary myeloid sarcoma without bone marrow and peripheral blood involvement, which may precede leukemic stage for months or years, and which is frequently misdiagnosed, mostly as malignant lymphoma. A case is presented of a 56-year-old female patient complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical examination revealed enhanced vascular pattern on the right chest and right arm edema. Computed tomography (CT) of the thorax showed an expansive growth measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle aspiration cytology of tumor mass yielded a scarcely cellular sample with individual atypical immature cells, fine chromatin structure and scarce cytoplasm with occasional granules and Auer rods. Considering the morphological, cytochemical and immunocytochemical characteristics of immature cells, the diagnosis of myeloid sarcoma was made and verified by histopathology of tumor biopsy sample. Immature cells were not found by analysis of bone marrow puncture sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As immature cell proliferation was not detected in bone marrow and peripheral blood, while spread of the disease beyond the mediastinum

  13. A new antistuttering device: treatment of stuttering using bone conduction stimulation with delayed temporal feedback.

    Science.gov (United States)

    Stidham, Katrina R; Olson, Lisa; Hillbratt, Martin; Sinopoli, Teri

    2006-11-01

    Stuttering is a communication disorder affecting approximately 1% of the adult population, some with severe manifestations. Speech therapy improves stuttering, but many do not receive enough benefit to communicate fluently. Antistuttering devices have been available for several years, but available technology has been limited in long-term success and reliability. The current study evaluates the effects of a prototype device using a modification of a currently used bone conduction hearing device with delayed auditory feedback on adult patients with significant stuttering problems. A prospective nonrandomized study evaluating effects of a prototype device on stuttering in adult subjects. Ten stutterers > or=18 years of age were fit with a bone conduction device on a headband with temporal feedback delayed according to patient preference between 5 and 130 msec. Patients were asked to wear the device at least 4 hours per day for 4 weeks. Stuttering Severity Index-3 (SSI-3) tests were completed at prefit, immediate postfit, and at 2-week, 4-week, and 6-week intervals. Questionnaires were also completed at each visit. : Nine patients completed the entire study. A statistically significant decline in SSI-3 scores was documented from prefit compared with immediate postfit and 4 weeks follow up (P < .001) using the Tukey test method. Statistical significance was approached but not reached at 2 weeks. There was no significant difference between prefit and the 6-week follow up when patients had returned the device. Patients subjectively noted improvement in their speech and confidence using the device. A new antistuttering prototype using a modification of a bone conduction device with delayed temporal feedback is effective in decreasing stuttering in patients over a short time course. Further studies need to be completed to evaluate the long-term effects of the device.

  14. Evaluation of temporal bone pneumatization on high resolution CT (HRCT) measurements of the temporal bone in normal and otitis media group and their correlation to measurements of internal auditory meatus, vestibular or cochlear aqueduct

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Miyako

    1988-07-01

    High resolution CT axial scans were made at the three levels of the temoral bone 91 cases. These cases consisted of 109 sides of normal pneumatization (NR group) and 73 of poor pneumatization resulted by chronic otitis (OM group). NR group included sensorineural hearing loss cases and/or sudden deafness on the side. Three levels of continuous slicing were chosen at the internal auditory meatus, the vestibular and the cochlear aqueduct, respectively. In each slice two sagittal and two horizontal measurements were done on the outer contour of the temporal bone. At the proper level, diameter as well as length of the internal acoustic meatus, the vestibular or the cochlear aqueduct were measured. Measurements of the temporal bone showed statistically significant difference between NR and OM groups. Correlation of both diameter and length of the internal auditory meatus to the temporal bone measurements were statistically significant. Neither of measurements on the vestibular or the cochlear aqueduct showed any significant correlation to that of the temporal bone.

  15. Testicular myeloid sarcoma: a rare manifestation of acute myeloid leukemia in an infant.

    Science.gov (United States)

    Tran, Christine N; Collie, Angela M B; Flagg, Aron; Rhee, Audrey

    2014-10-01

    Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Evaluation of the therapeutic potential of bone marrow-derived myeloid suppressor cell (MDSC adoptive transfer in mouse models of autoimmunity and allograft rejection.

    Directory of Open Access Journals (Sweden)

    Lucile Drujont

    Full Text Available Therapeutic use of immunoregulatory cells represents a promising approach for the treatment of uncontrolled immunity. During the last decade, myeloid-derived suppressor cells (MDSC have emerged as novel key regulatory players in the context of tumor growth, inflammation, transplantation or autoimmunity. Recently, MDSC have been successfully generated in vitro from naive mouse bone marrow cells or healthy human PBMCs using minimal cytokine combinations. In this study, we aimed to evaluate the potential of adoptive transfer of such cells to control auto- and allo-immunity in the mouse. Culture of bone marrow cells with GM-CSF and IL-6 consistently yielded a majority of CD11b+Gr1hi/lo cells exhibiting strong inhibition of CD8+ T cell proliferation in vitro. However, adoptive transfer of these cells failed to alter antigen-specific CD8+ T cell proliferation and cytotoxicity in vivo. Furthermore, MDSC could not prevent the development of autoimmunity in a stringent model of type 1 diabetes. Rather, loading the cells prior to injection with a pancreatic neo-antigen peptide accelerated the development of the disease. Contrastingly, in a model of skin transplantation, repeated injection of MDSC or single injection of LPS-activated MDSC resulted in a significant prolongation of allograft survival. The beneficial effect of MDSC infusions on skin graft survival was paradoxically not explained by a decrease of donor-specific T cell response but associated with a systemic over-activation of T cells and antigen presenting cells, prominently in the spleen. Taken together, our results indicate that in vitro generated MDSC bear therapeutic potential but will require additional in vitro factors or adjunct immunosuppressive treatments to achieve safe and more robust immunomodulation upon adoptive transfer.

  17. Pediatric temporal bone fractures: current trends and comparison of classification schemes.

    Science.gov (United States)

    Dunklebarger, Joshua; Branstetter, Barton; Lincoln, Anne; Sippey, Megan; Cohen, Michael; Gaines, Barbara; Chi, David

    2014-03-01

    1) Characterize the current presentation of pediatric temporal bone fractures, 2) compare two classification schemes for temporal bone fractures and illustrate complications in each fracture type. Retrospective medical record review. Tertiary-care, academic children's hospital. All children presenting from 1999 to 2009 with CT-proven temporal bone fracture and audiology examination with follow-up. All CT scans were reinterpreted by a dedicated head and neck radiologist. All fractures were characterized as otic capsule sparing (OCS) or otic capsule violating (OCV), as well as transverse (T) or longitudinal (L). CT findings, mechanisms of injury, sensorineural hearing loss (SNHL), conductive hearing loss (CHL), and facial nerve injury (FNI). Seventy-one children met inclusion criteria. Fifty-four (76%) children had longitudinal fractures versus 17 (24%) with transverse fractures. Sixty-four (90%) had OCS versus 7 (10%) with OCV. The otic capsule was involved in 7.4% of longitudinal fractures and 17.6% of transverse fractures. Eleven (15%) had facial weakness, 72% of whom had a visualized fracture through the facial nerve course. SNHL was detected in 14 (20%) patients and CHL in 17(23.9%). All patients with fractures classified as both transverse and OCV had SNHL. The OCS versus OCV and T versus L classification schemes were directly compared for statistical significance in predicting SNHL, CHL, and FNI using the Fisher's exact test. Both OCS/OCV and T/L were predictors of SNHL (P = .0025 and P = .0143, respectively), but the OCS/OCV scheme was more accurate. Neither classification significantly predicted CHL or FNI (P = .787 versus .825; P = .705 vs. .755). In this pediatric series, approximately 75% of the fractures are longitudinal and 25% are transverse. The otic capsule is spared in 90% and violated in 10%. Both OCS/OCV and L/T classification schemes predict SNHL, but the OCV/OCS scheme is more accurate in this prediction. Although the negative predictive value

  18. Pneumatization of the zygomatic process of temporal bone on computed tomograms

    Science.gov (United States)

    Friedrich, Reinhard E.; Viezens, Liska; Grzyska, Ulrich

    2016-01-01

    Purpose: Zygomatic air cells (ZAC) are a variant of temporal bone pneumatization that needs no treatment. However, ZAC can have an impact on surgical procedures in the temporo-mandibular joint region. Recent reports suggest that computed tomography will disclose more ZAC than can be diagnosed on panoramic radiography. The aim of this study was to analyze ZAC prevalence on CT in a population that was not pre-selected by admission to a dental clinic. Furthermore, an extensive literature review was performed to assess the prevalence of ZAC and to address the impact of imaging technique on the definition of the item. Material and methods: Digitalized cranial CTs of 2007 patients were retrospectively analyzed. The Frankfort horizontal was used to define a ZAC on sagittal CTs. Results: In this study group, 806 were female (40.16%) and 1,201 were male (59.84%). Mean age was 49.96 years in the whole group (female: 55.83 years, male: 46.01 years). A ZAC was diagnosed in 152 patients (female: 66, male: 86). Unilateral ZAC surpasses bilateral findings (115 vs. 37 patients). ZAC were diagnosed in children 5 years of age and older. Sectional imaging techniques show a better visualization of the region of interest. However, presently an increase of ZAC prevalence attributable to imaging technique cannot conclusively be derived from the current literature. The normal finding of a ZAC on radiograms is a sharply defined homogenous transparent lesion restricted to the zygomatic process of the temporal bone that has no volume effect on the shape of the process. Conclusion: ZAC is an anatomical variant of the temporal bone that has come into focus of maxillofacial radiology due to its noticeable aspect on panoramic radiograms. The harmless variant can be expected in about one in thirteen individuals undergoing facial radiology. Panoramic radiograms appear to be sufficient to present ZAC of relevant size. However, in preparation for surgical procedures affecting the articular eminence

  19. Translational Studies in Elderly Patients with Acute Myeloid Leukemia

    NARCIS (Netherlands)

    B. van der Holt (Bronno)

    2007-01-01

    textabstractThe production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid leukemia (AML) is a clonal disease, which is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a severe

  20. Decolonizing Straight Temporality Through Genre Trouble in Edwidge Danticat's The Farming of Bones

    Directory of Open Access Journals (Sweden)

    Eliana de Souza Ávila

    2014-12-01

    Full Text Available http://dx.doi.org/10.5007/2175-8026.2014n67p21 Framing genre trouble (McKenzie 2006 as a decolonial methodology, this paper considers the relevance of Edwidge Danticat’s The Farming of Bones (1998 for reading migrant texts against the grain of straight temporality which sustains the coloniality of power (Lugones 2007. Scrutinizing historiographic suppression, Danticat’s migrant text interrupts the chrononormative portrayal of the Trujillo genocide of Haitian workers in the Dominican Republic as a reality pertaining to an obsolete past and to the geocultural margins alone. Read in the aftermath of the testimonio controversy, it may thus decenter the ongoing deflection of attention from Rigoberta Menchú’s impact on the geocultural structures that sanction ongoing military intervention and genocide by refocusing on historiography as a terrain of relentless decolonial contestation rather than prescriptive narrative closure.

  1. Temporal bone trauma: correlative study between CT findings and clinical manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hee; Kim, Hyung Jin; Kim, Jae Hyoung [College of Medicine, Gyeongsang National University, Jinju (Korea, Republic of)

    1994-11-15

    To assess how accurately computed tomography (CT) can demonstrate the abnormal findings which are believed to cause the clinical signs and symptoms of hearing loss (HL), vertigo and facial paralysis (FP) in patients with temporal bone trauma. The authors studied CT scans of 39 ears in 35 patients with temporal bone trauma. CT scans were performed with 1-1.5 mm slice thickness and table incrementation. Both axial and coronal scans were obtained in 32 patients and in three patients only axial scans were obtained. We analyzed CT with special reference to the structural abnormalities of the external auditory canal, middle ear cavity, bony labyrinth, and facial nerve canal, and correlated these findings with the actual clinical signs and symptoms. As to hearing loss, we evaluated 32 ears in which pure tone audiometry or brainstem evoked response audiometry had been performed. With respect to the specific types of HL, CT accurately showed the abnormalities in 84% (16/19) in conductive HL, 100% (2/2) in sensorineural HL, and 25% (2/8) for mixed HL. When we categorized HL simply as conductive and sensorineural, assuming that mixed be the result of combined conductive and sensorineural HL, CT demonstrated the abnormalities in 89% (24/27) for conductive HL and 50% (5/10) for sensorineural HL. Concerning vertigo and FP, CT demonstrated abnormalities in 67%(4/6), and 29% (4/14), respectively. Except for conductive HL, CT seems to have a variable degree of limitation for the demonstration of the structural abnormalities resulting sensorineural HL, vertigo or facial paralysis. It is imperative to correlate the CT findings with the signs and symptoms in those clinical settings.

  2. 3D-CT of the temporal bone area with high-speed processing

    Energy Technology Data Exchange (ETDEWEB)

    Hattori, Taku [Nagoya Univ. (Japan). Branch Hospital

    1994-12-01

    Three-dimentional (3D)-CT was introduced to represent abnormal findings in the temporal bone area utilizing a SOMATOM DRH CT scanner with accessory 3D reconstruction software and an exclusive high-speed 3D processing system, VOXEL FLINGER. In a patient with eosinophilic granuloma, a defect in the squamous part of the temporal bone was demonstrated suggesting exposure of the dura mater during surgery. In a patient with a normal ear, well-developed mastoid cavity, a part of the handle and the head of the malleus, the incudomalleal joint, the short limb, body and a part of the long limb of the incus and the round window niche were demonstrated. In a case of chronic otitis media, poorly developed mastoid cavity and a possible defect of the tip of the long limb of the incus were demonstrated, in contrast to the patient with the normal ear. 3D-CT yields objective and solid images which are useful for diagnosis, treatment planning and explanation of the pathology to patients and their family. To obtain convincing 3D images, physicians themselves have to choose exact rotation angles. It is not adequate to reconstruct original CT data using a CT computer with accessory 3D software whose processing capability is not good enough for this purpose. The conclusion is as follows: (1) it is necessary and effective to transfer original CT data into the memory of the exclusive high-speed 3D processing system and (2) process the data by the voxel memory method to establish a clinically valuable 3D-CT imaging system. (author).

  3. Ultrasound-induced hyperthermia for the spatio-temporal control of gene expression in bone repair

    Science.gov (United States)

    Wilson, Christopher; Padilla, Frédéric; Zhang, Man; Vilaboa, Nuria; Kripfgans, Oliver; Fowlkes, Brian; Franceschi, Renny

    2012-10-01

    Spatial and temporal control over the expression of growth/differentiation factors is of great interest for regeneration of bone, but technologies capable of providing tight and active control over gene expression remain elusive. We propose the use of focused ultrasound for the targeted activation of heat shock-sensitive expression systems in engineered bone. We report in vitro results with cells that express firefly luciferase (fLuc) under the control of a heat shock protein promoter. Cells were embedded in fibrin scaffolds and exposed to focused ultrasound, using a custom 3.3MHz transducer (focal length 4", f-number 1.33", focal dimension 1.2mm lateral FWHM) in CW mode for 2-20 minutes at intensities ISPTA=120-440 W/cm2. The kinetics of ultrasound-mediated activation of the cells was compared with that of strictly thermal activation. Bioluminescence imaging revealed fLuc expression in an area ≥2.5mm in diameter at the position of the ultrasound focus, and the diameter and intensity of the signal increased with the amplitude of the acoustic energy. We also found that ultrasound activated fLuc expression with substantially shorter exposures than thermal activation. Our results demonstrate the potential for focused ultrasound to selectively activate the expression of a gene of interest in an engineered tissue and suggest that focused ultrasound activates the heat shock pathway by a combination of thermal and non-thermal mechanisms.

  4. Multi-temporal MRI carpal bone volumes analysis by principal axes registration

    Science.gov (United States)

    Ferretti, Roberta; Dellepiane, Silvana

    2016-03-01

    In this paper, a principal axes registration technique is presented, with the relevant application to segmented volumes. The purpose of the proposed registration is to compare multi-temporal volumes of carpal bones from Magnetic Resonance Imaging (MRI) acquisitions. Starting from the study of the second-order moment matrix, the eigenvectors are calculated to allow the rotation of volumes with respect to reference axes. Then the volumes are spatially translated to become perfectly overlapped. A quantitative evaluation of the results obtained is carried out by computing classical indices from the confusion matrix, which depict similarity measures between the volumes of the same organ as extracted from MRI acquisitions executed at different moments. Within the medical field, the way a registration can be used to compare multi-temporal images is of great interest, since it provides the physician with a tool which allows a visual monitoring of a disease evolution. The segmentation method used herein is based on the graph theory and is a robust, unsupervised and parameters independent method. Patients affected by rheumatic diseases have been considered.

  5. Analysis of Vibrant Soundbridge placement against the round window membrane in a human cadaveric temporal bone model.

    NARCIS (Netherlands)

    Pennings, R.J.E.; Ho, A.; Brown, J.; Wijhe, R.G. van; Bance, M.

    2010-01-01

    OBJECTIVE: To evaluate optimal placement of the Floating Mass Transducer of the Vibrant Soundbridge (Med-El, Innsbruck, Austria) against the round window membrane, particularly the impact of interposed coupling fascia and of covering materials. METHOD: : Six fresh human cadaveric temporal bones were

  6. Dual-time-point FDG-PET/CT Imaging of Temporal Bone Chondroblastoma: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Akira Toriihara

    2015-07-01

    Full Text Available Temporal bone chondroblastoma is an extremely rare benign bone tumor. We encountered two cases showing similar imaging findings on computed tomography (CT, magnetic resonance imaging (MRI, and dual-time-point 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/CT. In both cases, CT images revealed temporal bone defects and sclerotic changes around the tumor. Most parts of the tumor showed low signal intensity on T2- weighted MRI images and non-uniform enhancement on gadolinium contrast-enhanced T1-weighted images. No increase in signal intensity was noted in diffusion-weighted images. Dual-time-point PET/CT showed markedly elevated 18F-FDG uptake, which increased from the early to delayed phase. Nevertheless, immunohistochemical analysis of the resected tumor tissue revealed weak expression of glucose transporter-1 and hexokinase II in both tumors. Temporal bone tumors, showing markedly elevated 18F-FDG uptake, which increases from the early to delayed phase on PET/CT images, may be diagnosed as malignant bone tumors. Therefore, the differential diagnosis should include chondroblastoma in combination with its characteristic findings on CT and MRI.

  7. Delayed loss of hearing after hearing preservation cochlear implantation: Human temporal bone pathology and implications for etiology.

    Science.gov (United States)

    Quesnel, Alicia M; Nakajima, Hideko Heidi; Rosowski, John J; Hansen, Marlan R; Gantz, Bruce J; Nadol, Joseph B

    2016-03-01

    After initially successful preservation of residual hearing with cochlear implantation, some patients experience subsequent delayed hearing loss. The etiology of such delayed hearing loss is unknown. Human temporal bone pathology is critically important in investigating the etiology, and directing future efforts to maximize long term hearing preservation in cochlear implant patients. Here we present the temporal bone pathology from a patient implanted during life with an Iowa/Nucleus Hybrid S8 implant, with initially preserved residual hearing and subsequent hearing loss. Both temporal bones were removed for histologic processing and evaluated. Complete clinical and audiologic records were available. He had bilateral symmetric high frequency severe to profound hearing loss prior to implantation. Since he was implanted unilaterally, the unimplanted ear was presumed to be representative of the pre-implantation pathology related to his hearing loss. The implanted and contralateral unimplanted temporal bones both showed complete degeneration of inner hair cells and outer hair cells in the basal half of the cochleae, and only mild patchy loss of inner hair cells and outer hair cells in the apical half. The total spiral ganglion neuron counts were similar in both ears: 15,138 (56% of normal for age) in the unimplanted right ear and 13,722 (51% of normal for age) in the implanted left ear. In the basal turn of the implanted left cochlea, loose fibrous tissue and new bone formation filled the scala tympani, and part of the scala vestibuli. Delayed loss of initially preserved hearing after cochlear implantation was not explained by additional post-implantation degeneration of hair cells or spiral ganglion neurons in this patient. Decreased compliance at the round window and increased damping in the scala tympani due to intracochlear fibrosis and new bone formation might explain part of the post-implantation hearing loss. Reduction of the inflammatory and immune response to

  8. Objective assessment of learning curves for the Voxel-Man TempoSurg temporal bone surgery computer simulator.

    Science.gov (United States)

    Nash, R; Sykes, R; Majithia, A; Arora, A; Singh, A; Khemani, S

    2012-07-01

    Simulators are becoming an increasingly important part of surgical training. Temporal bone surgery is one area in which simulators, such as the Voxel-Man TempoSurg simulator, are likely to play a significant role in training. We present learning curve data from novice trainees using this simulator to learn cortical mastoidectomy, exposure of the sigmoid sinus, and exposure of the short process of the incus. We measured the time taken to perform the procedures, the volume of reference bone removed, and the structures damaged during dissection. We found improvement in a number of parameters over the course of the study. The overall scores, structural damage scores and time taken improved, to differing degrees, for each task. The volume of reference bone removed remained constant. These results indicate that the trainees' efficiency improved as they became more proficient at removing a given volume of reference bone.

  9. A non-genetic approach to labelling acute myeloid leukemia and bone marrow cells with quantum dots.

    Science.gov (United States)

    Zheng, Yanwen; Tan, Dongming; Chen, Zheng; Hu, Chenxi; Mao, Zhengwei J; Singleton, Timothy P; Zeng, Yan; Shao, Xuejun; Yin, Bin

    2014-06-01

    The difficulty in manipulation of leukemia cells has long hindered the dissection of leukemia pathogenesis. We have introduced a non-genetic approach of marking blood cells, using quantum dots. We compared quantum dots complexed with different vehicles, including a peptide Tat, cationic polymer Turbofect and liposome. Quantum dots-Tat showed the highest efficiency of marking hematopoietic cells among the three vehicles. Quantum dots-Tat could also label a panel of leukemia cell lines at varied efficiencies. More uniform intracellular distributions of quantum dots in mouse bone marrow and leukemia cells were obtained with quantum dots-Tat, compared with the granule-like formation obtained with quantum dots-liposome. Our results suggest that quantum dots have provided a photostable and non-genetic approach that labels normal and malignant hematopoietic cells, in a cell type-, vehicle-, and quantum dot concentration-dependent manner. We expect for potential applications of quantum dots as an easy and fast marking tool assisting investigations of various types of blood cells in the future.

  10. Usefulness of temporal bone prototype for drilling training: A prospective study.

    Science.gov (United States)

    Aussedat, C; Venail, F; Nguyen, Y; Lescanne, E; Marx, M; Bakhos, D

    2017-12-01

    Dissection of cadaveric temporal bones (TBs) is considered the gold standard for surgical training in otology. For many reasons, access to the anatomical laboratory and cadaveric TBs is difficult for some facilities. The aim of this prospective and comparative study was to evaluate the usefulness of a physical TB prototype for drilling training in residency. Prospective study. Tertiary referral centre. Thirty-four residents were included. Seventeen residents (mean age 26.7±1.6) drilled on only cadaveric TBs ("traditional" group), in the traditional training method, while seventeen residents (mean age 26.5±1.7) drilled first on a prototype and then on a cadaveric TB ("prototype" group). Drilling performance was assessed using a validated scale. Residents completed a mastoid image before and after each drilling to enable evaluation of mental representations of the mastoidectomy. No differences were observed between the groups with respect to age, drilling experience and level of residency. Regarding drilling performance, we found a significant difference across the groups, with a better score in the prototype group (P=.0007). For mental representation, the score was statistically improved (P=.0003) after drilling in both groups, suggesting that TB drilling improves the mental representation of the mastoidectomy whether prototype or cadaveric TB is used. The TB prototype improves the drilling performance and mental representation of the mastoidectomy in the young resident population. A drilling simulation with virtual or physical systems seems to be a beneficial tool to improve TB drilling. © 2017 John Wiley & Sons Ltd.

  11. A new malleostapedotomy prosthesis. Experimental analysis by laser doppler vibrometer in fresh cadaver temporal bones.

    Science.gov (United States)

    Vallejo, Luis A; Manzano, María T; Hidalgo, Antonio; Hernández, Alberto; Sabas, Juan; Lara, Hugo; Gil-Carcedo, Elisa; Herrero, David

    One of the problems with total ossicular replacement prostheses is their stability. Prosthesis dislocations and extrusions are common in middle ear surgery. This is due to variations in endo-tympanic pressure as well as design defects. The design of this new prosthesis reduces this problem by being joined directly to the malleus handle. The aim of this study is to confirm adequate acoustic-mechanical behaviour in fresh cadaver middle ear of a new total ossicular replacement prosthesis, designed using the finite elements method. Using the doppler vibrometer laser, we analysed the acoustic-mechanical behaviour of a new total ossicular replacement prosthesis in the human middle ear using 10 temporal bones from fresh cadavers. The transfer function of the ears in which we implanted the new prosthesis was superimposed over the non-manipulated ear. This suggests optimum acoustic-mechanical behaviour. The titanium prosthesis analysed in this study demonstrated optimum acoustic-mechanical behaviour. Together with its ease of implantation and post-surgical stability, these factors make it a prosthesis to be kept in mind in ossicular reconstruction. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  12. Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study.

    Science.gov (United States)

    Hızlı, Ömer; Kaya, Serdar; Hızlı, Pelin; Paparella, Michael M; Cureoglu, Sebahattin

    2016-12-01

    To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (Psyphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. A 3-D analysis of the protympanum in human temporal bones with chronic ear disease.

    Science.gov (United States)

    Pauna, Henrique F; Monsanto, Rafael C; Schachern, Patricia; Paparella, Michael M; Cureoglu, Sebahattin

    2017-03-01

    Eustachian tube dysfunction is believed to be an important factor to cholesteatoma development and recurrence of disease after surgical treatment. Although many studies have described prognostic factors, evaluation methods, or surgical techniques for Eustachian tube dysfunction, they relied on the soft tissues of its structure; little is known about its bony structure-the protympanum-which connects the Eustachian tube to the tympanic cavity, and can also be affected by several inflammatory conditions, both from the middle ear or from the nasopharynx. We studied temporal bones from patients with cholesteatoma, chronic otitis media (with and without retraction pockets), purulent otitis media, and non-diseased ears, looking for differences between the volume of the protympanum, the diameter of the Eustachian tube isthmus, and the distance between the anterior tympanic annulus and the promontory. Light microscopy and 3-D reconstruction software were used for the measurements. We observed a decrease of volume in the lumen of the four middle ear diseased ears compared to the control group. We observed a significant decrease in the volume of the protympanic space in the cholesteatoma group compared to the chronic otitis media group. We also observed a decrease in the bony space (protympanum space) in cholesteatoma, chronic otitis media with retraction pockets, and purulent otitis media compared to the control group. We found a correlation in middle ear diseases and a decrease in the middle ear space. Our findings may suggest that a smaller bony volume in the protympanic area may trigger middle ear dysventilation problems.

  14. Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Hurley, M Yadira; Ghahramani, Grant K; Frisch, Stephanie; Armbrecht, Eric S; Lind, Anne C; Nguyen, Tudung T; Hassan, Anjum; Kreisel, Friederike H; Frater, John L

    2013-05-01

    We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

  15. The developing temporal bone: computed tomography measurements and assessment of suture closure from birth to 18 years of age.

    Science.gov (United States)

    Paetz, P; Goetz, G F; Lanfermann, H; Giesemann, A M

    2017-06-01

    To describe the normal CT appearance of the developing temporal bone in children from birth to 18 years of age. Two hundred and six temporal bone CTs of children from 0.14 to 18.95 years were retrospectively selected and reviewed. Temporal bones were measured in a standardized slice orientation using the length of the basal turn of the cochlea, the length and width of the petrous bone, the coronal extent, trailing edge and anterior-posterior dimension of the temporal bone and the angle between petrous bone's length and the midsagittal line in the axial plane showing the basal turn of the cochlea in its greatest extent. Two sutures, two synchondroses and three fissures of the temporal bone were evaluated and graded. Chosen measurements and calculations demonstrate an increase of values from 0 to 18 years with the greatest increase occurring during the first 2 years of life. The angle between the basal turn of the cochlea and the midsagittal line shows a large variability. Logarithmic trend lines illustrate larger measurements of males as compared to females. The ratio of the basal turn of the cochlea and the length of the petrous bone is about 1:4.1 (f/m) during the first year of life and about 1:6.1 (f)/1:6.8 (m) from 17 years onwards. Results of suture closure are described using box-and-whisker plots. The developing temporal bone grows the most during the first 2 years of life. Knowledge of changing proportions and suture closure is essential for evaluation of temporal bone CT of children.

  16. Active middle ear implant application in case of stapes fixation: a temporal bone study.

    Science.gov (United States)

    Devèze, Arnaud; Koka, Kanthaiah; Tringali, Stéphane; Jenkins, Herman A; Tollin, Daniel J

    2010-09-01

    Driving the oval window directly with an active middle ear implant (AMEI) can produce high levels of input to the inner ear. Treatment of otosclerosis bypasses the stapes with a piston that penetrates the vestibule. Although this treats the conductive component of hearing loss, it does not treat the sensorineural part, which can be improved using an additional conventional hearing aid. Active middle ear implants have been proposed to be an alternative in treating otosclerosis in cases of mixed hearing losses. Seven temporal bones were prepared to expose the stapes and round window (RW). Stapes and RW velocities were measured while driving with an AMEI the stapes head with a bell-shaped tip. The stapes footplate was then fixed with acrylic cement; fixation was confirmed through attenuated RW velocities. A cylinder tip (0.5 mm) was then used to drive the inner ear through a stapedotomy with and without interposition of fascia. Driving the stapes with an AMEI produced mean maximum equivalent ear canal sound pressure levels (SPL) of 138 dB (0.25-8 kHz at 1 V [RMS]). Stapes fixation caused a approximately 25-dB attenuation. Driving with a cylinder tip through the stapedotomy produced 114 dB SPL (24 dB less than normal) and 110 dB SPL (28 dB less than normal) performance with and without fascia, respectively. Performance with fascia was greater than without. Driving the oval window with an AMEI in a scenario of stapes fixation was demonstrated to be feasible, with performance comparable to traditional AMEI coupling to the incus or stapes. These possibilities offer new perspectives to treat mixed hearing loss in case of fixed footplate.

  17. External ear canal exostosis and otitis media in temporal bones of prehistoric and historic chilean populations. A paleopathological and paleoepidemiological study.

    Science.gov (United States)

    Castro, Mario; Goycoolea, Marcos; Silva-Pinto, Verónica

    2017-04-01

    External ear canal exostosis is more prevalent in northern coastal groups than in the highlands, suggesting that ocean activities facilitate the appearance of exostosis. However, southern coastal groups exposed to colder ocean water have a lesser incidence of exostosis, possibly due to less duration of exposure. There was a high incidence of otitis media in all groups of native population in Chile. One coastal group had a higher incidence, presumably due to racial factors. This is a paleopathological and paleoepidemiological study in temporal bones which assesses external ear canal exostosis and otitis media in prehistoric and historic native populations in Chile. A total of 460 temporal bones were evaluated for exostosis (ex) and 542 temporal bones were evaluated for otitis media (om). The study involved four groups: (1) Prehistoric Coastal (400-1000 AD) populations in Northern Chile (Pisagua-Tiwanaku) (22 temporal bones ex; 28 om); (2) Prehistoric Highland (400-1000 AD) populations in Northern Chile (292 temporal bones ex; 334 om); (3) Pisagua-Regional Developments (coastal) in Northern Chile (1000-1450 AD) (66 temporal bones ex; 82 om); and (4) Historic (1500-1800 AD) coastal populations in Southern Chile (80 temporal bones ex: 18 Chonos, 62 Fuegians. 98 om: 22 Chonos, 76 Fuegians). Skulls were evaluated visually and with an operating microscope. In addition, the otitis media group was evaluated with Temporal bone radiology - -lateral XRays-Schuller view - to assess pneumatization as evidence of previous middle ear disease. Prehistoric northern coastal groups had an incidence of exostosis of 15.91%, the northern highlands group 1.37%, and the southern coastal group 1.25%. There were changes suggestive of otitis media in: Pisagua/Tiwanaku 53.57%; Pisagua/Regional Developments 70.73%; Northern Highlands population 47.90%; Chonos 63.64%; and Fuegian tribes 64.47%.

  18. Spatial and temporal changes of subchondral bone proceed to articular cartilage degeneration in rats subjected to knee immobilization.

    Science.gov (United States)

    Xu, Lei; Li, Zhe; Lei, Lei; Zhou, Yue-Zhu; Deng, Song-Yun; He, Yong-Bin; Ni, Guo-Xin

    2016-03-01

    This study was aimed to investigate the spatial and temporal changes of subchondral bone and its overlying articular cartilage in rats following knee immobilization. A total of 36 male Wistar rats (11-13 months old) were assigned randomly and evenly into 3 groups. For each group, knee joints in 6 rats were immobilized unilaterally for 1, 4, or 8 weeks, respectively, while the remaining rats were allowed free activity and served as external control groups. For each animal, femurs at both sides were dissected after sacrificed. The distal part of femur was examined by micro-CT. Subsequently, femoral condyles were collected for further histological observation and analysis. For articular cartilage, significant changes were observed only at 4 and 8 weeks of immobilization. The thickness of articular cartilage and chondrocytes numbers decreased with time. However, significant changes in subchondral bone were defined by micro-CT following immobilization in a time-dependent manner. Immobilization led to a thinner and more porous subchondral bone plate, as well as a reduction in trabecular thickness and separation with a more rod-like architecture. Changes in subchondral bone occurred earlier than in articular cartilage. More importantly, immobilization-induced changes in subchondral bone may contribute, at least partially, to changes in its overlying articular cartilage. © 2016 Wiley Periodicals, Inc.

  19. Calcium phosphate/poly(D,L-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect.

    NARCIS (Netherlands)

    Watering, F.C.J. van de; Beucken, J.J.J.P van den; Walboomers, X.F.; Jansen, J.A.

    2012-01-01

    OBJECTIVES: The present study aimed to provide temporal information on material degradation and bone formation using composite (C) bone defect filler materials consisting of calcium phosphate cement (CaP) and poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles (20 or 30 wt%) in rat

  20. European Society of Biomechanics S.M. Perren Award 2008: using temporal trends of 3D bone micro-architecture to predict bone quality.

    Science.gov (United States)

    Pauchard, Yves; Mattmann, Corinne; Kuhn, Andreas; Gasser, Jürg A; Boyd, Steven K

    2008-10-20

    In longitudinal studies, three-dimensional (3D) bone images are acquired at sequential time points essentially resulting in four-dimensional (4D) data for an individual. Based on the 4D data, we propose to calculate temporal trends and project these trends to estimate future bone architecture. Multiple consecutive deformation fields, calculated with Demons deformable image registration algorithm, were extrapolated on a voxel-by-voxel basis. Test data were from in vivo micro-computed tomography (microCT) scans of the proximal tibia of Wistar rats that were either ovariectomized (OVX; N=5) or sham operated (SHAM; N=6). Measurements performed at baseline, 4 and 8 weeks were the basis to predict the 12 week data. Predicted and actual 12 week data were compared using qualitative (3D rendering) and quantitative (geometry, morphology and micro-finite element, microFE) methods. The results indicated a voxel-based linear extrapolation scheme yielded mean geometric errors that were smaller than the voxel size of 15 microm. Key morphological parameters that were estimated included bone volume ratio (BV/TV; mean error 0.4%, maximum error 9%), trabecular thickness (Tb.Th; -1.1%, 11%), connectivity density (Conn.D; 9.0%, 18.5%) and the apparent Young's modulus (E(1); 6.0%, 32%). These data demonstrated a promising and novel approach for quantitatively capturing in vivo bone dynamics at the local trabecular level. The method does not require an a priori understanding of the diseases state, and can provide information about the trends of the bone remodeling process that may be used for better monitoring and treatment of diseases such as osteoporosis.

