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Sample records for acute demyelinating disease

  1. Charcot-Marie-Tooth disease masquerading as acute demyelinating encephalomyelitis-like illness.

    PubMed

    Kim, Gun-Ha; Kim, Kyoung Min; Suh, Sang-Il; Ki, Chang-Seok; Eun, Baik-Lin

    2014-07-01

    X-linked Charcot-Marie-Tooth disease (CMTX1) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX1 disease, as in other forms of Charcot-Marie-Tooth (CMT) disease, are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Mutations in the connexin-32 gene (gap junction protein β1 [GJB1]) are responsible for CMTX1 disease. In this report, we describe a patient with CMTX1 disease presenting with recurrent attacks of transient and episodic acute demyelinating encephalomyelitis (ADEM)-like symptoms without previous signs of lower extremity weakness or foot deformities; the patient, as well as his asymptomatic mother, exhibited a novel GJB1 mutation (p.Met1Ile). Differential diagnosis of recurrent and transient ADEM-like illness, if unexplained, should include the possibility of CMTX1 disease.

  2. Neuroradiological evaluation of demyelinating disease

    PubMed Central

    Tillema, Jan-Mendelt

    2013-01-01

    Central nervous system inflammatory demyelinating disease can affect patients across the life span. Consensus definitions and criteria of all of the different acquired demyelinating diseases that fall on this spectrum have magnetic resonance imaging criteria. The advances of both neuroimaging techniques and important discoveries in immunology have produced an improved understanding of these conditions and classification. Neuroimaging plays a central role in the accurate diagnosis, prognosis, disease monitoring and research efforts that are being undertaken in this disease. This review focuses on the imaging spectrum of acquired demyelinating disease. PMID:23858328

  3. Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

    PubMed

    Chevalier, N; Hieronimus, S; Vandenbos, F; Delmont, E; Cua, E; Cherick, F; Paquis, P; Michiels, J-F; Fenichel, P; Brucker-Davis, F

    2010-12-01

    Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient. PMID:20850107

  4. Nervonic acid and demyelinating disease.

    PubMed

    Sargent, J R; Coupland, K; Wilson, R

    1994-04-01

    Demyelination in adrenoleukodystrophy (ALD) is associated with an accumulation of very long chain saturated fatty acids such as 26:0 stemming from a genetic defect in the peroxisomal beta oxidation system responsible for the chain shortening of these fatty acids. Long chain monoenoic acids such as erucic acid, 22:1(n-9), can normalise elevated serum levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. Increased levels of 26:0 are accompanied by decreased nervonic acid biosynthesis in skin fibroblasts from ALD patients. Sphingolipids from post mortem MS brain have the same decreased 24:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n-9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of very long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the provision of nervonic acid in demyelinating diseases is indicated, suggesting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions.

  5. [Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

    PubMed

    Kanbayashi, Takamichi; Sonoo, Masahiro

    2015-11-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by an insidious onset showing progression over two months. However, up to 16% of CIDP patients may show acute presentation similar to Guillain-Barré syndrome (GBS). Such cases are termed acute-onset CIDP (A-CIDP). Distinguishing A-CIDP from GBS, especially the acute inflammatory demyelinating polyneuropathy (AIDP) subtype, is critical because therapeutic strategies and outcomes may differ between the two syndromes. Regarding clinical features, A-CIDP is less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with AIDP. Electrophysiological features are usually quite similar between the two, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy. Such a situation is termed treatment-related fluctuation (TRF; GBS-TRF). The distinction between GBS-TRF and A-CIDP is an important clinical issue because maintenance treatment is often required in CIDP. The diagnosis of A-CIDP should be considered when the condition of a patient with GBS deteriorates after nine weeks from onset, or when deterioration occurs three times or more.

  6. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  7. Gastroparesis secondary to a demyelinating disease: a case series

    PubMed Central

    Reddymasu, Savio C; Bonino, John; McCallum, Richard W

    2007-01-01

    Background Gastroparesis has a number of etiologies. The main ones are secondary to a complication from diabetes mellitus, related to post vagotomy or post gastric surgical resections, or idiopathic when the etiology is unclear. Gastroparesis secondary to a demyelinating disease of the brain is unusual. Case presentation A 22-year-old woman was referred for acute onset of intractable nausea and vomiting. She also had cerebellar deficits, dysphagia and paresthesias. Magnetic resonance imaging (MRI) of the brain revealed an isolated area of demyelination in the medullary region. Another 24-year-old woman had a similar presentation with right hemiplegia and MRI of the brain revealed a distal medullary region. Both these patients had an abnormal gastric emptying test. Gastroparesis and neurological deficits improved with intravenous corticosteroids. While the former patient has had no further recurrences, the latter patient developed multiple sclerosis within three months of presentation. Conclusion A demyelinating disease is a rare cause gastropareis, but should be suspected when symptoms of gastroparesis are associated with neurological deficits. MRI might help in the diagnosis and intravenous coriticosteroids can address the underlying disease process and improve gastric emptying, especially when used early during the course of the disease. PMID:17266755

  8. Self-inflicted tourniquet paralysis mimicking acute demyelinating polyneuropathy.

    PubMed

    Storm, S; Weiss, M D

    2003-05-01

    Tourniquet paralysis is an uncommon complication of surgery, and self-inflicted tourniquet paralysis has never been documented to our knowledge. We report a patient with bilateral self-induced tourniquet paralysis of the lower extremities, whose symptoms were initially attributed to an acute demyelinating sensorimotor polyneuropathy based on clinical presentation and electrodiagnostic study. After investigations failed to reveal a cause, he was found to have placed tourniquets on his legs because of a rare obsession with limb amputation known as apotemnophilia. Significant spontaneous partial resolution of clinical symptoms was noted after 6 weeks. Electrophysiologic evidence of segmental demyelination of multiple motor nerves localized to the same region may help to distinguish this condition from other forms of acute demyelinating polyneuropathy.

  9. Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases.

    PubMed

    Bar-Or, Amit; Hintzen, Rogier Q; Dale, Russell C; Rostasy, Kevin; Brück, Wolfgang; Chitnis, Tanuja

    2016-08-30

    Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatric-onset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. PMID:27572856

  10. [Magnetic-resonance tomography in differential diagnosis of brain lesions in demyelinating and systemic autoimmune diseases].

    PubMed

    Totolian, N A

    2005-01-01

    An aim of the study was to establish MRT signs that may be useful for differential diagnosis of multiple sclerosis (MS). Three groups of patients have been examined: 300 patients with MS, 35 with demyelinating diseases (acute disseminated encephalomyelitis, neuromyelitis optica--Devic's syndrome); 90 patients with systemic autoimmune diseases (systemic lupus erythematosus, primary antiphospholipid syndrome, sclerodermatitis, Sjugren's syndrome, autoimmune thyroiditis, vasculitis and vasculopathy). Classification of MRT syndromes in MS and their frequency are presented: syndrome of chronic inflammatory demyelination (79%), syndrome of acute inflammatory demyelination (9%), syndrome of multifocal degenerative leucoencephalopathy (8%), syndrome of combined multifocal diffusive leucoencephalopathy (4%). The similarity and differences in MRT semiotics of the above diseases and MS are described.

  11. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  12. Oligodendrocyte ablation as a tool to study demyelinating diseases.

    PubMed

    Pajoohesh-Ganji, Ahdeah; Miller, Robert H

    2016-06-01

    Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation. PMID:27482202

  13. Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler's virus infection.

    PubMed Central

    Dal Canto, M. C.; Lipton, H. L.

    1982-01-01

    Mice experimentally infected with Theiler's murine encephalomyelitis virus (TMEV) develop a persistent infection of the central nervous system (CNS). The most striking feature of this infection is the occurrence of inflammatory primary demyelination in the spinal cord white matter. The pathogenesis of myelin degeneration in this model has not been clarified, but morphologic and immunologic data suggest that the host immune response plays a major role in the production of myelin injury. Because of low virus titers in infected adult mice and of the small size of TMEV, virus particles have never been observed in this demyelinating model. Yet elucidation of the types of cells in the CNS supporting virus replication would be important for a better understanding of both virus persistence and virus-induced demyelinating pathology. The present paper is a sequential study of the localization of TMEV in the spinal cord in infected mice by ultrastructural immunohistochemical techniques. Results indicate that virus replication is mainly in neurons during the acute phase of the disease, while in the chronic phase viral inclusions are mainly found in macrophages in and around demyelinating lesions. Other cells are also infected, but to a lesser degree. In the neuronal system both axoplasmic and dendritic flow appear to facilitate the spread of virus in the CNS. In macrophages, the presence of virus particles and the association of virus with altered components of the cytoskeleton support active virus production rather than simple internalization. The macrophage appears to play an important role in both the establishment of virus persistence and in the process of demyelination in this animal model. Images Figure 1 and 2 Figure 3 and 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10-12 Figure 13 Figure 14 Figure 15 and 16 PMID:6275708

  14. Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler's virus infection.

    PubMed

    Dal Canto, M C; Lipton, H L

    1982-01-01

    Mice experimentally infected with Theiler's murine encephalomyelitis virus (TMEV) develop a persistent infection of the central nervous system (CNS). The most striking feature of this infection is the occurrence of inflammatory primary demyelination in the spinal cord white matter. The pathogenesis of myelin degeneration in this model has not been clarified, but morphologic and immunologic data suggest that the host immune response plays a major role in the production of myelin injury. Because of low virus titers in infected adult mice and of the small size of TMEV, virus particles have never been observed in this demyelinating model. Yet elucidation of the types of cells in the CNS supporting virus replication would be important for a better understanding of both virus persistence and virus-induced demyelinating pathology. The present paper is a sequential study of the localization of TMEV in the spinal cord in infected mice by ultrastructural immunohistochemical techniques. Results indicate that virus replication is mainly in neurons during the acute phase of the disease, while in the chronic phase viral inclusions are mainly found in macrophages in and around demyelinating lesions. Other cells are also infected, but to a lesser degree. In the neuronal system both axoplasmic and dendritic flow appear to facilitate the spread of virus in the CNS. In macrophages, the presence of virus particles and the association of virus with altered components of the cytoskeleton support active virus production rather than simple internalization. The macrophage appears to play an important role in both the establishment of virus persistence and in the process of demyelination in this animal model.

  15. Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

    NASA Astrophysics Data System (ADS)

    Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

    2007-09-01

    Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

  16. An Occult Malignancy Behind a Demyelinating Disease

    PubMed Central

    Lo Presti, Saberio; Kanagarajah, Prashanth; Pirela, Daniela; Morlote, Diana; Cusnir, Mike

    2016-01-01

    We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly); endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly. PMID:27790622

  17. Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy.

    PubMed

    Plante-Bordeneuve, Violaine; Said, Gérard

    2002-11-01

    Dejerine-Sottas disease (DSD) was originally described as a hypertrophic polyneuropathy characterized by onset in infancy or early childhood in patients born to unaffected parents. The clinical features included distal sensory changes with ataxia; pes cavus, at times with kyphoscoliosis; motor deficit and atrophy predominating in the distal lower limbs and progressing toward the proximal limbs following a length-dependent pattern; palpable nerve hypertrophy; and Argyll-Robertson pupils. The morphological hallmark was the extensive nerve and root hypertrophy associated with demyelination-remyelination of surviving, originally myelinated axons and profuse Schwann-cell proliferation forming onion bulbs. Wide variations in clinical manifestations of chronic demyelinating polyneuropathies of early onset in children born to unaffected parents have now been reported, with only some of the characteristics required in the original study, and at least seven genes encoding the myelin proteins P0, PMP22, the transcriptional factor EGR2, and others have been implicated. Thus, DSD is now a component of the hereditary demyelinating polyneuropathies of infancy that also include subsets of the recently individualized CMT4 neuropathies. The presumed recessive transmission of patients with DSD should be confirmed by molecular genetic analysis, which is still negative in a significant proportion of patients. The nerve biopsy can be useful in patients in whom genealogical or DNA abnormalities in favor of a genetic disorder are missing, because in a few patients with a progressive or relapsing course the diagnosis of early-onset chronic inflammatory demyelinating polyneuropathy must be considered. PMID:12402282

  18. Characterization of the spectrum of Korean inflammatory demyelinating diseases according to the diagnostic criteria and AQP4-Ab status