  1. Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response

    Directory of Open Access Journals (Sweden)

    Caroline Regina de Jesus

    2011-06-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22, resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM, which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR and bone marrow biopsies (BMB were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.A Leucemia Mielóide Crônica (LMC é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22, que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI, o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC e as biópsias de medula óssea (BMO antes e após o

  2. Simulador cirúrgico para treinamento de dissecção do osso temporal Surgical simulator for temporal bone dissection training

    Directory of Open Access Journals (Sweden)

    Daniel Mochida Okada

    2010-10-01

    Full Text Available A dissecção em ossos temporais tem papel fundamental na formação de cirurgiões e sua obtenção esbarra em diversas dificuldades. OBJETIVO: Desenvolver uma réplica sintética do osso temporal para treinamento de dissecção. FORMA DE ESTUDO: Experimental. MATERIAIS E MÉTODOS: Foi desenvolvida uma réplica de resina acrílica termopolimerizante através de técnicas de moldagem com silicone. Para a avaliação do método, foram selecionados cinco cirurgiões otológicos para dissecção do modelo em laboratório de cirurgia experimental. Foi preenchido questionário, levando em consideração a aparência externa, a simulação de procedimentos (colocação de tubo de ventilação, mastoidectomia, descompressão do nervo facial e acesso translabiríntico ao meato acústico interno e a impressão final. RESULTADOS: A avaliação apontou satisfação na utilização do modelo (80%, sendo mais evidente no que se referiu à dissecção do segmento mastoide do nervo facial e ao acesso translabiríntico ao meato acústico interno. A colocação de tubo de ventilação foi razoável para 60% e satisfatória para 40% deles. A mastoidectomia foi totalmente satisfatória para 40%. CONCLUSÃO: A dissecção neste simulador otológico não substitui o treinamento em ossos temporais de cadáveres, porém, dada a crescente dificuldade na obtenção destes, o desenvolvimento de novas ferramentas de ensino deve ser encorajado para o contínuo aprimoramento de cirurgiões.Temporal bone dissection plays an important role in the training of surgeons; however, they are difficult to obtain. AIM: To develop a synthetic replica of the temporal bone for dissection training. STUDY DESIGN: Experimental. MATERIALS AND METHODS: An acrylic synthetic resin replica was obtained from a human temporal bone. For the evaluation of the method, we selected five ear surgeons to dissect the model in a laboratory of experimental surgery. A questionnaire was filled, assessing

  3. Temporal bone CT findings of tuberculous otitis media : comparison with chronic otitis media

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jeong A; Rho, Myung Ho; Kim, Young Min; Lee, Ho Seung; Choi, Pil Yeob; Seong, Young Soon; Kwon, Jae Soo; Lee, Sang Wook [Masan Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of); Jung, Keon Sik [Pohang Sunrin Hospital, Pohang (Korea, Republic of)

    1999-06-01

    To compare the differential findings of tuberculous otitis media(TOM) with those of chronic sup purative otitis media with or without cholesteatoma, as seen on high resolution temporal bone CT. We retrospectively reviewed 14 cases of TOM, 30 cases of chronic suppurative otitis media(CSOM), and 30 cases of chronic otitis media with cholesteatoma(Chole). All had been pathologically confirmed. We evaluated the preservation of mastoid cells without sclerotic change, the location and extension of soft tissue to the external auditary canal, and erosion of ossicles, the tegmen tympani, scutum, bony labyrinth, facial nerve canal and sigmoid sinus, and the presence of intracranial complications. Soft tissue in the mastoid antrum was seen in all cases of TOM(100%), 29 cases of CSOM(96.7%), and 26 cases of Chole(86.7%). In contrast, the soft tissue in the entire middle ear cavity was noted in 13 cases of TOM(92.8%), 7 cases of CSOM(23.3%), and 12 cases of Chole(40%). Soft tissue extended to the superior aspect of the external auditory canal in 4 cases of TOM (28.6%) and 5 cases of Chole (16.7%). Mastoid air cells were seen in 9 cases of TOM (64.3%), 4 cases of CSOM (13.3%), and 3 cases of Chole(10%). Ossicular erosion was noted in 6 cases of TOM (42.9%), 12 cases of CSOM (40%), and 26 cases of Chole(86.7%), while in one case of TOM (7.1%), 5 cases of CSOM (16.7%), and 15 cases of Chole(50%) there was erosion of the scutum. In one case of TOM, follow-up CT study after 9 months of antituberculous medication without surgery revealed complete clearing of previously noted soft tissue in the middle ear cavity. Specific CT findings of TOM were not seen, but if there were findings of soft tissue in the entire middle ear cavity, soft tissue extension to the external auditory canal, preservation of mastoid air cells without sclerotic change, and intact scutum, TOM may be differentiated from other chronic otitis media.

  4. A novel approach for studying the temporal modulation of embryonic skeletal development using organotypic bone cultures and microcomputed tomography.

    Science.gov (United States)

    Kanczler, Janos M; Smith, Emma L; Roberts, Carol A; Oreffo, Richard O C

    2012-10-01

    Understanding the structural development of embryonic bone in a three dimensional framework is fundamental to developing new strategies for the recapitulation of bone tissue in latter life. We present an innovative combined approach of an organotypic embryonic femur culture model, microcomputed tomography (μCT) and immunohistochemistry to examine the development and modulation of the three dimensional structures of the developing embryonic femur. Isolated embryonic chick femurs were organotypic (air/liquid interface) cultured for 10 days in either basal, chondrogenic, or osteogenic supplemented culture conditions. The growth development and modulating effects of basal, chondrogenic, or osteogenic culture media of the embryonic chick femurs was investigated using μCT, immunohistochemistry, and histology. The growth and development of noncultured embryonic chick femur stages E10, E11, E12, E13, E15, and E17 were very closely correlated with increased morphometric indices of bone formation as determined by μCT. After 10 days in the organotpyic culture set up, the early aged femurs (E10 and E11) demonstrated a dramatic response to the chondrogenic or osteogenic culture conditions compared to the basal cultured femurs as determined by a change in μCT morphometric indices and modified expression of chondrogenic and osteogenic markers. Although the later aged femurs (E12 and E13) increased in size and structure after 10 days organotpypic culture, the effects of the osteogenic and chondrogenic organotypic cultures on these femurs were not significantly altered compared to basal conditions. We have demonstrated that the embryonic chick femur organotpyic culture model combined with the μCT and immunohistochemical analysis can provide an integral methodology for investigating the modulation of bone development in an ex vivo culture setting. Hence, these interdisciplinary techniques of μCT and whole organ bone cultures will enable us to delineate some of the temporal

  5. The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Francis, W.R., E-mail: w.francis@swansea.ac.uk [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Owens, S.E.; Wilde, C. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Pallister, I. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Trauma and Orthopaedics, Morriston Hospital, Swansea (United Kingdom); Kanamarlapudi, V. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom); Zou, W., E-mail: weizou60@hotmail.com [College of Life Sciences, Liaoning Normal University, Dalian 116081 (China); Liaoning Key Laboratories of Biotechnology and Molecular Drug Research and Development, Dalian 116081 (China); Xia, Z. [Institute of Life Science, College of Medicine, Swansea University (United Kingdom)

    2014-10-24

    Highlights: • ERα36 is the predominant ERα isoform involved in bone regulation in human BMSC. • ERα36 mRNA is significantly upregulated during the process of osteogenesis. • The pattern of ERα36 and runx2 mRNA expression is similar during osteogenesis. • ERα36 appears to be co-localised with runx2 during osteogenesis. - Abstract: During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments.

  6. Acute myeloid leukemia: update in diagnosis and treatment in Brazil

    Directory of Open Access Journals (Sweden)

    Ricardo Helman

    2011-06-01

    Full Text Available Objective: To identify how the Brazilian hematology centerstreated and diagnosed cases of acute myeloid leukemia in 2009.Methods: An epidemiological observational multicenter study of11 listed Brazilian centers that treat acute myeloid leukemia andperform bone marrow transplantation. Data were collected fromclinical charts of patients with acute myeloid leukemia treatedat the said centers between 2005 and 2009. The availability forimmunophenotyping and cytogenetic tests was assessed. Results:During 2009, a total of 345 new cases of acute myeloid leukemiawere diagnosed. Differences were noted in the tests performedbetween patients who initiated treatment at the center and thosereferred for treatment. Of the participating centers, 72% conductedsome type of molecular study in acute myeloid leukemia upondiagnosis. Conclusion: Treatment for acute myeloid leukemia inBrazil shows significantly inferior results when compared to othercenters worldwide.

  7. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    Directory of Open Access Journals (Sweden)

    Gayed Isis W

    2009-08-01

    Full Text Available Abstract Background It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. Methods We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. Results No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months or to bone (21.2 months than to the liver (9.8 months. Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

  8. [Severe temporal bone fractures in children: clinical presentation, complications and sequelae observed in the last 11 years].

    Science.gov (United States)

    Castellanos-Alcarria, A J; Navarro-Mingorance, A; Reyes-Domínguez, S B; León-León, M C; Cepillo-Boluda, A; López López-Guerrero, A

    2015-01-01

    To evaluate the clinical presentation, complications and sequelae in patients with temporal bone fracture in the last 11 years. A total of 27 patient medical records were retrospectively analysed. Of the 27 patients who were admitted for temporal bone fracture from 2001 to 2012, 13 (48%) had no petrous involvement (Group 1), and 14 (52%) with petrous involvement (Group 2). Patients in Group 2 had a longer P-ICU stay: median 4.5 days (RI: 2.75-22.25 d) vs 2 (RI: 1-3 d) (P=.018); more days on mechanical ventilation support: median 3 days (RI: 1.50-17 d) vs 1 (RI: 1-1.25 d). This group also had a higher frequency in sequelae (P=.04 OR=1.4 (95% CI: 1.05-1.95)) and a higher incidence in cerebrospinal fluid (CSF) fistula (P<.02; OR 2.33; 95% CI (1.27-4.27)). Severity scores (PRIMS III and PTI) showed no significant differences. Some degree of hearing loss was observed in 31% of the patients. Traffic accident was the main cause of trauma (33%), followed by falls (27%). There were 2 deaths and 4 (15%) had permanent sequelae. Isolated temporal bone fractures usually have a good outcome in children, but in some cases they can be fatal or have permanent sequelae. Long term follow up is recommended by authors. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  9. Myeloid sarcoma in children – diagnostic and therapeutic difficulties

    Directory of Open Access Journals (Sweden)

    Magdalena Samborska

    2017-01-01

    Full Text Available Myeloid sarcoma (MS is a malignant extramedullary tumour, which consists of immature cells of myeloid origin. It may occur de novo , concurrently or precede the diagnosis of acute myeloid leukemia (AML, myelodysplastic syndrome (MDS or chronic myeloid leukemia (CML. MS can also be a manifestation of the relapse of the disease. The more frequent sites of involvement are the skin, orbit, bone, periosteum, lymph nodes, gastrointestinal tract, soft tissue, central nervous system and testis. Because of its different localization and symptoms, and the lack of diagnostics algorithm, myeloid sarcoma is a real diagnostic challenge, in particular in patients without initial bone marrow involvement. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate. In the paper, the role of immunohistochemistry, cytogenetic and molecular genetic analyses is emphasized as well as the breadth of unclear aspects of this disorder in children.

  10. To study the anatomy of tympanomastoid segment of facial nerve and its variations in human cadaveric temporal bone

    OpenAIRE

    Nitika Gupta; Rohan Gupta; I P Singh; Sunil Kotwal; Anil Suri; Sunanda Raina

    2017-01-01

    Introduction: The facial nerve is one of the most significant and vulnerable structures in the temporal bone. Its dysfunction affects both voluntary and voluntary motion leading to noticeable disfigurement and emotional distress to those suffering from it. Iatrogenic facial paralysis is known to be a feared complication of ear surgery, and its incidence is reported to be 0.6–3.6% in all otologic surgical procedures, which increases to 4–10% in revision cases. Objective: The aim of this study ...

  11. Temporal Subtraction of Serial CT Images with Large Deformation Diffeomorphic Metric Mapping in the Identification of Bone Metastases.

    Science.gov (United States)

    Sakamoto, Ryo; Yakami, Masahiro; Fujimoto, Koji; Nakagomi, Keita; Kubo, Takeshi; Emoto, Yutaka; Akasaka, Thai; Aoyama, Gakuto; Yamamoto, Hiroyuki; Miller, Michael I; Mori, Susumu; Togashi, Kaori

    2017-11-01

    Purpose To determine the improvement of radiologist efficiency and performance in the detection of bone metastases at serial follow-up computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. CT image pairs (previous and current scans of the torso) in 60 patients with cancer (primary lesion location: prostate, n = 14; breast, n = 16; lung, n = 20; liver, n = 10) were included. These consisted of 30 positive cases with a total of 65 bone metastases depicted only on current images and confirmed by two radiologists who had access to additional imaging examinations and clinical courses and 30 matched negative control cases (no bone metastases). Previous CT images were semiautomatically registered to current CT images by the algorithm, and TS images were created. Seven radiologists independently interpreted CT image pairs to identify newly developed bone metastases without and with TS images with an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Reading time was recorded, and usefulness was evaluated with subjective scores of 1-5, with 5 being extremely useful and 1 being useless. Significance of these values was tested with the Wilcoxon signed-rank test. Results The subtraction images depicted various types of bone metastases (osteolytic, n = 28; osteoblastic, n = 26; mixed osteolytic and blastic, n = 11) as temporal changes. The average reading time was significantly reduced (384.3 vs 286.8 seconds; Wilcoxon signed rank test, P = .028). The average figure-of-merit value increased from 0.758 to 0.835; however, this difference was not significant (JAFROC analysis, P = .092). The subjective usefulness survey response showed a median score of 5 for use of the technique

  12. High strength, biodegradable and cytocompatible alpha tricalcium phosphate-iron composites for temporal reduction of bone fractures.

    Science.gov (United States)

    Montufar, E B; Casas-Luna, M; Horynová, M; Tkachenko, S; Fohlerová, Z; Diaz-de-la-Torre, S; Dvorak, K; Celko, L; Kaiser, J

    2018-02-09

    In this work alpha tricalcium phosphate (α-TCP)/ iron (Fe) composites were developed as a new family of biodegradable, load-bearing and cytocompatible materials. The composites with composition from pure ceramic to pure metallic samples were consolidated by pulsed electric current assisted sintering to minimise processing time and temperature while improving their mechanical performance. The mechanical strength of the composites was increased and controlled with the Fe content, passing from brittle to ductile failure. In particular, the addition of 25 vol.% of Fe produced a ceramic matrix composite with elastic modulus much closer to cortical bone than that of titanium or biodegradable magnesium alloys and specific compressive strength above that of stainless steel, chromium-cobalt alloys and pure titanium, currently used in clinic for internal fracture fixation. All the composites studied exhibited higher degradation rate than their individual components, presenting values around 200 μm/year, but also their compressive strength did not show a significant reduction in the period required for bone fracture consolidation. Composites showed preferential degradation of α-TCP areas rather than β-TCP areas, suggesting that α-TCP can produce composites with higher degradation rate. The composites were cytocompatible both in indirect and direct contact with bone cells. Osteoblast-like cells attached and spread on the surface of the composites, presenting proliferation rate similar to cells on tissue culture-grade polystyrene and they showed alkaline phosphatase activity. Therefore, this new family of composites is a potential alternative to produce implants for temporal reduction of bone fractures. Biodegradable alpha-tricalcium phosphate/iron (α-TCP/Fe) composites are promising candidates for the fabrication of temporal osteosynthesis devices. Similar to biodegradable metals, these composites can avoid implant removal after bone fracture healing, particularly in

  13. Temporal trends in obesity, osteoporosis treatment, bone mineral density, and fracture rates: a population-based historical cohort study.

    Science.gov (United States)

    Leslie, William D; Lix, Lisa M; Yogendran, Marina S; Morin, Suzanne N; Metge, Colleen J; Majumdar, Sumit R

    2014-04-01

    Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population-based historical cohorts from the Province of Manitoba, Canada (1996-2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model-based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n=27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n=36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (pobesity or osteoporosis treatment. © 2014 American Society for Bone and Mineral Research.

  14. Temporal Bone CT: Improved Image Quality and Potential for Decreased Radiation Dose Using an Ultra-High-Resolution Scan Mode with an Iterative Reconstruction Algorithm.

    Science.gov (United States)

    Leng, S; Diehn, F E; Lane, J I; Koeller, K K; Witte, R J; Carter, R E; McCollough, C H

    2015-09-01

    Radiation dose in temporal bone CT imaging can be high due to the requirement of high spatial resolution. In this study, we assessed whether CT imaging of the temporal bone by using an ultra-high-resolution scan mode combined with iterative reconstruction provides higher spatial resolution and lower image noise than a z-axis ultra-high-resolution mode. Patients with baseline temporal bone CT scans acquired by using a z-axis ultra-high-resolution protocol and a follow-up scan by using the ultra-high-resolution-iterative reconstruction technique were identified. Images of left and right temporal bones were reconstructed in the axial, coronal, and Poschl planes. Three neuroradiologists assessed the spatial resolution of the following structures: round and oval windows, incudomallear and incudostapedial joints, basal turn spiral lamina, and scutum. The paired z-axis ultra-high-resolution and ultra-high-resolution-iterative reconstruction images were displayed side by side in random order, with readers blinded to the imaging protocol. Image noise was compared in ROIs over the posterior fossa. We identified 8 patients, yielding 16 sets of temporal bone images (left and right). Three sets were excluded because the patient underwent surgery between the 2 examinations. Spatial resolution was comparable (Poschl) or slightly better (axial and coronal planes) with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution. A paired t test indicated that noise was significantly lower with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution (P iterative reconstruction scan mode has similar or slightly better resolution relative to the z-axis ultra-high-resolution mode for CT of the temporal bone but significantly (P < .01) lower image noise, which may enable the dose to be reduced by approximately 50%. © 2015 by American Journal of Neuroradiology.

  15. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Lucas E.B., E-mail: lucasebsouza@usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Almeida, Danilo C., E-mail: gudaalmeida@gmail.com [Department of Medicine – Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP (Brazil); Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com [Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo (Brazil); Covas, Dimas T., E-mail: dimas@fmrp.usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br [Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2016-07-15

    The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced

  16. A Rare Case of Myeloid Sarcoma Presenting as an Anorectal Ulcer

    Directory of Open Access Journals (Sweden)

    Laxmi Parsa

    2012-01-01

    Full Text Available Myeloid Sarcoma is a rare tumor composed of myeloblasts occurring at an extramedullary site like bones, or various soft tissues. Myeloid sarcoma may involve the gastrointestinal tract very rarely either solitarily, or occurring simultaneously with acute myeloid leukemia. Its diagnosis is challenging and needs biopsy and immunohistochemical staining. We are describing a case of myeloid sarcoma which presented as a painful anal ulcer mimicking an atypical fissure. Its appearance resembled crohn’s disease on sigmoidoscopy. A biopsy of the ulcer along with histochemical staining led to the diagnosis of myeloid sarcoma. Our case demonstrates the need for aggressive evaluation of any common gastrointestinal complaint with an atypical presentation.

  17. Significance of temporal bone CT scan for exposure of the facial canal and the lateral semicircular canal in cholesteatoma

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Ki Joon; Kim, Dong Jin; Kim, Myung Soon; Kim, Young Ju; Kweon, Joon [Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)

    1991-09-15

    By reviewing retrospectively the HRCT findings in 130 surgically proven cases of chronic otitis media with cholesteatoma, we estimated the sensitivity, specificity, and positive predictability of the HRCT compared to surgical findings. For exposure of the facial canal, the sensitivity, specificity, and positive predictability was 59.7%, 84.9%, and 85.2% respectively. For exposure of the lateral semicircular canal, the sensitivity was 80.6%, the specificity 99.0%, and the positive predictability 96.2%. Conclusively, the diagnostic accuracy of preoperative temporal bone CT regarding the state of the lateral semicircular canal seems to be highly reliable. Gross invasion of the facial canal can be usually detected. However, relatively low sensitivity suggests that evaluation of the ultra-thin structures of the tympanic segment is often problematic.

  18. Aggressiveness in cholesterol granuloma of the temporal bone may be determined by the vigor of its blood source.

    Science.gov (United States)

    Pfister, Markus H F; Jackler, Robert K; Kunda, Larisa

    2007-02-01

    Recently, it has been proposed that the aggressive behavior of cholesterol granuloma (CG) of the petrous apex is explained by its proximity to the richly vascular marrow of the petroclival junction. Most CGs of the lateral temporal bone are indolent. The purpose of the present study is to examine the factors responsible for atypical aggressive behavior in mastoid CG. Retrospective case series. : Tertiary academic practice. Four patients with atypically aggressive CG of the mastoid. In each case, the CG abutted a rich blood source: the sigmoid sinus, carotid artery, a large dural vein, or a rich deposit of vascular marrow in the mastoid tip. These observations lend further support to the theory that aggressiveness of CG is sustained by a robust source of ongoing hemorrhage.

  19. Anatomy-Specific Virtual Reality Simulation in Temporal Bone Dissection: Perceived Utility and Impact on Surgeon Confidence.

    Science.gov (United States)

    Locketz, Garrett D; Lui, Justin T; Chan, Sonny; Salisbury, Kenneth; Dort, Joseph C; Youngblood, Patricia; Blevins, Nikolas H

    2017-06-01

    Objective To evaluate the effect of anatomy-specific virtual reality (VR) surgical rehearsal on surgeon confidence and temporal bone dissection performance. Study Design Prospective pre- and poststudy of a novel virtual surgical rehearsal platform. Setting Academic otolaryngology-head and neck surgery residency training programs. Subjects and Methods Sixteen otolaryngology-head and neck surgery residents from 2 North American training institutions were recruited. Surveys were administered to assess subjects' baseline confidence in performing 12 subtasks of cortical mastoidectomy with facial recess. A cadaver temporal bone was randomly assigned to each subject. Cadaver specimens were scanned with a clinical computed tomography protocol, allowing the creation of anatomy-specific models for use in a VR surgical rehearsal platform. Subjects then rehearsed a virtual mastoidectomy on data sets derived from their specimens. Surgical confidence surveys were administered again. Subjects then dissected assigned cadaver specimens, which were blindly graded with a modified Welling scale. A final survey assessed the perceived utility of rehearsal on dissection performance. Results Of 16 subjects, 14 (87.5%) reported a significant increase in overall confidence after conducting an anatomy-specific VR rehearsal. A significant correlation existed between perceived utility of rehearsal and confidence improvement. The effect of rehearsal on confidence was dependent on trainee experience and the inherent difficulty of the surgical subtask. Postrehearsal confidence correlated strongly with graded dissection performance. Subjects rated anatomy-specific rehearsal as having a moderate to high contribution to their dissection performance. Conclusion Anatomy-specific virtual rehearsal improves surgeon confidence in performing mastoid dissection, dependent on surgeon experience and task difficulty. The subjective confidence gained through rehearsal correlates positively with subsequent

  20. Investigation of a novel completely-in-the-canal direct-drive hearing device: a temporal bone study.

    Science.gov (United States)

    Mahboubi, Hossein; Paulick, Peyton; Kiumehr, Saman; Merlo, Mark; Bachman, Mark; Djalilian, Hamid Reza

    2013-01-01

    Whether a prototype direct-drive hearing device (DHD) is effective in driving the tympanic membrane (TM) in a temporal bone specimen to enable it to potentially treat moderate-to-severe hearing loss. Patient satisfaction with air conduction hearing aids has been low because of sound distortion, occlusion effect, and feedback issues. Implantable hearing aids provide a higher quality sound but require surgery for placement. The DHD was designed to combine the ability of driving the ossicular chain with placement in the external auditory canal. DHD is a 3.5-mm wide device that could fit entirely into the bony ear canal and directly drive the TM rather than use a speaker. A cadaveric temporal bone was prepared. The device developed in our laboratory was coupled to the external surface of the TM and against the malleus. Frequency sweeps between 300 Hz to 12 kHz were performed in 2 different coupling methods at 104 and 120 dB, and the DHD was driven with various levels of current. Displacements of the posterior crus of the stapes were measured using a laser Doppler vibrometer. The DHD showed a linear frequency response from 300 Hz to 12 kHz. Placement against the malleus showed higher amplitudes and lower power requirements than when the device was placed on the TM. DHD is a small completely-in-the-canal device that mechanically drives the TM. This novel device has a frequency output wider than most air conduction devices. Findings of the current study demonstrated that the DHD had the potential of being incorporated into a hearing aid in the future.

  1. The usefulness of MR imaging of the temporal bone in the evaluation of patients with facial and audiovestibular dysfunction

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    Park, Sang Uk; Kim, Hyung Jin; Cho, Young Kuk; Lim, Myung Kwan; Kim, Won Hong; Suh, Chang Hae; Lee, Seung Chul [Inha University College of Medicine, Incheon (Korea, Republic of)

    2002-01-01

    To evaluate the clinical utility of MR imaging of the temporal bone in patients with facial and audiovestibular dysfunction with particular emphasis on the importance of contrast enhancement. We retrospectively reviewed the MR images of 179 patients [72 men, 107 women; average age, 44 (range, 1-77) years] who presented with peripheral facial palsy (n=15), audiometrically proven sensorineural hearing loss (n=104), vertigo (n=109), or tinnitus (n=92). Positive MR imaging findings possibly responsible for the patients' clinical manifestations were categorized according to the anatomic sites and presumed etiologies of the lesions. We also assessed the utility of contrast-enhanced MR imaging by analyzing its contribution to the demonstration of lesions which would otherwise not have been apparent. All MR images were interpreted by two neuroradiologists, who reached their conclusions by consensus. MR images demonstrated positive findings, thought to account for the presenting symptoms, in 78 (44%) of 179 patients, including 15 (100%) of 15 with peripheral facial palsy, 43 (41%) of 104 with sensorineural hearing loss, 40 (37%) of 109 with vertigo, and 39 (42%) of 92 with tinnitus. Thirty (38%) of those 78 patients had lesions that could be confidently recognized only at contrast-enhanced MR imaging. Even though its use led to positive findings in less than half of these patients, MR imaging of the temporal bone is a useful diagnostic procedure in the evaluation of those with facial and audiovestibular dysfunction. Because it was only at contrast-enhanced MR imaging that a significant number of patients showed positive imaging findings which explained their clinical manifestations, the use of contrast material is highly recommended.

  2. A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria.

    Science.gov (United States)

    Margolskee, Elizabeth; Mikita, Geoff; Rea, Bryan; Bagg, Adam; Zuo, Zhuang; Sun, Yi; Goswami, Maitrayee; Wang, Sa A; Oak, Jean; Arber, Daniel A; Allen, M Brandon; George, Tracy I; Rogers, Heesun J; Hsi, Eric; Hasserjian, Robert P; Orazi, Attilio

    2018-02-05

    The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid

  3. A novel framework for the temporal analysis of bone mineral density in metastatic lesions using CT images of the femur

    Science.gov (United States)

    Knoop, Tom H.; Derikx, Loes C.; Verdonschot, Nico; Slump, Cornelis H.

    2015-03-01

    In the progressive stages of cancer, metastatic lesions in often develop in the femur. The accompanying pain and risk of fracture dramatically affect the quality of life of the patient. Radiotherapy is often administered as palliative treatment to relieve pain and restore the bone around the lesion. It is thought to affect the bone mineralization of the treated region, but the quantitative relation between radiation dose and femur remineralization remains unclear. A new framework for the longitudinal analysis of CT-scans of patients receiving radiotherapy is presented to investigate this relationship. The implemented framework is capable of automatic calibration of Hounsfield Units to calcium equivalent values and the estimation of a prediction interval per scan. Other features of the framework are temporal registration of femurs using elastix, transformation of arbitrary Regions Of Interests (ROI), and extraction of metrics for analysis. Build in Matlab, the modular approach aids easy adaptation to the pertinent questions in the explorative phase of the research. For validation purposes, an in-vitro model consisting of a human cadaver femur with a milled hole in the intertrochanteric region was used, representing a femur with a metastatic lesion. The hole was incrementally stacked with plates of PMMA bone cement with variable radiopaqueness. Using a Kolmogorov-Smirnov (KS) test, changes in density distribution due to an increase of the calcium concentration could be discriminated. In a 21 cm3 ROI, changes in 8% of the volume from 888 ± 57mg • ml-1 to 1000 ± 80mg • ml-1 could be statistically proven using the proposed framework. In conclusion, the newly developed framework proved to be a useful and flexible tool for the analysis of longitudinal CT data.

  4. Presbycusis: a human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume.

    Science.gov (United States)

    Nelson, Erik G; Hinojosa, Raul

    2003-10-01

    The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. Retrospective case review. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.

  5. High-resolution CT of temporal bone trauma: review of 38 cases; L'apport du scanner dans les traumatismes du rocher: a propos de 38 cas

    Energy Technology Data Exchange (ETDEWEB)

    Hiroual, M.R.; Zougarhi, A.; Cherif Idrissi El Ganouni, N.; Essadki, O.; Ousehal, A. [CHU Mohamed 6, Service de Radiologie, Marrakech (Morocco); Tijani Adil, O.; Maliki, O.; Aderdour, L.; Raji, A. [CHU Mohamed 6, Service d' ORL, Marrakech (Morocco)

    2010-01-15

    Purpose Temporal bone trauma is frequent but difficult to assess due to the diversity of clinical presentations and complex anatomy. We have sought to assess the different types of fractures and complications on high-resolution CT. Materials and methods Descriptive retrospective study over a 24 month period performed in the ENT radiology section of the Mohammed 6 university medical center in Marrakech. A total of 38 cases of temporal bone trauma were reviewed. All patients underwent ENT evaluation and high-resolution CT of the temporal bone using 1 mm axial and coronal sections. Results Mean patient age was 33 years (range: 14-55 years) with male predominance (sex ratio: 36/2). Clinical symptoms were mainly otorrhagia and conductive hearing loss. Oblique extra-labyrinthine fractures were most frequent. Two cases of pneumo-labyrinth were noted. Management was conservative in most cases with deafness in 3 cases. Conclusion High-resolution CT of the temporal bone provides accurate depiction of lesions explaining the clinical symptoms and helps guide management. MRI is complimentary to further assess the labyrinth and VII-VIII nerve complex. (author)

  6. Myeloid Sarcoma Presenting as Nasal and Orbital Mass: An Initial Manifestation of an Acute Myeloid Leukaemia.

    Science.gov (United States)

    Gupta, Amita Jain; Mandal, Shramana; Gupta, Richa; Khurana, Nita; Gulati, Achal

    2017-07-01

    Myeloid sarcoma is an extramedullary manifestation of Acute Myeloid Leukaemia and sometimes is the only indicator of the disease. The incidence varies between 3-9.1% of acute leukaemia cases. The blast infiltration is seen most commonly in skin, lymph node, gastrointestinal tract, bone, soft tissue though can involve any body site usually as a solitary lesion and is rarely seen in nasal cavity. We present two cases of myeloid sarcoma presenting as a nasal mass in a six year old girl and other as orbital mass in 32-year-old as an initial manifestation of acute myeloid leukaemia. Histopathological examination along with immunohistochemistry clinched the diagnosis of myeloid sarcoma. Examination of bone marrow aspirate revealed blasts which fulfilled the criteria for acute leukaemia. These cases are usually misdiagnosed because often lymphoma and granulocytic sarcoma is not considered in initial list of differential diagnoses. These rare cases are being presented here as early recognition and diagnosis will ensure rapid treatment of the condition and improve the survival.

  7. Skull base, orbits, temporal bone, and cranial nerves: anatomy on MR imaging.

    Science.gov (United States)

    Morani, Ajaykumar C; Ramani, Nisha S; Wesolowski, Jeffrey R

    2011-08-01

    Accurate delineation, diagnosis, and treatment planning of skull base lesions require knowledge of the complex anatomy of the skull base. Because the skull base cannot be directly evaluated, imaging is critical for the diagnosis and management of skull base diseases. Although computed tomography (CT) is excellent for outlining the bony detail, magnetic resonance (MR) imaging provides better soft tissue detail and is helpful for evaluating the adjacent meninges, brain parenchyma, and bone marrow of the skull base. Thus, CT and MR imaging are often used together for evaluating skull base lesions. This article focuses on the radiologic anatomy of the skull base pertinent to MR imaging evaluation. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Acute myeloid leukemia: advances in diagnosis and classification.

    Science.gov (United States)

    Hasserjian, R P

    2013-06-01

    Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans. © 2013 Blackwell Publishing Ltd.

  9. Aspergillosis in immunocompromised children acute myeloid leukemia and bone marrow aplasia.: Report of two cases Aspergilose em crianças imunocomprometidas com leucemia mielóide aguda e aplasta de medula óssea: Registro de 2 casos

    Directory of Open Access Journals (Sweden)

    Maria Zilda de Aquino

    1994-10-01

    Full Text Available Two cases of Aspergillosis in immunocompromised children are reported. Both were caused by Aspergillns flavus. Early diagnosis and treatment led to the remission of the process. One patient had acute myeloid leukemia; the fungus was isolated from the blood. The other patient with bone marrow aplasia, presented an invasive aspergillosis of the paranasal sinuses with dissemination of fungal infection; the diagnosis was obtained by histology and culture of biopsied tissue from a palatal ulceration.No presente trabalho são registrados dois casos de aspergilose em crianças imunocomprometidas. O estudo micológico completo identificou Aspergillus flavus como agente dos dois processos. A presença cada vez mais frequente da aspergilose invasiva deve-se ao número crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos à quimioterapia. O diagnóstico precoce em um dos casos possibilitou remissão do processo. Tratava-se de paciente com leucemia mielóide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para óbito, com infecção fúngica generalizada.

  10. Leucemia Mielóide Crônica: transplante de medula óssea Cronic Myeloid Leukemia: bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Francisco J. P. Aranha

    2008-04-01

    Full Text Available A única terapia curativa para Leucemia Mielóide Crônica ainda é o transplante de células hematopoéticas progenitoras (TCHP; os atuais resultados com uso do imatinibe são suficientes para indicarmos o TCHP como um tratamento de segunda ou terceira linha. A decisão de realizar TCHP existe em uma variedade de momentos: falha em se conseguir remissão hemtológica, citogenética ou molecular, ou quando se perde a melhor resposta conseguida ou por progressão da doença para uma fase avançada. Há decisão também de como transplantar. Nesta revisão apontamos algumas destas decisões e as atuais controvérsias.Although the only curative therapy for chronic myeloid leukemia remains allogeneic stem cell transplantation (allo-SCT, the results of imatinib in newly diagnosed patients are sufficiently impressive to have displaced allo-SCT to second or third-line treatment. Patients now arrive at a decision for transplantation in a variety of disease situations: failing to achieve certain hematological, cytogenetic and molecular remission by some pre-determined timepoint, having lost a previous best response or due to progression to an advanced phase. The decision is also how to transplant. In this review article, the evidence supporting some of these decisions and current controversies are discussed.

  11. Influence of different chromosomal abnormalities in Ph-positive bone marrow cells on the chronic myeloid leukemia course during tyrosine kinase inhibitors therapy

    Directory of Open Access Journals (Sweden)

    O. Yu. Vinogradova

    2014-07-01

    Full Text Available The additional molecular and chromosomal abnormalities (ACA in Phositive cells usually considered as a genetic marker of chronic myeloid leukemia (CML progression. 457 patients in different CML phases received tyrosine kinase inhibitors (1st and 2nd generation were studied. During therapy 50 cases with additional chromosomal abnormalities in Ph+ clone (22 of them in chronic CML phase were revealed (median follow-up from CML diagnosis – 117 months, median imatinib therapy – 62 months. 86 % of patients in chronic phase with Ph+- cell abnormalities were cytogenetic resistance, and their 5-years overall survival was 80 % which was significantly lower than in patients without ACA (p < 0.005. The treatment results depend on chromosomal abnormalities detected. In patients with additional chromosome 8 imatinib therapy is effective, although complete cytogenetic response (CCR is achieved only in the later therapy stages. In patients with additional translocations CCR also achieved with imatinib or 2nd generation TKI. Only a third of patients with additional Ph-chromosome or BCR/ABL amplification achieved complete suppression of Ph+ clone using 2nd generation TKI. The presence of additional chromosome 7 abnormalities and complex karyotype disorders involving isochromosome i(17(q10 are poor prognostic factors of TKI treatment failures.

  12. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Labopin, Myriam; Shimoni, Avichai

    2012-01-01

    Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data...... to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from......-IV) and chronic GVHD did not differ between the groups. leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51 ± 2%, 32 ± 1%, and 17 ± 1% vs. 50 ± 6%, 38 ± 6%, and 12 ± 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS...

  13. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration-treated implant sites: a pilot study.

    Science.gov (United States)

    Milstein, Dan M J; Mathura, Keshen R; Lindeboom, Jérôme A H; Ramsoekh, Dewkoemar; Lindeboom, Robert; Ince, Can

    2009-10-01

    To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging for assessment of capillary density during the course of mucoperiosteal flap wound healing for 6 weeks in patients receiving dental implants. The greatest increase in capillary regeneration occurred in the early wound-healing phase, during weeks 1 and 2, and recovery to baseline was achieved between weeks 4 and 5. A comparison of adjacent OPS measurements indicated that differences between the time point immediately following administration of local anaesthesia and directly post-operatively ( p=0.002), between a directly post-operative time point and after 1 week (p=0.009), and between post-operative weeks 1 and 2 (p=0.036) were statistically significant. The early healing phase of mucoperiosteal flaps is characterized by rapid capillary regeneration. OPS imaging enabled the possibility to monitor and quantify the temporal development of mucoperiosteal flap revascularization following periodontal surgery.

  14. A totally implantable hearing system--design and function characterization in 3D computational model and temporal bones.

    Science.gov (United States)

    Gan, Rong Z; Dai, Chenkai; Wang, Xuelin; Nakmali, Don; Wood, Mark W

    2010-05-01

    Implantable middle ear hearing devices are emerging as an effective technology for patients with mild to moderately severe sensorineural hearing loss. Several devices with electromagnetic or piezoelectric transducers have been investigated or developed in the US and Europe since 1990. This paper reports a totally implantable hearing system (TIHS) currently under investigation in Oklahoma. The TIHS consists of implant transducer (magnet), implantable coil and microphone, DSP-audio signal processor, rechargeable battery, and remote control unit. The design of TIHS is based on a 3D finite element model of the human ear and the analysis of electromagnetic coupling of the transducer. Function of the TIHS is characterized over the auditory frequency range in three aspects: (1) mass loading effect on residual hearing with a passive implant, (2) efficiency of electromagnetic coupling between the implanted coil and magnet, and (3) functional gain of whole unit in response to acoustic input across the human skin. This paper focuses on mass loading effect and the efficiency of electromagnetic coupling of TIHS determined from the FE model of the human ear and the cadaver ears or temporal bones. Some preliminary data of whole unit function are also presented in the paper. Copyright (c0 2009 Elsevier B.V. All rights reserved.

  15. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects. Here...... signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query-based gene...