    PubMed Central

    2014-01-01

    Background The relative frequencies of demyelinating diseases among Korean patients with idiopathic inflammatory demyelinating disease of the central nervous system (IIDD) have not been sufficiently studied. We therefore describe a cohort of 203 patients with IIDD from three centers in Korea whose syndromes were identified precisely according to international clinical criteria and autoantibody to aquaporin 4 (AQP4-Ab) status. Methods In total, 260 consecutive patients were screened and 203 were included from three hospitals in Korea. All were tested for AQP4-Ab by using a cell-based assay. Patients who met the criteria for definite neuromyelitis optica (NMO) or had a positive AQP4-Ab test result were defined as the NMO group. Among the others, patients were assessed if they had acute disseminated encephalomyelitis, multiple sclerosis (MS), acute transverse myelitis, optic neuritis, or other demyelinating disease as a clinically isolated syndrome of the brain. Results Eighteen percent of patients were classified as the NMO group, 2% as acute disseminated encephalomyelitis, 18% as MS, 41% as acute transverse myelitis, 11% as optic neuritis, and 8% as other clinically isolated syndrome of the brain. AQP4-Ab was positive in 18% of patients and the relative frequency of NMO to MS (NMO/MS ratio) was 1.06. The mean duration of follow up in our patients was 64 months. Conclusions Among Korean patients with idiopathic inflammatory demyelinating diseases, the incidence of NMO may be similar to that of MS, and the overall positivity of AQP4-Ab could be lower than previously reported. In addition, acute transverse myelitis that is not associated with MS or NMO can be relatively common in these patients. Further population-based studies with AQP4-Ab are needed to determine the exact incidence of NMO and other idiopathic inflammatory demyelinating diseases in Korea. PMID:24779645

  19. The potential for oligodendrocyte proliferation during demyelinating disease.

    PubMed

    Prayoonwiwat, N; Rodriguez, M

    1993-01-01

    The potential for oligodendrocytes to proliferate in response to central nervous system injury was examined. We used intracerebral infection of Theiler's murine encephalomyelitis virus, a model for multiple sclerosis, which results in chronic demyelinating disease of SJL/J mice. Proliferating cells in spinal cord sections of adult mice were identified using simultaneous immunohistochemistry and in situ autoradiography ([3H]-thymidine incorporation). Seven different cell-specific markers were used to characterize proliferating cells as oligodendrocytes (myelin basic protein, proteolipid protein, galactocerebroside, CNPase), astrocytes (glial fibrillary acidic protein), microglia/macrophages (Griffonia simplicifolia isolectin B4) or T-lymphocytes (CD3). The average number of proliferating cells per area of spinal cord white matter was 11/mm2 in normal young adult mice compared to 61/mm2 in chronically infected mice. Most proliferating cells in normal spinal cord were not identified with these markers and were presumed to be progenitor glial cells. However, in spinal cord white matter of mice infected with Theiler's virus for approximately 4 months, 88% of proliferating cells were identified. Approximately one-third of all proliferating cells were in the oligodendrocyte lineage and expressed markers observed late in myelin differentiation. In demyelinated areas as compared to normal white matter, there was an 80- to 211-fold increase in the number of proliferating oligodendrocytes expressing myelin basic protein or proteolipid protein, respectively. The remainder of the proliferating cells in areas of demyelination were astrocytes, microglial cells and T-cells. These experiments support the hypothesis that factors within a demyelinating lesion promote the proliferation and differentiation of cells within the oligodendroglial lineage.

  20. Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with Crohn's disease.

    PubMed

    Ohyagi, Masaki; Ohkubo, Takuya; Yagi, Yousuke; Ishibashi, Satoru; Akiyama, Junko; Nagahori, Masakazu; Watanabe, Mamoru; Yokota, Takanori; Mizusawa, Hidehiro

    2013-01-01

    Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that is frequently accompanied by systemic complications. Neuropathologies have not been well investigated as extraintestinal manifestations of CD. We herein report the case of a 36-year-old man with CD who presented with progressive weakness and numbness. A neurological examination and the results of a nerve conduction study and a sural nerve biopsy led to a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Plasma exchanges were initially effective; however, the effects gradually declined starting 10 days after the plasma exchange (PE). These results suggest that humoral factors may play an important role in CIDP associated with CD.

  1. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  2. Infection with B. burgdorferi s.l., and the CNS demyelinating disease. A case report.

    PubMed

    Durovska, Judita; Bazovska, Sylvia; Pancak, Jaroslav; Zaborska, Magdalena; Derdakova, Marketa; Traubner, Pavel

    2011-01-01

    The work describes three cases of patients at various ages, diagnosed for CNS demyelinating disease. The presence of specific antibodies to B. burgdorferi sensu lato, and findings of B. burgdorferi s.l. DNA, identified in one case as the genospecies B. garinii in the liquor, indicated previous experience with the infection. Presumably, persistence of borrelia in the organism could act as one of the autoimmune process triggers, resulting in the demyelinating disease. PMID:21876503

  3. CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies

    PubMed Central

    Arévalo-Martín, Á; García-Ovejero, D; Gómez, O; Rubio-Araiz, A; Navarro-Galve, B; Guaza, C; Molina-Holgado, E; Molina-Holgado, F

    2007-01-01

    Amongst the various demyelinating diseases that affect the central nervous system, those induced by an inflammatory response stand out because of their epidemiological relevance. The best known inflammatory-induced demyelinating disease is multiple sclerosis, but the immune response is a common pathogenic mechanism in many other less common pathologies (e.g., acute disseminated encephalomyelitis and acute necrotizing haemorrhagic encephalomyelitis). In all such cases, modulation of the immune response seems to be a logical therapeutic approach. Cannabinoids are well known immunomodulatory molecules that act through CB1 and CB2 receptors. While activation of CB1 receptors has a psychotropic effect, activation of CB2 receptors alone does not. Therefore, to bypass the ethical problems that could result from the treatment of inflammation with psychotropic molecules, considerable effort is being made to study the potential therapeutic value of activating CB2 receptors. In this review we examine the current knowledge and understanding of the utility of cannabinoids as therapeutic molecules for inflammatory-mediated demyelinating pathologies. Moreover, we discuss how CB2 receptor activation is related to the modulation of immunopathogenic states. PMID:17891163

  4. Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions.

    PubMed

    Furusho, Miki; Roulois, Aude J; Franklin, Robin J M; Bansal, Rashmi

    2015-10-01

    Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of proregenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease.

  5. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease

    PubMed Central

    Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y.

    2016-01-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  6. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature.

    PubMed

    Li, Xiangling; Wang, Yanqiang

    2016-07-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  7. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  8. Environmental and genetic factors in pediatric inflammatory demyelinating diseases.

    PubMed

    Waubant, Emmanuelle; Ponsonby, Anne-Louise; Pugliatti, Maura; Hanwell, Heather; Mowry, Ellen M; Hintzen, Rogier Q

    2016-08-30

    The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501 In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS. The role of vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene-environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric neuromyelitis optica spectrum disorders and acute disseminated encephalomyelitis and only collaborative studies will answer those questions. PMID:27572857

  9. Pain and spinal cord imaging measures in children with demyelinating disease.

    PubMed

    Barakat, Nadia; Gorman, Mark P; Benson, Leslie; Becerra, Lino; Borsook, David

    2015-01-01

    Pain is a significant problem in diseases affecting the spinal cord, including demyelinating disease. To date, studies have examined the reliability of clinical measures for assessing and classifying the severity of spinal cord injury (SCI) and also to evaluate SCI-related pain. Most of this research has focused on adult populations and patients with traumatic injuries. Little research exists regarding pediatric spinal cord demyelinating disease. One reason for this is the lack of reliable and useful approaches to measuring spinal cord changes since currently used diagnostic imaging has limited specificity for quantitative measures of demyelination. No single imaging technique demonstrates sufficiently high sensitivity or specificity to myelin, and strong correlation with clinical measures. However, recent advances in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) measures are considered promising in providing increasingly useful and specific information on spinal cord damage. Findings from these quantitative imaging modalities correlate with the extent of demyelination and remyelination. These techniques may be of potential use for defining the evolution of the disease state, how it may affect specific spinal cord pathways, and contribute to the management of pediatric demyelination syndromes. Since pain is a major presenting symptom in patients with transverse myelitis, the disease is an ideal model to evaluate imaging methods to define these regional changes within the spinal cord. In this review we summarize (1) pediatric demyelinating conditions affecting the spinal cord; (2) their distinguishing features; and (3) current diagnostic and classification methods with particular focus on pain pathways. We also focus on concepts that are essential in developing strategies for the detection, monitoring, treatment and repair of pediatric myelitis. PMID:26509120

  10. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    PubMed

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases.

  11. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    PubMed

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases. PMID:27346352

  12. Effect of immunization with Theiler's virus on the course of demyelinating disease.

    PubMed

    Crane, M A; Yauch, R; Dal Canto, M C; Kim, B S

    1993-06-01

    Intracerebral (i.c.) inoculation of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) results in a demyelinating disease similar to human multiple sclerosis (MS). Mice develop a strong immune response to TMEV and the disease is believed to be immune-mediated. In order to investigate the effects of the immune response to TMEV on the course of demyelination, we immunized host mice with UV-inactivated TMEV at various time periods in relation to intracerebral inoculation with live TMEV. Here, we show that subcutaneous immunization of mice with TMEV prior to infection with virus is able to protect susceptible, SJL/J mice from demyelinating disease. This protective effect appears to be long-lasting; immunization greater than 90 days prior to i.c. inoculation of the virus protects mice from subsequent infection. However, immunization of mice after i.c. infection with TMEV does not confer protection, but rather exacerbates the disease symptoms. Thus, this system offers a model for studying viral capsid proteins and/or epitopes which are involved in either protection from disease or immune-mediated pathogenesis leading to myelin destruction in susceptible mice.

  13. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico.

    PubMed

    Flores, Jose; González, Silvia; Morales, Ximena; Yescas, Petra; Ochoa, Adriana; Corona, Teresa

    2012-01-01

    Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

  14. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

    PubMed Central

    Flores, Jose; González, Silvia; Morales, Ximena; Yescas, Petra; Ochoa, Adriana; Corona, Teresa

    2012-01-01

    Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants. PMID:22973516

  15. The immunopathogenesis and regulation of T-cell-mediated demyelinating diseases.

    PubMed

    Miller, S D; Karpus, W J

    1994-08-01

    A variety of experimental approaches are currently being evaluated for controlling CD4+ T helper 1 (Th1)-mediated autoimmune pathology. Here, Stephen Miller and William Karpus compare and contrast the efficacies of various antigen-specific regulatory strategies. Particular emphasis is placed on the mechanisms of peripheral immune tolerance and how this may be used in the treatment and analysis of the pathologic T-cell repertoire in autoimmune and virus-induced demyelinating diseases. PMID:7916948

  16. Protection of SJL/J mice from demyelinating disease mediated by Theiler's murine encephalomyelitis virus.

    PubMed

    Kurtz, C I; Sun, X M; Fujinami, R S

    1995-01-01

    Intracerebral infection with the DA strain of Theiler's murine encephalomyelitis virus induces a chronic demyelinating disease in SJL/J mice. Intraperitoneal inoculation with either the wild-type DA virus or an attenuated variant virus of DA, H7A6-2, results in protection from development of chronic demyelinating disease. Protective anti-viral immune responses result in reduced viral titers and decreased inflammation in the central nervous system within the first week following intracerebral challenge with virus. Development of protective immunity requires the presence of B cells and CD4+ T cells but does not require CD8+ T cells. High titers of serum anti-viral IgG and neutralizing antibodies are induced following the intraperitoneal inoculation with the DA virus or H7A6-2 virus prior to challenge. While protection could not be transferred with immune serum from DA virus-infected mice or neutralizing monoclonal antibodies, protection was correlated with increased numbers of DA virus-specific plasma cells in the central nervous system within the first week following intracerebral challenge. Protected mice also had enhanced levels of anti-DA virus IgG and neutralizing antibodies in the cerebral spinal fluid by 1 week following intracerebral challenge with DA virus. Thus, we conclude that vaccination with live virus results in protection from chronic demyelinating disease by inducing immune responses which are manifested in the central nervous system and rapidly clear infection after intracerebral challenge with DA virus.

  17. The Validation Study of Neurofilament Heavy Chain and 8-hydroxy-2'-deoxyguanosine as Plasma Biomarkers of Clinical/Paraclinical Activity in First and Relapsing-Remitting Demyelination Acute Attacks.

    PubMed

    Ljubisavljevic, S; Stojanovic, I; Basic, J; Pavlovic, D A

    2016-10-01

    Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T1-Gd-enhancing lesion volume) activities of disease. Both parameters were increased in CIS and RRMS compared to control subjects (p < 0.05). The positive correlations were observed between 8-OHdG values and index of BBB permeability, clinical severity of disease, and demyelinated brain lesion volume, in CIS group (r > 0.50; p < 0.05). Similar correlations were obtained between pNF-H values and the above parameters, as well as the index of disease progression, in RRMS group (r > 0.30; p < 0.05). There was a significant correlation between values of 8-OHdG and pNF-H only in CIS group, r = 0.52, p < 0.05. While the plasma values of 8-OHdG reflect the degree of acute demyelination in CIS, pNF-H values reflect that in RRMS. The obtained results must be reevaluated in similar prospective studies related to their prognostic values. PMID:27295058

  18. Chronic multifocal demyelinating neuropathy simulating motor neuron disease.

    PubMed

    Di Bella, P; Logullo, F; Dionisi, L; Danni, M; Scarpelli, M; Angeleri, F

    1991-02-01

    We describe a patient with a chronic acquired predominantly motor polyneuropathy. His clinical picture initially led to a diagnosis of lower motor neuron form of amyotrophic lateral sclerosis. However electrophysiological examination revealed multifocal, prevalently proximal, conduction blocks at sites not prone to compression. Distinguishing this unusual polyneuropathy from motor neuron diseases is critical, since the former is a potentially, treatable disorder.