  16. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects...... genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query...

  17. Initial results of a new generation dual source CT system using only an in-plane comb filter for ultra-high resolution temporal bone imaging.

    Science.gov (United States)

    Meyer, Mathias; Haubenreisser, Holger; Raupach, Rainer; Schmidt, Bernhard; Lietzmann, Florian; Leidecker, Christianne; Allmendinger, Thomas; Flohr, Thomas; Schad, Lothar R; Schoenberg, Stefan O; Henzler, Thomas

    2015-01-01

    To prospectively evaluate radiation dose and image quality of a third generation dual-source CT (DSCT) without z-axis filter behind the patient for temporal bone CT. Forty-five patients were either examined on a first, second, or third generation DSCT in an ultra-high-resolution (UHR) temporal bone-imaging mode. On the third generation DSCT system, the tighter focal spot of 0.2 mm(2) removes the necessity for an additional z-axis-filter, leading to an improved z-axis radiation dose efficiency. Images of 0.4 mm were reconstructed using standard filtered-back-projection or iterative reconstruction (IR) technique for previous generations of DSCT and a novel IR algorithm for the third generation DSCT. Radiation dose and image quality were compared between the three DSCT systems. The statistically significantly highest subjective and objective image quality was evaluated for the third generation DSCT when compared to the first or second generation DSCT systems (all p generation examination as compared to the first and second generation DSCT. Temporal bone imaging without z-axis-UHR-filter and a novel third generation IR algorithm allows for significantly higher image quality while lowering effective dose when compared to the first two generations of DSCTs. • Omitting the z-axis-filter allows a reduction in radiation dose of 50% • A smaller focal spot of 0.2 mm (2) significantly improves spatial resolution • Ultra-high-resolution temporal-bone-CT helps to gain diagnostic information of the middle/inner ear.

  18. Initial results of a new generation dual source CT system using only an in-plane comb filter for ultra-high resolution temporal bone imaging

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Mathias; Haubenreisser, Holger; Schoenberg, Stefan O.; Henzler, Thomas [Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Raupach, Rainer; Schmidt, Bernhard; Leidecker, Christianne; Allmendinger, Thomas; Flohr, Thomas [Siemens Healthcare, Imaging and Therapy Division, Forchheim (Germany); Lietzmann, Florian; Schad, Lothar R. [Heidelberg University, Computer Assisted Clinical Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany)

    2015-01-15

    To prospectively evaluate radiation dose and image quality of a third generation dual-source CT (DSCT) without z-axis filter behind the patient for temporal bone CT. Forty-five patients were either examined on a first, second, or third generation DSCT in an ultra-high-resolution (UHR) temporal bone-imaging mode. On the third generation DSCT system, the tighter focal spot of 0.2 mm{sup 2} removesthe necessity for an additional z-axis-filter, leading to an improved z-axis radiation dose efficiency. Images of 0.4 mm were reconstructed using standard filtered-back-projection or iterative reconstruction (IR) technique for previous generations of DSCT and a novel IR algorithm for the third generation DSCT. Radiation dose and image quality were compared between the three DSCT systems. The statistically significantly highest subjective and objective image quality was evaluated for the third generation DSCT when compared to the first or second generation DSCT systems (all p < 0.05). Total effective dose was 63 %/39 % lower for the third generation examination as compared to the first and second generation DSCT. Temporal bone imaging without z-axis-UHR-filter and a novel third generation IR algorithm allows for significantly higher image quality while lowering effective dose when compared to the first two generations of DSCTs. (orig.)

  19. Optical cochlear implant: evaluation of insertion forces of optical fibres in a cochlear model and of traumata in human temporal bones.

    Science.gov (United States)

    Balster, Sven; Wenzel, Gentiana I; Warnecke, Athanasia; Steffens, Melanie; Rettenmaier, Alexander; Zhang, Kaiyin; Lenarz, Thomas; Reuter, Guenter

    2014-02-01

    Optical stimulation for hearing restoration is developing as an alternative therapy to electrical stimulation. For a more frequency-specific activation of the auditory system, light-guiding fibres need to be inserted into the coiled cochlea. To enable insertion with minimal trauma, glass fibres embedded in silicone were used as models. Thus, glass fibres of varying core/cladding diameter with and without silicon coating (single as well as in bundles) were inserted into a human scala tympani (ST) model. Insertion cochlear model force measurements were performed, and the thinner glass fibres that showed low insertion forces in the model were inserted into cadaveric human temporal bones. Silicone-coated glass fibres with different core/cladding diameters and bundle sizes could be inserted up to a maximum depth of 20 mm. Fibres with a core/cladding diameter of 50/55 μm break during insertion deeper than 7-15 mm into the ST model, whereas thinner fibres (20/25 μm) could be inserted in the model without breakage and in human temporal bones without causing trauma to the inner ear structures. The insertion forces of silicone-coated glass fibres are comparable to those measured with conventional cochlear implant (CI) electrodes. As demonstrated in human temporal bones, a minimal traumatic implantation of an optical CI may be considered feasible.

  20. Comparative evaluation of bone marrow cells morpho-functional activity in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors of the first and second generation

    Directory of Open Access Journals (Sweden)

    I. O. Zhaleyko

    2014-07-01

    Full Text Available The efficiency of using the culture techniques of research for monitoring the patient’s response to the treatment by tyrosine kinase inhibitors of the first and second generation is shown. Thus, the functional activity of bone marrow cells in patients having the optimal treatment response to inhibitors of tyrosine kinases was significantly lower compared with patients with the acquired resistance to the drug, and patients who had CML diagnosed for first time. Furthermore, for patients with the optimal response to the nilotinib therapy, numbers of colonies in semi-solid agar in vitro was lower, than in patients with the optimal response to imatinib. When the leukaemic cell clone becomes resistant to tyrosine kinase inhibitors, the prevalence of early cells of granulocyte-macrophage hematopoietic stem cells is observed in CFU culture which can be an important prognostic factor for choosing the appropriate treatment strategy.

  1. Bone Marrow Chimeras and c-fms Conditional Ablation (Mafia) Mice Reveal an Essential Role for Resident Myeloid Cells in Lipopolysaccharide/TLR4-Induced Corneal Inflammation1

    Science.gov (United States)

    Chinnery, Holly R.; Carlson, Eric C.; Sun, Yan; Lin, Michelle; Burnett, Sandra H.; Perez, Victor L.; McMenamin, Paul G.; Pearlman, Eric

    2012-01-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4−/− mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)+/C57BL/6 or eGFP+/TLR4−/− mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4−/− mice reconstituted with C57BL/6, but not TLR4−/− bone marrow cells donor cells were found to cause infiltration of eGFP+ cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP+ cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1α production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation. PMID:19234168

  2. Bone marrow chimeras and c-fms conditional ablation (Mafia) mice reveal an essential role for resident myeloid cells in lipopolysaccharide/TLR4-induced corneal inflammation.

    Science.gov (United States)

    Chinnery, Holly R; Carlson, Eric C; Sun, Yan; Lin, Michelle; Burnett, Sandra H; Perez, Victor L; McMenamin, Paul G; Pearlman, Eric

    2009-03-01

    The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4(-/-) mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)(+)/C57BL/6 or eGFP(+)/TLR4(-/-) mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4(-/-) mice reconstituted with C57BL/6, but not TLR4(-/-) bone marrow cells donor cells were found to cause infiltration of eGFP(+) cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP(+) cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1alpha production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation.

  3. A new partial temporal bone of a juvenile hominin from the site of Kromdraai B (South Africa).

    Science.gov (United States)

    Braga, José; Thackeray, John Francis; Dumoncel, Jean; Descouens, Didier; Bruxelles, Laurent; Loubes, Jean-Michel; Kahn, Jean-Luc; Stampanoni, Marco; Bam, Lunga; Hoffman, Jakobus; de Beer, Frikkie; Spoor, Fred

    2013-10-01

    The site of Kromdraai B (KB) (Gauteng, South Africa) has yielded a minimum number of nine hominins including the type specimen of Paranthropus robustus (TM 1517), the only partial skeleton of this species known to date. Four of these individuals are juveniles, one is a subadult and four are young adults. They all occur with a macrofaunal assemblage spread across the succession of at least two time periods that occurred in South Africa approximately two million years ago. Here we report on an additional, newly discovered petrous temporal bone of a juvenile hominin, KB 6067. Following the description of KB 6067, we assess its affinities with Australopithecus africanus, P. robustus and early Homo. We discuss its developmental age and consider its association with other juvenile hominin specimens found at Kromdraai B. KB 6067 probably did not reach five years of age and in bony labyrinth morphology it is close to P. robustus, but also to StW 53, a specimen with uncertain affinities. However, its cochlear and oval window size are closer to some hominin specimens from Sterkfontein Member 4 and if KB 6067 is indeed P. robustus this may represent a condition that is evolutionarily less derived than that shown by TM 1517 and other conspecifics sampled so far. The ongoing fieldwork at KB, as well as the petrography and geochemistry of its deposits, will help to determine when the various KB breccias accumulated, and how time may be an important factor underlying the variation seen among KB 6067 and the rest of the fossil hominin sample from this site. Copyright © 2013. Published by Elsevier Ltd.

  4. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    DEFF Research Database (Denmark)

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin

    2012-01-01

    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  5. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  6. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects. Here......-lookup webservices, called HemaExplorer and BloodSpot. These web-services support the aim of making data and analysis of haematopoietic cells from mouse and human accessible for researchers without bioinformatics expertise. Finally, in order to aid the analysis of the very limited number of haematopoietic progenitor...... cells obtainable from bone marrow aspirations, this thesis presents a method developed to investigate transcription factor binding and histone modifications by ChIP-Seq using pico-scale amounts of DNA....

  7. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects......-based gene-lookup webservices, called HemaExplorer and BloodSpot. These web-services support the aim of making data and analysis of haematopoietic cells from mouse and human accessible for researchers without bioinformatics expertise. Finally, in order to aid the analysis of the very limited number...... of haematopoietic progenitor cells obtainable from bone marrow aspirations, this thesis presents a method developed to investigate transcription factor binding and histone modifications by ChIP-Seq using pico-scale amounts of DNA....

  8. Chemotherapy for myeloid malignancy in children with Fanconi anemia.

    Science.gov (United States)

    Mehta, Parinda A; Ileri, Talia; Harris, Richard E; Williams, David A; Mo, Jun; Smolarek, Teresa; Auerbach, Arleen D; Kelly, Patrick; Davies, Stella M

    2007-06-15

    Children with Fanconi anemia (FA) have a markedly increased risk of developing myeloid malignancies. Historically, patients with FA and myeloid malignancy have extremely poor outcomes. There are currently no clinical trials or case series addressing the use of chemotherapy for children with FA, except in the context of preparative regimens for stem cell transplantation (SCT). In this report we describe the toxicity of a chemotherapy approach for patients with FA and myeloid malignancy to achieve cytoreduction prior to SCT. Four patients with FA and myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were treated with chemotherapy (fludarabine 30 mg/m(2) and cytosine arabinoside 300 mg/m(2) each on days 2-4 and granulocyte-colony stimulating factor (G-CSF) 5 microg/kg on days 1-5), termed reduced intensity FLAG prior to SCT. The chemotherapy was well tolerated with expected hematologic toxicity and no measurable toxicity in other organs. Two of the three patients with AML cleared blasts from their bone marrow. Reduction in marrow cellularity was also achieved in one patient with hypercellular MDS. These data indicate that children with FA and myeloid malignancy can tolerate chemotherapy and achieve clearance of disease. It remains unclear whether pre-SCT chemotherapy improves currently poor survival rates for SCT in FA patients with myeloid malignancies and further studies are needed to determine if there is a clinical role for this strategy. (c) 2006 Wiley-Liss, Inc.

  9. The role of natural killer cells in chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Anna Carolyna Araújo Danier

    2011-06-01

    Full Text Available Chronic myeloid leukemia is a neoplasia resulting from a translocation between chromosomes 9 and 22 producing the BCR-ABL hybrid known as the Philadelphia chromosome (Ph. In chronic myeloid leukemia a proliferation of malignant myeloid cells occurs in the bone marrow due to excessive tyrosine kinase activity. In order to maintain homeostasis, natural killer cells, by means of receptors, identify the major histocompatibility complex on the surface of tumor cells and subsequently induce apoptosis. The NKG2D receptor in the natural killer cells recognizes the transmembrane proteins related to major histocompatibility complex class I chain-related genes A and B (MICA and MICB, and it is by the interaction between NKG2D and MICA that natural killer cells exert cytotoxic activity against chronic myeloid leukemia tumor cells. However, in the case of chronic exposure of the NKG2D receptor, the MICA ligand releases soluble proteins called sMICA from the tumor cell surface, which negatively modulate NKG2D and enable the tumor cells to avoid lysis mediated by the natural killer cells. Blocking the formation of sMICA may be an important antitumor strategy. Treatment using tyrosine kinase inhibitors induces modulation of NKG2DL expression, which could favor the activity of the natural killer cells. However this mechanism has not been fully described in chronic myeloid leukemia. In the present study, we analyze the role of natural killer cells to reduce proliferation and in the cellular death of tumor cells in chronic myeloid leukemia.

  10. Methimazole Induced Total Myeloid Aplasia with Delayed Recovery Despite Granulocyte Colony Stimulating Factor (G-CSF): Marrow Progenitor Recovery Kinetics.

    Science.gov (United States)

    Sarker, Tania; Özgönenel, Bülent; Gadgeel, Manisha; Buck, Steven; Adhikari, Amita; Ravindranath, Yaddanapudi

    2016-06-01

    An eighteen-year-old female with Graves thyrotoxicosis presented with methimazole-induced agranulocytosis and total myeloid aplasia. The bone marrow at presentation showed complete absence of myeloid precursors and striking plasmacytosis. 16 days later, myeloid precursors were still absent morphologically; however bone marrow flow cytometry and cell culture detected an improvement in myelogenesis, which was soon followed by clinical recovery of agranulocytosis. Neutrophil recovery was delayed until day 22 after cessation of methimazole despite G-CSF use, consistent with a direct toxic effect on committed myeloid cells. Our findings suggest that cell culture and flow cytometric evaluation of bone marrow myeloid progenitors can be used as a guide to anticipate neutrophil recovery.

  11. Presbycusis: a human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature.

    Science.gov (United States)

    Nelson, Erik G; Hinojosa, Raul

    2006-09-01

    The purpose of this retrospective case review was to identify patterns of cochlear element degeneration in individuals with presbycusis exhibiting downward sloping audiometric patterns of hearing loss and to correlate these findings with those reported in the literature to clarify conflicting concepts regarding the association between hearing loss and morphologic abnormalities. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for downward-sloping audiometric thresholds. Twenty-one temporal bones that met these criteria were identified and compared with 10 temporal bones from individuals with normal hearing. The stria vascularis volumes, spiral ganglion cell populations, inner hair cells, and outer hair cells were quantitatively evaluated. The relationship between the severity of hearing loss and the degeneration of cochlear elements was analyzed using univariate linear regression models. Outer hair cell loss and ganglion cell loss was observed in all individuals with presbycusis. Inner hair cell loss was observed in 18 of the 21 individuals with presbycusis and stria vascularis loss was observed in 10 of the 21 individuals with presbycusis. The extent of degeneration of all four of the cochlear elements evaluated was highly associated with the severity of hearing loss based on audiometric thresholds at 8,000 Hz and the pure-tone average at 500, 1,000, and 2,000 Hz. The extent of ganglion cell degeneration was associated with the slope of the audiogram. Individuals with downward-sloping audiometric patterns of presbycusis exhibit degeneration of the stria vascularis, spiral ganglion cells, inner hair cells, and outer hair cells that is associated with the severity of hearing loss. This association has not been previously reported in studies that did not use quantitative methodologies for evaluating the cochlear elements and strict audiometric criteria for selecting cases.

  12. MYC oncogene in myeloid neoplasias.

    Science.gov (United States)

    Delgado, M Dolores; Albajar, Marta; Gomez-Casares, M Teresa; Batlle, Ana; León, Javier

    2013-02-01

    MYC is a transcription factor that regulates many critical genes for cell proliferation, differentiation, and biomass accumulation. MYC is one of the most prevalent oncogenes found to be altered in human cancer, being deregulated in about 50 % of tumors. Although MYC deregulation has been more frequently associated to lymphoma and lymphoblastic leukemia than to myeloid malignancies, a body of evidence has been gathered showing that MYC plays a relevant role in malignancies derived from the myeloid compartment. The myeloid leukemogenic activity of MYC has been demonstrated in different murine models. Not surprisingly, MYC has been found to be amplified or/and deregulated in the three major types of myeloid neoplasms: acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, including chronic myeloid leukemia. Here, we review the recent literature describing the involvement of MYC in myeloid tumors.

  13. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-10-24

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  14. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study.

    Science.gov (United States)

    Rogers, Heesun J; Vardiman, James W; Anastasi, John; Raca, Gordana; Savage, Natasha M; Cherry, Athena M; Arber, Daniel; Moore, Erika; Morrissette, Jennifer J D; Bagg, Adam; Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio; Lin, Pei; Wang, Sa A; Bueso-Ramos, Carlos E; Foucar, Kathryn; Hasserjian, Robert P; Tiu, Ramon V; Karafa, Matthew; Hsi, Eric D

    2014-05-01

    Acute myeloid leukemia and myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) have a poor prognosis. Indeed, the inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has been recognized as a poor risk karyotype in the revised International Prognostic Scoring System. However, inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is not among the cytogenetic abnormalities pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast percentage in the 2008 WHO classification. This multicenter study evaluated the clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and applied the revised International Prognostic Scoring System to myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). A total of 103 inv(3)(q21q26.2)/t(3;3)(q21;q26.2) patients were reviewed and had a median bone marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute myeloid leukemia (n=63) (Pmyeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three percent of patients died (median follow up 7.9 months). Complex karyotype, monosomal karyotype and dysgranulopoiesis (but not blast percentage) were independent poor prognostic factors in the entire cohort on multivariable analysis. The revised International Prognostic Scoring System better reflected overall survival of inv(3)(q21q26.2)/t(3;3)(q21;q26.2) than the International Prognostic Scoring System but did not fully reflect the generally dismal prognosis. Our data support consideration of myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) as an acute myeloid leukemia with recurrent genetic abnormalities, irrespective of blast percentage.

  15. Chronic Myeloid Leukemia

    Science.gov (United States)

    ... around the eyes {{ Nausea and vomiting {{ Muscle cramps {{ Diarrhea {{ Rash {{ Chronic fatigue {{ Possible cardiac effects (see page 22 for ... be seen by a doctor who specializes in pediatric leukemia. See the free LLS ... Myeloid Leukemia I page 33 Fertility, Pregnancy and ...

  16. Histogenesis of the myeloid system in geese.

    Science.gov (United States)

    Glavits, R; Ratz, F; Varga, Z; Stipkovits, L; Molnar, E

    1987-01-01

    Using light- and electron-microscopy the location in organs and the time-course of appearance of cells of the myeloid system was studied in goose embryos and goslings. Large numbers of cell forms representing different stages of granulocytopoiesis were found between 15 and 28 days of incubation in the mesenchyma of the kidney and in the reticular tissue of the spleen, but not in the liver and other organs. Thus, before the haemocytopoietic activity of the bone marrow, an activity typical of adult birds, develops, in geese embryonic extra-medullary granulocytopoiesis is characterised by a renal-lienal stage.

  17. Right-to-left-shunt detected by c-TCD using the orbital window in comparison with temporal bone windows.

    Science.gov (United States)

    Kobayashi, Kazuto; Kimura, Kazumi; Iguchi, Yasuyuki; Sakai, Kenichirou; Aoki, Junya; Iwanaga, Takeshi; Shibazaki, Kensaku

    2012-01-01

    There have been some reports on right-to-left shunt as a cause of cryptogenic stroke. Although contrast transcranial Doppler (c-TCD) can detect RLS, an insufficient temporal window has occasionally restricted its applicability. Thus, we compared the rates of detecting RLS among temporal windows for the middle cerebral arteries (MCAs) and the orbital window for the internal carotid artery (ICA) on c-TCD. We used c-TCD to detect RLS in patients with suspected ischemic stroke. We enrolled patients who had both sufficient bilateral temporal windows for MCAs and a right orbital window for ICA and performed c-TCD using all three windows simultaneously. We enrolled 106 consecutive patients and identified microembolic signals (MES) in 30 (28%) of them. Among these 30 patients, 15 had MES from all 3 windows. When these 30 patients were defined as being positive for RLS, the rates of detection were 67%, 73%, and 80% from the right temporal, left temporal, and right orbital windows, respectively (P= .795). The right orbital window as well as the temporal window for c-TCD could detect RLS. Insonation from the orbital window should be useful for patients who lack temporal windows. Copyright © 2010 by the American Society of Neuroimaging.

  18. Definition of Metrics to Evaluate Cochlear Array Insertion Forces Performed with Forceps, Insertion Tool, or Motorized Tool in Temporal Bone Specimens

    Directory of Open Access Journals (Sweden)

    Yann Nguyen

    2014-01-01

    Full Text Available Introduction. In order to achieve a minimal trauma to the inner ear structures during array insertion, it would be suitable to control insertion forces. The aim of this work was to compare the insertion forces of an array insertion into anatomical specimens with three different insertion techniques: with forceps, with a commercial tool, and with a motorized tool. Materials and Methods. Temporal bones have been mounted on a 6-axis force sensor to record insertion forces. Each temporal bone has been inserted, with a lateral wall electrode array, in random order, with each of the 3 techniques. Results. Forceps manual and commercial tool insertions generated multiple jerks during whole length insertion related to fits and starts. On the contrary, insertion force with the motorized tool only rose at the end of the insertion. Overall force momentum was 1.16 ± 0.505 N (mean ± SD, n=10, 1.337 ± 0.408 N (n=8, and 1.573 ± 0.764 N (n=8 for manual insertion with forceps and commercial and motorized tools, respectively. Conclusion. Considering force momentum, no difference between the three techniques was observed. Nevertheless, a more predictable force profile could be observed with the motorized tool with a smoother rise of insertion forces.

  19. Isolated intracranial myeloid sarcoma occurring as relapse in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Geetha Narayanan

    2017-01-01

    Full Text Available Myeloid sarcoma (MS or chloroma is a rare extramedullary tumor composed of extramedullary proliferation of blasts of granulocytic, monocytic, erythroid, or megakaryocytic lineage occurring at sites outside the bone marrow. MS occurs in 2%–8% of patients with acute myeloid leukemia (AML, sometimes it occurs as the presenting manifestation of relapse in a patient in remission. We describe the case of a young male with AML in remission for 6 years presenting with central nervous system symptoms. Magnetic resonance imaging showed an extra-axial altered intensity lesion in the parasagittal parietal region, infiltrating anterosuperiorly into anterior falx, and posterosuperior aspect of the superior sagittal sinus. A biopsy from the lesion was diagnostic of MS which was positive for myeloperoxidase. He did not have any other sites of disease. He has received chemotherapy with FLAG ( Fludarabine, Cytosine arabinoside followed by cranial irradiation and is in complete remission.

  20. Genetics Home Reference: chronic myeloid leukemia

    Science.gov (United States)

    ... Home Health Conditions Chronic myeloid leukemia Chronic myeloid leukemia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Chronic myeloid leukemia is a slow-growing cancer of the blood- ...

  1. Diagnostic work-up of acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Sohani, Aliyah R; Bhargava, Parul; Nardi, Valentina

    2017-03-01

    Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment. © 2017 Wiley Periodicals, Inc.

  2. Hiperpneumatização do processo mastóide do osso temporal: relato de caso = Hyperpneumatization of mastoid process of temporal bone: report of a case

    Directory of Open Access Journals (Sweden)

    Fagundes, Demian Moreira

    2006-01-01

    Full Text Available O presente trabalho apresenta um caso de hiperpneumatização do osso temporal detectado em uma paciente do sexo feminino, 23 anos, saudável, que compareceu a clínica de Radiologia para um exame radiográfico de rotina. A radiografia panorâmica revelou imagens radiolúcidas bilaterais envolvendo a região correspondente às eminências articulares. Exames tomográficos convencional e computadorizado foram solicitados, adicionalmente, com objetivo de confirmação diagnóstica da hiperpneumatização. Um ano após o exame inicial, foi realizada nova tomada radiográfica panorâmica, que revelou estabilidade dimensional das imagens

  3. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, D.M.J.; Mathura, K.R.; Lindeboom, J.A.H.; Ramsoekh, D.; Lindeboom, R.; Ince, C.

    2009-01-01

    Aims: To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods: A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  4. The temporal course of mucoperiosteal flap revascularization at guided bone regeneration-treated implant sites: a pilot study

    NARCIS (Netherlands)

    Milstein, Dan M. J.; Mathura, Keshen R.; Lindeboom, Jerôme A. H.; Ramsoekh, Dewkoemar; Lindeboom, Robert; Ince, Can

    2009-01-01

    P>Aims To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites. Material and Methods A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging

  5. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects...... model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed...... genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query...

  6. Current perspective in agnogenic myeloid metaplasia.

    Science.gov (United States)

    Tefferi, A; Silverstein, M N

    1996-09-01

    Agnogenic myeloid metaplasia (AMM) carries the worst prognosis among the chronic myeloproliferative disorders. Substantial bone marrow fibrosis, extramedullary hematopoiesis, anemia and hepatosplenomegaly are the characteristic features of the disease. AMM is currently incurable and the available treatment agents are mostly palliative and do not prolong life. Two pathogenetic processes are responsible for the impaired hematopoiesis and the clinical manifestations. The primary disease process is a clonal hematopoietic stem cell disorder which results in chronic myeloproliferation and atypical megakaryocytic hyperplasia. The secondary process of bone marrow fibrosis is the result of non-clonal fibroblastic proliferation and hyperactivity induced by growth factors abnormally shed from clonal megakaryocytes. Therefore, experimental treatment strategies may be directed towards either one or both of these disease processes. This report summarizes the current management options and new therapeutic endeavours.

  7. Acute Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  8. Chronic Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  9. CT and MRI characteristica of tumours of the temporal bone and the cerebello-pontine angle; CT und MRT tumoroeser Veraenderungen des Schlaefenbeins

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Henk, C.B.; Dirisamer, A.; Czerny, C. [Abteilung fuer Osteologie/Universitaetsklinik Radiodiagnostik, Wien (Austria); Gstoettner, W. [Universitaetsklinik Hals-Nasen-Ohren-Heilkunde, Frankfurt/Main (Germany)

    2003-03-01

    Tumours lesions of the temporal bone and of the cerebello-pontine angle are rare.This tumours can be separated into benign and malignant lesions. In this paper the CT and MRI characteristica of tumours of the temporal bone and the cerebello-pontane angle will be demonstrated. High resolution CT (HRCT) as usually performed in the axial plane are using a high resolution bone window level setting, coronal planes are the reconstructed from the axial data set or will be obtained directly. With the MRI FLAIR sequence in the axial plane the whole brain will be scanned either to depict or exclude a tumour invasion into the brain. After this,T2-weighted fast spin echo sequences or fatsuppressed inversion recovery sequences in high resolution technique in the axial plane will be obtained from the temporal bone and axial T1-weighted spinecho sequences before and after the intravenous application of contrast material will be obtained of this region. Finally T1-weighted spinecho sequences in high resolution technique with fatsuppression after the intravenous application of contrast material will be performed in the coronal plane. HRCT and MRI are both used to depict the most exact tumorous borders. HRCT excellently depicts the osseous changes for example exostosis of the external auditory canal, while also with HRCT osseous changes maybe characterized into more benign or malignant types. MRI has a very high soft tissue contrast and may therefore either characterize vascular space-occupying lesions for example glomus jugulare tumours or may differentiate between more benign or malignant lesions. In conclusion HRCT and MRI of the temporal bone are excellent methods to depict and mostly characterize tumour lesions and can help to differentiate between benign and malignant lesion. These imaging methods shall be used complementary and may have a great impact for the therapeutic planning. (orig.) [German] Tumoroese Veraenderungen des Schlaefenbeins und Kleinhirnbrueckenwinkels sind

  10. Visualization of subtle temporal bone structures. Comparison of cone beam CT and MDCT; Darstellung subtiler Schlaefenbeinstrukturen. In-vivo-Vergleich digitale Volumentomographie vs. Multidetektor-CT

    Energy Technology Data Exchange (ETDEWEB)

    Pein, M.K.; Plontke, S.K. [Universitaetsklinikum Halle (Saale), Universitaetsklinik und Poliklinik fuer HNO-Heilkunde, Kopf- und Halschirurgie, Halle (Saale) (Germany); Brandt, S.; Koesling, S. [Universitaetsklinikum Halle (Saale), Universitaetsklinik und Poliklinik fuer Diagnostische Radiologie, Halle (Saale) (Germany)

    2014-03-15

    The purpose of this study was to compare the visualization of subtle, non-pathological temporal bone structures on cone beam computed tomography (CBCT) and multi-detector computed tomography (MDCT) in vivo. Temporal bone studies of images from 38 patients archived in the picture archiving and communication system (PACS) were analyzed (slice thickness MDCT 0.6 mm and CBCT 0.125 mm) of which 23 were imaged by MDCT and 15 by CBCT using optimized standard protocols. Inclusion criteria were normal radiological findings, absence of previous surgery and anatomical variants. Images were evaluated blind by three trained observers. Using a five-point scale the visualization of ten subtle structures of the temporal bone was analyzed. Subtle middle ear structures showed a tendency to be more easily distinguishable by CBCT with significantly better visualization of the tendon of the stapedius muscle and the crura of the stapes on CBCT (p = 0.003 and p = 0.033, respectively). In contrast, inner ear components, such as the osseus spiral lamina and the modiolus tended to be better detectable on MDCT, showing significant differences for the osseous spiral lamina (p = 0.001). The interrater reliability was 0.73 (Cohen's kappa coefficient) and intraobserver reliability was 0.89. The use of CBCT and MDCT allows equivalent and excellent imaging results if optimized protocols are chosen. With both imaging techniques subtle temporal bone structures could be visualized with a similar degree of definition. In vivo differences do not seem to be as large as suggested in several previous studies. (orig.) [German] Vergleich der Identifizierbarkeit subtiler Schlaefenbeinstrukturen in der digitalen Volumentomographie (DVT) und Multidetektor-CT (MDCT) in vivo. Analysiert wurden 38 im PACS (Picture Archiving and Communication System) duennschichtig gespeicherte Schlaefenbeinuntersuchungen (23 MDCTs, Schichtdicke 0,6 mm sowie 15 DVTs, Schichtdicke 0,125 mm). Einschlusskriterium war eine

  11. Trauma dos ossos temporais e suas complicações: aspectos na tomografia computadorizada Temporal bone trauma and complications: computed tomography findings

    Directory of Open Access Journals (Sweden)

    Ana Maria Doffémond Costa

    2013-04-01

    Full Text Available A maioria das fraturas dos ossos temporais resulta de traumas cranianos bruscos, de alta energia, estando muitas vezes relacionadas a outras fraturas cranianas ou a politraumatismo. As fraturas e os deslocamentos da cadeia ossicular, na orelha média, representam umas das principais complicações das injúrias nos ossos temporais e, por isso, serão abordadas de maneira mais profunda neste artigo. Os outros tipos de injúrias englobam as fraturas labirínticas, fístula dural, paralisia facial e extensão da linha de fratura ao canal carotídeo. A tomografia computadorizada tem papel fundamental na avaliação inicial dos pacientes politraumatizados, pois é capaz de identificar injúrias em importantes estruturas que podem causar graves complicações, como perda auditiva de condução ou neurossensorial, tonturas e disfunções do equilíbrio, fístulas perilinfáticas, paralisia do nervo facial, lesões vasculares, entre outras.Most temporal bone fractures result from high-energy blunt head trauma, and are frequently related to other skull fractures or to polytrauma. Fractures and displacements of ossicular chain in the middle ear represent some of the main complications of temporal bone injury, and hence they will be more deeply approached in the present article. Other types of injuries include labyrinthine fractures, dural fistula, facial nerve paralysis and extension into the carotid canal. Computed tomography plays a fundamental role in the initial evaluation of polytrauma patients, as it can help to identify important structural injuries that may lead to severe complications such as sensorineural hearing loss, conductive hearing loss, dizziness and balance dysfunction, perilymphatic fistulas, facial nerve paralysis, vascular injury and others.

  12. Image quality improvement in three-dimensional time-of-flight magnetic resonance angiography using the subtraction method for brain and temporal bone diseases.

    Science.gov (United States)

    Peng, Shu-Hui; Shen, Chao-Yu; Wu, Ming-Chi; Lin, Yue-Der; Huang, Chun-Huang; Kang, Ruei-Jin; Tyan, Yeu-Sheng; Tsao, Teng-Fu

    2013-08-01

    Time-of-flight (TOF) magnetic resonance (MR) angiography is based on flow-related enhancement using the T1-weighted spoiled gradient echo, or the fast low-angle shot gradient echo sequence. However, materials with short T1 relaxation times may show hyperintensity signals and contaminate the TOF images. The objective of our study was to determine whether subtraction three-dimensional (3D) TOF MR angiography improves image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. During the 12-month study period, patients who had masses with short T1 relaxation times noted on precontrast T1-weighted brain MR images and 24 healthy volunteers were scanned using conventional and subtraction 3D TOF MR angiography. The qualitative evaluation of each MR angiogram was based on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and scores in three categories, namely, (1) presence of misregistration artifacts, (2) ability to display arterial anatomy selectively (without contamination by materials with short T1 relaxation times), and (3) arterial flow-related enhancement. We included 12 patients with intracranial hematomas, brain tumors, or middle-ear cholesterol granulomas. Subtraction 3D TOF MR angiography yielded higher CNRs between the area of the basilar artery (BA) and normal-appearing parenchyma of the brain and lower SNRs in the area of the BA compared with the conventional technique (147.7 ± 77.6 vs. 130.6 ± 54.2, p angiography did not deteriorate image quality with misregistration artifacts and showed a better selective display of arteries (p angiography is more appropriate than the conventional method in improving the image quality in brain and temporal bone diseases with unwanted contaminations with short T1 relaxation times. Copyright © 2013. Published by Elsevier B.V.

  13. TPO/Mpl Studies in Agnogenic Myeloid Metaplasia

    OpenAIRE

    Novetsky Allan D; Hashmi Gazala; Suppiah Kathir; Hemavathy Kirugaval C; Wang Jen C

    2005-01-01

    Abstract Background Agnogenic myeloid metaplasia (AMM) is one of the Philadelphia chromosome negative myeloproliferative disorder and is diagnosed by hyperplasia of atypical megakaryocytes, hepatosplenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Fibrosis is considered to be a secondary consequence of enhanced levels of fibrogenic growth factors such as TGF β1, bFGF and PDGF produced by enhanced numbers of megakaryocytes, while the primary cause is considered to be the enhan...

  14. Acute Myeloid Leukaemia Presenting as Gaze Palsy

    Directory of Open Access Journals (Sweden)

    Evripidis Sykakis

    2011-11-01

    Full Text Available The most frequent initial ocular manifestation of acute myeloid leukaemia (AML is retinal involvement. Here, we report an unusual case of AML associated with a pontine chloroma presenting with gaze palsy as the initial symptom. A 77-year-old Caucasian man presented to the Eye Casualty complaining of a one-day history of blurred vision. On examination, his face was turned to the left, both eyes were fixed in dextroversion and the patient demonstrated left gaze palsy associated with left motor neurone VII palsy. Baseline blood investigations revealed leucocytosis with 60% circulating myeloblasts. A bone marrow biopsy confirmed the diagnosis of myelomonocytic leukaemia. A CT scan showed a well-circumscribed lesion in the dorsal pons, most likely representing a chloroma. Chloromas or myeloblastomas related to AML are localised extramedullary tumours composed of leukaemic myeloid cells. Chloromas may be present at the time of the initial diagnosis of leukaemia or may precede the diagnosis by 1 month to 2 years; however, their occurrence in the central nervous system is rare, comprising 1–6% of all chloromas. This case illustrates the many different ways that AML can manifest itself in the eyes, and ophthalmologists should be aware of the great variety of presenting symptoms in undiagnosed AML.

  15. Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression.

    Science.gov (United States)

    Dai, Jun; Kumbhare, Ajinkya; Youssef, Dima; Yao, Zhi Q; McCall, Charles E; El Gazzar, Mohamed

    2017-11-01

    Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs. Moreover, C/EBPβ-reconstituted myeloid cells expressed IL-10 and reduced T cell proliferation and function, similar to control MDSCs that express C/EBPβ. Exogenous expression of miR-21 and miR-181b in the C/EBPβ-deficient myeloid progenitors from septic mice produced similar results. Notably, NFI-A-dependent transactivation of NF-kB MDSC generating pathway was reversed in the C/EBPβ-deficient myeloid progenitors from septic mice. Together, these results support that decreasing C/EBPβ expression prevents MDSC generation and decreases immunosuppression in septic mice, providing a target for sepsis treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Chronic myeloid leukemia].

    Science.gov (United States)

    Usui, Noriko

    2014-06-01

    More than 10 years have passed since imatinib as a first developed BCR-ABL tyrosine kinase inhibitor (TKI) introduced in treatment of patients with chronic myeloid leukemia (CML). In globally, there are tremendous numbers of patients on imatinib therapy. Based upon randomized trials comparing second generation TKIs such as dasatinib and nilotinib versus imatinib, both TKIs produce faster and deeper response than imatinib and they can be selected as first-line therapy for newly diagnosed chronic phase of CML (CP-CML) as imatinib. Bosutinib is a potent for imatinib resistant/intolerant CP-CML and can be used as second or third-line therapy. Ponatinib is the only clinically available TKI that has activity against the T315 mutation that is resistant to all other TKIs. Currently, a choice among these potent TKIs should take into consideration the drug side effect profiles and the patient's comorbidities.