  19. Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

    PubMed Central

    Coggan, Jay S.; Bittner, Stefan; Stiefel, Klaus M.; Meuth, Sven G.; Prescott, Steven A.

    2015-01-01

    Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases. PMID:26370960

  20. Tangier's disease: An uncommon cause of facial weakness and non-length dependent demyelinating neuropathy

    PubMed Central

    Nagappa, Madhu; Taly, Arun B.; Mahadevan, Anita; Pooja, M.; Bindu, P. S.; Chickabasaviah, Y. T.; Gayathri, N.; Sinha, Sanjib

    2016-01-01

    Tangier disease is an autosomal recessive disorder characterized by an abnormal accumulation of cholesterol esters in various organs secondary to adenotriphosphate binding cassette transporter A-1 (ABCA-1) transporter deficiency and disrupted reverse cholesterol transport. It causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle aged gentleman of Tangier disease who was initially misdiagnosed leprosy and treated with antileprosy drugs. The presence of a demyelinating neuropathy on electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. The characteristic lipid profile of Tangier disease was noted in this patient viz. extremely low high density lipoprotein (HDL), elevated triglyceride (TG), and reduced apolipoprotein A1. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis. PMID:27011649

  1. Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells: implications for inflammatory demyelinating disease.

    PubMed

    Winkler, Clayton W; Foster, Scott C; Itakura, Asako; Matsumoto, Steven G; Asari, Akira; McCarty, Owen J T; Sherman, Larry S

    2013-04-24

    Inflammatory demyelinating diseases like multiple sclerosis are characterized by mononuclear cell infiltration into the central nervous system. The glycosaminoglycan hyaluronan and its receptor, CD44, are implicated in the initiation and progression of a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Digestion of hyaluronan tethered to brain vascular endothelial cells by a hyaluronidase blocks the slow rolling of lymphocytes along activated brain vascular endothelial cells and delays the onset of EAE. These effects could be due to the elimination of hyaluronan or the generation of hyaluronan digestion products that influence lymphocytes or endothelial cells. Here, we found that hyaluronan dodecasaccharides impaired activated lymphocyte slow rolling on brain vascular endothelial cells when applied to lymphocytes but not to the endothelial cells. The effects of hyaluronan dodecasaccharides on lymphocyte rolling were independent of CD44 and a receptor for degraded hyaluronan, Toll-like receptor-4. Subcutaneous injection of hyaluronan dodecasaccharides or tetrasaccharides delayed the onset of EAE in a manner similar to subcutaneous injection of hyaluronidase. Hyaluronan oligosaccharides can therefore act directly on lymphocytes to modulate the onset of inflammatory demyelinating disease.

  2. Prolonged gray matter disease without demyelination caused by Theiler's murine encephalomyelitis virus with a mutation in VP2 puff B.

    PubMed

    Tsunoda, I; Wada, Y; Libbey, J E; Cannon, T S; Whitby, F G; Fujinami, R S

    2001-08-01

    Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups based on neurovirulence. During the acute phase, DA virus infects cells in the gray matter of the central nervous system (CNS). Throughout the chronic phase, DA virus infects glial cells in the white matter, causing demyelinating disease. Although GDVII virus also infects neurons in the gray matter, infected mice developed a severe polioencephalomyelitis, and no virus is detected in the white matter or other areas in the CNS in rare survivors. Several sequence differences between the two viruses are located in VP2 puff B and VP1 loop II, which are located near each other, close to the proposed receptor binding site. We constructed a DA virus mutant, DApBL2M, which has the VP1 loop II of GDVII virus and a mutation at position 171 in VP2 puff B. While DApBL2M virus replicated less efficiently than DA virus during the acute phase, DApBL2M-induced acute polioencephalitis was comparable to that in DA virus infection. Interestingly, during the chronic phase, DApBL2M caused prolonged gray matter disease in the brain without white matter involvement in the spinal cord. This is opposite what is observed during wild-type DA virus infection. Our study is the first to demonstrate that conformational differences via interaction of VP2 puff B and VP1 loop II between GDVII and DA viruses can play an important role in making the transition of infection from the gray matter in the brain to the spinal cord white matter during TMEV infection. PMID:11462022

  3. The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection.

    PubMed

    Yamada, M; Zurbriggen, A; Fujinami, R S

    1990-12-01

    The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination.

  4. The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection.

    PubMed Central

    Yamada, M.; Zurbriggen, A.; Fujinami, R. S.

    1990-01-01

    The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2260633

  5. A novel EGR2 mutation within a family with a mild demyelinating form of Charcot-Marie-Tooth disease.

    PubMed

    Shiga, Kensuke; Noto, Yuichi; Mizuta, Ikuko; Hashiguchi, Akihiro; Takashima, Hiroshi; Nakagawa, Masanori

    2012-06-01

    Mutations of the early growth response 2 (EGR2) gene have been reported in a variety of severe demyelinating neuropathies such as autosomal recessive congenital hypomyelinating neuropathy, autosomal dominant child-onset Dejerine-Sottas neuropathy, and autosomal dominant adult-onset Charcot-Marie-Tooth disease (CMT). Here, we report on a heterozygous mutation in EGR2 (c.1160C>A), which results in threonine at position 387 being changed to asparagine, in a family with a mild demyelinating form of adult-onset CMT. Of note, both the proband and her asymptomatic son exhibited neither pes cavus nor champagne-bottle leg atrophy, suggesting that the heterozygous T387N mutation may result in a relatively mild phenotype of demyelinating CMT. PMID:22734907

  6. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cottenie, Ellen; Menezes, Manoj P; Rossor, Alexander M; Morrow, Jasper M; Yousry, Tarek A; Dick, David J; Anderson, Janice R; Jaunmuktane, Zane; Brandner, Sebastian; Blake, Julian C; Houlden, Henry; Reilly, Mary M

    2013-05-01

    Charcot-Marie-Tooth disease type 4J (CMT4J), a rare form of demyelinating CMT, caused by recessive mutations in the phosphoinositide phosphatase FIG4 gene, is characterised by progressive proximal and distal weakness and evidence of chronic denervation in both proximal and distal muscles. We describe a patient with a previous diagnosis of CMT1 who presented with a two year history of rapidly progressive weakness in a single limb, resembling an acquired inflammatory neuropathy. Nerve conduction studies showed an asymmetrical demyelinating neuropathy with conduction block and temporal dispersion. FIG4 sequencing identified a compound heterozygous I41T/K278YfsX5 genotype. CMT4J secondary to FIG4 mutations should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy, especially if there is a background history of a more slowly progressive neuropathy.

  7. Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

    PubMed

    García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

    2013-01-01

    Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

  8. Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis.

    PubMed

    Horellou, Philippe; Wang, Min; Keo, Vixra; Chrétien, Pascale; Serguera, Ché; Waters, Patrick; Deiva, Kumaran

    2015-12-15

    Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MOG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing full-length human MOG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n=17) compared to OND (n=12, p=0.0036) and to MS (n=17, p=0.0371). The C5a levels in MS were higher than in OND without reaching significance (p=0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p=0.0027) and to MS (p=0.0046). MOG antibody plasma levels were significantly higher in monophasic ADS (p<0.0001) and, to a lesser extent, in MS compared to OND (p=0.0023). Plasma MOG antibodies and CSF IL-6 levels were significantly correlated (r=0.51, p=0.018). CSF C5a and IL-6 levels are increased in monophasic ADS but not in MS when compared to OND, suggesting

  9. From fish to man: understanding endogenous remyelination in CNS demyelinating diseases

    PubMed Central

    Dubois-Dalcq, Monique; Williams, Anna; Stadelmann, Christine; Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine

    2008-01-01

    In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease Multiple Sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man. PMID:18474520

  10. Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation.

    PubMed Central

    Borrow, P; Nash, A A

    1992-01-01

    Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease. PMID:1628891

  11. Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation.

    PubMed

    Borrow, P; Nash, A A

    1992-05-01

    Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease.

  12. Demyelinizing Neurological Disease after Treatment with Tumor Necrosis Factor-α Antagonists

    PubMed Central

    Bruè, Claudia; Mariotti, Cesare; Rossiello, Ilaria; Saitta, Andrea; Giovannini, Alfonso

    2016-01-01

    Purpose Demyelinizing neurological disease is a rare complication after treatment with tumor necrosis factor (TNF)α antagonists. We report on a case of multiple sclerosis after TNFα antagonist treatment and discuss its differential diagnosis. Methods This is an observational case study. Results A 48-year-old male was referred to Ophthalmology in January 2015 for an absolute scotoma in the superior quadrant of the visual field in his right eye. Visual acuity was 20/50 in the right eye and 20/20 in the left. Fundus examination was unremarkable bilaterally. Spectral domain optical coherence tomography revealed a normal macular retina structure. Visual field examination revealed a superior hemianopsia in the right eye. Head magnetic resonance imaging showed findings compatible with optic neuritis. The visual evoked potentials confirmed the presence of optic neuritis. The patient had been under therapy with adalimumab since January 2014, for Crohn's disease. Suspension of adalimumab was recommended, and it was substituted with tapered deltacortene, from 1 mg/kg/day. After 1 month, the scotoma was resolved completely. Conclusions TNFα antagonists can provide benefit to patients with inflammatory autoimmune diseases. However, they can also be associated with severe adverse effects. Therefore, adequate attention should be paid to neurological abnormalities in patients treated with TNFα antagonists. PMID:27504093

  13. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. III. Failure of neuroantigen-specific immune tolerance to affect the clinical course of demyelination.

    PubMed

    Miller, S D; Gerety, S J; Kennedy, M K; Peterson, J D; Trotter, J L; Tuohy, V K; Waltenbaugh, C; Dal Canto, M C; Lipton, H L

    1990-01-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains produces a chronic demyelinating disease in which mononuclear cell-rich infiltrates in the central nervous system (CNS) are prominent. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility complex (MHC) class II-restricted delayed-type hypersensitivity (DTH) responses in which lymphokine-activated macrophages mediate bystander demyelination. The present study examined the possibility that concomitant or later-appearing neuroantigen-specific autoimmune T cell responses, such as those demonstrated in chronic-relapsing experimental allergic encephalomyelitis (R-EAE), may contribute to the demyelinating process following TMEV infection. T cell responses against intact, purified major myelin proteins (myelin basic protein (MBP) and proteolipid protein (PLP], and against altered myelin constituents were readily demonstrable in SJL/J mice with R-EAE, but were not detectable in SJL/J mice with TMEV-induced demyelinating disease. TMEV-infected mice also did not display T cell responses against the peptide fragments of MBP(91-104) and PLP(139-151) recently shown to be encephalitogenic in SJL/J mice. In addition, induction of neuroantigen-specific tolerance to a heterogeneous mixture of CNS antigens, via the i.v. injection of syngeneic SJL/J splenocytes covalently coupled with mouse spinal cord homogenate, resulted in significant suppression of clinical and histologic signs of R-EAE and the accompanying MBP- and PLP-specific DTH responses. In contrast, neuroantigen-specific tolerance failed to alter the development of clinical and histologic signs of TMEV-induced demyelinating disease or the accompanying virus-specific DTH and humoral immune responses. These findings demonstrate that TMEV-induced demyelinating disease can occur in the apparent absence of neuroantigen

  14. Diabetic polyneuropathy. Axonal or demyelinating?

    PubMed

    Valls-Canals, J; Povedano, M; Montero, J; Pradas, J

    2002-01-01

    Diabetic polyneuropathy is the most common subgroup of diabetic neuropathy, but its nature is controversial as it might be demyelinating and/or axonal. We have tried to determine whether diabetic polyneuropathy is electrophysiologically axonal, demyelinating, or both. We have studied the sural and peroneal nerves and the electromyographies of leg muscles in 50 healthy subjects (average age 67.2 years, range 45 to 84 years), in 50 diabetic patients (average age 66.34 years, range 44 to 82 years) showing no symptoms and/or signs of polyneuropathy (DP1), and in 50 diabetic patients (average age 67.10 years, range 49 to 87 years) showing symptoms and/or signs of polyneuropathy (DP2). The amplitude (AMP) of sural and peroneal nerves in healthy and DP1 subjects was similar. Conduction velocity (CV) of sural and peroneal nerves was slower in DP1 subjects than in healthy subjects. DP2 subjects showed AMP and CV values significantly lower than those in DP1 subjects, and signs of acute and chronic denervation/reinervation were found in the leg muscles. We believe that this result indicates that diabetic patients have two types of polyneuropathies: a demyelinating disease that could appear in diabetic patients with and without symptoms of polyneuropathy, and an axonal loss that is responsible for most of the symptoms.

  15. An isoelectric focusing overlay study of the humoral immune response in Theiler's virus demyelinating disease.

    PubMed

    Roos, R P; Nalefski, E A; Nitayaphan, S; Variakojis, R; Singh, K K

    1987-01-01

    Oligoclonal immunoglobulin G (IgG) bands are a frequent feature of inflammatory diseases of the central nervous system (CNS). In multiple sclerosis (MS), cerebrospinal fluid (CSF) oligoclonal IgG bands are a potential clue to the pathogenesis of the disease; however, their particular antigenic target is unknown. We sought to characterize the IgG response in an experimental CNS persistent demyelinating infection by isoelectric focusing (IEF) studies of serum and CSF from mice infected with Theiler's murine encephalomyelitis virus (TMEV). Following IEF, we used a new technique in order to identify TMEV-specific antibodies; focused immunoglobulins were blotted onto nitrocellulose paper which was then overlaid with radiolabeled virus. Autoradiograms showed that most of the TMEV antibody was locally synthesized within the CNS since CSF, but not serum, TMEV antibody had an anodal distribution. CSF IEF TMEV antibody spectrotypes were very similar, presumably because the CSFs were collected from the same inbred mouse strain. CSF TMEV antibody displayed less restricted heterogeneity than the very restricted cathodal CSF oligoclonal IgG bands seen in MS. The new IEF immunoblotting antigen overlay technique will be a powerful detection system to probe for the antigenic target against which MS CSF IgG may be directed.

  16. Characteristics of demyelinating Charcot-Marie-Tooth disease with concurrent diabetes mellitus

    PubMed Central

    Yu, Zhiliang; Wu, Xiaohua; Xie, Huijun; Han, Ying; Guan, Yangtai; Qin, Yong; Zheng, Huimin; Jiang, Jianming; Niu, Zhenmin

    2014-01-01

    Purpose: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with concurrent diabetes mellitus (DM) is rare. The purpose of this study is to explore the genetic, clinical and pathological characteristics of the patients with CMT and concurrent DM. Methods: We investigated gene mutations (the peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide-induced tumor necrosis factor-α factor gene, early growth response gene and the neurofilament light chain gene loci) of a relatively large and typical Chinese family with CMT1 and concurrent DM2. From the literature, we also retrieved all reported families and single cases with CMT and concurrent DM. We comprehensively analyzed the characteristics of total 33 patients with CMT and concurrent DM, and further compared these characteristics with those of patients of diabetic peripheral neuropathy (DPN). Results: Patients with CMT and concurrent DM had some relatively independent characteristics and pathogenic mechanisms. So we designated that kind of characteristic demyelinating CMT which accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT. Conclusion: CMT is an etiologic factor of DM, even though the intrinsic association between CMT and DM still remains further exploration. PMID:25120817

  17. Clinical and radiological characteristics of 17 Chinese patients with pathology confirmed tumefactive demyelinating diseases: follow-up study.

    PubMed

    Yao, Jiarui; Huang, Dehui; Gui, Qiuping; Chen, Xiaolei; Lou, Xin; Wu, Lei; Cheng, Chen; Li, Jie; Wu, Weiping

    2015-01-15

    Tumefactive demyelinating disease is a rare inflammatory demyelinating disease (IDD) of the central nervous system (CNS). The literature lacks a clear and consistent description of the clinical and radiological spectrum of this disorder, and few Chinese cases have been studied. Here we report 17 Chinese patients, with pathology confirmed CNS IDD, who had distinct clinical and imaging features from those in previous reports. Median age at onset was 47 years, with a female to male ratio of 1.1:1. Multifocal lesions were present in nine cases (53%) on their pre-biopsy magnetic resonance imagings (MRIs), with locations predominantly involving periventricular white matter (41%), subcortical white matter (41%), juxtacortical regions (41%), and cortical gray matter (35%). Moderate to severe perilesional edema and/or mass effect were present in 35% of cases. A variety of enhancement patterns were observed; most were heterogeneous, including ring-like, patchy, venular-like, nodular, punctate, and diffuse in a decreased frequency. Perilesional restriction on diffusion-weighted images (DWI) were evident in 70% cases. Clinical course prior to biopsy was a first neurological event in 82% cases. During a median follow-up of 4.1 years, 76% of cases remained as isolated demyelinating syndrome, and 70% experienced a total or near-total recovery regardless of whether they received immunotherapy. Further studies are needed, especially concerning series with pathological confirmation and long-term follow-up information.

  18. Molecular genetics of autosomal-dominant demyelinating Charcot-Marie-Tooth disease.

    PubMed

    Houlden, Henry; Reilly, Mary M

    2006-01-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of disorders and is the most common inherited neuromuscular disorder, with an estimated overall prevalence of 17-40/10,000. Although there has been major advances in the understanding of the genetic basis of CMT in recent years, the most useful classification is still a neurophysiological classification that divides CMT into type 1 (demyelinating; median motor conduction velocity < 38 m/s) and type 2 (axonal; median motor conduction velocity > 38 m/s). An intermediate type is also increasingly being described. Inheritance can be autosomal-dominant (AD), X-linked, or autosomal-recessive (AR). AD CMT1 is the most common type of CMT and was the first form of CMT in which a causative gene was described. This review provides an up-to-date overview of AD CMT1 concentrating on the molecular genetics as the clinical, neurophysiological, and pathological features have been covered elsewhere. Four genes (PMP22, MPZ, LITAF, and EGR2) have been described in the last 15 yr associated with AD CMTI and a further gene (NEFL), originally described as causing AD CMT2 can also cause AD CMT1 (by neurophysiological criteria). Studies have shown many of these genes, when mutated, can cause a wide range of CMT phenotypes from the relatively mild CMT1 to the more severe Dejerine-Sottas disease and congenital hypomyelinating neuropathy, and even in some cases axonal CMT2. This review discusses what is known about these genes and in particular how they cause a peripheral neuropathy, when mutated. PMID:16775366

  19. Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients.

    PubMed

    Kepes, J J

    1993-01-01

    Thirty-one patients with large, focal cerebral demyelinating lesions are reported. Twenty-four patients had solitary lesions and 7 had multiple foci, the latter apparently of identical age. The lesions presented clinically and radiologically as brain tumors (gliomas or metastases) or as multiple cysts. Six patients were older than 57 years (2 in their 70s) at the onset of their symptoms. The demyelinating nature of the lesions was established through biopsy in each patient and all improved significantly after corticosteroid therapy. Three patients developed additional lesions during the follow-up periods ranging from 9 months to 12 years consistent with the course of multiple sclerosis. Twenty-eight patients did not develop additional lesions. These included 6 patients with multiple lesions at the onset. In 1 of the patients, the first symptoms developed 10 days after receiving vaccination against influenza. Two patients had concomitant malignancy (chronic monomyelogenous leukemia and retroperitoneal seminoma respectively) and 1 patient developed immunoblastic sarcoma in the opposite hemisphere after biopsy diagnosis and steroid treatment of her demyelinating lesion. Tumor-like masses of demyelination may occupy an intermediate position between multiple sclerosis and postinfectious/postvaccination encephalitis. The clinical course (history of vaccination in one instance, acute onset, good response to corticosteroids, no clinical or radiological evidence of new lesions in the great majority of patients) favored postinfectious/postvaccination encephalitis. Lesion size however greatly exceeded that of the small foci of perivenous demyelination seen in typical postinfectious/postvaccination encephalitis and tended to present as space-occupying masses.

  20. Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

    PubMed Central

    Ferenczy, Michael W.; Marshall, Leslie J.; Nelson, Christian D. S.; Atwood, Walter J.; Nath, Avindra; Khalili, Kamel

    2012-01-01

    Summary: Progressive multifocal leukoencephalopathy (PML) is a debilitating and frequently fatal central nervous system (CNS) demyelinating disease caused by JC virus (JCV), for which there is currently no effective treatment. Lytic infection of oligodendrocytes in the brain leads to their eventual destruction and progressive demyelination, resulting in multiple foci of lesions in the white matter of the brain. Before the mid-1980s, PML was a relatively rare disease, reported to occur primarily in those with underlying neoplastic conditions affecting immune function and, more rarely, in allograft recipients receiving immunosuppressive drugs. However, with the onset of the AIDS pandemic, the incidence of PML has increased dramatically. Approximately 3 to 5% of HIV-infected individuals will develop PML, which is classified as an AIDS-defining illness. In addition, the recent advent of humanized monoclonal antibody therapy for the treatment of autoimmune inflammatory diseases such as multiple sclerosis (MS) and Crohn's disease has also led to an increased risk of PML as a side effect of immunotherapy. Thus, the study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies. PMID:22763635

  1. Identification of Theiler's virus infected cells in the central nervous system of the mouse during demyelinating disease.

    PubMed

    Aubert, C; Chamorro, M; Brahic, M

    1987-11-01

    Theiler's virus is a picornavirus responsible for a persistent, demyelinating infection of mouse central nervous system. We examined the nature of infected cells during the course of this disease using a simultaneous immunoperoxidase-in situ hybridization assay. Cell types were identified with antigenic markers and infected cells were recognized by the presence of viral RNA. We found that, depending on the animal, approximately 10% of infected cells were migroglia-macrophages, 5 to 10% were astrocytes and 25 to 40% were oligodendrocytes. Approximately half of the infected cells could not be identified.

  2. Genomic characterization of Japanese macaque rhadinovirus, a novel herpesvirus isolated from a nonhuman primate with a spontaneous inflammatory demyelinating disease.

    PubMed

    Estep, Ryan D; Hansen, Scott G; Rogers, Kelsey S; Axthelm, Michael K; Wong, Scott W

    2013-01-01

    Japanese macaque rhadinovirus (JMRV) is a novel gamma-2 herpesvirus that was isolated from a Japanese macaque (JM) with an inflammatory demyelinating encephalomyelitis referred to as Japanese macaque encephalomyelitis, a disease that possesses clinical and histopathological features resembling multiple sclerosis in humans. Genomic DNA sequence analysis reveals that JMRV is a gammaherpesvirus closely related to rhesus macaque rhadinovirus (RRV) and human herpesvirus 8. We describe here the complete nucleotide sequence and structure of the JMRV genome, as well as the sequence of two plaque isolates of this virus. Analysis of the JMRV genome not only demonstrates that this virus shares a number of genes with RRV that may be involved in pathogenesis but also indicates the presence of unique JMRV genes that could potentially contribute to disease development. The knowledge of the genomic sequence of JMRV, and the ability to easily propagate the virus in vitro, make JMRV infection of JM an attractive model for examining the potential role of an infectious viral agent in the development of demyelinating encephalomyelitis disease in vivo.