  17. Pediatric acute myeloid leukemia with genetic alterations.

    Science.gov (United States)

    Shimada, Akira

    2017-01-01

    Annually, it is estimated that approximately 150-200 children aged 0-16 years are diagnosed with acute myeloid leukemia (AML). In Japan, clinical studies with ANLL91, AML99, CCLSG-AML9805, and JPLSG-AML05 protocols were performed historically, and the risk stratification with a combination of chemotherapy and hematopoietic stem cell transplantation resulted in the improvement of clinical outcomes. Regarding the onset of pediatric AML at the molecular level, mutations in FLT3-ITD or KIT (Class I mutation) showed a poor prognosis, but the ratio of mutations in Class III-V genes was smaller than that in adult AML. In contrast, several pediatric AML cases are complicated due to chromosome fragility syndrome or congenital bone marrow failure syndrome. To improve the clinical outcomes, clinical application of next generation sequencing may allow for personalized therapy in each patient in the future.

  18. Sensorineural hearing loss: there is no correlation with isolated dysplasia of the lateral semi-circular canal on temporal bone CT

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Koji; Yoshiura, Takashi; Hiwatashi, Akio; Tuvshinjargal, Dashjamts; Kamano, Hironori; Honda, Hiroshi (Dept. of Clinical Radiology, Graduate School of Medical Sciences, Kyushu Univ. Fukuoka (Japan)), email: tyoshiu@radiol.med.kyushu-u.ac.jp; Inoguchi, Takashi (Dept. of Otolaryngology, Kitakyushu Municipal Medical Center, Kitakyushu (Japan))

    2011-02-15

    Background: Inner ear malformations may cause sensorineural hearing loss (SNHL). However, the correlation between the small lateral semi-circular canal (LSCC) and SNHL is controversial. Purpose: To determine whether there is a correlation between the two using CT-based measurement. Material and Methods: We retrospectively reviewed the high-resolution CT images of the temporal bone obtained from consecutive patients. A total 136 ears of 68 patients (25 men and 43 women; age range 20-85 years, mean 49.8 years) were included in this study. Patients who were clinically suspected to have otosclerosis were also excluded. Two radiologists independently measured the width and cross-sectional area of the bony island of LSCC. We evaluated the correlation between LSCC bone island width or cross-sectional area and hearing level in all cases using Pearson correlation co-efficients. In addition, we compared hearing levels among the patient group with normal-sized LSCC (>=mean-SD), small LSCC (0.05). No significant difference in hearing levels were found among groups of the normal-sized, small and very small LSCC (P>0.05). Conclusion: We conclude that there is no correlation between isolated small LSCC and SNHL

  19. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

  20. A Case of Acute Myeloid Leukemia (FAB M2 with Inversion 16 Who Presented with Pelvic Myeloid Sarcoma

    Directory of Open Access Journals (Sweden)

    Mustafa Çakan

    2014-01-01

    Full Text Available Acute leukemias are the most common childhood cancer in all age groups. Acute myeloid leukemias (AML constitute about 15–20% of acute leukemias. Fatigability, pallor, fever, and bleeding are the most common presenting symptoms of AML. Hepatosplenomegaly and lymphadenopathy are commonly encountered during physical examination. In rare instances eruptions due to skin involvement and localized tumor masses (myeloid sarcoma may be found. Myeloid sarcoma is especially seen in AML-M2 subtype. By cytogenetic analysis, in AML-M2 subtype t(8;21 is often seen and it is more probable to find inversion 16 in AML-M4Eos subtype. Herein, we present a 15-year-old girl whose initial symptom was abdominal pain for three days and her pathological sign was a large abdominal mass which was verified by imaging studies and diagnosed as myeloid sarcoma by biopsy. On bone marrow examination, she had diagnosis of AML-M2 and by cytogenetic analysis inversion 16 was positive. She was treated with AML-BFM 2004 protocol and she is being followed up in remission on her ninth month of the maintenance therapy.

  1. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

    2016-06-10

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  2. Production and differentiation of myeloid cells driven by proinflammatory cytokines in response to acute pneumovirus infection in mice.

    Science.gov (United States)

    Maltby, Steven; Hansbro, Nicole G; Tay, Hock L; Stewart, Jessica; Plank, Maximilian; Donges, Bianca; Rosenberg, Helene F; Foster, Paul S

    2014-10-15

    Respiratory virus infections are often pathogenic, driving severe inflammatory responses. Most research has focused on localized effects of virus infection and inflammation. However, infection can induce broad-reaching, systemic changes that are only beginning to be characterized. In this study, we assessed the impact of acute pneumovirus infection in C57BL/6 mice on bone marrow hematopoiesis. We hypothesized that inflammatory cytokine production in the lung upregulates myeloid cell production in response to infection. We demonstrate a dramatic increase in the percentages of circulating myeloid cells, which is associated with pronounced elevations in inflammatory cytokines in serum (IFN-γ, IL-6, CCL2), bone (TNF-α), and lung tissue (TNF-α, IFN-γ, IL-6, CCL2, CCL3, G-CSF, osteopontin). Increased hematopoietic stem/progenitor cell percentages (Lineage(-)Sca-I(+)c-kit(+)) were also detected in the bone marrow. This increase was accompanied by an increase in the proportions of committed myeloid progenitors, as determined by colony-forming unit assays. However, no functional changes in hematopoietic stem cells occurred, as assessed by competitive bone marrow reconstitution. Systemic administration of neutralizing Abs to either TNF-α or IFN-γ blocked expansion of myeloid progenitors in the bone marrow and also limited virus clearance from the lung. These findings suggest that acute inflammatory cytokines drive production and differentiation of myeloid cells in the bone marrow by inducing differentiation of committed myeloid progenitors. Our findings provide insight into the mechanisms via which innate immune responses regulate myeloid cell progenitor numbers in response to acute respiratory virus infection. Copyright © 2014 by The American Association of Immunologists, Inc.

  3. Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): sine qua non radiology-pathology and the University of Texas MD Anderson Cancer Center experience.

    Science.gov (United States)

    Bell, Diana; Gidley, Paul; Levine, Nicholas; Fuller, Gregory N

    2011-04-01

    Endolymphatic sac tumor (ELST) is a rare lesion of the skull base for which the origin has recently been ascertained. The endolymphatic sac is derived from neuroectoderm and is located subjacent to the posteromedial surface of the temporal bone. Patients characteristically present with hearing loss, tinnitus, and vertigo; facial nerve paralysis occurs less commonly. An indolent clinical course and long-standing symptom history is typical. Endolymphatic sac tumors are known to occur more frequently in patients with von Hippel-Lindau disease, but this is not a prerequisite for diagnosis because sporadic occurrence is common. Morphologically, all of the ELSTs showed a papillary and glandular architecture. The papillary and glandular structures were lined by a single layer of flattened cuboidal-to-columnar cells that were variably ciliated. Surgery is the treatment of choice for small ELST. Remission may last for years, but local recurrence after surgery, likely secondary to incomplete resection, can occur. Radiotherapy has a 50% cure rate with large or residual tumors. Endolymphatic sac tumor is a rare tumor that can easily be confused with other papillary lesions on histopathologic grounds, with significant treatment implications. Precise preoperative anatomic localization and computed tomography and magnetic resonance imaging feature interpretation play a paramount role in achieving an accurate final diagnosis. Published by Elsevier Inc.

  4. Sensing and three-dimensional imaging of cochlea and surrounding temporal bone using swept source high-speed optical coherence tomography

    Science.gov (United States)

    Zhao, Mingtao; Chien, Wade W.; Taylor, Russ; Iordachita, Iulian; Huang, Yong; Niparko, John; Kang, Jin U.

    2013-03-01

    We describe a novel dual-functional optical coherence tomography (OCT) system with both a fiber probe using a sapphire ball lens for cross-sectional imaging and sensing, and a 3-D bulk scanner for 3-D OCT imaging. A theoretical sensitivity model for Common Path (CP)-OCT was proposed to assess its optimal performance based on an unbalanced photodetector configuration. A probe design with working distances (WD) 415μm and lateral resolution 11 μm was implemented with sensitivity up to 88dB. To achieve high-speed data processing and real-time three-dimensional visualization, we use graphics processing unit (GPU) based real-time signal processing and visualization to boost the computing performance of swept source optical coherence tomography. Both the basal turn and facial nerve bundles inside the cadaveric human cochlea temporal bone can be clearly identified and 3D images can be rendered with the OCT system, which was integrated with a flexible robotic arm for robotically assisted microsurgery.

  5. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kazuya Takahashi

    2007-04-01

    Full Text Available BACKGROUND: In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS, are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2, an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. METHODS AND FINDINGS: EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS. CONCLUSIONS: Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.

  6. Acute Myeloid Leukemia (AML) (For Parents)

    Science.gov (United States)

    ... the Flu Vaccine? Eating Disorders Arrhythmias Acute Myeloid Leukemia (AML) KidsHealth > For Parents > Acute Myeloid Leukemia (AML) ... Treatment Coping en español Leucemia mieloide aguda About Leukemia Leukemia is a type of cancer that affects ...

  7. Treatment Options for Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  8. Stages of Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  9. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  10. General Information about Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  11. New Treatment Approved for Acute Myeloid Leukemia

    Science.gov (United States)

    ... 167596.html New Treatment Approved for Acute Myeloid Leukemia Vyxeos combines two previously approved drugs To use ... for certain high-risk types of acute myeloid leukemia (AML). AML is an aggressive blood cancer that ...

  12. Neurological Complications Of Chronic Myeloid Leukaemia: Any ...

    African Journals Online (AJOL)

    , of the neurological deficits complicating chronic myeloid leukaemia. Method: Using patients\\' case folders and haematological malignancy register all cases of chronic myeloid leukaemia seen in Jos University Teaching Hospital between July ...

  13. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  14. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-11-08

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  15. A study of KIT activating mutations in acute myeloid leukemia M0 ...

    African Journals Online (AJOL)

    Acute Myeloid Leukemia (AML)-M0 is a cancer of blood-forming cells in the bone marrow. KIT gene is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. Mutations of KIT receptor ...

  16. A study of KIT activating mutations in acute myeloid leukemia M0 ...

    African Journals Online (AJOL)

    Syed Rizwan Hussain

    2012-03-04

    Mar 4, 2012 ... Abstract Acute Myeloid Leukemia (AML)-M0 is a cancer of blood-forming cells in the bone mar- row. KIT gene is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival.

  17. One month priapism in a 39 year old man with chronic myeloid ...

    African Journals Online (AJOL)

    There is a high index of suspicion of chronic myeloid leukemia in a non sickle cell adult patient presenting with priapism. ... investigations for diagnosis eg peripheral and bone marrow aspiration blood film and BCR- ABL quantification; the ancilliary investigations ; liver function test, serum electrolyte, urea and creatinine etc.

  18. Modeling of Chronic Myeloid Leukemia : An Overview of In Vivo Murine and Human Xenograft Models

    NARCIS (Netherlands)

    Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone

  19. Establishing long-term cultures with self-renewing acute myeloid leukemia stem/progenitor cells

    NARCIS (Netherlands)

    van Gosliga, Djoke; Schepers, Hein; Rizo, Aleksandra; van der Kolk, Dorina; Vellenga, Edo; Schuringa, Jan Jacob

    2007-01-01

    Objective. With the emergence of the concept of the leukemia stem cell, assays to study them remain pivotal in understanding (leukemic) stem cell biology. Methods. We have cultured acute myeloid leukemia CD34(+) cells on bone marrow stroma. Long-term expansion was monitored and self-renewal was

  20. Osteodistrofias do Osso Temporal: Revisão dos Conceitos Atuais, Manifestações Clínicas e Opções Terapêuticas Osteodysplasia of the Temporal Bone: Up-date Concepts, Clinical Presentations and Therapeutic Options

    Directory of Open Access Journals (Sweden)

    Oswaldo Laércio M. Cruz

    Full Text Available Sob a designação de osteodistrofias do osso temporal, podemos encontrar uma série de doenças que apresentam em comum a desorganização da arquitetura ou da composição do tecido ósseo. A otospongiose é, com larga margem, a osteodistrofia mais comum nessa localização e suas alterações, repercussões clínicas e tratamentos são amplamente discutidos na literatura. Entretanto, formas menos freqüentes, como a displasia fibrosa e a osteogênese imperfeita, não são entidades raras e merecem atenção. Este artigo tem como objetivo discutir essas formas menos comuns de osteodistrofia do temporal através de uma revisão sobre os conceitos atuais dessas entidades, da apresentação de três exemplos clínicos e a discussão sobre opções de tratamento.Osteodysplasia of the temporal bone included a significant amount of osseous diseases sharing bone matrix structural and composition damage. Otospongiosis is, by far, the most frequent form of this involvement in the temporal bone. Nevertheless, fibrous dysplasia and osteogenesis imperfecta are not rare and deserve attention. In this article, the authors present a discussion about the recent concepts of those less frequent forms of osteodysplasia of temporal bone, its options of treatment, illustrated with three clinical cases.

  1. Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression.

    Science.gov (United States)

    Beer, Philip A; Knapp, David J H F; Miller, Paul H; Kannan, Nagarajan; Sloma, Ivan; Heel, Kathy; Babovic, Sonja; Bulaeva, Elizabeth; Rabu, Gabrielle; Terry, Jefferson; Druker, Brian J; Loriaux, Marc M; Loeb, Keith R; Radich, Jerald P; Erber, Wendy N; Eaves, Connie J

    2015-01-15

    Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML) evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid or B-lymphoid characteristics. This transition is often preceded by a clinically recognized, but biologically poorly characterized, accelerated phase (AP). Here, we report that IKAROS protein is absent or reduced in bone marrow blasts from most CML patients with advanced myeloid disease (AP or BC). This contrasts with primitive CP-CML cells and BCR-ABL1-negative acute myeloid leukemia blasts, which express readily detectable IKAROS. To investigate whether loss of IKAROS contributes to myeloid disease progression in CP-CML, we examined the effects of forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML patients' CD34(+) cells. We confirmed that IK6 disrupts IKAROS activity in transduced CP-CML cells and showed that it confers on them features of AP-CML, including a prolonged increased output in vitro and in xenografted mice of primitive cells with an enhanced ability to differentiate into basophils. Expression of IK6 in CD34(+) CP-CML cells also led to activation of signal transducer and activator of transcription 5 and transcriptional repression of its negative regulators. These findings implicate loss of IKAROS as a frequent step and potential diagnostic harbinger of progressive myeloid disease in CML patients. © 2015 by The American Society of Hematology.

  2. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2017-07-28

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  3. A Case with Neurofibromatosis and Chronic Myeloid Leukemia in Blastic Crisis Treated with Imatinib

    Directory of Open Access Journals (Sweden)

    Gamal Abdul Hamid

    2014-03-01

    Full Text Available A 61-year-old female presented with complaints of fever, general weakness and hepatosplenomegaly. She had a history of nonfamilial peripheral neurofibromatosis diagnosed as von Recklinghausen's disease since 30 years previous. Physical examination was remarkable for skin colored cutaneous circumscribed nodules which appeared soft to the touch in both arms, the upper part of her abdomen, back, and posterior thigh. The liver was palpable 10 cm below the inferior border of the costal margin and she had evidence of significant splenomegaly. Laboratory results were as follows: hemoglobin 7.9 g/dl; ESR142 mm/hour; leukocytes 22400x109/L; neutrophils 35%; eosinophils 3%; basophils 4%; myelocytes40%; myeloblasts 14%; promyelocytes 2%; and band form 2%. The bone marrow picture was chronic myeloid leukemia in blastic form. Chest CT scan showed the presence of numerous cutaneous nodules (neurofibromatosis. A biopsy of the tissue fragment from the nodules confirmed the presence of diffuse neurofibromatosis. Bone marrow cytology that included cytogenetic and immunophenotyping confirmed the presence of chronic myeloid leukemia with a positive Philadelphia chromosome and diploidy female clone in a blastic form (acute myeloid leukemia. Addition of 600 mg oral imatinib mesylate daily for one month and reduced to 400 mg daily yields complete hematological remission and complete cytogenetic responses. This case illustrated an association between chronic myeloid leukemia, acute myeloid leukemia and neurofibromatosis in an adult.

  4. Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression.

    Science.gov (United States)

    McCarrel, Taralyn; Fortier, Lisa

    2009-08-01

    Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet alpha-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-beta1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis. Copyright 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma.

    Science.gov (United States)

    Mao, Yumeng; Eissler, Nina; Blanc, Katarina Le; Johnsen, John Inge; Kogner, Per; Kiessling, Rolf

    2016-08-01

    Neuroblastoma is the most common extracranial solid cancer type in childhood, and high-risk patients have poor prognosis despite aggressive multimodal treatment. Neuroblastoma-driven inflammation contributes to the induction of suppressive myeloid cells that hamper efficient antitumor immune responses. Therefore, we sought to enhance antitumor immunity by removing immunosuppression mediated by myeloid cells. The prognostic values of myeloid cells are demonstrated by analyzing genomic datasets of neuroblastoma patients. The impact of tumor-derived factors on myelopoiesis and local induction of suppressive myeloid cells is dissected by in vitro culture models using freshly isolated human CD34(+) hematopoietic stem cells, primary human monocytes, and murine bone marrow cells. To test the therapeutic efficacy of BLZ945 as a monotherapy or in combination with checkpoint inhibitors, we used a transgenic murine model (TH-MYCN) that develops aggressive spontaneous neuroblastoma. We report that infiltrating CSF-1R(+) myeloid cells predict poor clinical outcome in patients with neuroblastoma. In vitro, neuroblastoma-derived factors interfere with early development of myeloid cells and enable suppressive functions on human monocytes through M-CSF/CSF-1R interaction. In a transgenic mouse model (TH-MYCN) resembling high-risk human neuroblastoma, antagonizing CSF-1R with a selective inhibitor (BLZ945) modulates the induction of human and murine suppressive myeloid cells and efficiently limit tumor progression. While checkpoint inhibitors are insufficient in controlling tumor growth, combining BLZ945 with PD-1/PD-L1 blocking antibodies results in superior tumor control. Our results demonstrate the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its clinical potential as an immunotherapy for human cancers. Clin Cancer Res; 22(15); 3849-59. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Regulatory Myeloid Cells in Transplantation

    Science.gov (United States)

    Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

    2013-01-01

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

  7. [Acute myeloid Leukemia].

    Science.gov (United States)

    Braess, Jan

    2016-11-01

    Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future.The basis of curative treatment is intensive combination chemotherapy comprizing cytarabine and an anthracycline ("7 + 3" regimen). The prolonged duration of aplasia can be reduced significantly by accelerated therapy ("S-HAM" regimen). Following achievement of a complete remission patients with a low risk of relapse - based on genetic and clinical features - receive chemotherapy based consolidation therapy whereas high risk patients - and potentially also those with an intermediate risk - receive an allogeneic stem cell transplantation. Whereas adding the rather unspecific tyrosinekinase inhibitor sorafenib to standard treatment in unselected AML patients has not improved overall survival (OS), the addition of midostaurin to standard therapy in the selected group FLT3 mutated patients has resulted in a moderate but significant OS benefit.Real world data show that in patients below 50 years a cure rate of ca. 50 % can be achieved. However less than 10 % of patients above the age of 70 will be alive after five years even after intensive treatment. Therefore when curative and intensive treatment is deemed impossible the therapeutic standard in elderly and unfit patients used to be low-dose cytarabine with an average OS of 4 months. This has now been replaced by a new standard of care of hypomethylating agents - azacytidine and decitabine - which both achieve higher remission rates and show strong trends towards a prolonged OS

  8. Genomics in acute myeloid leukemia: from identification to personalization.

    Science.gov (United States)

    Martin, James M; Winer, Eric S

    2015-11-02

    Acute Myeloid Leukemia (AML) is an aggressive bone marrow malignancy that is fatal if left untreated. Previous classification was strictly based on morphology, which gave little information in terms of prognosis or guide to treatment. Recent research has provided vital information into the chromosomal and molecular pathogenesis of leukemia development. The discovery of these abnormalities via proteomics and genomics have provided two key insights. First, these novel discoveries provide prognostic significance into the predictive result of chemotherapy. Second, these chromosomal and protein abnormalities have provided potential drug targets for new treatment modalities. This article will elaborate on many of these new molecular findings and discuss their implications on the treatment of AML.

  9. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir

    2015-01-01

    mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state....... Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest...... that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution....

  10. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study.

    Science.gov (United States)

    Takahashi, Koichi; Wang, Feng; Kantarjian, Hagop; Doss, Denaha; Khanna, Kanhav; Thompson, Erika; Zhao, Li; Patel, Keyur; Neelapu, Sattva; Gumbs, Curtis; Bueso-Ramos, Carlos; DiNardo, Courtney D; Colla, Simona; Ravandi, Farhad; Zhang, Jianhua; Huang, Xuelin; Wu, Xifeng; Samaniego, Felipe; Garcia-Manero, Guillermo; Futreal, P Andrew

    2017-01-01

    Therapy-related myeloid neoplasms are secondary malignancies that are often fatal, but their risk factors are not well understood. Evidence suggests that individuals with clonal haemopoiesis have increased risk of developing haematological malignancies. We aimed to identify whether patients with cancer who have clonal haemopoiesis are at an increased risk of developing therapy-related myeloid neoplasms. We did this retrospective case-control study to compare the prevalence of clonal haemopoiesis between patients treated for cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls). All patients in both case and control groups were treated at MD Anderson Cancer Center (Houston, TX, USA) from 1997 to 2015. We used the institutional medical database to locate these patients. Patients were included as cases if they were treated for a primary cancer, subsequently developed therapy-related myeloid neoplasms, and had available paired samples of bone marrow from the time of therapy-related myeloid neoplasm diagnosis and peripheral blood from the time of primary cancer diagnosis. Patients were eligible for inclusion as age-matched controls if they were treated for lymphoma, received combination chemotherapy, and did not develop therapy-related myeloid neoplasms after at least 5 years of follow-up. We used molecular barcode sequencing of 32 genes on the pretreatment peripheral blood samples to detect clonal haemopoiesis. For cases, we also used targeted gene sequencing on bone marrow samples and investigated clonal evolution from clonal haemopoiesis to the development of therapy-related myeloid neoplasms. To further clarify the association between clonal haemopoiesis and therapy-related myeloid neoplasm development, we also analysed the prevalence of clonal haemopoiesis in an external cohort of patients with lymphoma who were treated in a randomised trial of front-line chemotherapy with cyclophosphamide

  11. Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era.

    Science.gov (United States)

    Ali, Ridvan; Ozkalemkas, Fahir; Ozkocaman, Vildan; Yakut, Tahsin; Nazlioglu, Hulya Ozturk; Budak, Ferah; Pekgoz, Murat; Korkmaz, Serhat; Karkucak, Mutlu; Ozcelik, Tulay; Tunali, Ahmet

    2009-12-01

    Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.

  12. Differential diagnosis of isolated myeloid sarcoma: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Patrick A. Hagen

    2015-06-01

    Full Text Available Myeloid sarcoma (MS is a rare disease entity identified as a variety of manifestations defined by the occurrence of extramedullary myeloid cell masses with or without bone marrow involvement. This case describes an unusual presentation of isolated MS in a 60-year-old otherwise healthy male, who initially presented to his primary care physician with vague abdominal pain. After extensive workup including three omental biopsies, umbilical core biopsy, and inguinal lymph node biopsy, he was ultimately diagnosed with isolated MS with extensive extramedullary tumor burden. Despite advanced extramedullary disease, peripheral cell counts were normal and bilateral bone marrow biopsies unremarkable with normal cellular lineages, morphology, and cytogenetics. The patient underwent induction chemotherapy and is now greater than 100 days post myeloablative unrelated donor marrow transplantation with no evidence of disease recurrence and 100% donor status with full chimerism. This case demonstrates that making a prompt diagnosis with rapid initiation of treatment in myeloid sarcoma can be challenging due to its varied clinical presentation, cytomorphology, cytochemistry, and cytogenetic overlap with other lymphoid malignancies. Once a diagnosis of MS has been made, moving quickly to induction therapy is important. Several studies have shown that improved overall survival is attained when MS is treated as acute myeloid leukemia and increased survival is noted for patients undergoing bone marrow transplantation. Further prospective studies are needed to elucidate the many remaining questions in regards to the natural history, prognosis, and optimal treatment strategies for this deadly disease.

  13. Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

    DEFF Research Database (Denmark)

    Porse, Bo T; Bryder, David; Theilgaard-Mönch, Kim

    2005-01-01

    CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, and is found mutated in 9% of patients who have acute myeloid leukemia (AML). We previously showed that mutations which...... dissociate the ability of C/EBP alpha to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid...... progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation...

  14. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    Science.gov (United States)

    ... normal acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer ...

  15. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

    DEFF Research Database (Denmark)

    Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

    2010-01-01

    tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool...... and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF......-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb...

  16. The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in Allo- and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Qi Zhang

    2015-01-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are a heterogeneous population of cells that consists of myeloid progenitor cells and immature myeloid cells. They have been identified as a cell population that may affect the activation of CD4+ and CD8+ T-cells to regulate the immune response negatively, which makes them attractive targets for the treatment of transplantation and autoimmune diseases. Several studies have suggested the potential suppressive effect of MDSCs on allo- and autoimmune responses. Conversely, MDSCs have also been found at various stages of differentiation, accumulating during pathological situations, not only during tumor development but also in a variety of inflammatory immune responses, bone marrow transplantation, and some autoimmune diseases. These findings appear to be contradictory. In this review, we summarize the roles of MDSCs in different transplantation and autoimmune diseases models as well as the potential to target these cells for therapeutic benefit.

  17. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion

    DEFF Research Database (Denmark)

    Nygren, J.M.; Liuba, K.; Breitbach, M.

    2008-01-01

    Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion with haematopoietic cells of the myeloid lineage. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes...... and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types...... is induced by organ-specific injuries or whole-body irradiation, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion...

  18. Prognostic significance of cellular vascular endothelial growth factor (VEGF expression in the course of chronic myeloid leukaemia

    Directory of Open Access Journals (Sweden)

    Vidović Ana

    2009-01-01

    Full Text Available Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML, a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years. At the commencement of the study, 29 patients were in chronic phase (CP, 25 in an accelerated phase (AP, and 31 in the blast crisis (BC. The temporal expression (percentage positivity per 1000 analysed cells VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts and clinical parameters (organomegaly, duration of CP, AP, and BC of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033. The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011. High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042. Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

  19. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects passed down ...

  20. Is Acute Myeloid Leukemia a Liquid Tumor?

    Science.gov (United States)

    Ohanian, Maro; Faderl, Stefan; Ravandi, Farhad; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Cortes, Jorge; Estrov, Zeev

    2014-01-01

    Extramedullary manifestations of acute myeloid leukemia (AML) were described as early as the 19th century. However, the incidence, clinical significance, and pathobiology of extramedullary AML remain ill defined. We reviewed case reports, retrospective case series, pilot studies, and imaging studies of extramedullary leukemia (EML) to determine its frequency, characteristics, clinical presentation, and significance. EML precedes or accompanies development of AML and occurs during or following treatment, even during remission. Although imaging studies are rarely conducted and the true incidence of EML has yet to be verified, authors have reported several estimates based on retrospective and autopsy studies. The incidence of EML in patients with AML of all ages is estimated to be about 9% and EML in children with AML was detected in 40% of patients at diagnosis. The combination of positron emission tomography and computed tomography were the most sensitive and reliable techniques of detecting and monitoring EML. Based on our literature review, the frequency of EML is likely underreported. The well-documented nature of EML in AML patients suggests that AML can manifest as a solid tumor. The extent to which EML accompanies AML and whether EML is derived from bone marrow are unknown. Furthermore, questions remain regarding the role of the microenvironment, which may or may not facilitate the survival and proliferation of EML, and the implications of these interactions with regard to minimal residual disease, tumor cell quiescence, and relapse. Therefore, prospective studies of detection and characterization of EML in AML patients are warranted. PMID:23280377

  1. Acute Myeloid Leukemia Presenting as Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Sherri Rauenzahn

    2013-01-01

    Full Text Available Appendicitis in leukemic patients is uncommon but associated with increased mortality. Additionally, leukemic cell infiltration of the appendix is extremely rare. While appendectomy is the treatment of choice for these patients, diagnosis and management of leukemia have a greater impact on remission and survival. A 59-year-old Caucasian female was admitted to the surgical service with acute right lower quadrant pain, nausea, and anorexia. She was noted to have leukocytosis, anemia, and thrombocytopenia. Abdominal imaging demonstrated appendicitis with retroperitoneal and mesenteric lymphadenopathy for which she underwent laparoscopic appendectomy. Peripheral smear, bone marrow biopsy, and surgical pathology of the appendix demonstrated acute myeloid leukemia (AML with nonsuppurative appendicitis. In the setting of AML, prior cases described the development of appendicitis with active chemotherapy. Of these cases, less than ten patients had leukemic infiltration of the appendix, leading to leukostasis and nonsuppurative appendicitis. Acute appendicitis with leukemic infiltration as the initial manifestation of AML has only been described in two other cases in the literature with an average associated morbidity of 32.6 days. The prompt management in this case of appendicitis and AML resulted in an overall survival of 185 days.

  2. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  3. Philadelphia chromosome-positive acute myeloid leukemia with masses and osteolytic lesions: finding of 18F-FDG PET/CT.

    Science.gov (United States)

    Su, Zhan; Wu, Fengyu; Hu, Weiyu; Liu, Xiaodan; Wu, Shaoling; Feng, Xianqi; Cui, Zhongguang; Yang, Jie; Wang, Zhenguang; Guan, Hongzai; Zhao, Hongguo; Wang, Wei; Zhao, Chunting; Peng, Jun

    2017-09-01

    Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions. Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker. For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities, a diagnosis of Philadelphia-positive acute myeloid leukemia was made, although the type (de novo or blast crisis) remained unclear.

  4. Bone marrow examination findings at Aga Khan University Hospital ...

    African Journals Online (AJOL)

    Acute myeloid leukaemia was the most common malignant haematological disorder. The most common indication for bone marrow examination was anaemia followed by diagnostic work up of fever of unknown origin. Conclusion: Nutritional anaemia predominated as the commonest benign haematological finding on bone ...

  5. Fatal cardiac tamponade as the first manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Leptidis, John; Aloizos, Stavros; Chlorokostas, Panagiotis; Gourgiotis, Stavros

    2014-10-01

    Acute myeloid leukemia is a hemopoietic myeloid stem cell neoplasm. It is the most common acute leukemia affecting adults,and its incidence increases with age. Acute myeloid leukemia is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. As the leukemic cells keep filling the bone marrow, symptoms of the disease started to appear: fatigue, bleeding, increased frequency of infections, and shortness of breath. Cardiac tamponade or pericardial tamponade is an acute medical condition in which the accumulation of pericardial fluid prevents the function of the heart. Signs and symptoms include Beck triad (hypotension, distended neck veins, and muffled heart sounds), paradoxus pulses, tachycardia, tachypnea, and breathlessness. Pericardial effusion and cardiac tamponade are rare and severe complications of leukemia; they often develop during the radiation therapy, chemotherapy, or infections in the course of leukemia. This study sought to assess the fatal cardiac tamponade as the first manifestation of acute myeloid leukemia (AML). We found no reports in the literature linking these 2 clinical entities. Although the patient had no signs or diagnosis of AML previously, this case was remarkable for the rapidly progressive symptoms and the fatal outcome. The pericardial effusion reaccumulated rapidly after its initial drainage; it is a possible explanation that the leukemic cells interfered with cardiac activity or that they decreased their contractility myocytes secreting a toxic essence.

  6. The Danish National Chronic Myeloid Neoplasia Registry

    DEFF Research Database (Denmark)

    Bak, Marie; Ibfelt, Else Helene; Stauffer Larsen, Thomas

    2016-01-01

    AIM: The Danish National Chronic Myeloid Neoplasia Registry (DCMR) is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital...

  7. Malignant pleural effusion in acute myeloid leukemia with hepatitis B virus infection.

    Science.gov (United States)

    Suharti, C; Santosa; Setiawan, Budi

    2015-04-01

    Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML). Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification).

  8. Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

    Directory of Open Access Journals (Sweden)

    Adam Stelling

    2015-12-01

    Full Text Available Primary myelofibrosis (PMF, per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7. Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF, erythroid markers (hemoglobin and E-cadherin, and lymphoid markers (CD3, CD19, and TdT. Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and

  9. Priapism – A Rare Presentation in Chronic Myeloid Leukemia: Case Report

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    Rajendra B. Nerli

    2016-01-01

    Full Text Available Priapism is a complication rarely seen in leukemia. We report a 19-year-old man presented with persistent painful erection of penis for over 24 hours at home. The patient had underwent immediate irrigation and decompression of priapism by urologist at emergency services of the hospital. This approach resulted in a flaccid penis later. During hospitalization, peripheral blood smear and bone marrow aspiration confirmed the diagnosis of chronic myeloid leukemia.

  10. Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner.

    Science.gov (United States)

    Al-Matary, Yahya S; Botezatu, Lacramioara; Opalka, Bertram; Hönes, Judith M; Lams, Robert F; Thivakaran, Aniththa; Schütte, Judith; Köster, Renata; Lennartz, Klaus; Schroeder, Thomas; Haas, Rainer; Dührsen, Ulrich; Khandanpour, Cyrus

    2016-10-01

    The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia. Copyright© Ferrata Storti Foundation.

  11. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease.

    Science.gov (United States)

    Horvath, Emoke; Demian, Smaranda; Nagy, Elod

    2016-01-01

    Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient's case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  12. Bosutinib for Chronic Myeloid Leukemia.

    Science.gov (United States)

    Breccia, Massimo; Binotto, Gianni

    In recent years the availability of several tyrosine kinase inhibitors (TKI) in the therapeutic armamentarium for chronic myeloid leukemia has dramatically changed the objectives and expectations of healthcare providers and patients. For many, but not all, patients the forerunner of TKI, imatinib, is still an excellent treatment option. Unfortunately, nearly 30-40% of imatinib-treated patients discontinue therapy in the long-term, because of failure and/or intolerance. Second-generation tyrosine kinase inhibitors are more potent drugs which are suitable for treatment of approximately 50% of patents for whom imatinib is unsuitable, and with high success and rapid responses. Bosutinib, an orally bioavailable Src/Abl tyrosine kinase inhibitor, has proved to be effective in vitro against resistant chronic myeloid leukemia cells that do not harbor the T315I or V299L ABL kinase domain mutations. During clinical development the manageable safety profile of bosutinib have become evident for both simple and more advanced treatment. In this review we summarize preclinical and clinical data for bosutinib and discuss its ideal field of action in comparison with other TKI.

  13. Molecular pathways: myeloid complicity in cancer.

    Science.gov (United States)

    Stromnes, Ingunn M; Greenberg, Philip D; Hingorani, Sunil R

    2014-10-15

    Cancer-induced inflammation results in accumulation of myeloid cells. These myeloid cells include progenitors and progeny of monocytes, granulocytes, macrophages, and dendritic cells. It has become increasingly evident that tumor-dependent factors can condition myeloid cells toward an immunosuppressive and protumorigenic phenotype. Thus, myeloid cells are not simply bystanders in malignancy or barometers of disease burden. Reflecting their dynamic and plastic nature, myeloid cells manifest a continuum of cellular differentiation and are intimately involved at all stages of neoplastic progression. They can promote tumorigenesis through both immune-dependent and -independent mechanisms and can dictate response to therapies. A greater understanding of the inherent plasticity and relationships among myeloid subsets is needed to inform therapeutic targeting. New clinical trials are being designed to modulate the activities of myeloid cells in cancer, which may be essential to maximize the efficacy of both conventional cytotoxic and immune-based therapies for solid tumors. Clin Cancer Res; 20(20); 5157-70. ©2014 AACR. ©2014 American Association for Cancer Research.

  14. Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis.