  3. Strains from both Theiler's virus subgroups encode a determinant for demyelination.

    PubMed Central

    Fu, J; Rodriguez, M; Roos, R P

    1990-01-01

    The GDVII strain and other members of the GDVII subgroup of Theiler's murine encephalomyelitis viruses (TMEV) cause an acute lethal neuronal infection in mice, whereas the DA strain and other members of the TO subgroup of TMEV cause a chronic demyelinating disease associated with a persistent virus infection. We used GDVII/DA chimeric infectious cDNAs to produce intratypic recombinant viruses in order to clarify reasons for the TMEV subgroup-specific difference in demyelinating activity. We found that both the GDVII and DA strains contain a genetic determinant(s) for demyelinating activity. No demyelination occurs following GDVII strain inoculation because this strain produces an early neuronal disease that kills mice before white matter disease and persistent infection can occur. Images PMID:2243399

  4. Antibody-Mediated Oligodendrocyte Remyelination Promotes Axon Health in Progressive Demyelinating Disease.

    PubMed

    Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

    2016-10-01

    Demyelination underlies early neurological symptoms in multiple sclerosis (MS); however, axonal damage is considered critical for permanent chronic deficits. The precise mechanisms by which axonal injury occurs in MS are unclear; one hypothesis is the absence or failure of remyelination, suggesting that promoting remyelination may protect axons from death. This report provides direct evidence that promoting oligodendrocyte remyelination protects axons and maintains transport function. Persistent Theiler's virus infection of Swiss Jim Lambert (SJL)/J mice was used as a model of MS to assess the effects of remyelination on axonal injury following demyelination in the spinal cord. Remyelination was induced using an oligodendrocyte/myelin-specific recombinant human monoclonal IgM, rHIgM22. The antibody is endowed with strong anti-apoptotic and pro-proliferative effects on oligodendrocyte progenitor cells. We used (1)H-magnetic resonance spectroscopy (MRS) at the brainstem to measure N-acetyl-aspartate (NAA) as a surrogate of neuronal health and spinal cord integrity. We found increased brainstem NAA concentrations at 5 weeks post-treatment with rHIgM22, which remained stable out to 10 weeks. Detailed spinal cord morphology studies revealed enhanced remyelination in the rHIgM22-treated group but not in the isotype control antibody- or saline-treated groups. Importantly, we found rHIgM22-mediated remyelination protected small- and medium-caliber mid-thoracic spinal cord axons from damage despite similar demyelination and inflammation across all experimental groups. The most direct confirmation of remyelination-mediated protection of descending neurons was an improvement in retrograde transport. Treatment with rHIgM22 significantly increased the number of retrograde-labeled neurons in the brainstem, indicating that preserved axons are functionally competent. This is direct validation that remyelination preserves spinal cord axons and protects functional axon integrity

  5. Influenza Vaccine-Induced CNS Demyelination in a 50-Year-Old Male

    PubMed Central

    Sacheli, Aaron; Bauer, Raymond

    2014-01-01

    Patient: Male, 50 Final Diagnosis: Acute post-vaccination CNS demyelinating disorder Symptoms: Blurred vision • hemiparesis • hemiplegia • hypertonia • itching • paresthesia Medication: — Clinical Procedure: MRI Specialty: Neurology Objective: Rare disease Background: There are several categories of primary inflammatory demyelinating disorders, which comprise clinically similar neurologic sequelae. Of interest, clinically isolated syndrome (CIS) and acute disseminated encephalomyelitis (ADEM) are 2 demyelinating conditions of the central nervous system (CNS), whose clinical similarity pose a significant challenge to definitive diagnosis. Yet, both remain important clinical considerations in patients with neurologic signs and symptoms in the context of recent vaccination. Case Report: We report a case of a 50-year-old Caucasian male with a course of progressive, focal, neurologic deficits within 24 h after receiving the influenza vaccine. Subsequent work-up revealed the possibility of an acute central nervous system (CNS) demyelinating episode secondary to the influenza vaccine, best described as either CIS or ADEM. Conclusions: Case reports of CNS demyelination following vaccinations have been previously noted, most often occurring in the context of recent influenza vaccination. This report serves to document a case of CNS demyelination occurring 24 h after influenza vaccination in a middle-aged patient, and will describe some salient features regarding the differential diagnosis of CIS and ADEM, as well as their potential management. PMID:25175754

  6. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-11-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination.

  7. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed Central

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-01-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination. Images PMID:2214025

  8. [Chronic inflammatory demyelinating polyradiculoneuropathy].

    PubMed

    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  9. Dimethyl fumarate suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway.

    PubMed

    Kobayashi, Kunitoshi; Tomiki, Hiroki; Inaba, Yuji; Ichikawa, Motoki; Kim, Byung S; Koh, Chang-Sung

    2015-07-01

    Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A. PMID:25721871

  10. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    PubMed

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future.

  11. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    PubMed

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future. PMID:24032475

  12. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

    PubMed

    Karussis, Dimitrios; Petrou, Panayiota

    2014-03-01

    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  13. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients.

  14. Diagnoses in Pediatric Patients With Magnetic Resonance Imaging (MRI) Lesions Suspicious for Demyelination.

    PubMed

    Sweeney, Michael L; Kukreja, Marcia; Horn, Paul S; Standridge, Shannon M

    2015-10-01

    Magnetic resonance imaging (MRI) studies of the brain in pediatric patients frequently show abnormal white matter lesions, which may be concerning for demyelinating disease. This study aimed to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. A retrospective chart review was performed on MRI reports of patients who underwent imaging evaluation at a single tertiary pediatric hospital. Of 299 patients identified, 192 presented with acute neurologic complaints. In this group, ≥ 5 discrete lesions, African American race, and having brain stem, thalamic, cerebellar, or optic nerve lesions was associated with the patient being diagnosed with a disease that required further treatment. The other 107 patients underwent MRI for other indications. Among these subjects, having lesions within the corpus callosum or cerebellum was associated with being diagnosed with a disease requiring further treatment.

  15. Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease.

    PubMed

    Berer, Kerstin; Boziki, Marina; Krishnamoorthy, Gurumoorthy

    2014-01-01

    Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple sclerosis (MS). The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of TH17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred TH17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of TH17 cells in the gut was partially dependent on the gut homing receptor α4β7-mediated adhesion to the intestine. Administration of α4β7 blocking-antibodies increased the peripheral availability of TH17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.

  16. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases.

    PubMed

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda; Locht, Henning

    2014-05-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all patients who developed neurological symptoms during this time period. We found six patients with signs of demyelinizing neurological disorders: four resembling MS, one MS-like condition, and one multifocal motor neuropathy. During a relatively short time period, we found a remarkably high number of neurological demyelinizing AEs probably linked to anti TNF-alpha treatment. The AEs were not associated with a single anti TNF-alpha agent and were thus presumably a class effect. The data presented suggest that neurological AEs may be underreported. We advocate that physicians handling patients during treatment with TNF inhibitors are aware of this potentially serious AE and report these events to the proper medical authorities.

  17. Regulatory T cells inhibit T cell proliferation and decrease demyelination in mice chronically infected with a coronavirus1

    PubMed Central

    Trandem, Kathryn; Anghelina, Daniela; Zhao, Jingxian; Perlman, Stanley

    2010-01-01

    Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) develop acute and chronic demyelinating diseases with histopathological similarities to MS. The process of demyelination is largely immune-mediated, as immunodeficient mice (RAG1−/− mice) do not develop demyelination upon infection; however, demyelination develops if these mice are reconstituted with either JHMV-immune CD4 or CD8 T cells. Since myelin destruction is a consequence of the inflammatory response associated with virus clearance, we reasoned that decreasing the amount of inflammation would diminish clinical disease and demyelination. Given that regulatory T cells (Tregs) have potent anti-inflammatory effects, we adoptively transferred Tregs into infected C57BL/6 and RAG1−/− mice. In both instances, transfer of Tregs decreased weight loss, clinical scores and demyelination. Transferred Tregs were not detected in the CNS of infected RAG1−/− mice, but rather appeared to mediate their effects in the draining cervical lymph nodes. We show that Tregs dampen the inflammatory response mediated by transferred JHMV-immune splenocytes in infected RAG1−/− mice by decreasing T cell proliferation, dendritic cell activation and pro-inflammatory cytokine/chemokine production, without inducing apoptosis. By extension, decreasing inflammation, whether by Treg transfer or by otherwise enhancing the anti-inflammatory milieu, could contribute to improved clinical outcomes in patients with virus-induced demyelination. PMID:20208000

  18. Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies.

    PubMed

    Dalakas, Marinos C

    2002-12-24

    Intravenous immunoglobulin (IVIg) is an immunomodulating agent that has multiple activities, including modulation of complement activation products, suppressing idiotypic antibody, saturating Fc receptors on macrophages, and suppressing various inflammatory mediators including cytokines, chemokines, and metalloproteinases. Because all these factors are implicated to various degrees in the pathogenesis of immune-mediated demyelination of the PNS, administration of IVIg could be beneficial in treating neuropathies by suppressing the immune-mediated processes that are directed against myelin or axonal antigenic targets. This article outlines the actions of IVIg in CIDP and other autoimmune neuropathies based on data derived from in vivo and in vitro studies. The predominant mechanisms by which IVIg exerts its action on these neuropathies appear to be a combined effect on complement inactivation, neutralization of idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on endoneurial macrophages.

  19. Characterization of oligodendrocyte lineage precursor cells in the mouse cerebral cortex: a confocal microscopy approach to demyelinating diseases.

    PubMed

    Girolamo, Francesco; Strippoli, Maurizio; Errede, Mariella; Benagiano, Vincenzo; Roncali, Luisa; Ambrosi, Glauco; Virgintino, Daniela

    2010-01-01

    The identification of stem cells resident in the adult central nervous system has redirected the focus of research into demyelinating diseases, such as multiple sclerosis, mainly affecting the brain white matter. This immunocytochemical and morphometrical study was carried out by confocal microscopy in the adult mouse cerebral cortex, with the aim of analysing, in the brain grey matter, the characteristics of the oligodendrocyte lineage cells, whose capability to remyelinate is still controversial. The observations demonstrated the presence in all the cortex layers of glial restricted progenitors, reactive to A2B5 marker, oligodendrocyte precursor cells, expressing the NG2 proteoglycan, and pre-oligodendrocytes and pre-myelinating oligodendrocytes, reactive to the specific marker O4. NG2 expressing cells constitute the major immature population of the cortex, since not only oligodendrocyte precursor cells and pre-oligodendrocytes but also a part of the glial restrict progenitors express the NG2 proteoglycan. Together with the population of these immature cells, a larger population of mature oligodendrocytes was revealed by the classical oligodendrocyte and myelin markers, 2',3'-cyclic nucleotide 3'-phosphodiesterase, myelin basic protein and myelin oligodendrocyte glycoprotein. The results indicate that oligodendrocyte precursors committed to differentiate into myelin forming oligodendrocytes are present through all layers of the adult cortex and that their phenotypic features exactly recall those of the oligodendroglial lineage cells during development.

  20. The role of CD8+T cells in the acute and chronic phases of Theiler's murine encephalomyelitis virus-induced disease in mice.

    PubMed

    Borrow, P; Tonks, P; Welsh, C J; Nash, A A

    1992-07-01

    The technique of in vivo depletion with T cell subset-specific monoclonal antibodies was used to study the involvement of CD8+T cells in protection/pathogenesis during the acute and chronic demyelinating phases of Theiler's murine encephalomyelitis virus (TMEV)-induced disease. Mice rendered CD8-deficient prior to infection with TMEV were less efficient at clearing virus from the central nervous system compared to intact animals and also suffered demyelinating disease of earlier onset and increased severity. This indicates that CD8+ cells have a protective role in virus clearance at early times post-infection, and may also be involved in downregulating the severity of the chronic demyelinating disease. How CD8+ T cells function to produce these effects is discussed.

  1. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or

  2. Persistent infection of a glioma cell line generates a Theiler's virus variant which fails to induce demyelinating disease in SJL/J mice.

    PubMed

    Patick, A K; Oleszak, E L; Leibowitz, J L; Rodriguez, M

    1990-09-01

    Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26-20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence.

  3. Demyelinizing neurological disease after treatment with tumor necrosis factor alpha-inhibiting agents in a rheumatological outpatient clinic: description of six cases.

    PubMed

    Theibich, Ali; Dreyer, Lene; Magyari, Melinda; Locht, Henning

    2014-05-01

    Biological treatment with inhibitors of the pro-inflammatory cytokine TNF-alpha has dramatically improved the disease course of several chronic rheumatologic conditions. Adverse events (AEs) are primarily infections and hypersensitivity reactions. Demyelinizing neurological symptoms resembling multiple sclerosis (MS) have been described as a rare AE. During about 10-year use of anti TNF-alpha, the Danish Medicines Agency has recorded eight cases of MS like AEs. The objective of this study was to estimate the incidence of demyelinizing AEs both in the central and peripheral nervous system after treatment with anti TNF-alpha in a cohort of patients from a large rheumatologic outpatient clinic in Copenhagen. In a 4-year period from January 2008 to December 2011, approximately 550 patients annually were undergoing treatment with anti TNF-alpha inhibitors in our department. We collected data on all patients who developed neurological symptoms during this time period. We found six patients with signs of demyelinizing neurological disorders: four resembling MS, one MS-like condition, and one multifocal motor neuropathy. During a relatively short time period, we found a remarkably high number of neurological demyelinizing AEs probably linked to anti TNF-alpha treatment. The AEs were not associated with a single anti TNF-alpha agent and were thus presumably a class effect. The data presented suggest that neurological AEs may be underreported. We advocate that physicians handling patients during treatment with TNF inhibitors are aware of this potentially serious AE and report these events to the proper medical authorities. PMID:24202614

  4. TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease.

    PubMed

    Miller, Patrick G; Bonn, Michael B; Franklin, Craig L; Ericsson, Aaron C; McKarns, Susan C

    2015-11-15

    TNF-α antagonists provide benefit to patients with inflammatory autoimmune disorders such as Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis. However, TNF antagonism unexplainably exacerbates CNS autoimmunity, including multiple sclerosis and neuromyelitis optica. The underlying mechanisms remain enigmatic. We demonstrate that TNFR2 deficiency results in female-biased spontaneous autoimmune CNS demyelination in myelin oligodendrocyte glycoprotein-specific 2D2 TCR transgenic mice. Disease in TNFR2(-/-) 2D2 mice was associated with CNS infiltration of T and B cells as well as increased production of myelin oligodendrocyte glycoprotein-specific IL-17, IFN-γ, and IgG2b. Attenuated disease in TNF(-/-) 2D2 mice relative to TNFR2(-/-) 2D2 mice identified distinctive roles for TNFR1 and TNFR2. Oral antibiotic treatment eliminated spontaneous autoimmunity in TNFR2(-/-) 2D2 mice to suggest role for gut microbiota. Illumina sequencing of fecal 16S rRNA identified a distinct microbiota profile in male TNFR2(-/-) 2D2 that was associated with disease protection. Akkermansia muciniphila, Sutterella sp., Oscillospira sp., Bacteroides acidifaciens, and Anaeroplasma sp. were selectively more abundant in male TNFR2(-/-) 2D2 mice. In contrast, Bacteroides sp., Bacteroides uniformis, and Parabacteroides sp. were more abundant in affected female TNFR2(-/-) 2D2 mice, suggesting a role in disease causation. Overall, TNFR2 blockade appears to disrupt commensal bacteria-host immune symbiosis to reveal autoimmune demyelination in genetically susceptible mice. Under this paradigm, microbes likely contribute to an individual's response to anti-TNF therapy. This model provides a foundation for host immune-microbiota-directed measures for the prevention and treatment of CNS-demyelinating autoimmune disorders. PMID:26475926

  5. Acute Chagas Disease in a Returning Traveler

    PubMed Central

    Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

    2012-01-01

    Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

  6. Commentary on "Possible induction of acute disseminated encephalomyelitis (ADEM)-like demyelinating illness by intrathecal mesenchymal stem cell injection".