    Science.gov (United States)

    Berry, Patricia A; Jones, Simon W; Cicuttini, Flavia M; Wluka, Anita E; Maciewicz, Rose A

    2011-03-01

    The association of obesity with both hand and knee osteoarthritis (OA) is suggestive of a link between dysfunctional metabolism and joint integrity. Given the role of adipokines in mediating bone and cartilage homeostasis, we undertook this study to examine the relationship between adipokines and bone and cartilage biomarkers in a population of subjects with OA, and to determine whether adipokine levels predicted 2-year cartilage integrity. One hundred seventeen subjects underwent magnetic resonance imaging at baseline and at 2-year followup. Cartilage volume was assessed from these images. Serum adipokine levels were measured at baseline. Bone and cartilage biomarker levels were measured at baseline and at 2-year followup. Linear regression was used to examine the relationship between baseline levels of adipokines and adipokine receptors (leptin, soluble leptin receptor [sOB-Rb], resistin, and adiponectin) and changes in levels of bone biomarkers (osteocalcin, N-terminal type I procollagen propeptide [PINP], C-terminal crosslinking telopeptide of type I collagen, N-terminal crosslinking telopeptide of type I collagen, or C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases), levels of cartilage biomarkers (cartilage oligomeric matrix protein, N-terminal type IIA procollagen propeptide [PIIANP], or C2C), cartilage defects score, and cartilage volume over 2 years. Baseline leptin was associated with increased levels of bone formation biomarkers (osteocalcin and PINP) over 2 years, while sOB-Rb was associated with reduced levels of osteocalcin. Baseline sOB-Rb was associated with reduced levels of the cartilage formation biomarker PIIANP, an increased cartilage defects score, and increased cartilage volume loss over 2 years. All results were independent of age, sex, and body mass index. The findings of this study support the concept that serum adipokines may provide a nonmechanical link between obesity and joint integrity

  15. Additional chromosome abnormalities in chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Hui-Hua Hsiao

    2011-02-01

    Full Text Available The Philadelphia (Ph chromosome and/or Breakpoint cluster region-Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML. However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1% with the classic Ph chromosome, 6 (7.2% with a variant Ph chromosome, and 9 (10.7% with additional chromosome abnormalities. Fifty-four (64.3% cases harbored b3a2 transcripts, 29 (34.5% had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first- and second-line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second-line therapy had a significant poor impact (p<0.05. In conclusion, we presented the cytogenetic and molecular pattern of CML patients and demonstrated that the additional chromosome abnormality was associated with poor outcome.

  16. The effect of smoking on myeloid-related protein-8 and myeloid-related protein-14.

    Science.gov (United States)

    Ertugrul, Abdullah Seckin; Sahin, Hacer

    2016-05-20

    The aim of this study was to determine the myeloid-related protein-8 and myeloid-related protein-14 levels in the gingival crevicular fluid of smoker patients with generalized aggressive periodontitis (SAgP), smoker patients with chronic periodontitis (SCP), smoker patients with gingivitis (SG-smoker control), non-smoker patients with generalized aggressive periodontitis (AgP), non-smoker patients with chronic periodontitis (CP), and non-smoker patients with gingivitis (G-non-smoker control). The periodontal statuses of the patients were determined by periodontal clinical measurements and radiographical evaluations. The levels of myeloid-related protein-8 and myeloid-related protein-14 in the gingival crevicular fluid were assessed using enzyme-linked immuno sorbent assay. The myeloid-related protein-8 and myeloid-related protein-14 levels in the gingival crevicular fluid of patients with generalized aggressive periodontitis (non-smoker and smoker) were found to be statistically higher than patients with chronic periodontitis (non-smoker and smoker) and patients with gingivitis (non-smoker and smoker). Myeloid-related protein-8 and myeloid-related protein-14 levels of non-smokers were significantly higher than smokers in all types of periodontitis and gingivitis. The decreased myeloid-related protein-8 and myeloid-related protein-14 level could have prevented the haemostasis of calcium which plays a significant role in the migration of neutrophiles. Smoking affects myeloid-related protein-8 and myeloid-related protein-14 levels and may inhibit the antimicrobial efficiency against microorganisms. Due to these reasons smoker generalized aggressive periodontitis patients need to be treated in detail and their maintenance durations should be shortened.

  17. The effect of smoking on myeloid-related protein-8 and myeloid-related protein-14

    Directory of Open Access Journals (Sweden)

    Abdullah Seckin ERTUGRUL

    2016-01-01

    Full Text Available Abstract The aim of this study was to determine the myeloid-related protein-8 and myeloid-related protein-14 levels in the gingival crevicular fluid of smoker patients with generalized aggressive periodontitis (SAgP, smoker patients with chronic periodontitis (SCP, smoker patients with gingivitis (SG-smoker control, non-smoker patients with generalized aggressive periodontitis (AgP, non-smoker patients with chronic periodontitis (CP, and non-smoker patients with gingivitis (G-non-smoker control. The periodontal statuses of the patients were determined by periodontal clinical measurements and radiographical evaluations. The levels of myeloid-related protein-8 and myeloid-related protein-14 in the gingival crevicular fluid were assessed using enzyme-linked immuno sorbent assay. The myeloid-related protein-8 and myeloid-related protein-14 levels in the gingival crevicular fluid of patients with generalized aggressive periodontitis (non-smoker and smoker were found to be statistically higher than patients with chronic periodontitis (non-smoker and smoker and patients with gingivitis (non-smoker and smoker. Myeloid-related protein-8 and myeloid-related protein-14 levels of non-smokers were significantly higher than smokers in all types of periodontitis and gingivitis. The decreased myeloid-related protein-8 and myeloid-related protein-14 level could have prevented the haemostasis of calcium which plays a significant role in the migration of neutrophiles. Smoking affects myeloid-related protein-8 and myeloid-related protein-14 levels and may inhibit the antimicrobial efficiency against microorganisms. Due to these reasons smoker generalized aggressive periodontitis patients need to be treated in detail and their maintenance durations should be shortened.

  18. Metalloproteinases: a Functional Pathway for Myeloid Cells.

    Science.gov (United States)

    Chou, Jonathan; Chan, Matilda F; Werb, Zena

    2016-04-01

    Myeloid cells have diverse roles in regulating immunity, inflammation, and extracellular matrix turnover. To accomplish these tasks, myeloid cells carry an arsenal of metalloproteinases, which include the matrix metalloproteinases and the adamalysins. These enzymes have diverse substrate repertoires, and are thus involved in mediating proteolytic cascades, cell migration, and cell signaling. Dysregulation of metalloproteinases contributes to pathogenic processes, including inflammation, fibrosis, and cancer. Metalloproteinases also have important nonproteolytic functions in controlling cytoskeletal dynamics during macrophage fusion and enhancing transcription to promote antiviral immunity. This review highlights the diverse contributions of metalloproteinases to myeloid cell functions.

  19. New emerging applications of molgramostim in acute myeloid leukaemia.

    Science.gov (United States)

    Thomas, Xavier

    2008-06-01

    Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and differentiation of hematopoietic progenitor cells in the myeloid lineage, and plays a key role in host defence and the inflammatory process. The main schedules adopted for clinical applications of GM-CSF in acute myeloid leukaemia (AML) were post-chemotherapy, in order to shorten the duration of neutropenia, and as a mobilising agent to induce release of progenitor cells from bone marrow into circulation. Based on the variety of biologic effects being attributed to GM-CSF, additional clinical uses for GM-CSF have been under investigation. Concurrent administration to chemotherapy has been used to recruit blast cells into active cell cycle phases, and to increase their sensitivity to cell cycle-dependent cytotoxic drugs. Exposure to GM-CSF also has recently been shown to enhance cellular immunity and indirectly stimulate anti-tumour immunity. On the other hand, GM-CSF can directly enhance immunogenicity of tumours.

  20. RhoA: A therapeutic target for chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Molli Poonam R

    2012-03-01

    Full Text Available Abstract Background Chronic Myeloid Leukemia (CML is a malignant pluripotent stem cells disorder of myeloid cells. In CML patients, polymorphonuclear leukocytes (PMNL the terminally differentiated cells of myeloid series exhibit defects in several actin dependent functions such as adhesion, motility, chemotaxis, agglutination, phagocytosis and microbicidal activities. A definite and global abnormality was observed in stimulation of actin polymerization in CML PMNL. Signalling molecules ras and rhoGTPases regulate spatial and temporal polymerization of actin and thus, a broad range of physiological processes. Therefore, status of these GTPases as well as actin was studied in resting and fMLP stimulated normal and CML PMNL. Methods To study expression of GTPases and actin, Western blotting and flow cytometry analysis were done, while spatial expression and colocalization of these proteins were studied by using laser confocal microscopy. To study effect of inhibitors on cell proliferation CCK-8 assay was done. Significance of differences in expression of proteins within the samples and between normal and CML was tested by using Wilcoxon signed rank test and Mann-Whitney test, respectively. Bivariate and partial correlation analyses were done to study relationship between all the parameters. Results In CML PMNL, actin expression and its architecture were altered and stimulation of actin polymerization was absent. Differences were also observed in expression, organization or stimulation of all the three GTPases in normal and CML PMNL. In normal PMNL, ras was the critical GTPase regulating expression of rhoGTPases and actin and actin polymerization. But in CML PMNL, rhoA took a central place. In accordance with these, treatment with rho/ROCK pathway inhibitors resulted in specific growth inhibition of CML cell lines. Conclusions RhoA has emerged as the key molecule responsible for functional defects in CML PMNL and therefore can be used as a

  1. Genomics of Acute Myeloid Leukemia Diagnosis and Pathways.

    Science.gov (United States)

    Bullinger, Lars; Döhner, Konstanze; Döhner, Hartmut

    2017-03-20

    In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such mutations may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. In contrast, mutations involving NPM1 or signaling molecules (eg, FLT3, RAS) typically are secondary events that occur later during leukemogenesis. Genetic data are now being used to inform disease classification, risk stratification, and clinical care of patients. Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current update of the WHO classification of myeloid neoplasms and AML, and mutations in three genes- RUNX1, ASXL1, and TP53-have been added in the risk stratification of the 2017 European LeukemiaNet recommendations for AML. Integrated evaluation of baseline genetics and assessment of minimal residual disease are expected to further improve risk stratification and selection of postremission therapy. Finally, the identification of disease alleles will guide the development and use of novel molecularly targeted therapies.

  2. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  3. Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.

    Science.gov (United States)

    Tsai, Donald E; Luger, Selina M; Kemner, Allison; Swider, Cezary; Goradia, Ami; Tomczak, Ewa; DiPatri, Doris; Bagg, Adam; Nowell, Peter; Loren, Alison W; Perl, Alexander; Schuster, Stephen; Thompson, James E; Porter, David; Andreadis, Charlambos; Stadtmauer, Edward A; Goldsteini, Steven; Ghalie, Richard; Carroll, Martin

    2007-01-01

    All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.

  4. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Targeting myeloid cells to the brain using non-myeloablative conditioning.

    Directory of Open Access Journals (Sweden)

    Chotima Böttcher

    Full Text Available Bone marrow-derived cells (BMDCs are able to colonize the central nervous system (CNS at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft in the brain, which so far has been achieved by total body irradiation (TBI and by chemotherapy (e.g. busulfan treatment. Unfortunately, both regimens massively disturb the host's hematopoietic compartment. Here, we established a conditioning protocol to target myeloid cells to sites of brain damage in mice using non-myeloablative focal head irradiation (HI. This treatment was associated with comparatively low inflammatory responses in the CNS despite cranial radiation doses which are identical to TBI, as revealed by gene expression analysis of cytokines/chemokines such as CCL2, CXCL10, TNF-α and CCL5. HI prior to bone marrow transplantation resulted in much lower levels of blood chimerism defined as the percentage of donor-derived cells in peripheral blood ( 95% or busulfan treatment (> 50%. Nevertheless, HI effectively recruited myeloid cells to the area of motoneuron degeneration in the brainstem within 7 days after facial nerve axotomy. In contrast, no donor-derived cells were detected in the lesioned facial nucleus of busulfan-treated animals up to 2 weeks after transplantation. Our findings suggest that myeloid cells can be targeted to sites of brain damage even in the presence of very low levels of peripheral blood chimerism. We established a novel non-myeloablative conditioning protocol with minimal disturbance of the host's hematopoietic system for targeting BMDCs specifically to areas of pathology in the brain.

  6. Key Data Elements in Myeloid Leukemia

    NARCIS (Netherlands)

    Varghese, J.; Holz, C.; Neuhaus, P.; Bernardi, M.; Boehm, A.; Ganser, A.; Gore, S.; Heaney, M.; Hochhaus, A.; Hofmann, W.K.; Krug, U.; Muller-Tidow, C.; Smith, A.; Weltermann, A.; Witte, T.J.M. de; Hehlmann, R.; Dugas, M.

    2016-01-01

    Data standards consisting of key data elements for clinical routine and trial documentation harmonize documentation within and across different health care institutions making documentation more efficient and improving scientific data analysis. This work focusses on the field of myeloid leukemia

  7. Acute myeloid leukemia presenting as galactorrhea

    OpenAIRE

    Nambiar, K. Rakul; Nair, Sreejith G.; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea.

  8. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

    de Jonge, H. J. M.; Huls, G.; de Bont, E. S. J. M.

    Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on

  9. Exploring the acute myeloid leukaemias

    Directory of Open Access Journals (Sweden)

    TB Thapa

    2013-10-01

    Full Text Available The acute myeloid leukemias are genetically a diverse group of neoplasm with varied clinical behavior and response to treatment. Advances in immunophenotyping, cytogenetics and molecular genetics have resulted in better understanding of their genesis. Risk stratification of different variants is now emerging. Therapy strategies are now increasingly being developed considering the inherent biological behavior of the different subtypes. It is anticipated that in the future, deeper secrets of these once fatal diseases will be unraveled by advances in newer genomic techniques. It is hoped that future use of gene specific tailored therapy and strategies will result in longer survival in cases showing poorer prognosis at present. DOI: http://dx.doi.org/10.3126/jpn.v3i6.9001 Journal of Pathology of Nepal (2013 Vol. 3, 497-501

  10. Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells.

    Science.gov (United States)

    Wu, Hao; Weidinger, Carl; Schmidt, Franziska; Keye, Jacqueline; Friedrich, Marie; Yerinde, Cansu; Willimsky, Gerald; Qin, Zhihai; Siegmund, Britta; Glauben, Rainer

    2017-08-08

    Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation. Furthermore, sodium oleate potentiated nitric oxide (NO) production in MSC-2, thereby increasing their suppressive capacity. In primary polarized bone marrow cells, sodium oleate (C18:1) and linoleate (C18:2), but not stearate (C18:0) were identified as potent FFA to induce a regulatory phenotype. This effect was abrogated in MSC-2 as well as primary cells by specific inhibition of droplets formation while the inhibition of de novo FFA synthesis proved ineffective, suggesting a critical role for exogenous FFA in the functional induction of MSCs. Taken together our data introduce a new unsaturated fatty acid-dependent pathway shaping the functional phenotype of MSCs, facilitating the tumor escape from the immune system.

  11. Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies.

    Science.gov (United States)

    Cole, Christopher B; Russler-Germain, David A; Ketkar, Shamika; Verdoni, Angela M; Smith, Amanda M; Bangert, Celia V; Helton, Nichole M; Guo, Mindy; Klco, Jeffery M; O'Laughlin, Shelly; Fronick, Catrina; Fulton, Robert; Chang, Gue Su; Petti, Allegra A; Miller, Christopher A; Ley, Timothy J

    2017-10-02

    The gene that encodes de novo DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia genomes. Point mutations at position R882 have been shown to cause a dominant negative loss of DNMT3A methylation activity, but 15% of DNMT3A mutations are predicted to produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with WT DNMT3A, strongly supporting the haploinsufficiency hypothesis. We therefore evaluated hematopoiesis in mice heterozygous for a constitutive null Dnmt3a mutation. With no other manipulations, Dnmt3a+/- mice developed myeloid skewing over time, and their hematopoietic stem/progenitor cells exhibited a long-term competitive transplantation advantage. Dnmt3a+/- mice also spontaneously developed transplantable myeloid malignancies after a long latent period, and 3 of 12 tumors tested had cooperating mutations in the Ras/MAPK pathway. The residual Dnmt3a allele was neither mutated nor downregulated in these tumors. The bone marrow cells of Dnmt3a+/- mice had a subtle but statistically significant DNA hypomethylation phenotype that was not associated with gene dysregulation. These data demonstrate that haploinsufficiency for Dnmt3a alters hematopoiesis and predisposes mice (and probably humans) to myeloid malignancies by a mechanism that is not yet clear.

  12. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

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    Xueqing Jiang

    Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

  13. Myb expression is critical for myeloid leukemia development induced by Setbp1 activation.

    Science.gov (United States)

    Nguyen, Nhu; Vishwakarma, Bandana A; Oakley, Kevin; Han, Yufen; Przychodzen, Bartlomiej; Maciejewski, Jaroslaw P; Du, Yang

    2016-12-27

    SETBP1 missense mutations have been frequently identified in multiple myeloid neoplasms; however, their oncogenic potential remains unclear. Here we show that expression of Setbp1 mutants carrying two such mutations in mouse bone marrow progenitors efficiently induced development of acute myeloid leukemias (AMLs) in irradiated recipient mice with significantly shorter latencies and greater penetrance than expression of wild-type Setbp1, suggesting that these mutations are highly oncogenic. The increased oncogenicity of Setbp1 missense mutants could be due in part to their capability to drive significantly higher target gene transcription. We further identify Myb as a critical mediator of Setbp1-induced self-renewal as its knockdown caused efficient differentiation of myeloid progenitors immortalized by wild-type Setbp1 and Setbp1 missense mutants. Interestingly, Myb is also a direct transcriptional target of Setbp1 and Setbp1 missense mutants as they directly bind to the Myb locus in immortalized cells and dramatically activate a critical enhancer/promoter region of Myb in luciferase reporter assays. Furthermore, Myb knockdown in Setbp1 and Setbp1 missense mutations-induced AML cells also efficiently induced their differentiation in culture and significantly prolonged the survival of their secondary recipient mice, suggesting that targeting MYB pathway could be a promising strategy for treating human myeloid neoplasms with SETBP1 activation.

  14. Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: Impact on WHO classification.

    Science.gov (United States)

    Pasqualucci, Laura; Liso, Arcangelo; Martelli, Maria Paola; Bolli, Niccolò; Pacini, Roberta; Tabarrini, Alessia; Carini, Manola; Bigerna, Barbara; Pucciarini, Alessandra; Mannucci, Roberta; Nicoletti, Ildo; Tiacci, Enrico; Meloni, Giovanna; Specchia, Giorgina; Cantore, Nicola; Di Raimondo, Francesco; Pileri, Stefano; Mecucci, Cristina; Mandelli, Franco; Martelli, Massimo Fabrizio; Falini, Brunangelo

    2006-12-15

    Because of a lack of specific clonality markers, information on lineage involvement and cell of origin of acute myeloid leukemia with normal karyotype (AML-NK), is missing. Because Nucleophosmin (NPM) gene is frequently mutated in AML-NK and causes aberrant NPM cytoplasmic localization (NPMc+), it was used as an AML lineage clonality marker. Clonal NPM exon 12 mutations were detected in myeloid, monocytic, erythroid, and megakaryocytic cells but not in fibroblasts or endothelia that were laser-microdissected from 3 patients with NPMc+ AML. Aberrant cytoplasmic expression of mutated NPM proteins was identified with anti-NPM antibodies in 2 or more myeloid hemopoietic cell lineages in 99 (61.5%) of 161 of NPMc+ AML paraffin-embedded bone marrow biopsies; lymphoid involvement was excluded in 3 investigated cases. These findings suggest that NPMc+ AML derives from either a common myeloid or earlier progenitor. Immunohistochemical studies show that varying combinations and ratios of NPMc+ leukemic cells from distinct lineages are responsible for heterogeneity within each French-American-British (FAB) classification type and for NPMc+ AML falling into different FAB categories. These findings question the value of FAB criteria in subdividing the WHO category of "AML not otherwise characterized" and suggest that, for clinical use, NPMc+ AML be provisionally regarded as a separate AML with prognostic significance.

  15. Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

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    Angelica Trujillo

    2012-01-01

    Full Text Available Acute myeloid leukemia (AML arises from neoplastic transformation of hematopoietic stem and progenitor cells, and relapsed disease remains one of the greater challenges in treating this hematologic malignancy. This paper focuses on angiogenic aspects of AML including the significance and prognostic value of bone marrow microvessel density and circulating cytokine levels. We show three general mechanisms whereby AML exploits angiogenic pathways, including direct induction of angiogenesis, paracrine regulation, and autocrine stimulation. We also present early evidence that leukemia cells contribute directly to vascular endothelia. Novel treatment strategies are proposed, and a review of relevant antiangiogenic clinical trials is presented. By understanding how blood vessels can serve as a reservoir for refractory and relapsed AML, new diagnostics and promising treatment strategies can be developed.

  16. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

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    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  17. Neuropatía sensitiva trigeminal secundaria a granuloma de colesterol de la punta del peñasco del temporal Trigeminal neuralgia secondary to cholesterol granuloma of the petrous bone apex

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    M.A. Pons García

    2009-10-01

    Full Text Available La neuropatía aislada de la rama sensitiva del trigémino es una entidad poco habitual. Los pacientes suelen referir hipoestesia y /o disestesia generalmente a nivel de la segunda y tercera rama del trigémino, mientras que la neuralgia es muy infrecuente.¹ Su asociación con enfermedades sistémicas del tejido conectivo es bien conocida.² Se ha descrito asociada a distintas lesiones del SNC sobre todo tumores de fosa posterior o base de cráneo, así como neoplasias mandibulares.3,4 Presentamos una paciente con hipoestesia en el territorio V2-V3 asociada a dolor hemifacial paroxístico secundario a una lesión del peñasco del temporal.Trigeminal Neuralgia is an uncommon entity. The patients report hypoesthesia and/or dysesthesia of the second and third ramus of trigeminal nerve, while neuralgia is very rare.¹ Its association with systemic diseases of connective tissue is well know.² It has been described as being associated with different lesions of the central nervous system, especially with the posterior cavity or cranial base tumors, as well as jaw neoplasias.3,4 We presented a patient with hypoesthesia V2-V3 and hemi facial paroxysmal pain secondary to lesion of petrous apex of temporal bone.

  18. Sarcopenic Obesity and Its Temporal Associations With Changes in Bone Mineral Density, Incident Falls, and Fractures in Older Men: The Concord Health and Ageing in Men Project.

    Science.gov (United States)

    Scott, David; Seibel, Markus; Cumming, Robert; Naganathan, Vasi; Blyth, Fiona; Le Couteur, David G; Handelsman, David J; Waite, Louise M; Hirani, Vasant

    2017-03-01

    Body composition and muscle function have important implications for falls and fractures in older adults. We aimed to investigate longitudinal associations between sarcopenic obesity and its components with bone mineral density (BMD) and incident falls and fractures in Australian community-dwelling older men. A total of 1486 men aged ≥70 years from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005-2007), 2-year follow-up (2007-2009; n = 1238), and 5-year follow-up (2010-2013; n = 861). At all three time points, measurements included appendicular lean mass (ALM), body fat percentage and total hip BMD, hand-grip strength, and gait speed. Participants were contacted every 4 months for 6.1 ± 2.1 years to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Sarcopenic obesity was defined using sarcopenia algorithms of the European Working Group on Sarcopenia (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) and total body fat ≥30% of total mass. Sarcopenic obese men did not have significantly different total hip BMD over 5 years compared with non-sarcopenic non-obese men (p > 0.05). EWGSOP-defined sarcopenic obesity at baseline was associated with significantly higher 2-year fall rates (incidence rate ratio [IRR] 1.66; 95% confidence interval [CI] 1.16-2.37), as were non-sarcopenic obesity (1.30; 1.04-1.62) and sarcopenic non-obesity (1.58; 1.14-2.17), compared with non-sarcopenic non-obese. No association with falls was found for sarcopenic obesity using the FNIH definition (1.01; 0.63-1.60), but after multivariable adjustment, the FNIH-defined non-sarcopenic obese group had a reduced hazard for any 6-year fracture compared with sarcopenic obese men (hazard ratio 0.44; 95% CI 0.23-0.86). In older men, EWGSOP-defined sarcopenic obesity is associated with increased fall rates over 2 years, and FNIH-defined sarcopenic obese men have increased

  19. Unilateral eyelid swelling, proptosis and diplopia as initial manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Chaudhry, Imtiaz A; Alaraj, Ahmad M; Alkatan, Hind M

    2012-04-01

    Myeloid sarcoma is a tumor of immature myeloid cells occurring in many extramedullary sites, orbit being one of them where the tumor may occur prior to or after the diagnosis of underlying disease. We report a case of a 17-year-old male who presented with upper eyelid swelling, proptosis and diplopia after presumed blunt trauma without any other clinical signs and symptoms. Initial imaging suggested possibility of subperiosteal hematoma. Magnetic resonance imaging studies demonstrated a solid tumor. Complete excision of the tumor and histopathologic diagnosis revealed evidence of acute myeloid leukemia (AML). There were no other sites indicating any tumoral process; however, bone marrow aspirate revealed an evidence of systemic disease. After chemotherapy and allogenic bone marrow transplant, the patient had complete remission of his disease. An episode of graft vs host reaction resulting in severe dry eyes along with skin eruptions was treated successfully by immunosuppression and topical lubrication without any visual or systemic sequela. This case emphasizes on the need for an aggressive work-up for any unusual orbital lesion in the absence of any explainable etiology. Further, AML may be suspected in the cases of orbital tumors even in the absence of systemic manifestations of leukemia at any age.

  20. O transplante de medula óssea na leucemia mielóide aguda: análise de 80 pacientes transplantados no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo The allogeneic and autologous bone marrow transplantation in acute myeloid leukemia: analysis of 80 patients - Bone Marrow Transplantation Service - Hospital das Clínicas of the Medical School, University of São Paulo

    Directory of Open Access Journals (Sweden)

    Nadjanara D. Bueno

    2004-01-01

    Full Text Available Oitenta pacientes consecutivos portadores de Leucemia Mielóide Aguda (LMA submetidos a transplante de medula óssea alogênico (TMO alo e autogênico (TMO auto, foram selecionados entre 1989 e 2001. Quarenta por cento dos mesmos estavam vivos ao final do estudo; no TMO alo 37,9% e no TMO auto 45,4%. Fatores como sexo, classificação Franco-Americano-Britânica de LMA, tratamento de indução, número de células infundidas e regime de condicionamentos não tiveram significância estatística na sobrevida. Pacientes portadores de LMA M1 a M4 e que foram submetidos à consolidação com altas doses de arabinosídeo tiveram melhor sobrevida (p= 0,0148. Pacientes em 1º remissão completa se beneficiaram com TMO alo e auto, com uma sobrevida de 52,6% e 69,2% respectivamente. A presença de doença enxerto contra o hospedeiro (DECH aguda teve impacto na sobrevida dos pacientes quando se comparou ausência de DECH aguda, grau I/II com III/IV (p= 0,0285. Infecção foi a causa de óbito mais freqüente no TMO alo. No TMO auto, a recidiva foi a principal causa de óbito. Morte por toxicidade relacionada ao procedimento ocorreu em 38,9% dos pacientes que morreram no TMO alo e em 16,7% no TMO auto. Na análise univariada de Cox para fatores prognósticos, tiveram significância a fase da doença e a DECH aguda, que perderam significância na análise multivariada (p=0,069.The patients records of eighty consecutive patients with acute myeloid leukemia (AML submitted to allogeneic (allo BMT and autologous (auto BMT bone marrow transplantation (BMT between 1989 and 2001 were assessed. Forty percent were alive in the end of the study; 37.9% of allogeneic patients and 45.4% of autologous. Factors such as gender, the French-American-British AML classification, induction treatment, number of infused cells and the conditioning regiment did not have any impact in survival. Patients with AML from M1 to M4, and who were consolidated with high doses of arabinoside

  1. Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine 153 Malignant Pleural Effusion in Acute Myeloid Leukemia with Hepatitis B Virus Infection

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    C Suharti

    2016-05-01

    Full Text Available Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural fluid cytology was myeloblast consistent with acute myeloid leukemia (AML. Bone marrow aspiration smear, bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without maturation (AML M0-FAB classification. Key words: Acute myeloid leukemia, pleural effusion, infection.

  2. Idhifa Approved for Some with Acute Myeloid Leukemia

    Science.gov (United States)

    ... html Idhifa Approved for Some With Acute Myeloid Leukemia For adults with specific genetic mutation To use ... that leads to relapsed or refractory acute myeloid leukemia (AML). The mutation in the IDH2 gene can ...

  3. Combined orbital proptosis and exudative retinal detachment as initial manifestations of acute myeloid leukemia.

    Science.gov (United States)

    Khaja, Wassia A; Pogrebniak, Alexander E; Bolling, James P

    2015-10-01

    We report bilateral orbital and choroidal involvement as the presenting sign of acute myeloid leukemia in a 2-year-old white girl. The patient presented with painless proptosis and subconjunctival hemorrhage. Ophthalmic examination and magnetic resonance imaging revealed bilateral leukemic infiltrates of the orbits and choroid, with an exudative retinal detachment in the right eye. Bone marrow biopsy confirmed acute myeloid leukemia. Following radiation treatment, chemotherapy, and hematopoietic stem cell transplantation, the patient was doing well 12 months after presentation. Outcomes can be poor, even with treatment; prompt recognition of ophthalmic manifestations of leukemia, including proptosis, choroidal infiltration, and retinal detachment, is necessary. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  4. Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author's Institution.

    Science.gov (United States)

    Cervantes, Gustavo M; Cayci, Zuzan

    2015-05-21

    Myeloid sarcoma (MS) of the central nervous system (CNS) is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author's institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.

  5. Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author’s Institution

    Directory of Open Access Journals (Sweden)

    Gustavo M. Cervantes

    2015-05-01

    Full Text Available Myeloid sarcoma (MS of the central nervous system (CNS is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML, chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author’s institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.

  6. Capacidade da matriz extracelular da medula óssea de induzir proliferação de células mielóides in vitro no modelo de desnutrição protéica em camundongos Capacity of the extracellular matrix of the bone marrow to induce proliferation of myeloid cells in vitro in model of protein malnutrition in mice

    Directory of Open Access Journals (Sweden)

    Cidônia de Lourdes Vituri

    2008-09-01

    Full Text Available Este trabalho tem por objetivo verificar se a matriz extracelular (MEC obtida da medula óssea de camundongos com desnutrição protéica energética sustenta a sobrevivência, se induz proliferação de células mielóides, bem como avaliar a capacidade desta MEC de interagir com citocinas hematopoiéticas in vitro. Camundongos machos "Swiss" foram submetidos à desnutrição protéica (4% de caseína até que perdessem 20% do peso inicial e o grupo-controle foi mantido com uma dieta contendo 14% de caseína. A medula óssea foi extraída com tampão PBS suplementado com 1 mg de aprotinina/mL. Os ensaios de proliferação foram realizados com a linhagem mielóide FDC-P1, pelo método colorimétrico de redução do MTT. A MEC obtida tanto do grupo-controle como do desnutrido induziu proliferação celular in vitro. Os ensaios de interação foram realizados com IL-3 e GM-CSF na concentração de 10 ρg e 500 ρg/mL, que demonstraram efeito sinérgico e efeito regulatório, respectivamente. A MEC obtida de animais do grupo desnutrido quando submetida ao ensaio de ligação ao GM-CSF mostrou maior proliferação celular do que a MEC obtida de animais do grupo-controle (pThe aim of this study was to verify the capacity of the extracellular matrix (ECM obtained from bone marrow of malnourished mice to sustain survival and to induce the proliferation of myeloid cells. We also verified the capacity of the tests to interact with in vitro hematopoietic cytokines. Male "Swiss" mice were submitted to protein malnutrition with a diet content of '4% casein until they lost 20% of the original weight, while the group-control was kept with a diet content of 14% of casein. The bone marrow was extracted with 1.0 mg of aprotinin/mL in PBS. The proliferation tests were carried out with myeloid cell line FDCP-1, by the colorimetric method of reduction of the MTT. The obtained ECM from nourished and undernourished mice induced cellular proliferation invitro. Tests

  7. Differentiation Therapy of Acute Myeloid Leukemia

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    Elzbieta Gocek

    2011-05-01

    Full Text Available Acute Myeloid Leukemia (AML is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA, which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL in which a PML-RARA fusion protein is generated by a t(15;17(q22;q12 chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS. Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  8. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  9. Nucleophosmin 1 expression in acute myeloid leukemia

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    Mohammad Davoudi

    2015-09-01

    Full Text Available Nucleophosmin1 is a multifunctional protein that shuttles between nucleus and cytoplasm in some subtypes of acute myeloid leukemias. Mutated Nucleophosmin1 expresses aberrantly in the cytoplasm of the cell and transports from nucleolus to the cytoplasm. It is diagnosed by immunohistochemical techniques, flow cytometry assay and mutational analysis.The aim of this study is to evaluate the effects of Nucleophosmin1 mutation on the clinical presentations, prognosis, diagnosis and the treatment of acute myeloid leukemia. Thirteen articles were extracted from PubMed, Google scholar and Scopus in which the Nucleophosmin1 mutation correlated with gingival hyperplasia, high white blood cell count, lymphadenopathy, high platelet count and other signs and symptoms of myelomonocytic and monocytic acute myeloid leukemias. This mutation is a provisional entity in the classification of acute myeloid leukemia, which influences on the prognosis, clinical course and the treatment of some subtypes of acute myeloid leukemias. Nucleophosmin1 mutation has favorable prognostic value in the absence of other concomitant mutations.

  10. Temporal assessment of bone marrow lesions on magnetic resonance imaging in a canine model of knee osteoarthritis: impact of sequence selection.

    Science.gov (United States)

    d'Anjou, M-A; Troncy, E; Moreau, M; Abram, F; Raynauld, J-P; Martel-Pelletier, J; Pelletier, J-P

    2008-11-01

    To assess the evolution of bone marrow lesions (BMLs) in a canine model of knee osteoarthritis (OA) using three different magnetic resonance imaging (MRI) sequences. Three MRI sequences [coronal, T1-weighted three-dimensional fast gradient recalled echo (T1-GRE), sagittal fat-suppressed 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo with fat saturation (T2-FS)] were performed at baseline, and at week 4, 8 and 26 in five dogs following transection of the anterior cruciate ligament. The same reader scored (0-3) subchondral BMLs twice, in blinded conditions, according to their extent in nine joint subregions, for all imaging sessions, and independently on the three MRI sequences. Correlation coefficients and Bland-Altman plots evaluated intra-reader repeatability. Readings scores were averaged and the nine subregions were summed to generate global BML scores. BMLs were most prevalent in the central and medial portions of the tibial plateau. Intra-reader repeatability was good to excellent for each sequence (r(s)=0.87-0.97; Pcanine OA model, the extent of BMLs varies in time on different MRI sequences. Until the complex nature of these lesions is fully resolved, it is suggested that to accurately assess the size and extent of BMLs, a combination of different sequences should be used.

  11. High expression of lnc-CRNDE presents as a biomarker for acute myeloid leukemia and promotes the malignant progression in acute myeloid leukemia cell line U937.

    Science.gov (United States)

    Wang, Y; Zhou, Q; Ma, J-J

    2018-02-01

    To detect the expression of long non-coding RNA-CRNDE in patients with acute myeloid leukemia and its effect on proliferation and apoptosis in acute myeloid leukemia cell line U937. 81 cases of newly diagnosed acute myeloid leukemia (AML) were enrolled, and 35 non-malignant hematological patients were selected as controls. Quantitative RT-PCR (qRT-PCR) was performed to detect the expression of lncRNA-CRNDE in the bone marrow specimens of the subjects, and the difference between the two groups was also compared. The correlation between the expression of lncRNA-CRNDE and the sex, age, classification and total survival of clinical patients was analyzed according to the clinical data. U937 cells and monocytes isolated from normal people were cultured, and the expression of lncRNA-CRNDE in acute myeloid leukemia cell line U937 and normal monocytes was compared. SiRNA-CRNDE and pcDNA-CRNDE were transfected into U937 cells, and cell counting kit-8 (CCK-8) assay was performed to detect proliferation of U937 cells, Annexin V/PI flow cytometry was carried out to detect cell apoptosis. Cell cycle was measured by flow cytometry. The expression of lncRNA-CRNDE in patients with AML and U937 cells was significantly higher than that in non-malignant hematological controls. Results of clinical data showed that the expression of lncRNA-CRNDE was associated with the classification and total survival of myeloid leukemia in clinical patients. After transfection of siRNA-CRNDE, the proliferation and cloning ability of U937 cells decreased, while the apoptosis increased (p < 0.01) and cells were arrested in G0-G1 phase. Meanwhile, after transfection of pcDNA-CRNDE, the proliferation ability of U937 cells increased significantly, which indicated that the expression of lncRNA-CRNDE might play an essential role in promoting the proliferation of U937 cells. LncRNA-CRNDE is highly expressed in the bone marrow tissues of AML patients, and the expression level is negatively correlated with the

  12. Differential Cell Count of Bone Marrow Aspirates in Steady-state ...

    African Journals Online (AJOL)

    About 4.5 ml of blood was obtained from the antecubital vein of each child, for full blood count. Bone marrow was aspirated from the posterior superior iliac spine. Slides were stained with MayGrünwald-Giemsa stain. Proportions of erythroid, myeloid, lymphoid and megakaryocytic cells out of 250 nucleated bone marrow ...

  13. Round Window Membrane Implantation with an Active Middle Ear Implant: A Study of the Effects on the Performance of Round Window Exposure and Transducer Tip Diameter in Human Cadaveric Temporal Bones

    Science.gov (United States)

    Tringali, Stéphane; Koka, Kanthaiah; Deveze, Arnaud; Holland, N. Julian; Jenkins, Herman A.; Tollin, Daniel J.

    2010-01-01

    Objectives To assess the importance of 2 variables, transducer tip diameter and resection of the round window (RW) niche, affecting the optimization of the mechanical stimulation of the RW membrane with an active middle ear implant (AMEI). Materials and Methods: Ten temporal bones were prepared with combined atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the bony rim of the RW niche. The RW drive performance, assessed by stapes velocities using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25–1 kHz), medium (1–3 kHz) and high (3–8 kHz). Results Driving the RW produced mean peak stapes velocities (HEV) of 0.305 and 0.255 mm/s/V at 3.03 kHz, respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche drilling increased the HEV to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips, respectively. The tip diameter produced no difference in output at low and medium frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at high frequencies before and after niche drilling, respectively. Drilling the niche significantly improved the output by 4 dB at high frequencies for the 1-mm tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm tip. Conclusion The AMEI was able to successfully drive the RW membrane in cadaveric temporal bones using a classical facial recess approach. Stimulation of the RW membrane with an AMEI without drilling the niche is sufficient for successful hearing outputs. However, the resection of the bony rim of the RW niche significantly improved the RW stimulation at medium and higher frequencies. Drilling the niche enhances the exposure of the RW membrane and facilitates positioning the implant tip. PMID:20150727

  14. Formaldehyde-Associated Changes in microRNAs: Tissue and Temporal Specificity in the Rat Nose, White Blood Cells, and Bone Marrow

    Science.gov (United States)

    Fry, Rebecca C.

    2014-01-01

    MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses to formaldehyde, a critical air pollutant and known carcinogen that disrupts miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde for 7, 28, or 28 days followed by a 7-day recovery. Genome-wide miRNA expression profiles were assessed within the nasal respiratory epithelium, circulating white blood cells (WBC), and bone marrow (BM). miRNAs showed altered expression in the nose and WBC but not in the BM. Notably in the nose, miR-10b and members of the let-7 family, known nasopharyngeal carcinoma players, showed decreased expression. To integrate miRNA responses with transcriptional changes, genome-wide messenger RNA profiles were assessed in the nose and WBC. Although formaldehyde-induced changes in miRNA and transcript expression were largely tissue specific, pathway analyses revealed an enrichment of immune system/inflammation signaling in the nose and WBC. Specific to the nose was enrichment for apoptosis/proliferation signaling, involving let-7a, let-7c, and let-7f. Across all tissues and time points assessed, miRNAs were predicted to regulate between 7% and 35% of the transcriptional responses and were suggested to play a role in signaling processes including immune/inflammation-related pathways. These data inform our current hypothesis that formaldehyde-induced inflammatory signals originating in the nose may drive WBC effects. PMID:24304932

  15. Leukostasis Retinopathy: A New Clinical Manifestation of Chronic Myeloid Leukemia With Severe Hyperleukocytosis.

    Science.gov (United States)

    Awh, Caroline C; Miller, John B; Wu, David M; Eliott, Dean

    2015-01-01

    The authors report a new clinical manifestation of chronic myeloid leukemia. A 41-year-old man presented with significant visual loss, leading to a diagnosis of chronic myeloid leukemia. His white blood count exceeded that of any previously reported case of the disease with documented retinal findings (562,000/mm(3)), and clinical evaluation revealed the blockage of temporal retinal vessels by white blood cells. Hematologic findings resolved within 1 month of chemotherapy with dasatinib, and further treatment with intravitreal anti-VEGF agents resulted in the complete resolution of fundus findings. The authors propose that leukostasis retinopathy be recognized as a clinical manifestation of this life-threatening disease. Copyright 2015, SLACK Incorporated.

  16. Myeloid Sarcoma and Acute Myelomonocytic Leukemia in an Adolescent with Tetrasomy 8: Staging With {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William [Brandon Regional Health Centre, Brandon (Canada); Rakheja, Rajan; Lavoie, Josee; Marc Hickeson [McGill Univ. Health Centre, Brandon (Canada)

    2012-06-15

    Tetrasomy 8 is a relatively rare chromosomal abnormality that has been reported in only 33 cases in hematologic disorders, It is known for its association with aggressive acute myeloid leukemia (AML) and myeloid sarcoma and is considered a very poor prognostic factor. Myeloid sarcoma is a rare hematologic malignancy characterized by tumor masses consisting of immature myeloid cells, presenting at an extramedullary site. We present a case of a 17-year-old boy referred for an {sup 18}F-FDG PET/CT for the evaluation of pleural masses and spinal bone lesions seen on CT, after presenting with a 4 month history of chest pain. The PET/CT revealed extensive FDG-avid extrame-dullary disease in the soft tissues of the chest, abdomen, and pelvis, which were biopsy-proven to be myeloid sarcoma, as well as extensive intramedullary disease biopsy proven to be AML. This is the first report of the use of {sup 18}F-FDG PET/CT to stage a subset of aggressive AML and myeloid sarcoma in a patient with an associated chromosomal abnormality (tatrasomy 8)

  17. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-10-04

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  18. Suboccipital neuropathy after bone conduction device placement

    NARCIS (Netherlands)

    Faber, H.T.; Ru, J.A. de

    2013-01-01

    OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed

  19. Case Report: Myelodysplastic syndrome- associated myeloid sarcoma: an unusual clinical presentation of a rare disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Emoke Horvath

    2016-02-01

    Full Text Available Myeloid sarcoma results from the extramedullary homing and proliferation of immature myeloid precursors. We present the timeline, events and diagnostic pitfalls related to a 66 year-old male patient’s case, admitted to the Hematology Clinic for pancytopenia, fever, weight loss and fatigue. The severe cytopenia and the few blasts observed in his blood smear indicated a bone marrow biopsy. The bone marrow showed hypercellularity and multilineage dysplasia with the presence of 15% myeloblasts. After the biopsy, he promptly developed paraplegia and nuclear magnetic resonance revealed an epidural tumour which was then resected.In the epidural tumour mass blast-like, round cells were observed with a complex immunophenotype, characterized by myeloperoxidase, CD117, CD15, CD99, leucocyte common antigen positivity and a high Ki-67 proliferation index. Considering the main differential diagnostic issues, the final diagnosis was stated as myelodysplastic syndrome-associated myeloid sarcoma. The prognosis was unfavourable, the bone marrow was quickly invaded by proliferating blast cells, and despite chemotherapy attempts, the patient died.

  20. Functional exhaustion of CD4+T cells induced by co-stimulatory signals from myeloid leukaemia cells.

    Science.gov (United States)

    Ozkazanc, Didem; Yoyen-Ermis, Digdem; Tavukcuoglu, Ece; Buyukasik, Yahya; Esendagli, Gunes

    2016-12-01

    To cope with immune responses, tumour cells implement elaborate strategies such as adaptive resistance and induction of T-cell exhaustion. T-cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of co-stimulatory molecules to T-cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukaemia-derived co-stimulatory signals on CD4 + T helper (Th) cell exhaustion, which may limit anti-tumour immunity. Here, CD86 and inducible T-cell co-stimulator ligand (ICOS-LG) co-stimulatory molecules that are found on myeloid leukaemia cells supported Th cell activation and proliferation. However, under continuous stimulation, T cells co-cultured with leukaemia cells, but not with peripheral blood monocytes, became functionally exhausted. These in vitro-generated exhausted Th cells were defined by up-regulation of programmed cell death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) inhibitory receptors. They were reluctant to proliferate upon re-stimulation and produced reduced amounts of interleukin-2 (IL-2), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Nonetheless, IL-2 supplementation restored the proliferation capacity of the exhausted Th cells. When the co-stimulation supplied by the myeloid leukaemia cells were blocked, the amount of exhausted Th cells was significantly decreased. Moreover, in the bone marrow aspirates from patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS), a subpopulation of Th cells expressing PD-1, TIM-3 and/or LAG3 was identified together with CD86 + and/or ICOS-LG + myeloid blasts. Collectively, co-stimulatory signals derived from myeloid leukaemia cells possess the capacity to facilitate functional exhaustion in Th cells. © 2016 John Wiley & Sons Ltd.

  1. Mesenchymal stromal cells in myeloid malignancies.

    Science.gov (United States)

    Schroeder, Thomas; Geyh, Stefanie; Germing, Ulrich; Haas, Rainer

    2016-12-01

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis. Additionally, it was demonstrated as a 'proof of principle' that genetic disruption of cells of the mesenchymal or osteoblastic lineage can induce MDS, MPS or AML in mice. In this review, we summarize the current knowledge about the contribution of the BM microenvironment, in particular mesenchymal stromal cells (MSC) to the pathogenesis of AML and MDS. Furthermore, potential models integrating the BM microenvironment into the pathophysiology of these myeloid disorders are discussed. Finally, strategies to therapeutically exploit this knowledge and to interfere with the crosstalk between clonal hematopoietic cells and altered stem cell niches are introduced.

  2. Luteoloside Inhibits Proliferation of Human Chronic Myeloid ...

    African Journals Online (AJOL)

    Purpose: To investigate the effects of luteoloside on the proliferation of human chronic myeloid leukemia K562 cells and whether luteoloside induces cell cycle arrest and apoptosis in K562 cells. Methods: Luteoloside's cytotoxicity was assessed using a cell counting kit. Cell cycle distribution was analysed by flow cytometry ...

  3. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

    Han Li-na, [No Value; Zhou Jin, [No Value; Schuringa, Jan Jacob; Vellenga, Edo

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials. Data sources The data in this article were collected from PubMed database with relevant

  4. Chronic myeloid leukemia presented with priapism: Effective ...

    African Journals Online (AJOL)

    2015-02-01

    Feb 1, 2015 ... of sexual stimulation, trauma, previous similar episodes, use of medications or any chronic illness. On physical examination, the patient had pallor. The spleen and liver. Chronic myeloid leukemia presented with priapism: Effective management with prompt leukapheresis. H Ergenc, C Varım, C Karacaer, ...

  5. Acute myeloid leukemia in the vascular niche

    NARCIS (Netherlands)

    Cogle, Christopher R.; Bosse, Raphael C.; Brewer, Takae; Migdady, Yazan; Shirzad, Reza; Kampen, Kim Rosalie; Saki, Najmaldin

    2016-01-01

    The greatest challenge in treating acute myeloid leukemia (AML) is refractory disease. With approximately 60-80% of AML patients dying of relapsed disease, there is an urgent need to define and target mechanisms of drug resistance. Unfortunately, targeting cell-intrinsic resistance has failed to

  6. Recurrent Cytogenetic Abnormalities in Acute Myeloid Leukemia.

    Science.gov (United States)

    Yang, John J; Park, Tae Sung; Wan, Thomas S K

    2017-01-01

    The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification. Brief morphologic, cytogenetic, and clinical characteristics are summarized, so as to provide a concise reference to cancer cytogenetic laboratories. Morphology based on FAB classification is used together with the current WHO classification due to frequent mentioning in a vast number of reference literatures. Characteristic chromosomal aberrations of other myeloid neoplasms such as myelodysplastic syndrome and myeloproliferative neoplasm will be discussed in separate chapters-except for certain abnormalities such as t(9;22) in de novo AML. Gene mutations detected in normal karyotype AML by cutting edge next generation sequencing technology are also briefly mentioned.

  7. Myeloid malignancies: mutations, models and management

    Directory of Open Access Journals (Sweden)

    Murati Anne

    2012-07-01

    Full Text Available Abstract Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia and acute (acute myeloid leukemia stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS, transcription factors (e.g. CEBPA, ETV6, RUNX1, epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX, tumor suppressors (e.g. TP53, and components of the spliceosome (e.g. SF3B1, SRSF2. Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach.

  8. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone.

    Science.gov (United States)

    Cho, Sun Wook; Soki, Fabiana N; Koh, Amy J; Eber, Matthew R; Entezami, Payam; Park, Serk In; van Rooijen, Nico; McCauley, Laurie K

    2014-01-28

    Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms(+) myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTH-induced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68(+) cells, whereas clodronate liposome-treated mice had increased CD68(+) and CD163(+) cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis.

  9. Chloroma of the testis in a patient with a history of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Sanei

    2017-01-01

    Full Text Available Chloroma, or granulocytic sarcoma, is a rare extramedullary solid hematologic cancer, found concomitant with acute myeloid leukemia. It is infrequently associated with other myeloproliferative disorders or chronic myelogenous leukemia. Chloroma of the testis after allogeneic bone marrow transplantation is particularly sparsely represented in the literature. It is suggested that an appropriate panel of marker studies be performed along with clinical correlation and circumspection to avoid misleading conclusions. We report an interesting case of a 32-year-old male with a clinical history of acute myelogenous leukemia, postallogeneic peripheral blood stem cell transplantation that was found to have chloroma of the right testis.

  10. DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE

    OpenAIRE

    A. V. Vinogradov; A. V. Rezaykin; A. G. Sergeev

    2015-01-01

    Aim: to estimate the frequency of DNMT3A gene exons 18–26 point mutations in acute myeloid leukemia (AML) patients (pts) using target automatic sequencing technique.Material and Methods. Bone marrow and peripheral blood samples were obtained from 34 AML pts aged 21 to 64, who were treated in Sverdlovsk Regional Hematological Centre (Ekaterinburg) during the period 2012–2014. Distribution of the pts according to FAB-classification was as follows: AML M0 – 3, M1 – 1, M2 – 12, M3 – 3, M4 – 10, M...

  11. Bone Diseases

    Science.gov (United States)

    ... need to get enough calcium, vitamin D, and exercise. You should also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds of bone problems include Low bone density and osteoporosis, which make your bones weak and ...

  12. XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells.

    Science.gov (United States)

    Moreno-Martínez, Daniel; Nomdedeu, Meritxell; Lara-Castillo, María Carmen; Etxabe, Amaia; Pratcorona, Marta; Tesi, Niccolò; Díaz-Beyá, Marina; Rozman, María; Montserrat, Emili; Urbano-Ispizua, Alvaro; Esteve, Jordi; Risueño, Ruth M

    2014-06-30

    Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.

  13. Small Intestinal Obstruction with Intussusception due to Acute Myeloid Leukemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Sangeeta Kini

    2012-01-01

    Full Text Available Myeloid sarcoma is known to precede the development of acute myeloid leukemia (AML and can be the only clinical manifestation. Gastrointestinal involvement by AML is rare with the commonest site being small intestine. Patients present with vague abdominal pain and/or obstruction. Prognosis is usually poor as most of them rapidly progress to AML. We report a case of 25-year-old man with complaints of abdominal pain and vomiting of one-year duration. OGD scopy revealed infiltration of lesser curvature of stomach. Subsequently patient came back within a week with signs and symptoms of acute intestinal obstruction for which an ileal resection was done. Although the histology of stomach biopsy and ileal segments showing similar features were thought to be non-Hodgkin's lymphoma, immunohistochemistry confirmed the diagnosis of myeloid sarcoma. Bone marrow investigations confirmed involvement by AML. Patient succumbed to the disease due to extensive involvement of AML. This case highlights the primary gastrointestinal manifestation of AML which can often prove to be a diagnostic difficulty clinically and histologically. Prompt diagnosis is essential to hasten the management.

  14. The Past, Present and Future Subclassification of Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Forthun, Rakel B; Hinrichs, Carina; Dowling, Tara H; Bruserud, Øystein; Selheim, Frode

    2016-01-01

    Acute myeloid leukemia (AML) is characterized as a heterogeneous disease where the patients are sub grouped according to several classification systems and mutational analyses. Diagnosis of AML is based on identification of the specific myeloid cell initiating the disease, quantification of immature blasts in bone marrow and peripheral blood, as well as detection of mutations and translocations. The heterogeneity of AML is caused by a block in differentiation that may occur in any of the different myeloid cell populations. These undifferentiated cells also harbor an increased proliferation potential that leads to accumulation of immature leukemic cells. The current development of more sensitive and less labor intensive analysis methods has led classification of patients from being a system based on morphology of the leukemic cells to being more sophisticated, detecting translocations and small mutations found in the whole leukemic clone or in a minor subclone. This review aims to describe the most common classification systems of AML, including frequently occurring translocations, mutations and epigenetic alterations, as well as describe traditional and novel methods for diagnosis and analysis of these patients.

  15. Bone Metastasis

    Science.gov (United States)

    ... help reduce pain and other symptoms of bone metastases. Symptoms Sometimes, bone metastasis causes no signs and ... cancers most likely to cause bone metastasis include: Breast cancer Kidney cancer Lung cancer Lymphoma Multiple myeloma Prostate ...

  16. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  17. A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia.

    Science.gov (United States)

    Găman, Amelia Maria; Dobrea, Camelia; Rotaru, Ionela

    2013-01-01

    Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH

  18. The relationship between clinical feature, complex immunophenotype, chromosome karyotype, and outcome of patients with acute myeloid leukemia in China.

    Science.gov (United States)

    Ding, Bingjie; Zhou, Lanlan; Jiang, Xuejie; Li, Xiaodong; Zhong, Qingxiu; Wang, Zhixiang; Yi, Zhengshan; Zheng, Zhongxin; Yin, Changxin; Cao, Rui; Liao, Libin; Meng, Fanyi

    2015-01-01

    Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly(+)AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly(-)AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly(+)AML and Ly(-)AML. With regard to the patients with normal karyotype only, the OS and RFS of MPAL were significantly lower than those of the Ly(+)AML and Ly(-)AML; but there were no significant differences in OS and RFS among the patients with complex karyotype. The OS rates of 3 groups with complex karyotype were lower than those of patients with normal karyotype. In Cox multivariate analysis, complex karyotype was an independent pejorative factor for both OS and RFS. Therefore, MPAL is confirmed to be a poor-risk disease while Ly(+)AML does not impact prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients with different immunophenotype. Mixed immunophenotype and complex karyotype increase the adverse risk when they coexist.

  19. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    Science.gov (United States)

    2017-09-14

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm

  20. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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  9. Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders.

    Science.gov (United States)

    Barnie, Prince Amoah; Zhang, Pan; Lv, Hongxiang; Wang, Dan; Su, Xiaolian; Su, Zhaoliang; Xu, Huaxi

    2017-02-01

    Myeloid-derived suppressor cells (MDSCs) were originally described as a heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts. In recent years, increasing number of studies have described various populations of myeloid cells with MDSC-like properties in murine models of cancer and autoimmune diseases. These studies have observed that the populations of MDSCs are increased during inflammation and autoimmune conditions. In addition, MDSCs can effectively suppress T cell responses and modulate the activity of natural killer cells and other myeloid cells. MDSCs have also been implicated in the induction of regulatory T cell production. Furthermore, these cells have the potential to suppress the autoimmune response, thereby limiting tissue injury. Myeloid regulatory cells (Mregs) are recently attracting increasing attention, since they function in proinflammatory and immune suppression in autoimmune diseases, as well as in various types of cancer. Currently, research focus is directed from MDSCs to Mregs in cancer and autoimmune diseases. The present study reviewed the suppressive roles of MDSCs in various autoimmune murine models, the immune modulation of MDSCs to T helper 17 lymphocytes, as well as the proinflammatory and immunosuppressive roles of Mregs in various types of cancer and autoimmune diseases.

  10. Epigenetic aberrations in myeloid malignancies (Review).

    Science.gov (United States)

    Takahashi, Shinichiro

    2013-09-01

    The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status. This review focuses on the current findings of aberrant epigenetic signatures by these newly described genetic alterations. Moreover, epigenetic aberrations resulting from transcription factor aberrations, such as mixed lineage leukemia (MLL) rearrangement, ecotropic viral integration site 1 (Evi1) overexpression, chromosomal translocations and the downregulation of PU.1 are also described.

  11. Molecular Pathology: Prognostic and Diagnostic Genomic Markers for Myeloid Neoplasms.

    Science.gov (United States)

    Kuo, Frank C

    2016-09-01

    Application of next-generation sequencing (NGS) on myeloid neoplasms has expanded our knowledge of genomic alterations in this group of diseases. Genomic alterations in myeloid neoplasms are complex, heterogeneous, and not specific to a disease entity. NGS-based panel testing of myeloid neoplasms can complement existing diagnostic modalities and is gaining acceptance in the clinics and diagnostic laboratories. Prospective, randomized trials to evaluate the prognostic significance of genomic markers in myeloid neoplasms are under way in academic medical centers. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. [An immunological approach to acute myeloid leukaemia].

    Science.gov (United States)

    González, B; Bueno, D; Rubio, P M; San Román, S; Plaza, D; Sastre, A; García-Miguel, P; Fernández, L; Valentín, J; Martínez, I; Pérez-Martínez, A

    2016-04-01

    Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes. A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre during 1996-2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid. A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55-67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31-45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells. Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  13. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    Science.gov (United States)

    2017-02-17

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  14. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2017-05-25

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  15. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  16. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia.

    Science.gov (United States)

    Geyh, S; Rodríguez-Paredes, M; Jäger, P; Khandanpour, C; Cadeddu, R-P; Gutekunst, J; Wilk, C M; Fenk, R; Zilkens, C; Hermsen, D; Germing, U; Kobbe, G; Lyko, F; Haas, R; Schroeder, T

    2016-03-01

    Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.

  17. Maxillo-orbital granulocytic sarcoma in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2016-01-01

    Full Text Available Granulocytic sarcoma or chloroma, a manifestation of acute myeloid leukemia (AML is a rare cause of childhood proptosis. A 14-year-old boy presented with progressively increasing unilateral proptosis and swelling of lower eyelid and face on the right side. Contrast enhanced computed tomographic images revealed enhancing infiltrates occupying the right orbit, maxillary antrum, and infratemporal fossa. Incisional biopsy from the orbital swelling and the bone marrow aspirate showing leukemic blast cells confirmed the diagnosis of AML. The peripheral smear was normal initially, but high total leukocytic count with immature blast cells was evident after 1-month of presentation. Chemotherapy brought about the remission of the disease. However, the delay in diagnosis because of negative peripheral blood smear examination and inconclusive fine-needle aspiration biopsy led to the loss of vision in right eye. Diagnosis of such case can be made by a combination of good clinical examination and relevant investigations. This case of maxillo-orbital granulocytic sarcoma is reported because of its rarity and to emphasize the clinical and cyto-histological features and problems concerning differential diagnosis.

  18. [Myeloid/natural killer cell precursor and myeloid/natural killer cell acute leukemia].

    Science.gov (United States)

    Ni, Ming; Chen, Bao-An

    2014-04-01

    With the popularity of flow cytometry, the classification of leukemia become more detailed. Myeloid/natural killer cell precursor acute leukemia and myeloid/natural killer cell acute leukemias are generally recognized as two kinds of rare leukemias and have poor prognosis. The cells expressed both myeloid and lymphatic antigens in these two leukemia and can not be diagnosed by morphology. The only basis to make a definite diagnosis is their unique Immunophenotyping. The role of CD7 and CD56 in these two leukemia are compelling, in the other hand, as the progress of cell differentiation research, there are many new awareness of NK cell differentiation. In this article, the biological origin, clinical manifestation, diagnosis, treatment and the role of CD7 and CD56 in these two leukemia are briefly summarized.

  19. Project Temporalities

    DEFF Research Database (Denmark)

    Tryggestad, Kjell; Justesen, Lise; Mouritsen, Jan

    2013-01-01

    Purpose – The purpose of this paper is to explore how animals can become stakeholders in interaction with project management technologies and what happens with project temporalities when new and surprising stakeholders become part of a project and a recognized matter of concern to be taken...... into account. Design/methodology/approach – The paper is based on a qualitative case study of a project in the building industry. The authors use actor-network theory (ANT) to analyze the emergence of animal stakeholders, stakes and temporalities. Findings – The study shows how project temporalities can...... multiply in interaction with project management technologies and how conventional linear conceptions of project time may be contested with the emergence of new non-human stakeholders and temporalities. Research limitations/implications – The study draws on ANT to show how animals can become stakeholders...

  20. Spontaneous Bilateral Meningoencephalocoeles of the Temporal Bones

    Directory of Open Access Journals (Sweden)

    Oliver Rose

    2013-01-01

    Full Text Available Spontaneous tegmen tympani defects are rare with even rarer bilateral cases. The symptoms are nonspecific; hence, a high index of suspicion is required to prevent serious intracranial complications. We present a case of spontaneous bilateral tegmen tympani defects with associated meningoencephalocoeles in a 54-year-old male who presented with the signs and symptoms of severe meningitis. After careful workup which included a lumbar puncture, CT and MRI scans, both defects were repaired using a middle fossa approach. The patient made an uneventful recovery with complete cessation of otorrhoea and improvement in his hearing.

  1. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  2. The Danish National Chronic Myeloid Neoplasia Registry

    Directory of Open Access Journals (Sweden)

    Bak M

    2016-10-01

    Full Text Available Marie Bak,1 Else Helene Ibfelt,2 Thomas Stauffer Larsen,3 Dorthe Rønnov-Jessen,4 Niels Pallisgaard,5 Ann Madelung,6 Lene Udby,1 Hans Carl Hasselbalch,1 Ole Weis Bjerrum,7 Christen Lykkegaard Andersen1,7 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Research Centre for Prevention and Health, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, 3Department of Hematology, Odense University Hospital, Odense, 4Department of Hematology, Vejle Hospital, Vejle, 5Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Roskilde, 6Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Næstved, 7Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: The Danish National Chronic Myeloid Neoplasia Registry (DCMR is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. Study population: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia. Main variables: Data are collected using standardized registration forms (so far up to four forms per patient, which are consecutively filled out online at time of diagnosis, after 2-year and 5-year follow-ups, and at end of follow-up. The forms include variables that describe clinical/paraclinical assessments, treatment, disease progression, and survival – disease-specific variables – as well as variables that are identical for all chronic myeloid malignancies. Descriptive

  3. Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia.

    Science.gov (United States)

    Niu, Jihong; Li, Henan; Zhang, Yao; Li, Jinlan; Xie, Min; Li, Lingdi; Qin, Xiaoying; Qin, Yazhen; Guo, Xiaohuan; Jiang, Qian; Liu, Yanrong; Chen, Shanshan; Huang, Xiaojun; Han, Wenling; Ruan, Guorui

    2011-06-01

    CMTM5 has been shown to exhibit tumor suppressor activities, however, its role in leukemia is unclear. Herein we firstly reported the expression and function of CMTM5 in myeloid leukemia. CMTM5 was down-regulated, or undetectable, in leukemia cell lines and bone marrow cells from leukemia patients with promoter methylation. Ectopic expression of CMTM5-v1 strongly inhibited the proliferation of K562 and MEG-01 cells. In addition, significant negative correlations were observed between CMTM5 and three leukemia-specific fusion genes (AML1-ETO, PML-RARα and BCR/ABL1). CMTM5 expression was up-regulated in patients who had undergone treatment. Therefore, CMTM5 may be involved in the pathomechanism of myeloid leukemias. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  5. BCR-ABL1- positive chronic myeloid leukemia with erythrocytosis presenting as polycythemia vera: a case report.

    Science.gov (United States)

    Cornea, Mihaela I Precup; Levrat, Emmanuel; Pugin, Paul; Betticher, Daniel C

    2015-04-08

    The World Health Organization classification of chronic myeloproliferative disease encompasses eight entities of bone marrow neoplasms, among them Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia and polycythemia vera. Polycythemia vera requires, in the majority of cases (95%), the negativity of Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 rearrangement and the presence of the Janus kinase 2 mutation. We report a case of erythrocytosis as the primary manifestation of a chronic myeloid leukemia, with the presence of the Philadelphia chromosome and the Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion gene, and in the absence of any Janus kinase 2 mutation. A 68-year-old Caucasian woman, with a history of cigarette consumption and obstructive sleep apnoea syndrome (undergoing continuous positive airway pressure treatment) had presented to our institution with fatigue and a hemoglobin level of 18.6g/L, with slight leukocytosis at 16G/L, and no other anomalies on her complete blood cell count. Examination of her arterial blood gases found only a slight hypoxemia; erythropoietin and ferritin levels were very low and could not explain a secondary erythrocytosis. Further analyses revealed the absence of any Janus kinase 2 mutation, thus excluding polycythemia vera. Taken together with a high vitamin B12 level, we conducted a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 gene analysis and bone marrow cytogenetic analysis, both of which returned positive, leading to the diagnosis of chronic myeloid leukemia. To date, this case is the first description of a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia, presenting with erythrocytosis as the initial manifestation, and mimicking a Janus kinase 2 V617F-negative polycythemia vera. Her impressive response to imatinib

  6. Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor-alpha.

    Science.gov (United States)

    Drach, J; McQueen, T; Engel, H; Andreeff, M; Robertson, K A; Collins, S J; Malavasi, F; Mehta, K

    1994-04-01

    CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T- and B-lymphocytes. In myeloid cells, CD38 is expressed during early stages of differentiation. Virtually no information is available on regulation and functions of CD38. Recently we reported that all-trans-retinoic acid (ATRA) is a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells. Here we report that ATRA-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid-alpha receptor (RAR alpha). ATRA failed to induce CD38 expression in a mutant subclone of the HL-60 myeloid leukemia cell line (designated HL-60R) that is relatively resistant to ATRA-induced granulocytic differentiation. Retroviral vector-mediated transduction of RA receptor (RAR alpha) into this HL-60R subclone completely restored the sensitivity of these cells to ATRA in terms of their ability to express CD38. In contrast, CD38 expression was not inducible by ATRA in HL-60R cells, transfected with a functional RAR beta, RAR gamma, or RXR alpha receptor. Induction of CD38 in acute promyelocytic and acute myeloblastic leukemia cells was independent of ATRA-induced cytodifferentiation. Following culture with ATRA, increased CD38 protein levels were also observed in normal CD34+ bone marrow cells, but not on normal circulating granulocytes. From these results, we conclude that CD38 is ATRA inducible in myeloid leukemia cells and normal CD34+ bone marrow cells. This effect is independent of differentiation and is mediated by RAR alpha in HL-60 cells, suggesting a similar role for RAR alpha in CD38 expression in other hematopoietic cells.

  7. Association of mutations with morphologic dysplasia in de novo acute myeloid leukemia without 2016 WHO Classification-defined cytogenetic abnormalities.

    Science.gov (United States)

    Weinberg, Olga K; Gibson, Christopher J; Blonquist, Traci M; Neuberg, Donna; Pozdnyakova, Olga; Kuo, Frank; Ebert, Benjamin L; Hasserjian, Robert P

    2018-01-11

    Despite improvements in our understanding of the molecular basis of acute myeloid leukemia, the association between genetic mutations with morphologic dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies. We found that cohesin pathway mutations (q (FDR-adjusted p)=0.046) were associated with a higher degree of megakaryocytic dysplasia and STAG2 mutations were marginally associated with greater myeloid lineage dysplasia (q=0.052). Frequent megakaryocytes with separated nuclear lobes were more commonly seen among cases with cohesin pathway mutations (q=0.010) and specifically in those with STAG2 mutations (q=0.010), as well as NPM1 mutations (q=0.022 when considering the presence of any versus no megakaryocytes with separated nuclear lobes). RAS pathway mutations (q=0.006) and FLT3-ITD (q=0.006) were significantly more frequent in cases without evaluable erythroid cells. In univariate analysis of the 153 patients treated with induction chemotherapy, NPM1 mutations were associated with longer event-free survival (EFS, p=0.042), while RUNX1 (p=0.042), NF1 (p=0.040), frequent micromegakaryocytes (p=0.018) and presence of a subclone (p=0.002) were associated with shorter EFS. In multivariable modelling, NPM1 was associated with longer EFS, while presence of a subclone and frequent micromegakaryocytes remained significantly associated with shorter EFS. Copyright © 2018, Ferrata Storti Foundation.

  8. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  9. Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia.

    Science.gov (United States)

    Rydström, Anna; Hallner, Alexander; Aurelius, Johan; Sander, Frida Ewald; Bernson, Elin; Kiffin, Roberta; Thoren, Fredrik Bergh; Hellstrand, Kristoffer; Martner, Anna

    2017-08-01

    Relapse of leukemia in the postchemotherapy phase contributes to the poor prognosis and survival in patients with acute myeloid leukemia (AML). In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse. The dynamics of myeloid cell counts and expression of activation markers was assessed before and after cycles of immunotherapy and correlated with clinical outcome in terms of relapse risk and survival. During cycles, a pronounced increase in blood eosinophil counts was observed along with a reduction in monocyte and neutrophil counts. A strong reduction of blood monocyte counts during the first HDC/IL-2 treatment cycle predicted leukemia-free survival. The HDC component of the immunotherapy exerts agonist activity at histamine type 2 receptors (H2Rs) that are expressed by myeloid cells. It was observed that the density of H2 R expression in blood monocytes increased during cycles of immunotherapy and that high monocyte H2R expression implied reduced relapse risk and improved overall survival. Several other activation markers, including HLA-DR, CD86, and CD40, were induced in monocytes and dendritic cells during immunotherapy but did not predict clinical outcome. In addition, expression of HLA-ABC increased in all myeloid populations during therapy. A low expression of HLA-ABC was associated with reduced relapse risk. These results suggest that aspects of myeloid cell biology may impact clinical benefit of relapse-preventive immunotherapy in AML. © Society for Leukocyte Biology.

  10. Bone Markers

    Science.gov (United States)

    ... Diabetes Diarrhea Disseminated Intravascular Coagulation (DIC) Down Syndrome Ebola Virus Infection Endocrine System and Syndromes Epilepsy Excessive ... to keep bones alive and sturdy. During early childhood and in the teenage years, new bone is ...

  11. The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification

    OpenAIRE

    Ko, Po-Shen; Liu, Yao-Chung; Yeh, Chiu-Mei; Gau, Jyh-Pyng; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Tzeng, Cheng-Hwai; Chen, Po-Min; Chiou, Tzeon-Jye; Liu, Chia-Jen; Liu, Jin-Hwang

    2017-01-01

    We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other gr...

  12. The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Yonal Ipek

    2012-02-01

    Full Text Available Abstract Introduction Therapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens. Case presentation We report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a. Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34, deletion 20 (q11.2q13.1 karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situhybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine and our patient died in the 11th month after diagnosis. Conclusions The median survival in therapy-related acute myeloid leukemia is shorter compared to de novoacute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.

  13. A segmentation method based on HMRF for the aided diagnosis of acute myeloid leukemia.

    Science.gov (United States)

    Su, Jie; Liu, Shuai; Song, Jinming

    2017-12-01

    The diagnosis of acute myeloid leukemia (AML) is purely dependent on counting the percentages of blasts (>20%) in the peripheral blood or bone marrow. Manual microscopic examination of peripheral blood or bone marrow aspirate smears is time consuming and less accurate. The first and very important step in blast recognition is the segmentation of the cells from the background for further cell feature extraction and cell classification. In this paper, we aimed to utilize computer technologies in image analysis and artificial intelligence to develop an automatic program for blast recognition and counting in the aspirate smears. We proposed a method to analyze the aspirate smear images, which first performs segmentation of the cells by k-means cluster, then builds cell image representing model by HMRF (Hidden-Markov Random Field), estimates model parameters through probability of EM (expectation maximization), carries out convergence iteration until optimal value, and finally achieves second stage refined segmentation. Furthermore, the segmentation results are compared with several other methods using six classes of cells respectively. The proposed method was applied to six groups of cells from 61 bone marrow aspirate images, and compared with other algorithms for its performance on the analysis of the whole images, the segmentation of nucleus, and the efficiency of calculation. It showed improved segmentation results in both the cropped images and the whole images, which provide the base for down-stream cell feature extraction and identification. Segmentation of the aspirate smear images using the proposed method helps the analyst in differentiating six groups of cells and in the determination of blasts counting, which will be of great significance for the diagnosis of acute myeloid leukemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Hepatic myeloid sarcoma preceding acute megakaryoblastic leukemia with t(1;22 in an infant: Case report

    Directory of Open Access Journals (Sweden)

    Zeynep Canan Özdemir

    2016-10-01

    Full Text Available Myeloid sarcoma (MS is the tumor of immature myeloid cells involving extramedullary sites. Liver involvement of MS is rare in infant. Three months old female infant presented with hepatosplenomegaly and bicytopenia. Repeated bone marrow aspiration detected no blasts and flow cytometric analysis was normal. Abdominal magnetic resonance imaging revealed multiple nodular lesions in the liver. The biopsy results were consistent with MS. She presented with paleness and fever 8 months later. She had ongoing deep anemia, thrombocytopenia and hepatosplenomegaly. Bone marrow biopsy showed blast cell infiltration with 20% cells positive for CD61. The bone marrow karyotype investigation revealed complex quadruplet-translocation with the 46, X, t(X; 11; 22; 1 [15]/46, XX [1] karyotype. AML M7 was diagnosed and chemotherapy started. MS may occur as initial manifestation of AML with t(1;22 which is often associated with marrow fibrosis making sampling difficult. Hence cytogenetic analysis is of paramount importance in making an accurate diagnosis.

  15. Myeloid DLL4 Does Not Contribute to the Pathogenesis of Non-Alcoholic Steatohepatitis in Ldlr-/- Mice.

    Directory of Open Access Journals (Sweden)

    Mike L J Jeurissen

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by liver steatosis and inflammation. Currently, the underlying mechanisms leading to hepatic inflammation are not fully understood and consequently, therapeutic options are poor. Non-alcoholic steatohepatitis (NASH and atherosclerosis share the same etiology whereby macrophages play a key role in disease progression. Macrophage function can be modulated via activation of receptor-ligand binding of Notch signaling. Relevantly, global inhibition of Notch ligand Delta-Like Ligand-4 (DLL4 attenuates atherosclerosis by altering the macrophage-mediated inflammatory response. However, the specific contribution of macrophage DLL4 to hepatic inflammation is currently unknown. We hypothesized that myeloid DLL4 deficiency in low-density lipoprotein receptor knock-out (Ldlr-/- mice reduces hepatic inflammation. Irradiated Ldlr-/- mice were transplanted (tp with bone marrow from wild type (Wt or DLL4f/fLysMCre+/0 (DLL4del mice and fed either chow or high fat, high cholesterol (HFC diet for 11 weeks. Additionally, gene expression was assessed in bone marrow-derived macrophages (BMDM of DLL4f/fLysMCreWT and DLL4f/fLysMCre+/0 mice. In contrast to our hypothesis, inflammation was not decreased in HFC-fed DLL4del-transplanted mice. In line, in vitro, there was no difference in the expression of inflammatory genes between DLL4-deficient and wildtype bone marrow-derived macrophages. These results suggest that myeloid DLL4 deficiency does not contribute to hepatic inflammation in vivo. Since, macrophage-DLL4 expression in our model was not completely suppressed, it can't be totally excluded that complete DLL4 deletion in macrophages might lead to different results. Nevertheless, the contribution of non-myeloid Kupffer cells to notch signaling with regard to the pathogenesis of steatohepatitis is unknown and as such it is possible that, DLL4 on Kupffer cells promote the pathogenesis of steatohepatitis.