    PubMed

    Butzkueven, Helmut

    2013-02-01

    The case report that is the subject of this Commentary describes a 27-year-old woman, who, 3 months after a devastating low cervical myelitis, underwent intrathecal mesenchymal stem cell (MSC) infusions. Six hours after the third infusion, she became unconscious, febrile and cerebral MRI showed acute bitemporal and left cerebellar lesions, consistent with an acute disseminated encephalomyelitis. It is likely that this is the first reported patient with neuroinflammatory exacerbation after MSC therapy. This case suggests that, in addition to their malignant potential, autologous MSC expanded in vitro can exhibit immune-activating properties leading to autoimmune exacerbation.

  7. Gliopathy of Demyelinating and Non-Demyelinating Strains of Mouse Hepatitis Virus

    PubMed Central

    Kenyon, Lawrence C.; Biswas, Kaushiki; Shindler, Kenneth S.; Nabar, Manasi; Stout, Marjorie; Hingley, Susan T.; Grinspan, Judith B.; Das Sarma, Jayasri

    2015-01-01

    Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter. In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes. In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes. Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination. Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease. PMID:26733813

  8. Chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Van den Bergh, Peter Y K; Rajabally, Yusuf A

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common autoimmune neuropathy. The diagnosis depends on the clinical presentation with a progressive or relapsing course over at least 2 months and electrophysiological evidence of primary demyelination. Whereas typical CIDP is quite easily recognizable because virtually no other neuropathies present with both distal and proximal motor and sensory deficit, atypical CIDP, focal and multifocal variants in particular, may represent a difficult diagnostic challenge. CIDP very likely is an underdiagnosed condition as suggested also by a positive correlation between prevalence rates and sensitivity of electrophysiological criteria. Since no 'gold standard' diagnostic marker exists, electrophysiological criteria have been optimized to be at the same time as sensitive and as specific as possible. Additional supportive laboratory features, such as increased spinal fluid protein, MRI abnormalities of nerve segments, and in selected cases nerve biopsy lead to the correct diagnosis in the large majority of the cases. Objective clinical improvement following immune therapy is also a useful parameter to confirm the diagnosis. The pathogenesis and pathophysiology of CIDP remain poorly understood, but the available evidence for an inflammatory origin is quite convincing. Steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) have been proven to be effective treatments. IVIG usually leads to rapid improvement, which is useful in severely disabled patients. Repeat treatment over regular time intervals for many years is often necessary. The effect of steroids is slower and the side-effect profile may be problematic, but they may induce disease remission more frequently than IVIG. An important and as of yet uncompletely resolved issue is the evaluation of long-term outcome to determine whether the disease is still active and responsive to treatment.

  9. Autoimmune antigenic targets at the node of Ranvier in demyelinating disorders.

    PubMed

    Stathopoulos, Panos; Alexopoulos, Harry; Dalakas, Marinos C

    2015-03-01

    Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.

  10. [Autopsy case of a patient with Charcot-Marie-Tooth disease type 1A and suspected chronic inflammatory demyelinating polyradiculoneuropathy, which was later diagnosed as amyotrophic lateral sclerosis].

    PubMed

    Higuchi, Yujiro; Sakiyama, Yusuke; Nishihira, Yasushi; Endo, Kazuhiro; Suwazono, Shugo; Suehara, Masahito

    2012-01-01

    We report an autopsy case of a 74-year-old man with late onset Charcot-Marie-Tooth disease type 1A (CMT1A) diagnosed by genetic screening, later associated with amyotrophic lateral sclerosis (ALS). At the age of 70 years, the patient was admitted to our hospital because of progressive weakness and dysesthesia in the right upper limb. In the early stages of the illness, he was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and transient improvement was achieved with intravenous immunoglobulin. However, the symptoms progressively worsened and became refractory. Gene analysis revealed PMP22 gene duplication, which confirmed CMT1A. On sural nerve biopsy, severe demyelinating neuropathy and abundant onion-bulb formations with endoneurial infiltration of inflammatory cells were observed. Thereafter, pseudo-bulbar palsy and respiratory muscle weakness developed insidiously and progressed rapidly along with muscle weakness in the limbs and trunk. The patient died about four years after the onset of this disease. Postmortem examination showed moderate neuronal cell loss, Bunina bodies, and TDP-43-positive inclusions in the anterior horn cells. The spinal cord revealed axonal loss and extensive macrophage permeation in the corticospinal tracts. On the basis of these findings, the final neuropathological diagnosis was ALS. This is the first report of an autopsy case of CMT1A complicated with ALS. We here discuss the significant clinical and neuropathological findings of this case.

  11. Acute exacerbations of fibrotic interstitial lung disease.

    PubMed

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  12. Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions.

    PubMed

    Islam, Mohammad Shyful; Tatsumi, Kouko; Okuda, Hiroaki; Shiosaka, Sadao; Wanaka, Akio

    2009-01-01

    Many oligodendrocyte progenitor cells (OPCs) are found in acute or chronic demyelinated area, but not all of them differentiate efficiently into mature oligodendrocytes in the demyelinated central nervous system (CNS). Recent studies have shown that the basic helix-loop-helix transcription factor Olig2, which stimulates OPCs to differentiate into oligodendrocyte, is strongly up-regulated in many pathological conditions including acute or chronic demyelinating lesions in the adult CNS. Despite their potential role in the treatment of demyelinating diseases, the long-term fate of these up-regulated Olig2 cells has not been identified due to the lack of stable labeling methods. To trace their fate we have used double-transgenic mice, in which we were able to label Olig2-positive cells conditionally with green fluorescent protein (GFP). Demyelination was induced in these mice by feeding cuprizone, a copper chelator. After 6 weeks of cuprizone exposure, GFP-positive (GFP(+)) cells were processed for a second labeling with antibodies to major neural cell markers APC (mature oligodendrocyte marker), GFAP (astrocyte marker), NeuN (neuron marker), Iba1 (microglia marker) and NG2 proteoglycan (oligodendrocyte progenitor marker). More than half of the GFP(+) cells in the external capsule showed co-localization with NG2 proteoglycan. While the percentages of NG2-positive (NG2(+)) and APC-positive (APC(+)) oligodendrocyte lineage cells in cuprizone-treated mice were significantly higher than those in the normal diet group, no significant difference was observed for GFAP-positive (GFAP(+)) astrocytic lineage cells. Our data therefore provide direct evidence that proliferation and differentiation of local and/or recruited Olig2 progenitors contribute to remyelination in demyelinated lesions. PMID:19070638

  13. Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4).

    PubMed

    Piscosquito, Giuseppe; Saveri, Paola; Magri, Stefania; Ciano, Claudia; Gandioli, Claudia; Morbin, Michela; Bella, Daniela D; Moroni, Isabella; Taroni, Franco; Pareyson, Davide

    2016-09-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive (AR) demyelinating neuropathy associated to SH3TC2 mutations, characterized by early onset, spine deformities, and cranial nerve involvement. We screened 43 CMT4 patients (36 index cases) with AR inheritance, demyelinating nerve conductions, and negative testing for PMP22 duplication, GJB1 and MPZ mutations, for SH3TC2 mutations. Twelve patients (11 index cases) had CMT4C as they carried homozygous or compound heterozygous mutations in SH3TC2. We found six mutations: three nonsense (p.R1109*, p.R954*, p.Q892*), one splice site (c.805+2T>C), one synonymous variant (p.K93K) predicting altered splicing, and one frameshift (p.F491Lfs*32) mutation. The splice site and the frameshift mutations are novel. Mean onset age was 7 years (range: 1-14). Neuropathy was moderate-to-severe. Scoliosis was present in 11 patients (severe in 4), and cranial nerve deficits in 9 (hearing loss in 7). Scoliosis and cranial nerve involvement are frequent features of this CMT4 subtype, and their presence should prompt the clinician to look for SH3TC2 gene mutations. In our series of undiagnosed CMT4 patients, SH3TC2 mutation frequency is 30%, confirming that CMT4C may be the most common AR-CMT type.

  14. Olfactory system and demyelination.

    PubMed

    Garcia-Gonzalez, D; Murcia-Belmonte, V; Clemente, D; De Castro, F

    2013-09-01

    Within the central nervous system, the olfactory system represents one of the most exciting scenarios since it presents relevant examples of long-life sustained neurogenesis and continuous axonal outgrowth from the olfactory epithelium with the subsequent plasticity phenomena in the olfactory bulb. The olfactory nerve is composed of nonmyelinated axons with interesting ontogenetic interpretations. However, the centripetal projections from the olfactory bulb are myelinated axons which project to more caudal areas along the lateral olfactory tract. In consequence, demyelination has not been considered as a possible cause of the olfactory symptoms in those diseases in which this sense is impaired. One prototypical example of an olfactory disease is Kallmann syndrome, in which different mutations give rise to combined anosmia and hypogonadotropic hypogonadism, together with different satellite symptoms. Anosmin-1 is the extracellular matrix glycoprotein altered in the X-linked form of this disease, which participates in cell adhesion and migration, and axonal outgrowth in the olfactory system and in other regions of the central nervous system. Recently, we have described a new patho-physiological role of this protein in the absence of spontaneous remyelination in multiple sclerosis. In the present review, we hypothesize about how both main and satellite neurological symptoms of Kallmann syndrome may be explained by alterations in the myelination. We revisit the relationship between the olfactory system and myelin highlighting that minor histological changes should not be forgotten as putative causes of olfactory malfunction.

  15. Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed Central

    Melvold, R W; Jokinen, D M; Miller, S D; Dal Canto, M C; Lipton, H L

    1990-01-01

    Theiler's virus-induced demyelinating disease results from a chronic infection in the white matter of the central nervous system and provides an excellent model for human multiple sclerosis. Like multiple sclerosis, there are genetic risk factors in disease development, including genes associated with the major histocompatibility complex and with those encoding the beta chain of the T-cell receptor. Comparisons of the susceptible DBA/2 and resistant C57BL/6 strains have indicated an important role for the H-2D locus and for a non-H-2 gene (not involving the beta chain of the T-cell receptor) in differential susceptibility. In the present report, analysis of recombinant-inbred strains (BXD) between the DBA/2 and C57BL/6 strains indicated that this non-H-2 locus is located at the centromeric end of chromosome 3 near (4 +/- 4 centimorgans) the carbonic anhydrase-2 (Car-2) enzyme locus. PMID:2296080

  16. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies.

    PubMed

    Gonzalez, Sergio; Berthelot, Jade; Jiner, Jennifer; Perrin-Tricaud, Claire; Fernando, Ruani; Chrast, Roman; Lenaers, Guy; Tricaud, Nicolas

    2016-03-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

  17. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies

    PubMed Central

    Berthelot, Jade; Jiner, Jennifer; Perrin-Tricaud, Claire; Fernando, Ruani; Chrast, Roman; Lenaers, Guy

    2016-01-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

  18. Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model

    PubMed Central

    Tagge, Ian; O’Connor, Audrey; Chaudhary, Priya; Pollaro, Jim; Berlow, Yosef; Chalupsky, Megan; Bourdette, Dennis; Woltjer, Randy; Johnson, Mac; Rooney, William

    2016-01-01

    Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across

  19. Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model.

    PubMed

    Tagge, Ian; O'Connor, Audrey; Chaudhary, Priya; Pollaro, Jim; Berlow, Yosef; Chalupsky, Megan; Bourdette, Dennis; Woltjer, Randy; Johnson, Mac; Rooney, William

    2016-01-01

    Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100 μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping

  20. A novel MPZ gene mutation in exon 2 causing late-onset demyelinating Charcot-Marie-Tooth disease.

    PubMed

    Chavada, Govindsinh; Rao, D Ganesh; Martindale, Joanne; Hadjivassiliou, Marios

    2012-06-01

    The myelin protein zero gene (MPZ) encodes the major structural protein component of myelin in the peripheral nervous system. More than 120 mutations in MPZ have been detected so far. Clinical phenotypes include CMT1B, CMT2, Dejerine-Sottas syndrome, and congenital hypomyelination neuropathy. We report a new previously unreported mutation in the MPZ gene causing a demyelinating peripheral neuropathy. The initial apparent absence of a family history resulted in the patient being treated for an inflammatory neuropathy with some subjective improvement. We subsequently identified another affected member of the same family with the same genotype leading to the correct diagnosis. Both the affected individuals had an 8-base pair deletion, c.160_167delTCCCGGGT in MPZ exon 2. PMID:22622165

  1. [Chronic inflammatory demyelinating polyneuropathy associated with chronic liver disease due to type B and type C hepatitis virus].

    PubMed

    Ohyama, T; Okiyama, R; Yamada, M; Mitani, M; Tamaki, M; Endo, M; Kubo, M

    1995-02-01

    A patient with chronic inflammatory demyelinating polyneuropathy (CIDP) associated with type B and type C hepatitis virus infection is reported. A 54-year-old female who had a blood transfusion at the age of 31 years was diagnosed as a carrier of hepatitis B virus at the age of 43. Liver dysfunction was first noted in 1987 and gradually grew worse year by year. Beginning in early June 1992, the patients general fatigue became worse, her serum GOT and GPT levels became elevated, and she complained of a tingling sensation in her arms and legs. Neurological examination revealed moderate sensory disturbance of the glove-and-stocking type in all of her extremities. Deep tendon reflexes were all diminished. Hepatitis C antibody was detected in the serum at this time. On June 12, 1993, progression of her sensory disturbance was found to be associated with generalized muscle weakness. Cerebrospinal fluid studies showed increased protein without pleocytosis. Motor nerve conduction studies revealed marked prolongation of terminal latencies, reduction of conduction velocities, and abnormal temporal dispersion of the motor potentials. No sensory potentials could be evoked at any of the sites stimulated. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation. A diagnosis of CIDP was made. Treatment with corticosteroids was started, but there was little improvement in neurological function. The liver dysfunction progressed further and ultimately the patient died of hepatic failure. An autopsy demonstrated liver cirrhosis, but no malignant tumors were evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7669415

  2. Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system.

    PubMed

    Rash, J E

    2010-07-28

    The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is "potassium siphoning," a process originally proposed to explain astrocytic sequestration and long-distance disposal of K(+) released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K(+) efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K(+) by nearby astrocytes. Molecular mechanisms for entry of excess K(+) and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K(+) and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte "intermediaries" that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K(+) and water throughout the panglial syncytium, thereby greatly reducing K(+)-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K(+) efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented "dynamic" potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K(+) siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium

  3. Molecular Disruptions of the Panglial Syncytium Block Potassium Siphoning and Axonal Saltatory Conduction: Pertinence to Neuromyelitis Optica and other Demyelinating Diseases of the Central Nervous System

    PubMed Central

    Rash, John E.

    2009-01-01

    The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is “potassium siphoning”, a process originally proposed to explain astrocytic sequestration and long-distance disposal of K+ released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K+ efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K+ by nearby astrocytes. Molecular mechanisms for entry of excess K+ and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K+ and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte “intermediaries” that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K+ and water throughout the panglial syncytium, thereby greatly reducing K+-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K+ efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented “dynamic” potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K+ siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium. Continued

  4. [Peripheral artery disease and acute coronary syndrome].

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Peripheral arterial disease is a common manifestation of systemic atherosclerosis that is associated with increased cardiovascular risk. When presented in the context of an acute coronary syndrome a differential diagnosis with aorta dissection should be made, because peripheral arterial disease may be asymptomatic despite the absence or asymmetry of femoral pulses.

  5. [Demyelinating processes of a viral nature].

    PubMed

    Konovalov, G V; Dobykin, A M

    1981-01-01

    Demyelination processes due to viral infections (encephalomyelitis induced by mouse hepatitis virus, Theiler's encephalomyelitis, canine distemper, and marek's disease) were simulated in laboratory animals to study the corresponding human diseases (multiple sclerosis, multifocal leucoencephalopathy, Guillain-Barre's syndrome). The following mechanisms of tissue injury are discussed: (1) viral damage of myelin-supporting cells, (2) demyelination occurring as a side effect of specific and non-specific inflammatory reactions to the viruses persisting in the nervous system, (3) autoimmune reaction triggered by virus infection. Special attention is paid to the role of virus agents in the development of these processes.

  6. Aggregation of MBP in chronic demyelination

    PubMed Central

    Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

    2015-01-01

    Objectives Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer’s diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. Methods To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). Results We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Interpretation Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS. PMID:26273684

  7. Acute cerebrovascular disease in women.

    PubMed

    Arboix, A; Oliveres, M; García-Eroles, L; Maragall, C; Massons, J; Targa, C

    2001-01-01

    In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.

  8. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. II. Survey of host immune responses and central nervous system virus titers in inbred mouse strains.

    PubMed

    Clatch, R J; Lipton, H L; Miller, S D

    1987-11-01

    Previous studies using mouse strains with limited genetic differences and H-2 haplotypes demonstrated that susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease strongly correlated with chronically high levels of TMEV-specific delayed-type hypersensitivity (DTH), but not with TMEV-specific T cell proliferation (Tprlf), serum antibody responses, or with CNS virus titers. To determine if this correlation would be supported by analysis of these parameters in a more thorough genetic survey, ten inbred mouse strains, representing a wide variety of genetic backgrounds and H-2 haplotypes, were inoculated intracerebrally (i.c.) with the BeAn strain of TMEV. Significant TMEV-specific DTH was observed in all highly susceptible strains, but was not detectable in intermediate and resistant strains. TMEV-specific serum antibody titers also appeared to correlate with susceptibility to demyelinating disease, however even resistant strains had high antibody responses. Significant differences in CNS TMEV titers existed between strains, but did not correlate with disease susceptibility. DTH and Tprlf responses were observed in 3/4 resistant strains following peripheral immunization with UV-inactivated TMEV indicating that most resistant strains are genetically capable of mounting virus-specific cell-mediated immune (CMI) responses. The data extends our knowledge of host immune responses and virus titers in many different inbred mouse strains persistently infected with TMEV, supports the hypothesis that the demyelination in highly susceptible mice involves a TMEV-specific DTH response, and suggests that the genetic ability to mount specific DTH responses is necessary, but not sufficient for development of the demyelinating disease.

  9. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

    PubMed

    Guglielmetti, C; Veraart, J; Roelant, E; Mai, Z; Daans, J; Van Audekerke, J; Naeyaert, M; Vanhoutte, G; Delgado Y Palacios, R; Praet, J; Fieremans, E; Ponsaerts, P; Sijbers, J; Van der Linden, A; Verhoye, M

    2016-01-15

    cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.

  10. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

    PubMed

    Guglielmetti, C; Veraart, J; Roelant, E; Mai, Z; Daans, J; Van Audekerke, J; Naeyaert, M; Vanhoutte, G; Delgado Y Palacios, R; Praet, J; Fieremans, E; Ponsaerts, P; Sijbers, J; Van der Linden, A; Verhoye, M

    2016-01-15

    cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

  11. Brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease.

    PubMed

    Raivich, Gennadij; Banati, Richard

    2004-11-01

    Microglia and macrophages, one a brain-resident, the other a mostly hematogenous cell type, represent two related cell types involved in the brain pathology in multiple sclerosis and its autoimmune animal model, the experimental allergic encephalomyelitis. Together, they perform a variety of different functions: they are the primary sensors of brain pathology, they are rapidly recruited to sites of infection, trauma or autoimmune inflammation in experimental allergic encephalomyelitis and multiple sclerosis and they are competent presenters of antigen and interact with T cells recruited to the inflamed CNS. They also synthesise a variety of molecules, such as cytokines (TNF, interleukins), chemokines, accessory molecules (B7, CD40), complement, cell adhesion glycoproteins (integrins, selectins), reactive oxygen radicals and neurotrophins, that could exert a damaging or a protective effect on adjacent axons, myelin and oligodendrocytes. The current review will give a detailed summary on their cellular response, describe the different classes of molecules expressed and their attribution to the blood derived or brain-resident macrophages and then discuss how these molecules contribute to the neuropathology. Recent advances using chimaeric and genetically modified mice have been particularly telling about the specific, overlapping and nonoverlapping roles of macrophages and microglia in the demyelinating disease. Interestingly, they point to a crucial role of hematogenous macrophages in initiating inflammation and myelin removal, and that of microglia in checking excessive response and in the induction and maintenance of remission.

  12. Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis.

    PubMed

    Hintzen, Rogier Q; Dale, Russell C; Neuteboom, Rinze F; Mar, Soe; Banwell, Brenda

    2016-08-30

    Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS. PMID:27572864

  13. Monoclonal antibody to Theiler's murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis.

    PubMed

    Yamada, M; Zurbriggen, A; Fujinami, R S

    1990-06-01

    Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease in mice. The mechanisms underlying the demyelination have not been fully elucidated. We have raised a mAb to TMEV (DA strain), H8, that reacts both with TMEV VP-1 and galactocerebroside (GC). In mouse brain cultures, cells positive for the mAb H8 epitope were double labeled with antibody to myelin basic protein, indicating that those cells were oligodendrocytes. Further, mAb H8 could immunostain myelin structures in frozen sections from mouse brains. When injected intravenously into mice with acute allergic encephalomyelitis, mAb H8 increased by 10-fold the size of demyelinated areas within the spinal cords. This is the first report demonstrating that an antibody to virus can enhance demyelination of a central nervous system disease. Ig fractions from the sera of mice with chronic TMEV infection had antibody(s) to GC, as well as to TMEV, as determined by ELISA. Furthermore, a competition ELISA for TMEV or GC antigen revealed that sera from these infected mice contained antibody(s) with the same specificity as mAb H8. Our results indicate that antibodies generated by immune response to TMEV can react with myelin and oligodendrocytes, and contribute to demyelination through an immune process.

  14. Monoclonal antibody to Theiler's murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis

    PubMed Central

    1990-01-01

    Theiler's murine encephalomyelitis virus (TMEV) causes a chronic demyelinating disease in mice. The mechanisms underlying the demyelination have not been fully elucidated. We have raised a mAb to TMEV (DA strain), H8, that reacts both with TMEV VP-1 and galactocerebroside (GC). In mouse brain cultures, cells positive for the mAb H8 epitope were double labeled with antibody to myelin basic protein, indicating that those cells were oligodendrocytes. Further, mAb H8 could immunostain myelin structures in frozen sections from mouse brains. When injected intravenously into mice with acute allergic encephalomyelitis, mAb H8 increased by 10-fold the size of demyelinated areas within the spinal cords. This is the first report demonstrating that an antibody to virus can enhance demyelination of a central nervous system disease. Ig fractions from the sera of mice with chronic TMEV infection had antibody(s) to GC, as well as to TMEV, as determined by ELISA. Furthermore, a competition ELISA for TMEV or GC antigen revealed that sera from these infected mice contained antibody(s) with the same specificity as mAb H8. Our results indicate that antibodies generated by immune response to TMEV can react with myelin and oligodendrocytes, and contribute to demyelination through an immune process. PMID:1693653

  15. Functional recovery of callosal axons following demyelination: a critical window.

    PubMed

    Crawford, D K; Mangiardi, M; Xia, X; López-Valdés, H E; Tiwari-Woodruff, S K

    2009-12-29

    Axonal dysfunction as a result of persistent demyelination has been increasingly appreciated as a cause of functional deficit in demyelinating diseases such as multiple sclerosis. Therefore, it is crucial to understand the ultimate causes of ongoing axonal dysfunction and find effective measures to prevent axon loss. Our findings related to functional deficit and functional recovery of axons from a demyelinating insult are important preliminary steps towards understanding this issue. Cuprizone diet for 3-6 wks triggered extensive corpus callosum (CC) demyelination, reduced axon conduction, and resulted in loss of axon structural integrity including nodes of Ranvier. Replacing cuprizone diet with normal diet led to regeneration of myelin, but did not fully reverse the conduction and structural deficits. A shorter 1.5 wk cuprizone diet also caused demyelination of the CC, with minimal loss of axon structure and nodal organization. Switching to normal diet led to remyelination and restored callosal axon conduction to normal levels. Our findings suggest the existence of a critical window of time for remyelination, beyond which demyelinated axons become damaged beyond the point of repair and permanent functional loss follows. Moreover, initiating remyelination early within the critical period, before prolonged demyelination-induced axon damage ensues, will improve functional axon recovery and inhibit disease progression. PMID:19800949