  16. CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis.

    Science.gov (United States)

    Hirai, Hideyo; Fujishita, Teruaki; Kurimoto, Kazuki; Miyachi, Hitoshi; Kitano, Satsuki; Inamoto, Susumu; Itatani, Yoshiro; Saitou, Mitinori; Maekawa, Taira; Taketo, M Mark

    2014-12-01

    To understand colon cancer metastasis, we earlier analyzed a mouse model that developed liver metastasis of cancer cells disseminated from the spleen. We suggested that CCR1(+) bone marrow (BM)-derived cells are recruited to the microenvironment of disseminated colon cancer cells, and produce metalloproteinases MMP9 and MMP2, helping metastatic colonization. In the present study, we have examined these myeloid cells expressing CCR1 and/or MMPs in detail. To this end, we have established bacterial artificial chromosome (BAC)-based transgenic mouse lines in which membrane-targeted Venus fluorescent protein (mVenus) was expressed under the control of Ccr1 gene promoter. Then, myeloid cells obtained from the BM and liver metastatic foci were analyzed by the combination of flow cytometry and cytology/immunohistochemistry, in situ RNA hybridization, or quantitative RT-PCR. We have found four distinct types of myeloid cells recruited to the metastatic foci; neutrophils, eosinophils, monocytes and fibrocytes. These cell types exhibited distinct expression patterns for CCR1, MMP2 and MMP9. Namely, neutrophils found in the early phase of cancer cell dissemination expressed CCR1 exclusively and MMP9 preferentially, whereas fibrocytes accumulated in later phase expressed MMP2 exclusively. Either genetic inactivation of Ccr1 or antibody-mediated neutrophil depletion reduced subsequent recruitment of fibrocytes. The recruitment of CCR1(+) neutrophils in early phase of colon cancer dissemination appears to cause that of fibrocytes in late phase. These results implicate the key role of CCR1 in colon cancer metastasis in this mouse model, and explain why both MMP9 and MMP2 are essential as genetically demonstrated previously. The results also suggest relevant mechanisms in humans.

  17. The role of myeloid-derived suppressor cells in immune ontogeny

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    Soren eGantt

    2014-08-01

    Full Text Available Myeloid derived suppressor cells (MDSC are a heterogeneous population of granulocytic or monocytic cells that suppress innate as well as adaptive immune responses. In healthy adults, immature myeloid cells differentiate into macrophages, dendritic cells, and granulocytes in the bone marrow, and MDSC are rarely detected in peripheral blood. However, in certain pathologies, in particular malignancies and chronic infection, differentiation of these cells is altered resulting in accumulation of circulating suppressive myeloid cells. MDSC express suppressive factors such as arginase-1, reactive oxygen species, and inducible nitric oxide synthase, which have the ability to inhibit T cell proliferation and cytoxicity, induce the expansion of regulatory T cells, and block natural killer cell activation. It is increasingly recognized that MDSC alter the immune response to several cancers, and perhaps chronic viral infections, in clinically important ways. In this review, we outline the potential contribution of MDSC to the generation of feto-maternal tolerance and to the ineffective immune responses to many infections and vaccines observed in early post-natal life. Granulocytic MDSC are present in large numbers in pregnant women and in cord blood, and wane rapidly during infancy. Furthermore, cord blood MDSC suppress in vitro T cell and NK responses, suggesting that they may play a significant role in human immune ontogeny. However, there are currently no data that demonstrate in vivo effects of MDSC on feto-maternal tolerance or immune ontogeny. Studies are ongoing to evaluate the functional importance of MDSC, including their effects on control of infection and response to vaccination in infancy. Importantly, several pharmacologic interventions have the potential to reverse MDSC function. Understanding the role of MDSC in infant ontogeny and their mechanisms of action could lead to interventions that reduce mortality due to early-life infections.

  18. BCR-ABL1-associated reduction of beta catenin antagonist Chibby1 in chronic myeloid leukemia.

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    Elisa Leo

    Full Text Available Beta Catenin signaling is critical for the self-renewal of leukemic stem cells in chronic myeloid leukemia. It is driven by multiple events, enhancing beta catenin stability and promoting its transcriptional co-activating function. We investigated the impact of BCR-ABL1 on Chibby1, a beta catenin antagonist involved in cell differentiation and transformation. Relative proximity of the Chibby1 encoding gene (C22orf2 on chromosome 22q12 to the BCR breakpoint (22q11 lets assume its involvement in beta catenin activation in chronic myeloid leukemia as a consequence of deletions of distal BCR sequences encompassing one C22orf2 allele. Forty patients with chronic myeloid leukemia in chronic phase were analyzed for C22orf2 relocation and Chibby1 expression. Fluorescent in situ hybridization analyses established that the entire C22orf2 follows BCR regardless of chromosomes involved in the translocation. In differentiated hematopoietic progenitors (bone marrow mononuclear cell fractions of 30/40 patients, the expression of Chibby1 protein was reduced below 50% of the reference value (peripheral blood mononuclear cell fractions of healthy persons. In such cell context, Chibby1 protein reduction is not dependent on C22orf2 transcriptional downmodulation; however, it is strictly dependent upon BCR-ABL1 expression because it was not observed at the moment of major molecular response under tyrosine kinase inhibitor therapy. Moreover, it was not correlated with the disease prognosis or response to therapy. Most importantly, a remarkable Chibby1 reduction was apparent in a putative BCR-ABL1+ leukemic stem cell compartment identified by a CD34+ phenotype compared to more differentiated hematopoietic progenitors. In CD34+ cells, Chibby1 reduction arises from transcriptional events and is driven by C22orf2 promoter hypermethylation. These results advance low Chibby1 expression associated with BCR-ABL1 as a component of beta catenin signaling in leukemic stem cells.

  19. The role of myeloid-derived suppressor cells in immune ontogeny.

    Science.gov (United States)

    Gantt, Soren; Gervassi, Ana; Jaspan, Heather; Horton, Helen

    2014-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of granulocytic or monocytic cells that suppress innate as well as adaptive immune responses. In healthy adults, immature myeloid cells differentiate into macrophages, dendritic cells, and granulocytes in the bone marrow and MDSC are rarely detected in peripheral blood. However, in certain pathologies, in particular malignancies and chronic infection, differentiation of these cells is altered resulting in accumulation of circulating suppressive myeloid cells. MDSC express suppressive factors such as arginase-1, reactive oxygen species, and inducible nitric oxide synthase, which have the ability to inhibit T cell proliferation and cytoxicity, induce the expansion of regulatory T cells, and block natural killer cell activation. It is increasingly recognized that MDSC alter the immune response to several cancers, and perhaps chronic viral infections, in clinically important ways. In this review, we outline the potential contribution of MDSC to the generation of feto-maternal tolerance and to the ineffective immune responses to many infections and vaccines observed in early post-natal life. Granulocytic MDSC are present in large numbers in pregnant women and in cord blood, and wane rapidly during infancy. Furthermore, cord blood MDSC suppress in vitro T cell and NK responses, suggesting that they may play a significant role in human immune ontogeny. However, there are currently no data that demonstrate in vivo effects of MDSC on feto-maternal tolerance or immune ontogeny. Studies are ongoing to evaluate the functional importance of MDSC, including their effects on control of infection and response to vaccination in infancy. Importantly, several pharmacologic interventions have the potential to reverse MDSC function. Understanding the role of MDSC in infant ontogeny and their mechanisms of action could lead to interventions that reduce mortality due to early-life infections.

  20. Temporal naturalism

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    Smolin, Lee

    2015-11-01

    Two people may claim both to be naturalists, but have divergent conceptions of basic elements of the natural world which lead them to mean different things when they talk about laws of nature, or states, or the role of mathematics in physics. These disagreements do not much affect the ordinary practice of science which is about small subsystems of the universe, described or explained against a background, idealized to be fixed. But these issues become crucial when we consider including the whole universe within our system, for then there is no fixed background to reference observables to. I argue here that the key issue responsible for divergent versions of naturalism and divergent approaches to cosmology is the conception of time. One version, which I call temporal naturalism, holds that time, in the sense of the succession of present moments, is real, and that laws of nature evolve in that time. This is contrasted with timeless naturalism, which holds that laws are immutable and the present moment and its passage are illusions. I argue that temporal naturalism is empirically more adequate than the alternatives, because it offers testable explanations for puzzles its rivals cannot address, and is likely a better basis for solving major puzzles that presently face cosmology and physics. This essay also addresses the problem of qualia and experience within naturalism and argues that only temporal naturalism can make a place for qualia as intrinsic qualities of matter.

  1. Prolonged T1 relaxation of the hemopoietic bone marrow in patients with chronic leukemia

    DEFF Research Database (Denmark)

    Jensen, K E; Sørensen, P G; Thomsen, C

    1990-01-01

    Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior...

  2. Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm.

    Science.gov (United States)

    Wang, Jen Chin; Kundra, Ajay; Andrei, Mirela; Baptiste, Stacey; Chen, Chi; Wong, Ching; Sindhu, Hemant

    2016-04-01

    Although BCR-ABL negative myeloproliferative neoplasms (MPN)--and especially myelofibrosis (MF)--are recognized to be associated with autoimmune phenomena, immune derangements in MPN have been much less studied. Myeloid-derived suppressor cells (MDSC) are one type of important immune modulator cell. Therefore, we studied MDSCs in MPN disease. MDSCs were studied in two cohorts: the first cohort was 55 patients including 16 primary myelofibrosis (PMF), 7 post-polycythemia vera (PV)-MF, 2 post-essential thrombocythemia (ET)-MF, 11 ET, 17 PV, 2 undefined MPN disorder, and 23 normal controls; the second cohort included 38 patients: 17 ET, 7 PMF, 3 ET-MF, 2 PV-MF, 9 PV patients, and 20 normal volunteers. The second cohort was studied using freshly collected specimens and a comparable age group as controls. CD11b(+), CD14(-), and CD33(+) cells were defined as MDSCs in both cohorts by flow cytometry. Since there are no differences in MDSC levels among different MPN categories, they were grouped as MPNs. The results showed that MDSCs were significantly elevated in MPNs compared with controls in both cohorts. We also performed RT-PCR and found that MPN patients have significantly elevated arginase-1 mRNA compared with controls, and sorted MDSCs were found to have suppressor T cell activity in MPNs, substantiating the hypothesis that levels of MDSCs are, in fact, deranged in MPNs. MDSC levels were not correlated with JAK2 status, white blood cells, Hb levels, platelet counts, splenomegaly, or the degree of bone marrow fibrosis (in MF). Further studies in immune therapy involving MDSC inhibitors or differentiation may be developed to treat MPN disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Acute Myeloid Leukemia: analysis of epidemiological profile and survival rate.

    Science.gov (United States)

    de Lima, Mariana Cardoso; da Silva, Denise Bousfield; Freund, Ana Paula Ferreira; Dacoregio, Juliana Shmitz; Costa, Tatiana El Jaick Bonifácio; Costa, Imaruí; Faraco, Daniel; Silva, Maurício Laerte

    2016-01-01

    To describe the epidemiological profile and the survival rate of patients with acute myeloid leukemia (AML) in a state reference pediatric hospital. Clinical-epidemiological, observational, retrospective, descriptive study. The study included new cases of patients with AML, diagnosed between 2004 and 2012, younger than 15 years. Of the 51 patients studied, 84% were white; 45% were females and 55%, males. Regarding age, 8% were younger than 1 year, 47% were aged between 1 and 10 years, and 45% were older than 10 years. The main signs/symptoms were fever (41.1%), asthenia/lack of appetite (35.2%), and hemorrhagic manifestations (27.4%). The most affected extra-medullary site was the central nervous system (14%). In 47% of patients, the white blood cell (WBC) count was below 10,000/mm(3) at diagnosis. The minimal residual disease (MRD) was less than 0.1%, on the 15th day of treatment in 16% of the sample. Medullary relapse occurred in 14% of cases. When comparing the bone marrow MRD with the vital status, it was observed that 71.42% of the patients with type M3 AML were alive, as were 54.05% of those with non-M3 AML. The death rate was 43% and the main proximate cause was septic shock (63.6%). In this study, the majority of patients were male, white, and older than 1 year. Most patients with WBC count <10,000/mm(3) at diagnosis lived. Overall survival was higher in patients with MRD <0.1%. The prognosis was better in patients with AML-M3. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. Methylation status of DDIT3 gene in Chronic Myeloid Leukemia

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    Zhu Zhao-hui

    2010-05-01

    Full Text Available Abstract Background DNA-damage-inducible transcript 3 (DDIT3, a candidate tumor suppressor gene (TSG, has been found involved in the regulation of cellular growth and differentiation. The epigenetic changes of TSGs are recently recognized as an abnormal mechanism contributing to the development of chronic myeloid leukemia (CML. The aim of this study was to investigate the methylation status of DDIT3 gene in CML patients. Methods The methylation status of DDIT3 promoter was detected in the bone marrow mononuclear cells from 53 patients with CML using methylation-specific PCR (MSP. The expression levels of DDIT3 and bcr/abl transcript were determined by real-time quantitative PCR (RQ-PCR. Clinical data of these patients were collected and analyzed. Results The aberrant methylation of DDIT3 gene promoter was found in 35 of 53 (66% CML cases. Correlation was not found between DDIT3 promoter hypermethylation and the age, sex, hemoglobin concentration, platelet counts, chromosomal abnormalities, bcr/abl transcript, and staging of CML patients (P > 0.05, but found between DDIT3 promoter hypermethylation and WBC counts of CML cases (R = 0.781, P DDIT3 transcript in CML patients was significantly lower than that in controls (median 3.28 vs 19.69, P DDIT3 transcript between methylation-positive CML cases (0.05-65.32, median 2.13 and methylation- negative CML cases (0.12-126.04, median 3.92 (P > 0.05. Conclusion Our results demonstrate that aberrant methylation of DDIT3 occurs in CML frequently.

  5. TPO/Mpl Studies in Agnogenic Myeloid Metaplasia

    Science.gov (United States)

    Hemavathy, Kirugaval C; Suppiah, Kathir; Hashmi, Gazala; Novetsky, Allan D; Wang, Jen C

    2005-01-01

    Background Agnogenic myeloid metaplasia (AMM) is one of the Philadelphia chromosome negative myeloproliferative disorder and is diagnosed by hyperplasia of atypical megakaryocytes, hepatosplenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Fibrosis is considered to be a secondary consequence of enhanced levels of fibrogenic growth factors such as TGF β1, bFGF and PDGF produced by enhanced numbers of megakaryocytes, while the primary cause is considered to be the enhanced proliferation of a defective stem cell. We have previously reported that thrombopoietin (TPO) is elevated in patients with AMM. Others have reported that Mpl protein is decreased in these patients. Since TPO is essential for the development of megakaryocytes, and Mpl protein is the receptor for TPO, we extended the study of TPO/Mpl to in vitro and in vivo cell culture systems to better understand the mechanism that leads to reduced Mpl protein in AMM patients. Results Plasma TPO levels were significantly elevated and Mpl protein levels were significantly reduced in AMM patients in concordance with previous studies. Platelet Mpl transcripts in AMM were however similar to those in controls. We also cloned Mpl cDNA from AMM patients and tested for their ability to make functional proteins in vitro and in the in vivo system of 293 T human embryonic kidney cells. Their expression including the glycosylated forms was similar to those from the controls. We also measured the level of translation initiation factor, eIF4E and found it to be increased in patients with AMM demonstrating that the reduced Mpl protein may not be due to translation defects. Conclusions Our studies using the in vitro and in vivo systems further confirm that reduced Mpl protein levels are not due to defects in its transcription/translation. Reduced Mpl protein could be due to its increased internalisation owing to enhanced plasma TPO or in vivo intrinsic defects in patients with AMM. PMID:15691382

  6. TPO/Mpl Studies in Agnogenic Myeloid Metaplasia

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    Novetsky Allan D

    2005-02-01

    Full Text Available Abstract Background Agnogenic myeloid metaplasia (AMM is one of the Philadelphia chromosome negative myeloproliferative disorder and is diagnosed by hyperplasia of atypical megakaryocytes, hepatosplenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Fibrosis is considered to be a secondary consequence of enhanced levels of fibrogenic growth factors such as TGF β1, bFGF and PDGF produced by enhanced numbers of megakaryocytes, while the primary cause is considered to be the enhanced proliferation of a defective stem cell. We have previously reported that thrombopoietin (TPO is elevated in patients with AMM. Others have reported that Mpl protein is decreased in these patients. Since TPO is essential for the development of megakaryocytes, and Mpl protein is the receptor for TPO, we extended the study of TPO/Mpl to in vitro and in vivo cell culture systems to better understand the mechanism that leads to reduced Mpl protein in AMM patients. Results Plasma TPO levels were significantly elevated and Mpl protein levels were significantly reduced in AMM patients in concordance with previous studies. Platelet Mpl transcripts in AMM were however similar to those in controls. We also cloned Mpl cDNA from AMM patients and tested for their ability to make functional proteins in vitro and in the in vivo system of 293 T human embryonic kidney cells. Their expression including the glycosylated forms was similar to those from the controls. We also measured the level of translation initiation factor, eIF4E and found it to be increased in patients with AMM demonstrating that the reduced Mpl protein may not be due to translation defects. Conclusions Our studies using the in vitro and in vivo systems further confirm that reduced Mpl protein levels are not due to defects in its transcription/translation. Reduced Mpl protein could be due to its increased internalisation owing to enhanced plasma TPO or in vivo intrinsic defects in patients with AMM.

  7. Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET)

    DEFF Research Database (Denmark)

    Barosi, Giovanni; Bordessoule, Dominique; Briere, Jean

    2005-01-01

    The European Myelofibrosis Network (EUMNET), a European research network on myelofibrosis with myeloid metaplasia (MMM), has developed a definition of response for the disease by using clinicohematologic, histologic, and cytogenetic criteria. A core set of 5 clinicohematologic criteria was selected...... (Hb) and spleen size and the presence of constitutional symptoms, while changes in platelet count and white blood cell (WBC) count served as complementary criteria and were of value for defining minor responses. A histologic response was defined by changes in bone marrow fibrosis and cellularity...

  8. Bilateral orbital myeloid sarcoma as initial manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Hmidi, Kamel; Zaouali, Sonia; Messaoud, Riadh; Mahjoub, Bahri; Ammari, Wafa; Bacha, Leila; Laatiri, Adnene; Jenzeri, Salah; Khairallah, Moncef

    2007-12-01

    Granulocytic sarcoma is a rare orbital complication of acute leukemia. It concerns primarily children under 10 years of age suffering from primitive acute myeloid leukemia. The diagnosis is made by clinical examination, computed tomography and confirmed by haematological investigations. The treatment approach is based on chemotherapy associated with intravenous steroid therapy. We report the case of a 6-year-old girl who presented with bilateral proptosis revealing acute myeloid leukemia. The patient was treated by a combination of chemotherapeutic drugs in two phases, associated with intravenous steroids. After a follow-up period of 24 months, the patient was in complete remission. The diagnosis of granulocytic sarcoma should be considered in any orbital mass of uncertain origin, particularly if it is bilateral. Special stains and immunohistochemistry play an important role in the diagnosis.

  9. T-cell/myeloid mixed-phenotype acute leukemia with monocytic differentiation and isolated 17p deletion

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    Germison Silva Lopes

    2014-07-01

    Full Text Available Mixed phenotype acute leukemia is a rare subtype of leukemia that probably arises from a hematopoietic pluripotent stem cell. The co-expression of two of myeloid, B- or T-lymphoid antigens is the hallmark of this disease. Herein, the case of a 28-year-old female patient is reported who presented with hemoglobin of 5.8 g/dL, white blood cell count of 138 × 109/L and platelet count of 12 × 109/L. The differential count of peripheral blood revealed 96% of blasts. Moreover, the patient presented with lymphadenopathy, splenomegaly and bone marrow infiltration by monocytoid blasts characterized as 7% positivity by Sudan Black cytochemical staining. Immunophenotyping revealed the involvement of blasts of both T- and monocytic lineages. The cytogenetic analysis showed an isolated 17p deletion. Thus, the diagnosis of T-cell/myeloid mixed phenotype acute leukemia was made with two particular rare features, that is, the monocytic differentiation and the 17p deletion as unique cytogenetic abnormalities. The possibility of concomitant expressions of T-cell and monocytic differentiation antigens in the same blast population is hard to explain using the classical model of hematopoiesis. However, recent studies have suggested that myeloid potential persists even when the lineage branches segregate toward B- and T-cells. The role of an isolated 17p deletion in the pathogenesis of this condition is unclear. At present, the patient is in complete remission after an allogeneic stem cell transplantation procedure.

  10. The incidence of acute myeloid leukemia in Calgary, Alberta, Canada: a retrospective cohort study

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    Andrea Christine Shysh

    2017-08-01

    Full Text Available Abstract Background The incidence rate of acute myeloid leukemia (AML was determined in the Calgary Metropolitan Area, a major Canadian city. Methods Data from all patients diagnosed with AML between January 1, 2011 and December 31, 2015 were retrieved from a single, centralized cancer cytogenetics laboratory for bone marrow samples, the sole diagnostic facility of its kind in Southern Alberta. Results The calculated incidence rate was 2.79 cases per 100,000 person-years with a median age of 60, slightly lower than previously published data. The age-standardized incidence rate for Canada was 3.46 cases per 100,000 person-years. The higher value is reflective of Calgary’s younger population compared to the rest of Canada. Higher male incidence and greatest incidence occurring at approximately the age of 85 is similar to data from other developed countries. The lower incidence rates and median age of diagnosis, in comparison with that of other high-income nations, may be due to differences in the proportion of aging citizens in the population. Conclusion This is the first published incidence rate of acute myeloid leukemia (AML in Canada across all age groups.

  11. Schlafen 4–expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia

    Science.gov (United States)

    Ding, Lin; Hayes, Michael M.; Photenhauer, Amanda; Eaton, Kathryn A.; Li, Qian; Ocadiz-Ruiz, Ramon; Merchant, Juanita L.

    2016-01-01

    Chronic Helicobacter pylori infection triggers neoplastic transformation of the gastric mucosa in a small subset of patients, but the risk factors that induce progression to gastric metaplasia have not been identified. Prior to cancer development, the oxyntic gastric glands atrophy and are replaced by metaplastic cells in response to chronic gastritis. Previously, we identified schlafen 4 (Slfn4) as a GLI1 target gene and myeloid differentiation factor that correlates with spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. Here, we tested the hypothesis that migration of SLFN4-expressing cells from the bone marrow to peripheral organs predicts preneoplastic changes in the gastric microenvironment. Lineage tracing in Helicobacter-infected Slfn4 reporter mice revealed that SLFN4+ cells migrated to the stomach, where they exhibited myeloid-derived suppressor cell (MDSC) markers and acquired the ability to inhibit T cell proliferation. SLFN4+ MDSCs were not observed in infected GLI1-deficient mice. Overexpression of sonic hedgehog ligand (SHH) in infected WT mice accelerated the appearance of SLFN4+ MDSCs in the gastric corpus. Similarly, in the stomachs of H. pylori–infected patients, the human SLFN4 ortholog SLFN12L colocalized to cells that expressed MDSC surface markers CD15+CD33+HLA-DRlo. Together, these results indicate that SLFN4 marks a GLI1-dependent population of MDSCs that predict a shift in the gastric mucosa to a metaplastic phenotype. PMID:27427984

  12. Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia.

    Science.gov (United States)

    Ding, Lin; Hayes, Michael M; Photenhauer, Amanda; Eaton, Kathryn A; Li, Qian; Ocadiz-Ruiz, Ramon; Merchant, Juanita L

    2016-08-01

    Chronic Helicobacter pylori infection triggers neoplastic transformation of the gastric mucosa in a small subset of patients, but the risk factors that induce progression to gastric metaplasia have not been identified. Prior to cancer development, the oxyntic gastric glands atrophy and are replaced by metaplastic cells in response to chronic gastritis. Previously, we identified schlafen 4 (Slfn4) as a GLI1 target gene and myeloid differentiation factor that correlates with spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. Here, we tested the hypothesis that migration of SLFN4-expressing cells from the bone marrow to peripheral organs predicts preneoplastic changes in the gastric microenvironment. Lineage tracing in Helicobacter-infected Slfn4 reporter mice revealed that SLFN4+ cells migrated to the stomach, where they exhibited myeloid-derived suppressor cell (MDSC) markers and acquired the ability to inhibit T cell proliferation. SLFN4+ MDSCs were not observed in infected GLI1-deficient mice. Overexpression of sonic hedgehog ligand (SHH) in infected WT mice accelerated the appearance of SLFN4+ MDSCs in the gastric corpus. Similarly, in the stomachs of H. pylori-infected patients, the human SLFN4 ortholog SLFN12L colocalized to cells that expressed MDSC surface markers CD15+CD33+HLA-DRlo. Together, these results indicate that SLFN4 marks a GLI1-dependent population of MDSCs that predict a shift in the gastric mucosa to a metaplastic phenotype.

  13. Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells

    Science.gov (United States)

    Zhang, Luoping; Tang, Xiaojiang; Rothman, Nathaniel; Vermeulen, Roel; Ji, Zhiying; Shen, Min; Qiu, Chuangyi; Guo, Weihong; Liu, Songwang; Reiss, Boris; Laura Beane, Freeman; Ge, Yichen; Hubbard, Alan E.; Hua, Ming; Blair, Aaron; Galvan, Noe; Ruan, Xiaolin; Alter, Blanche P.; Xin, Kerry X.; Li, Senhua; Moore, Lee E.; Kim, Sungkyoon; Xie, Yuxuan; Hayes, Richard B.; Azuma, Mariko; Hauptmann, Michael; Xiong, Jun; Stewart, Patricia; Li, Laiyu; Rappaport, Stephen M.; Huang, Hanlin; Fraumeni, Joseph F.; Smith, Martyn T.; Lan, Qing

    2010-01-01

    There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing and other industries. Epidemiological studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on formaldehyde’s ability to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse impact on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures. PMID:20056626

  14. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia.

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C; Moura, Ivan C; Hermine, Olivier

    2010-04-12

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.

  15. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C.

    2010-01-01

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML. PMID:20368581

  16. Significance of Neuropilin-1 Expression in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Tarif H. Sallam

    2013-09-01

    Full Text Available Objective: Neuropilin-1 is a vascular endothelial growth factor receptor that acts as a mediator of angiogenesis. Its importance in hematological malignancies such as acute myeloid leukemia (AML remains to be elucidated. The aim of this study was to evaluate the significance of neuropilin-1 expression in AML patients by both flow cytometry and real-time polymerase chain reaction (PCR in regard to its diagnostic and prognostic values. Materials and Methods: Bone marrow aspirates of 44 patients with de novo AML and 12 relapsed AML patients were examined in this study. Ten subjects with nonhematological malignancy serving as the control group were also included. Results: Neuropilin-1 expression by flow cytometry showed a highly significant increase in de novo and relapsed AML patients with a mean of 27.1±17.5% and 21.5±16.6%, respectively, compared to control group’s mean of 3.4±1.9%. A cut-off value of 6% was established as differentiating patients from the control group. By real-time PCR, no statistical significance was found in de novo and relapsed AML patients with a mean of 1.9±3.6 IU/L and 0.3±0.2 IU/L, respectively, compared to the control group’s mean of 0.3±0.1 IU/L. Neuropilin-1 surface expression by flow cytometry showed a significant correlation with total leukocyte count and a negative correlation with hemoglobin level in de novo AML patients. In relapsed AML patients, positive significant correlations were found with age, bone marrow blast percentage, and CD14. Neuropilin-1 mRNA level by real-time PCR showed a positive significant correlation with peripheral blood blast percentage and CD117 and a negative correlation with hemoglobin level in de novo AML patients. In relapsed patients, a positive correlation was found with lactate dehydrogenase. Conclusion: Neuropilin-1 can be used as a tool for diagnosis and prognosis in AML patients.

  17. Digitalization of a non-irradiated acute myeloid leukemia model.

    Science.gov (United States)

    Li, Rudong; Cheng, Hui; Cheng, Tao; Liu, Lei

    2016-08-26

    Computer-aided, interdisciplinary researches for biomedicine have valuable prospects, as digitalization of experimental subjects provide opportunities for saving the economic costs of researches, as well as promoting the acquisition of knowledge. Acute myeloid leukemia (AML) is intensively studied over long periods of time. Till nowaday, most of the studies primarily focus on the leukemic cells rather than how normal hematopoietic cells are affected by the leukemic environment. Accordingly, the conventional animal models for AML are mostly myeloablated as leukemia can be induced with short latency and complete penetrance. Meanwhile, most previous computational models focus on modeling the leukemic cells but not the multi-tissue leukemic body resided by both leukemic and normal blood cells. Recently, a non-irradiated AML mouse model has been established; therefore, normal hematopoietic cells can be investigated during leukemia development. Experiments based on the non-irradiated animal model have monitored the kinetics of leukemic and (intact) hematopoietic cells in multiple tissues simultaneously; and thus a systematic computational model for the multi-tissue hematopoiesis under leukemia has become possible. In the present work, we adopted the modeling methods in previous works, but aimed to model the tri-tissue (peripheral blood, spleen and bone marrow) dynamics of hematopoiesis under leukemia. The cell kinetics generated from the non-irradiated experimental model were used as the reference data for modeling. All mathematical formulas were systematically enumerated, and model parameters were estimated via numerical optimization. Multiple validations by additional experimental data were then conducted for the established computational model. In the results, we illustrated that the important fact of functional depression of hematopoietic stem/progenitor cells (HSC/HPC) in leukemic bone marrow (BM), which must require additional experiments to be established, could

  18. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  19. Chromosomal aberrations and fusion genes in myeloid malignancies.

    Science.gov (United States)

    Gianfelici, Valentina; Lahortiga, Idoya; Cools, Jan

    2012-08-01

    Since the discovery of the BCR-ABL1 fusion gene in chronic myeloid leukemia, many more fusion genes resulting from chromosomal rearrangements have been identified and characterized. The study of these fusion genes has been extremely important for our understanding of the role of chromosomal rearrangements in leukemogenesis and in oncology in general. In chronic myeloid leukemia, or related myeloproliferative malignancies caused by the expression of oncogenic fusion kinases, tyrosine kinase inhibitors are now successfully used to treat these diseases. In acute myeloid leukemias, the presence of chromosomal rearrangements, oncogenic fusion genes and point mutations in key oncogenic drivers has important prognostic value and determines the choice of therapy. In this review, the authors provide an overview of the important fusion genes present in various myeloid malignancies and their importance for clinical practice.

  20. Genetics Home Reference: core binding factor acute myeloid leukemia

    Science.gov (United States)

    ... L, Mardis ER, Wilson RK. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012 ... care or advice. Users with questions about a personal health condition should consult with a qualified healthcare ...

  1. The role of mutations in epigenetic regulators in myeloid malignancies.

    Science.gov (United States)

    Woods, Brittany A; Levine, Ross L

    2015-01-01

    Over the past decade, genomic studies have identified a number of novel and recurrent somatic mutations that affect epigenetic patterning in patients with myeloid malignancies, including myeloproliferative neoplasms, myelodysplastic syndrome, and acute myeloid leukemia. Many of these mutations occur in genes with established roles in the regulation and maintenance of DNA methylation and/or chromatin modifications in hematopoietic stem/progenitor cells. Subsequent genetic and functional studies have revealed that these mutations affect epigenetic patterning in myeloid diseases. In this review, we discuss historical and recent studies implicating epigenetic modifiers in the development and evolution of the various myeloid malignancies and discuss how this knowledge has and will lead to future clinical and biologic insights. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Myeloid sarcoma of the rib: An atypical isolated chest finding

    Directory of Open Access Journals (Sweden)

    Antonio Raucci

    2015-03-01

    Systemic treatment was administered and currently neither systemic nor local relapse has been identified. Our experience suggests surgical resection could be a valid treatment in isolated myeloid sarcoma patients.

  3. Endometrial and acute myeloid leukemia cancer genomes characterized

    Science.gov (United States)

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  4. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    F.P.G. Silva (Fernando); I. Almeida (Inês); B. Morolli (Bruno); G. Brouwer-Mandema (Geeske); H. Wessels (Hans); R. Vossen (Rolf); H. Vrieling (Harry); E.W.A. Marijt (Erik); P.J.M. Valk (Peter); J.C. Kluin-Nelemans (Hanneke); W.R. Sperr (Wolfgang); W.D. Ludwig; M. Giphart-Gassler (Micheline)

    2009-01-01

    textabstractBackground: Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when

  5. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    Silva, Fernando P. G.; Almeida, Ines; Morolli, Bruno; Brouwer-Mandema, Geeske; Wessels, Hans; Vossen, Rolf; Vrieling, Harry; Marijt, Erik W. A.; Valk, Peter J. M.; Kluin-Nelemans, Hanneke C.; Sperr, Wolfgang R.; Ludwig, Wolf-Dieter; Giphart-Gassler, Micheline

    2009-01-01

    Background Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when other

  6. Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Subramanian Murali

    2010-01-01

    Full Text Available The nephrotic syndrome (NS is a well documented complication of hematological malignancies. However, chronic myeloid leukemia (CML is rarely complicated by the NS, and it occurs usually after allogenic stem cell transplantation or interferon alpha therapy for CML. The NS as a complication of untreated CML is also rare. We report a 31-year-old patient who pre-sented with features of The NS. He was diagnosed to have CML one year ago and was on irre-gular treatment with imatinib mesylate. The renal biopsy and immunofluorescence revealed mem-branoproliferative glomerulonephritis type I. The patient was retreated with imatinib mesylate and the NS resolved gradually over three months. This maybe the third case in literature of mem-branoproliferative glomerulonephritis associated with CML.

  7. New drugs in acute myeloid leukemia.

    Science.gov (United States)

    Kadia, T M; Ravandi, F; Cortes, J; Kantarjian, H

    2016-05-01

    The standard therapy for acute myeloid leukemia (AML) has not changed meaningfully for the past four decades. Improvements in supportive care and modifications to the dose and schedule of existing agents have led to steady improvements in outcomes. However, developing new therapies for AML has been challenging. Although there have been advances in understanding the biology of AML, translating this knowledge to viable treatments has been slow. Active research is currently ongoing to address this important need and several promising drug candidates are currently in the pipeline. Here, we review some of the most advanced and promising compounds that are currently in clinical trials and may have the potential to be part of our future armamentarium. These drug candidates range from cytotoxic chemotherapies, targeted small-molecule inhibitors, and monoclonal antibodies. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Emerging therapies for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Caner Saygin

    2017-04-01

    Full Text Available Abstract Acute myeloid leukemia (AML is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH inhibitors, vadastuximab or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin, epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC inhibitors, bromodomain and extraterminal (BET inhibitors, FMS-like tyrosine kinase receptor 3 (FLT3 inhibitors, and antibody-drug conjugates (vadastuximab, as well as cell cycle inhibitors (volasertib, B-cell lymphoma 2 (BCL-2 inhibitors, and aminopeptidase inhibitors. These agents are actively undergoing clinical investigation alone or in combination with available chemotherapy.

  9. Current Management of Childhood Acute Myeloid Leukemia.

    Science.gov (United States)

    Rubnitz, Jeffrey E

    2017-02-01

    The outcome for children with acute myeloid leukemia (AML) has improved significantly over the past 30 years, with complete remission and overall survival rates exceeding 90 and 60%, respectively, in recent clinical trials. However, these improvements have not been achieved by the introduction of new agents. Instead, intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy have all contributed to this success. Nevertheless, novel therapies are needed, as the cure rates for many subtypes of childhood AML remain unacceptably low. Here, we briefly review advances in our understanding of the biology and genetics of AML, the results of recent clinical trials, and current recommendations for the treatment of children with AML.

  10. Molecular techniques for the personalised management of patients with chronic myeloid leukaemia.

    Science.gov (United States)

    Alikian, Mary; Gale, Robert Peter; Apperley, Jane F; Foroni, Letizia

    2017-03-01

    Chronic myeloid leukemia (CML) is the paradigm for targeted cancer therapy. RT-qPCR is the gold standard for monitoring response to tyrosine kinase-inhibitor (TKI) therapy based on the reduction of blood or bone marrow BCR-ABL1. Some patients with CML and very low or undetectable levels of BCR-ABL1 transcripts can stop TKI-therapy without CML recurrence. However, about 60 percent of patients discontinuing TKI-therapy have rapid leukaemia recurrence. This has increased the need for more sensitive and specific techniques to measure residual CML cells. The clinical challenge is to determine when it is safe to stop TKI-therapy. In this review we describe and critically evaluate the current state of CML clinical management, different technologies used to monitor measurable residual disease (MRD) focus on comparingRT-qPCR and new methods entering clinical practice. We discuss advantages and disadvantages of new methods.

  11. Treatment-related Myelodysplastic Syndrome in a Child With Acute Myeloid Leukemia and TPMT Heterozygosity

    DEFF Research Database (Denmark)

    Stensman, Lars M; Kjeldsen, Eigil; Nersting, Jacob

    2014-01-01

    INTRODUCTION: We describe a patient diagnosed with acute myeloid leukemia (AML) and low activity of thiopurine methyltransferase (TPMT) who developed secondary myelodysplastic syndrome after treatment. OBSERVATION: A 10-year-old boy presented with AML-M2 with t(8;21)(q22;q22) and genotyping...... revealing 3*B TPMT heterozygosity. The patient was treated according to the NOPHO-AML 2004 protocol. Two years after the treatment, the patient presented with neutropenia and thrombocytopenia. Bone marrow, including fluorescent in situ hybridization and retrospective aCGH analysis, verified therapy......-related myelodysplastic syndrome with ring chromosome 6. DISCUSSION: The clinical course of this patient raises the possibility that low-activity TPMT genotypes may influence 6TG toxicity in patients with AML and lead to an increased risk of developing secondary malignant neoplasms....

  12. Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia.

    Science.gov (United States)

    Lewis, Timothy A; Sykes, David B; Law, Jason M; Muñoz, Benito; Rustiguel, Joane K; Nonato, Maria Cristina; Scadden, David T; Schreiber, Stuart L

    2016-12-08

    Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derived from the bone marrow of a lysozyme-GFP mouse. In this fashion, GFP served as an endogenous reporter of differentiation, permitting a high-throughput phenotypic screen against the MLPCN library. Two chemical scaffolds were optimized for activity yielding compound ML390, and genetic resistance and sequencing efforts identified dihydroorotate dehydrogenase (DHODH) as the target enzyme. The DHODH inhibitor brequinar works against these leukemic cells as well. The X-ray crystal structure of ML390 bound to DHODH elucidates ML390s binding interactions.

  13. Genetics of therapy-related myelodysplasia and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Andersen, Mette Klarskov; Andersen, M.T.

    2008-01-01

    Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according to cytog......Myelodysplasia (MDS) and acute myeloid leukemia (AML) are heterogeneous, closely associated diseases arising de novo or following chemotherapy with alkylating agents, topoisomerase II inhibitors, or after radiotherapy. Whereas de novo MDS and AML are almost always subclassified according...

  14. Complement receptors in myeloid cell adhesion and phagocytosis

    OpenAIRE

    Dustin, Michael L.

    2016-01-01

    Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis and other effector functions. There are several types of complement receptors on myeloid cells including G-proteins coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosis-complement receptor 1, a single chain type I membrane protein with tandem complement regulatory repeats, complement receptor...

  15. Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    E. Bernadette Cabigas

    2014-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2, has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option.

  16. [High expression of p15 antisense RNA is a frequent event in acute myeloid leukemia].

    Science.gov (United States)

    Liao, Yufeng; Le, Donghai; Zhu, Zhankun

    2016-04-01

    To detect the presence of p15 antisense RNA(p15AS) in acute myeloid leukemia(AML). p15AS and p15 mRNA in two leukemia cell lines was detected with strand-specific primer RT-qPCR. To explore the connection between p15AS and AML, 43 patients with newly diagnosed AML and 21 patients with benign diseases (Iron deficiency anemia) as controls were enrolled. The expression level of p15AS in bone marrow cells derived from the patients and the controls were determined by strand-specific primer RT-qPCR, and its relationship with clinical features was analyzed. The two AML lines displayed high p15AS and low p15 expression. Samples derived from the AML patients showed relatively increased expression of p15AS and down-regulated p15 expression in their bone cells. In contrast, the 21 controls showed high expression of p15 but relatively low expression of the p15AS. Compared with the normal controls, the expression levels of p15 protein were significantly lower among the AML patients (PFAB subtype, total white blood cell count, platelet count, proliferative degree of bone marrow cell and karyotype classification (P>0.05 for all comparisons). High expression of p15 antisense RNA was frequently found among AML patients, and may play an important role in epigenetic silencing of p15.

  17. Acute Panmyelosis with Myelofibrosis - A Rare Subtype of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Tathagata Chatterjee

    2013-06-01

    Full Text Available One case of acute panmyelosis with myelofibrosis (APMF is being reported. A 45 year old male presented with abrupt onset of rapidly progressing low backache, weakness and pancytopenia. On examination there was no organomegaly. Peripheral blood examination revealed normocytic normochromic red blood cells with 10% circulating blasts. Flowcytometric examination of peripheral blood revealed blasts which were positive for CD 34 ,HLA- DR and myeloid associated antigens (i.e. CD13 and CD33.Blasts were negative for anti MPO. Bone marrow aspirate resulted in a dry tap. Bone marrow biopsy revealed panmyeloid proliferation with scattered blasts which were CD 34 positive on imunohistochemistry and negative for anti MPO. Reticulin stain showed grade III myelofibrosis (WHO. Differential diagnosis considered included AML-M7, MDS-RAEB II and AML with myelodysplasia . He was started on chemotherapy [idarubicin and cytarabine; 3+7 induction regimen followed by three cycles of HIDAC (High dose cytosine arabinoside] after which patient was in complete morphological remission with markedly reduced bone marrow fibrosis. He is now being worked up for allogeneic stem cell transplantation. Patient is asymptomatic at eight months of diagnosis. In conclusion these patients should be managed aggressively with AML therapy and this case report reaffirms the fact that APMF is subtype of AML.

  18. Primary aneurysmal bone cyst of coronoid process.

    Science.gov (United States)

    Goyal, Amit; Tyagi, Isha; Syal, Rajan; Agrawal, Tanu; Jain, Manoj

    2006-03-14

    Aneurysmal bone cysts are relatively uncommon in the facial skeleton. These usually affect the mandible but origin from the coronoid process is even rarer. To the best of our knowledge, this is the first reported case of a coronoid process aneurysmal bone cyst presenting as temporal fossa swelling. A 17 year old boy presented with a progressively increasing swelling in the left temporal region developed over the previous 8 months. An expansile lytic cystic lesion originating from the coronoid process of the left mandible and extending into the infratemporal and temporal fossa regions was found on CT scan. It was removed by a superior approach to the infratemporal fossa. Aneurysmal bone cyst of the coronoid process can attain enormous dimensions until the temporal region is also involved. A superior approach to the infratemporal fossa is a reasonable approach for such cases, providing wide exposure and access to all parts of the lesion and ensuring better control and complete excision.

  19. Decreased calpain activity in chronic myeloid leukemia impairs apoptosis by increasing survivin in myeloid progenitors and xiap1 in differentiating granulocytes

    Science.gov (United States)

    Huang, Weiqi; Bei, Ling; Hjort, Elizabeth E.; Eklund, Elizabeth A.

    2017-01-01

    Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure. Apoptosis resistance is one proposed mechanism. In prior studies, we identified increased expression of Growth Arrest Specific 2 (Gas2; a Calpain inhibitor) in Bcr-abl+ bone marrow progenitor cells. A number of previously described Calpain substrates might influence apoptosis in CML, including βcatenin and the X-linked Inhibitor of Apoptosis Protein 1 (Xiap1). We previously found Gas2/Calpain dependent stabilization of βcatenin in CML, and increased expression of βcatenin target genes, including Survivin (also an IAP). In the current work, we investigate contributions of Survivin and Xiap1 to Fas-resistance in Bcr-abl+ bone marrow cells. Inhibitors of these proteins are currently in clinical trials for other malignancies, but a role for either IAP in CML-LSC persistence is unknown. PMID:28881589

  20. Risk of myeloid neoplasms after solid organ transplantation

    Science.gov (United States)

    Morton, Lindsay M.; Gibson, Todd M.; Clarke, Christina A.; Lynch, Charles F.; Anderson, Lesley A.; Pfeiffer, Ruth; Landgren, Ola; Weisenburger, Dennis D.; Engels, Eric A.

    2014-01-01

    Solid organ transplant recipients have elevated cancer risks, due in part to pharmacologic immunosuppression. However, little is known about risks for hematologic malignancies of myeloid origin. We linked the US Scientific Registry of Transplant Recipients with 15 population-based cancer registries to ascertain cancer occurrence among 207,859 solid organ transplants (1987–2009). Solid organ transplant recipients had significantly elevated risk for myeloid neoplasms, with standardized incidence ratios (SIRs) of 4.6 (95% confidence interval 3.8–5.6; N=101) for myelodysplastic syndromes (MDS), 2.7 (2.2–3.2; N=125) for acute myeloid leukemia (AML), 2.3 (1.6–3.2; N=36) for chronic myeloid leukemia, and 7.2 (5.4–9.3; N=57) for polycythemia vera. SIRs were highest among younger individuals and varied by time since transplantation and organ type (Poisson regression Pneoplasms after solid organ transplantation supports a role for immune dysfunction in myeloid neoplasm etiology. The increased risks and inferior survival should heighten clinician awareness of myeloid neoplasms during follow-up of transplant recipients. PMID:24727673

  1. Blocking the APRIL circuit enhances acute myeloid leukemia cell chemosensitivity.

    Science.gov (United States)

    Bonci, Désirée; Musumeci, Maria; Coppola, Valeria; Addario, Antonio; Conticello, Concetta; Hahne, Michael; Gulisano, Massimo; Grignani, Francesco; De Maria, Ruggero

    2008-12-01

    Resistance to chemotherapy-induced cell death represents a major obstacle in the treatment of acute myeloid leukemia. APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor superfamily that plays a key role in normal B-cell development, while promoting survival and proliferation of malignant B cells. We investigated APRIL expression and activity in acute myeloid leukemia. We found that APRIL mRNA and protein, including the secreted form, are expressed in leukemic cells of patients with M0, M2 and M4 acute myeloid leukemia subtypes but not in normal hematopoietic progenitors. Retrovirus-mediated APRIL expression in normal hematopoietic progenitors confers resistance to chemotherapeutic drugs-induced apoptosis. Conversely, blocking APRIL function by recombinant soluble APRIL receptors increased chemotherapeutic drugs-induced cell adeath in acute myeloid leukemia cells. These results indicate that APRIL acts in an autocrine fashion to protect acute myeloid leukemia cells from drug-induced death and foresee a therapeutic potential of APRIL antagonists in the treatment of acute myeloid leukemia.

  2. Twist-2 controls myeloid lineage development and function.

    Directory of Open Access Journals (Sweden)

    Andrew B Sharabi

    2008-12-01

    Full Text Available Basic helix-loop-helix (bHLH transcription factors play critical roles in lymphoid and erythroid development; however, little is known about their role in myeloid lineage development. In this study, we identify the bHLH transcription factor Twist-2 as a key negative regulator of myeloid lineage development, as manifested by marked increases in mature myeloid populations of macrophages, neutrophils, and basophils in Twist-2-deficient mice. Mechanistic studies demonstrate that Twist-2 inhibits the proliferation as well as differentiation of granulocyte macrophage progenitors (GMP by interacting with and inhibiting the transcription factors Runx1 and C/EBPalpha. Moreover, Twist-2 was found to have a contrasting effect on cytokine production: inhibiting the production of proinflammatory cytokines such as interleukin-12 (IL-12 and interferon-gamma (IFNgamma while promoting the regulatory cytokine IL-10 by myeloid cells. The data from further analyses suggest that Twist-2 activates the transcription factor c-Maf, leading to IL-10 expression. In addition, Twist-2 was found to be essential for endotoxin tolerance. Thus, this study reveals the critical role of Twist-2 in regulating the development of myeloid lineages, as well as the function and inflammatory responses of mature myeloid cells.

  3. Peptide Vaccination Against Cancer Testis Antigens in Combination With Azacitidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia

    DEFF Research Database (Denmark)

    Holmberg, S.; Ortved Gang, A.; Svane, I.M.

    2016-01-01

    Myelodysplastic Syndrome (MDS) is a clonal disorder and characterized by increasing bone marrow failure due to accumulation of genetic and epigenetic changes in hematopoietic stem cells. Patients with high-risk disease have a poor prognosis and a high risk of progression to Acute Myeloid Leukemia...... (AML). The dysplastic cells harbor chromosomal breakage, point mutations and promoter hyper-methylation of tumor suppressor genes.For most patients, who are not eligible for bone marrow transplantation, hypomethylating agents, such as azacitidine (AZA), are currently the only treatment option......), which could lead to increased immune recognition of tumor cells and immune-mediated tumor cell killing. CTA’s are known to be immunogenic and are only expressed at immunoprivileged sites and on malignant cells, making them attractive as targets for therapeutic cancer vaccination....

  4. Bone Marrow Aspiration and Biopsy

    Science.gov (United States)

    ... this is short for myeloid/erythroid ratio. This calculation compares the number of myeloid cells (WBC precursors ) to erythroid cells (RBC precursors). Differential—determines whether cells in each lineage (WBC, RBC, ...

  5. Chondroblastoma of the sphenoid bone

    Directory of Open Access Journals (Sweden)

    Patrocíni, Tomas Gomes

    2008-12-01

    Full Text Available Introduction: Chondroblastoma is an uncommon cartilaginous benign neoplasm, highly destructive, which specifically appears in the epiphysis of long bones in young patients. Its occurrence is extremely rare in the cranial base, normally occurring in the temporal bone. Objective: To describe a rare case in a patient presenting with a sphenoid bone chondroblastoma that invaded the middle cranial cavity, submitted to a successful surgical resection, without recurrence after 2 years. Case Report: W.J.S, 37 years old, male, forwarded to the otorhinolaryngology service with persistent and strong otalgia for 3 months. He had normal otoscopy and without visible tumorations. The computerized tomography confirmed tumor mass in the left infra-temporal cavity, invading the middle cranial cavity. The biopsy suggested giant cells tumor. After wide resection by frontal approach via orbitozygomatic osteotomy. During the surgery, we confirmed tomographic statements and didn't find temporal bone involvement. The histopathological exam confirmed chondroblastoma. After 18 months after the surgery, he doesn't present with complaints, without motor, sensitive deficits or of cranial nerves and without recurrence tomographic signals. Conclusion: The importance of differential diagnosis of chondroblastoma is remarkable in the cranial base lesions and its therapeutic approach, whose objective must always be the major possible resection with the maximum function conservation.

  6. Radionuclide imaging of bone marrow disorders

    Energy Technology Data Exchange (ETDEWEB)

    Agool, Ali [Department of Nuclear Medicine, Medical Center Twente, Hengelo (Netherlands); University Medical Center Groningen, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, P.O. Box 30,001, Groningen (Netherlands); Glaudemans, Andor W.J.M.; Boersma, Hendrikus H.; Slart, Riemer H.J.A. [University Medical Center Groningen, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, P.O. Box 30,001, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University Medical Center Groningen, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, P.O. Box 30,001, Groningen (Netherlands); Ghent University, Ghent (Belgium); Vellenga, Edo [University Medical Center Groningen, University of Groningen, Department of Hematology, Groningen (Netherlands)

    2011-01-15

    Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as {sup 99m}Tc-nanocolloid, {sup 99m}Tc-sulphur colloid, {sup 111}In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using {sup 18}F-FDG and {sup 18}F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed. (orig.)

  7. Macrophages: Their Emerging Roles in Bone

    Science.gov (United States)

    Sinder, Benjamin P; Pettit, Allison R; McCauley, Laurie K

    2016-01-01

    Macrophages are present in nearly all tissues and are critical for development, homeostasis, and regeneration. Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis. Genetic or pharmacological modulation of macrophages in vivo results in significant bone phenotypes, and these phenotypes depend on which macrophage subsets are altered. Macrophages are also key mediators of osseous wound healing and fracture repair, with distinct roles at various stages of the repair process. A central function of macrophages is their phagocytic ability. Each day, billions of cells die in the body and efferocytosis (phagocytosis of apoptotic cells) is a critical process in both clearing dead cells and recruitment of replacement progenitor cells to maintain homeostasis. Recent data suggest a role for efferocytosis in bone biology and these new mechanisms are outlined. Finally, although macrophages have an established role in primary tumors, emerging evidence suggests that macrophages in bone support cancers which preferentially metastasize to the skeleton. Collectively, this developing area of osteoimmunology raises new questions and promises to provide novel insights into pathophysiologic conditions as well as therapeutic and regenerative approaches vital for skeletal health. PMID:26531055

  8. Karyotype of cryopreserved bone marrow cells

    Directory of Open Access Journals (Sweden)

    M.L.L.F. Chauffaille

    2003-07-01

    Full Text Available The analysis of chromosomal abnormalities is important for the study of hematological neoplastic disorders since it facilitates classification of the disease. The ability to perform chromosome analysis of cryopreserved malignant marrow or peripheral blast cells is important for retrospective studies. In the present study, we compared the karyotype of fresh bone marrow cells (20 metaphases to that of cells stored with a simplified cryopreservation method, evaluated the effect of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF as an in vitro mitotic index stimulator, and compared the cell viability and chromosome morphology of fresh and cryopreserved cells whenever possible (sufficient metaphases for analysis. Twenty-five bone marrow samples from 24 patients with hematological disorders such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, megaloblastic anemia and lymphoma (8, 3, 3, 8, 1, and 1 patients, respectively were selected at diagnosis, at relapse or during routine follow-up and one sample was obtained from a bone marrow donor after informed consent. Average cell viability before and after freezing was 98.8 and 78.5%, respectively (P < 0.05. Cytogenetic analysis was successful in 76% of fresh cell cultures, as opposed to 52% of cryopreserved samples (P < 0.05. GM-CSF had no proliferative effect before or after freezing. The morphological aspects of the chromosomes in fresh and cryopreserved cells were subjectively the same. The present study shows that cytogenetic analysis of cryopreserved bone marrow cells can be a reliable alternative when fresh cell analysis cannot be done, notwithstanding the reduced viability and lower percent of successful analysis that are associated with freezing.

  9. Dasatinib in chronic myeloid leukemia: a review

    Directory of Open Access Journals (Sweden)

    Dolly G Aguilera

    2009-03-01

    Full Text Available Dolly G Aguilera1, Apostolia M Tsimberidou21Department of Hematology-Oncology and Stem Cell Transplantation, Children’s Memorial Hospital, Northwestern University, Chicago, IL, USA; 2Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston Texas USAAbstract: Deregulated BCR-ABL tyrosine kinase (TK activity is the molecular marker for chronic myeloid leukemia (CML, which provides an identifiable target for developing therapeutic agents. Imatinib mesylate, a BCR-ABL TK inhibitor, is the frontline therapy for CML. Despite the stunning efficacy of this agent, a small number of patients develop a suboptimal response or resistance to imatinib. In newly diagnosed patients with chronic phase CML, the rate of resistance to imatinib at 4 years was up to 20%, increasing to 70% to 90% for patients in the accelerated/blastic phase. Resistance to imatinib led to the development of novel TK inhibitors such as dasatinib. Several clinical trials have reported more durable complete hematologic and cytogenetic responses with this agent in patients who are resistant or intolerant to imatinib. Dasatinib is well tolerated and has broad efficacy, resulting in durable responses in patients with any BCR-ABL mutation except for T3151 and mutations in codon 317 – most commonly F317L – including mutations that were highly resistant to imatinib, such as L248, Y253, E255, F359, and H396. Dasatinib is recommended for CML in chronic, blastic or accelerated phase that is resistant or intolerant to imatinib. Dasatinib was approved by the FDA at 100 mg once daily as the starting dose in patients with chronic phase CML and at 70 mg twice daily in patients with accelerated or blastic phase CML. Various clinical trial results provided evidence that resistance to one TK inhibitor can be reversed with the use of a different TK inhibitor (TKI. Other second-generation TKIs with activity in CML include nilotinib, bosutinib and

  10. Lamin B receptor regulates the growth and maturation of myeloid progenitors via its sterol reductase domain: implications for cholesterol biosynthesis in regulating myelopoiesis.

    Science.gov (United States)

    Subramanian, Gayathri; Chaudhury, Pulkit; Malu, Krishnakumar; Fowler, Samantha; Manmode, Rahul; Gotur, Deepali; Zwerger, Monika; Ryan, David; Roberti, Rita; Gaines, Peter

    2012-01-01

    Lamin B receptor (LBR) is a bifunctional nuclear membrane protein with N-terminal lamin B and chromatin-binding domains plus a C-terminal sterol Δ(14) reductase domain. LBR expression increases during neutrophil differentiation, and deficient expression disrupts neutrophil nuclear lobulation characteristic of Pelger-Huët anomaly. Thus, LBR plays a critical role in regulating myeloid differentiation, but how the two functional domains of LBR support this role is currently unclear. We previously identified abnormal proliferation and deficient functional maturation of promyelocytes (erythroid, myeloid, and lymphoid [EML]-derived promyelocytes) derived from EML-ic/ic cells, a myeloid model of ichthyosis (ic) bone marrow that lacks Lbr expression. In this study, we provide new evidence that cholesterol biosynthesis is important to myeloid cell growth and is supported by the sterol reductase domain of Lbr. Cholesterol biosynthesis inhibitors caused growth inhibition of EML cells that increased in EML-derived promyelocytes, whereas cells lacking Lbr exhibited complete growth arrest at both stages. Lipid production increased during wild-type neutrophil maturation, but ic/ic cells exhibited deficient levels of lipid and cholesterol production. Ectopic expression of a full-length Lbr in EML-ic/ic cells rescued both nuclear lobulation and growth arrest in cholesterol starvation conditions. Lipid production also was rescued, and a deficient respiratory burst was corrected. Expression of just the C-terminal sterol reductase domain of Lbr in ic/ic cells also improved each of these phenotypes. Our data support the conclusion that the sterol Δ(14) reductase domain of LBR plays a critical role in cholesterol biosynthesis and that this process is essential to both myeloid cell growth and functional maturation.

  11. Pathways of retinoid synthesis in mouse macrophages and bone marrow cells.

    Science.gov (United States)

    Niu, Haixia; Hadwiger, Gayla; Fujiwara, Hideji; Welch, John S

    2016-06-01

    In vivo pathways of natural retinoid metabolism and elimination have not been well characterized in primary myeloid cells, even though retinoids and retinoid receptors have been strongly implicated in regulating myeloid maturation. With the use of a upstream activation sequence-GFP reporter transgene and retrovirally expressed Gal4-retinoic acid receptor α in primary mouse bone marrow cells, we identified 2 distinct enzymatic pathways used by mouse myeloid cells ex vivo to synthesize retinoic acid receptor α ligands from free vitamin A metabolites (retinyl acetate, retinol, and retinal). Bulk Kit(+) bone marrow progenitor cells use diethylaminobenzaldehyde-sensitive enzymes, whereas bone marrow-derived macrophages use diethylaminobenzaldehyde-insensitive enzymes to synthesize natural retinoic acid receptor α-activating retinoids (all-trans retinoic acid). Bone marrow-derived macrophages do not express the diethylaminobenzaldehyde-sensitive enzymes Aldh1a1, Aldh1a2, or Aldh1a3 but instead, express Aldh3b1, which we found is capable of diethylaminobenzaldehyde-insensitive synthesis of all trans-retinoic acid. However, under steady-state and stimulated conditions in vivo, diverse bone marrow cells and peritoneal macrophages showed no evidence of intracellular retinoic acid receptor α-activating retinoids, despite expression of these enzymes and a vitamin A-sufficient diet, suggesting that the enzymatic conversion of retinal is not the rate-limiting step in the synthesis of intracellular retinoic acid receptor α-activating retinoids in myeloid bone marrow cells and that retinoic acid receptor α remains in an unliganded configuration during adult hematopoiesis. © Society for Leukocyte Biology.

  12. Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1.

    Directory of Open Access Journals (Sweden)

    Karine Z Oben

    Full Text Available An understanding of how each individual 5q chromosome critical deleted region (CDR gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs. Early Growth Response 1 (EGR1 is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell quiescence as well as the master regulator of apoptosis-p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.

  13. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    Energy Technology Data Exchange (ETDEWEB)

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2013-05-15

    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

  14. Bone marrow precursors of nonobese diabetic mice develop into defective macrophage-like dendritic cells in vitro

    NARCIS (Netherlands)

    T. Nikolic (Tatjana); M. Bunk; H.A. Drexhage (Hemmo); P.J. Leenen (Pieter)

    2004-01-01

    textabstractThe NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid

  15. Epigenetic mechanisms in acute myeloid leukemia.

    Science.gov (United States)

    Peters, Antoine H F M; Schwaller, Juerg

    2011-01-01

    Acute leukemia is characterized by clonal expansion of hematopoietic stem and progenitor cells with blocked differentiation. Clinical and experimental evidences suggest that acute myeloid leukemia (AML) is the product of several functionally cooperating genetic alterations including chromosomal translocations leading to expression of leukemogenic fusion proteins. Several AML-associated lesions target chromatin regulators like histone methyltransferases or histone acetyltransferases, including mixed-lineage leukemia 1 (MLL1) or CREB bindung protein/p300. Molecular and biochemical studies start to provide useful insights into the mechanisms of targeting and mode-of-action of such leukemogenic fusion proteins resulting in aberrant gene expression programs and AML. Chromatin modulating mechanisms are also mediating the transforming activity of key drivers of leukemogenesis by aberrant recruitment of corepressors. Recent large-scale screening efforts demonstrated that both aberrant DNA promoter methylation and aberrantly expressed microRNAs play an important role in the pathogenesis of AML as well. Current efforts to therapeutically exploit the potential reversibility of epigenetic mechanisms are focused on small molecules that inhibit DNA methyltransferases or histone deacetylases. Several phase I/II clinical trials using such compounds have reported promising, but mostly transient, clinical responses. This underscores the need to further dissect the molecular players of epigenetic mechanisms driving induction, maintenance, and potential reversibility of leukemic state to develop efficient and long-lasting targeted therapeutic strategies.

  16. Ever-advancing chronic myeloid leukemia treatment.

    Science.gov (United States)

    Kimura, Shinya; Ando, Toshihiko; Kojima, Kensuke

    2014-02-01

    Treatment of chronic myeloid leukemia (CML) has been drastically changed by the emergence of the ABL tyrosine kinase inhibitor (TKI), imatinib mesylate. However, resistance and intolerance have frequently been reported, particularly in patients with advanced-stage disease. Point mutations within the ABL kinase domain that interfere with imatinib binding are the most critical cause of imatinib resistance. To overcome this resistance, four second-generation ATP competitive ABL TKIs, dasatinib, nilotinib, bosutinib and bafetinib, have been developed. Dasatinib and nilotinib also demonstrated higher efficacy than imatinib in previously untreated CML patients in chronic phase. Despite promising clinical results, the frequently observed mutant T315I is not effectively targeted by any of the second-generation ABL TKIs. Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harbouring T315I. CML treatment is rapidly progressing and further evolution is surely expected. Moreover, it was recently reported that some CML patients who achieved sustained complete molecular response could stop TKI. CML may become the first human cancer to be conquered solely with oral medicines.

  17. Targeted therapy in chronic myeloid leukemia.

    Science.gov (United States)

    Jabbour, Elias; Cortes, Jorge E; Ghanem, Hady; O'Brien, Susan; Kantarjian, Hagop M

    2008-01-01

    Chronic myeloid leukemia (CML) is characterized by the formation of the Philadelphia chromosome and oncogenic signaling by the resulting Bcr-Abl fusion protein. Understanding the molecular basis of CML has led to the development of highly effective targeted therapies that block Bcr-Abl tyrosine kinase activity. Imatinib, the current first-line therapy for CML, induces durable treatment responses in most patients. However, patients may develop imatinib resistance, which is often due to BCR-ABL mutations. With the availability of second generation tyrosine kinase inhibitors, an effective therapeutic option other than stem cell transplantation is available following imatinib failure. Randomized trial data suggest that dasatinib treatment is superior to imatinib dose escalation in patients with imatinib resistance. Nilotinib, a recently approved analogue of imatinib, has also demonstrated encouraging treatment responses in patients with imatinib-resistant CML. Other agents (including bosutinib and INNO-406) are in clinical development. With the potential availability of multiple treatment options for patients with CML, it may be possible to tailor treatment according to individual patient or disease characteristics, for example, BCR-ABL mutations. Future CML treatment may involve combination strategies. Overall, targeted agents have significantly improved the prognosis of patients diagnosed with CML.

  18. Myeloid Sarcoma: The Clinician's Point of View

    Directory of Open Access Journals (Sweden)

    M. Malagola

    2011-01-01

    Full Text Available Myeloid Sarcoma may occur in patients with an acute or chronic myeloproliferative disorder as well as de novo, with no apparent sign or symptom of concomitant haematological disease. The patients are preferentially young male and the site of disease localization may vary from central nervous system to pleura and thorax, with a common involvement of the reticuloendothelial system. The disease often shows chromosomal rearrangements, involving chromosomes 7, 8 and 3 and sometimes a complex karyotype (more than 3 abnormalities is detected at diagnosis. The prognosis of this disease is dismal and only high-dose chemotherapy with autologous or allogeneic stem cells transplantation (auto or allo-SCT may be potentially curative. In the absence of definitive elements that can define the prognosis of extra-medullary localization of “standard risk” AML, Clinicians should pursue the collection of data from different Centres and design of homogeneous treatment strategies, that could integrate standard chemotherapy with specific approaches, such as radiotherapy, transplant procedures or, in selected cases (such as those displaying molecular abnormalities involving protein tyrosine-kinases, molecularly targeted therapies.

  19. The Epigenetic Landscape of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  20. Optimized Treatment Schedules for Chronic Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Qie He

    2016-10-01

    Full Text Available Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib have been developed to treat Chronic Myeloid Leukemia (CML. Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies. However, the design of such combination therapies (timing, sequence, etc. remains an open challenge. In this work we mathematically model the dynamics of CML response to combination therapy and analyze the impact of combination treatment schedules on treatment efficacy in patients with preexisting resistance. We then propose an optimization problem to find the best schedule of multiple therapies based on the evolution of CML according to our ordinary differential equation model. This resulting optimization problem is nontrivial due to the presence of ordinary different equation constraints and integer variables. Our model also incorporates drug toxicity constraints by tracking the dynamics of patient neutrophil counts in response to therapy. We determine optimal combination strategies that maximize time until treatment failure on hypothetical patients, using parameters estimated from clinical data in the literature.

  1. Novel therapeutic options in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Especially for patients with intermediate or high-risk AML, which often show relapse. Allogeneic hematopoietic stem cell transplantation (HSCT remains the best chance for cure. Here we review the state of the art therapy of AML, with special focus on new developments in immunotherapies and cellular therapies including HSCT and particularly discuss the impact of new conditioning and haplo-identical donor regimens for HSCT, post-transplant strategies for preventing and treating relapse, and emerging novel therapeutic options.

  2. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  3. Unfavorable-risk acute myeloid leukemia dissected.

    Science.gov (United States)

    Strickland, Stephen A; Mohan, Sanjay R; Savona, Michael R

    2016-03-01

    Acute myeloid leukemia (AML) is an immensely heterogeneous disease based on the presence of varying combinations of morphologic, immunophenotypic, genetic, and molecular characteristics identified among those diagnosed with this disease. Although current therapeutic strategies provide a reasonable likelihood of achieving a complete remission for the majority of patients, relapse rates and subsequent disease-related mortality remain unacceptably high. Improved methods of risk stratification are needed to better identify patients at considerable risk of relapse in hopes of allowing for early therapeutic intervention and/or intensification that may lead to a higher likelihood of cure. The current status of risk stratification of AML and emerging technologies with potential to improve prognostic classification and outcomes are summarized in this review. Refinement of our understanding of the impact of current pretreatment AML cytogenetic, immunophenotypic, and molecular aberrations to predict outcomes and guide therapeutic decision-making is ongoing. Emerging data suggest that incorporation of the degree of posttreatment response and/or the detection of minimal residual disease can improve the accuracy of risk stratification for individual patients. Although pretreatment disease characteristics remain the hallmark of prognostication for AML patients, posttreatment parameters such as minimal residual disease assessment and degree of response to therapy possess the ability to further refine our identification of patients with unfavorable disease and thereby influence decisions regarding therapeutic planning.

  4. Your Bones

    Science.gov (United States)

    ... the top are called the cervical (say: SIR-vih-kul) vertebrae. These bones are in the back ... purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  5. Bone Scan

    Science.gov (United States)

    ... posts Join Mayo Clinic Connect Bone scan About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  6. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  7. Novel transforming genes in murine myeloid leukemia

    NARCIS (Netherlands)

    A.M.S. Joosten (Marieke)

    2002-01-01

    textabstractLeukemia is characterised by an accumulation in the bone marrow of non-functional blood cells arrested at a particular stage of differentiation. In the process of normal hematopoiesis, errors may occur as the result of mutations in the DNA of hematopoietic precursor cells. These genetic

  8. Myeloid-derived cells in tumors: effects of radiation.

    Science.gov (United States)

    Vatner, Ralph E; Formenti, Silvia C

    2015-01-01

    The discrepancy between the in vitro and in vivo response to radiation is readily explained by the fact that tumors do not exist independently of the host organism; cancer cells grow in the context of a complex microenvironment composed of stromal cells, vasculature, and elements of the immune system. As the antitumor effect of radiotherapy depends in part on the immune system, and myeloid-derived cells in the tumor microenvironment modulate the immune response to tumors, it follows that understanding the effect of radiation on myeloid cells in the tumor is likely to be essential for comprehending the antitumor effects of radiotherapy. In this review, we describe the phenotype and function of these myeloid-derived cells, and stress the complexity of studying this important cell compartment owing to its intrinsic plasticity. With regard to the response to radiation of myeloid cells in the tumor, evidence has emerged demonstrating that it is both model and dose dependent. Deciphering the effects of myeloid-derived cells in tumors, particularly in irradiated tumors, is key for attempting to pharmacologically modulate their actions in the clinic as part of cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension.

    Science.gov (United States)

    Shah, Kandarp H; Shi, Peng; Giani, Jorge F; Janjulia, Tea; Bernstein, Ellen A; Li, You; Zhao, Tuantuan; Harrison, David G; Bernstein, Kenneth E; Shen, Xiao Z

    2015-10-23

    Chronic inflammation is a major contributor to the progressive pathology of hypertension, and T-cell activation is required for the genesis of hypertension. However, the precise role of myeloid cells in this process is unclear. To characterize and understand the role of peripheral myeloid cells in the development of hypertension. We examined myeloid cells in the periphery of hypertensive mice and found that increased numbers of CD11b(+)Gr1(+) myeloid cells in blood and the spleen are a characteristic of 3 murine models of experimental hypertension (angiotensin II, L-NG-nitroarginine methyl ester, and high salt). These cells express surface markers and transcription factors associated with immaturity and immunosuppression. Also, they produce hydrogen peroxide to suppress T-cell activation. These are characteristics of myeloid-derived suppressor cells (MDSCs). Depletion of hypertensive MDSCs increased blood pressure and renal inflammation. In contrast, adoptive transfer of wild-type MDSCs to hypertensive mice reduced blood pressure, whereas the transfer of nicotinamide adenine dinucleotide phosphate oxidase 2-deficient MDSCs did not. The accumulation of MDSCs is a characteristic of experimental models of hypertension. MDSCs limit inflammation and the increase of blood pressure through the production of hydrogen peroxide. © 2015 American Heart Association, Inc.

  10. Outcomes following splenectomy in patients with myeloid neoplasms.

    Science.gov (United States)

    Rialon, Kristy L; Speicher, Paul J; Ceppa, Eugene P; Rendell, Victoria R; Vaslef, Steven N; Beaven, Anne; Tyler, Douglas S; Blazer, Dan G

    2015-03-15

    Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. Eighty-nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality. © 2014 Wiley Periodicals, Inc.

  11. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

    Directory of Open Access Journals (Sweden)

    Sivakumar Periasamy

    2016-03-01

    Full Text Available Inhalation of Francisella tularensis (Ft causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection.

  12. ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.

    Science.gov (United States)

    Chee, L C Y; Hendy, J; Purton, L E; McArthur, G A

    2013-06-01

    All-trans retinoic acid (ATRA) is used successfully in the treatment of acute promyelocytic leukemia (APL). ATRA enhances hematopoietic stem cell self-renewal through retinoic acid receptor (RAR)γ activation while promoting differentiation of committed myeloid progenitors through RARα activation. Its lack of success in the treatment of non-APL acute myeloid leukemia (AML) may be related to ATRA's non-selectivity for the RARα and RARγ isotypes, and specific RARα activation may be more beneficial in promoting myeloid differentiation. To investigate this hypothesis, the effects of ATRA and the specific RARα agonist NRX195183 was assessed in AML1-ETO (AE)-expressing murine bone marrow (BM) progenitors. ATRA potentiated the in vitro clonogenicity of these cells while NRX195183 had the opposite effect. Morphological and flow cytometric analysis confirmed a predominantly immature myeloid population in the ATRA-treated AE cells while the NRX195183-treated cells demonstrated an increase in the mature myeloid population. Similarly, NRX195183 treatment promoted myeloid differentiation in an AE9a in vivo murine model. In the ATRA-treated AE cells, gene expression analyses revealed functional networks involving SERPINE1 and bone morphogenetic protein 2; AKT phosphorylation was upregulated. Collectively, these findings confirm the contrasting roles of specific RARα and RARγ activation in the clonogenicity and differentiation of AE cells with potential significant implications in the treatment of non-APL AML using a specific RARα agonist.

  13. File list: His.Bld.10.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: ALL.Bld.20.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Bld.50.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: ALL.Bld.05.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Unc.Bld.05.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: His.Bld.10.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: NoD.Bld.50.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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