  16. pSTAT1, pSTAT3, and T-bet as markers of disease activity in chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Madia, Francesca; Frisullo, Giovanni; Nociti, Viviana; Conte, Amelia; Luigetti, Marco; Del Grande, Alessandra; Patanella, Agata Katia; Iorio, Raffaele; Tonali, Pietro Attilio; Batocchi, Anna Paola; Sabatelli, Mario

    2009-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an auto-immune disorder. We evaluated expression of pSTAT1, T-bet, and pSTAT3 in circulating T-cells, B-cells, and monocytes and spontaneous production of interleukin-17 (IL17), interferon-gamma (IFN gamma), and interleukin-10 (IL10) by peripheral blood mononuclear cells (PBMCs) from 14 active CIDP patients compared with 6 patients with long-lasting remission and 20 controls. Active disease patients showed higher pSTAT1, T-bet, and pSTAT3 in CD4(+) T-cells than controls (p < 0.001, p = 0.0002, p = 0.0097, respectively) and remission patients (p < 0.001, p = 0.0036, p = 0.0008, respectively). pSTAT1, T-bet, and pSTAT3 were also higher in monocytes from active CIDP patients than controls (p = 0.0011, p = 0.0041, p = 0.0413, respectively) and remission patients (p = 0.0073, p = 0.0274, p = 0.0251, respectively). Moreover in CD8(+) T-cells, pSTAT3 expression was higher in active CIDP patients than in remission patients (p = 0.0345) and in controls (p = 0.0023). IL17 and IFN gamma production were significantly higher in active CIDP patients than in controls (p < 0.0395, p = 0.0010, respectively); IFN gamma levels were higher also in remission CIDP patients (p = 0.0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T-bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies.

  17. Anorexia during acute and chronic disease.

    PubMed

    Plata-Salamán, C R

    1996-02-01

    Anorexia is associated with disorders of all systems. Anorexia represents a consistent clinical manifestation during acute and chronic pathophysiological processes (infection, inflammation, injury, toxins, immunological reactions, malignancy and necrosis). Anorexia during disease can be beneficial or deleterious depending on the timing and duration. Temporary anorexia during acute disease may be beneficial to an organism since a restriction in the intake of micro- and macro-nutrients will inhibit bacterial growth. Long-term anorexia during chronic disease, however, is deleterious to an organism and may be associated with cachexia, which can ultimately result in death. Various mechanisms participate in the anorexia observed during disease, including cytokine action. Anorexia induced by cytokines is proposed to involve modulation of hypothalamic-feeding associated sites, prostaglandin-dependent mechanisms, modifications of neurotransmitter systems, gastrointestinal, metabolic, and endocrine factors. In addition, the anorexia-cachexia syndrome is multifactorial and may involve chronic pain, depression or anxiety, hypogeusia and hyposmia, chronic nausea, early satiety, malfunction of the gastrointestinal system, metabolic alterations, cytokine action, production of other anorexigenic substances and/or iatrogenic causes (chemotherapy, radiotherapy). Cachexia may result not only from anorexia and a decreased caloric intake, but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions), or a change in body metabolism. Research has focused on potential interventions to modify anorexia during disease and the anorexia-cachexia syndrome. Nutritional modifications and the use of specific steroids (such as megestrol acetate) are being tested in the clinical setting. Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexia (during a critical

  18. [Chronic inflammatory demyelinating polyradiculoneuropathy: clinical heterogeneity and therapeutic perspectives].

    PubMed

    Leger, Jean-Marc; Bombelli, Francesco; Tran-Thanh, Hung; Chassande, Bénédicte; Maisonobe, Thierry; Viala, Karine

    2010-01-01

    Since the first description of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) by PJ Dyck's group at the Mayo Clinic 35 years ago, a wide range of publications have underlined the clinical, electrophysiologic and histopathologic heterogeneity of this disease. Expert consensus opinion is that CIDP should be considered in any patient with progressive symmetrical or asymmetrical polyradiculoneuropathy whose clinical course is relapsing and remitting or progresses for more than two months, especially if there are positive sensory symptoms, proximal weakness, are flexia without wasting, or preferential loss of vibration or joint-position sense. Electrophysiologic features of demyelinating polyneuropathy (especially conduction blocks) and elevated protein levels in cerebrospinal fluid may assist with the diagnosis. However, various clinical pictures have been described in patients with CIDP including pure motor or sensory impairment, and distal, multifocal or focal distribution. Two specific points have recently been emphasized:--while most CIDP patients have chronic onset, acute onset resembling Guillain-Barré syndrome may sometimes occur;--pure sensory forms may require different diagnostic strategies, including the use of somatosensory evoked potentials showing abnormal proximal sensory conduction, and nerve biopsy showing macrophage-associated demyelination, onion bulb formation, demyelinated and partially remyelinated nerve fibres, endoneurial edema, endoneurial mononuclear cell infiltration, and variation between fascicles. Several sets of diagnostic criteria for CIDP have been proposed, with different sensitivities and specificities. The European Federation of Neurological Societies/Peripheral Nerve Society criteria strike a balance between specificity, which needs to be higher for research purposes than for clinical diagnosis, and sensitivity, which, if too low, might lead to some cases being missed. CIDP patients may have a variety of

  19. Crohn's disease and acute pancreatitis. A review of literature.

    PubMed

    Jasdanwala, Sarfaraz; Babyatsky, Mark

    2015-03-01

    Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  20. Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

    PubMed Central

    Ferrari, Carina C.; Depino, Amaicha M.; Prada, Federico; Muraro, Nara; Campbell, Sandra; Podhajcer, Osvaldo; Perry, V. Hugh; Anthony, Daniel C.; Pitossi, Fernando J.

    2004-01-01

    Interleukin-1β (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases. PMID:15509551

  1. Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus.

    PubMed

    Das Sarma, J; Fu, L; Tsai, J C; Weiss, S R; Lavi, E

    2000-10-01

    Demyelination is the pathologic hallmark of the human immune-mediated neurologic disease multiple sclerosis, which may be triggered or exacerbated by viral infections. Several experimental animal models have been developed to study the mechanism of virus-induced demyelination, including coronavirus mouse hepatitis virus (MHV) infection in mice. The envelope spike (S) glycoprotein of MHV contains determinants of properties essential for virus-host interactions. However, the molecular determinants of MHV-induced demyelination are still unknown. To investigate the mechanism of MHV-induced demyelination, we examined whether the S gene of MHV contains determinants of demyelination and whether demyelination is linked to viral persistence. Using targeted RNA recombination, we replaced the S gene of a demyelinating virus (MHV-A59) with the S gene of a closely related, nondemyelinating virus (MHV-2). Recombinant viruses containing an S gene derived from MHV-2 in an MHV-A59 background (Penn98-1 and Penn98-2) exhibited a persistence-positive, demyelination-negative phenotype. Thus, determinants of demyelination map to the S gene of MHV. Furthermore, viral persistence is insufficient to induce demyelination, although it may be a prerequisite for the development of demyelination.

  2. Initial analysis of non-typical Leber hereditary optic neuropathy (LHON) at onset and late developing demyelinating disease in Italian patients by SSCP and automated DNA sequence analysis

    SciTech Connect

    Sartore, M.; Semeraro, A.; Fortina, P.

    1994-09-01

    LHON is a mitochondrial genetic disease characterized by maternal inheritance and late onset of blindness caused by bilateral retinal degeneration. A number of molecular defects are known affecting expression of seven mitochondrial genes encoding subunits of respiratory chain complex I, III and IV. We screened genomic DNA from Italian patients for seven of the known point mutations in the ND-1, ND-4 and ND-6 subunits of complex I by PCR followed by SSCP and restriction enzyme digestion. Most of the patients had nonfamilial bilateral visual loss with partial or no recovery and normal neurological examination. Fundoscopic examination revealed that none of the patients had features typical of LHON. Nine of 21 patients (43%) showed multifocal CNS demyelination on MRI. Our results show aberrant SSCP patterns for a PCR product from the ND-4 subunit in one affected child and his mother. Sfa NI and Mae III digestions suggested the absence of a previously defined LHON mutation, and automated DNA sequence analysis revealed two A to G neutral sequence polymorphisms in the third position of codons 351 and 353. In addition, PCR products from the same two samples and an unrelated one showed abnormal SSCP patterns for the ND-1 subunit region of complex I due to the presence of a T to C change at nt 4,216 which was demonstrated after Nla III digestion of PCR products and further confirmed by DNA sequence analysis. Our results indicate that additional defects are present in the Italian population, and identification of abnormal SSCP patterns followed by targeted automated DNA sequence analysis is a reasonable strategy for delineation of new LHON mutations.

  3. Blood pressure control in acute cerebrovascular disease.

    PubMed

    Owens, William B

    2011-03-01

    Acute cerebrovascular diseases (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) affect 780,000 Americans each year. Physicians who care for patients with these conditions must be able to recognize when acute hypertension requires treatment and should understand the principles of cerebral autoregulation and perfusion. Physicians should also be familiar with the various pharmacologic agents used in the treatment of cerebrovascular emergencies. Acute ischemic stroke frequently presents with hypertension, but the systemic blood pressure should not be treated unless the systolic pressure exceeds 220 mm Hg or the diastolic pressure exceeds 120 mm Hg. Overly aggressive treatment of hypertension can compromise collateral perfusion of the ischemic penumbra. Hypertension associated with intracerebral hemorrhage can be treated more aggressively to minimize hematoma expansion during the first 3 to 6 hours of illness. Subarachnoid hemorrhage is usually due to aneurysmal rupture; systolic blood pressure should be kept <150 mm Hg to prevent re-rupture of the aneurysm. Nicardipine and labetalol are recommended for rapidly treating hypertension during cerebrovascular emergencies. Sodium nitroprusside is not recommended due to its adverse effects on cerebral autoregulation and intracranial pressure. Hypoperfusion of the injured brain should be avoided at all costs.

  4. Minimal residual disease in acute promyelocytic leukemia.

    PubMed

    Weil, S C

    2000-03-01

    In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from "indolent disease" remains among the future challenges in APL. PMID:10702899

  5. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.

    PubMed Central

    Major, E O; Amemiya, K; Tornatore, C S; Houff, S A; Berger, J R

    1992-01-01

    disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols. Images PMID:1310438

  6. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-01

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID:27188830

  7. Acute Respiratory Distress: from syndrome to disease.

    PubMed

    Cardinal-Fernández, P; Correger, E; Villanueva, J; Rios, F

    2016-04-01

    The acute respiratory distress syndrome (ARDS) is currently one of the most important critical entities given its high incidence, rate of mortality, long-term sequelae and non-specific pharmacological treatment. The histological hallmark of ARDS is diffuse alveolar damage (DAD). Approximately 50% of ARDS patients present DAD, the rest is made up of a heterogeneous group of histological patterns, many of which correspond to a well-recognized disease. For that reason, if these patterns could be diagnosed, patients could benefit from a treatment. Recently, the effect of DAD in clinical and analytical evolution of ARDS has been demonstrated, so the classical approach to ARDS as an entity defined solely by clinical, radiological and gasometrical variables should be reconsidered. This narrative review aims to examine the need to evolve from the concept of ARDS as a syndrome to ARDS as a specific disease. So we have raised 4 critical questions: a) What is a disease?; b) what is DAD?; c) how is DAD considered according to ARDS definition?, and d) what is the relationship between ARDS and DAD?

  8. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-14

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

  9. [Acute bacterial meningitis as an occupational disease].

    PubMed

    Seixas, Diana; Lebre, Ana; Crespo, Pedro; Ferreira, Eugénia; Serra, José Eduardo; Saraiva da Cunha, José Gabriel

    2014-01-01

    Streptococcus suis is a zoonotic pathogen with worldwide distribution, responsible for more than 700 human cases globally reported. This infection affects mostly men, exposed to pig or pork, which leads to its usual classification as an occupational disease. We report a case of acute bacterial meningitis in a 44 years old male. According to his past medical history, the patient had chronic alcoholism and worked in a restaurant as a piglet roaster. Microbiological examination of blood and CSF revealed S. suis. After 14 days of ceftriaxone the patient fully recovered. The authors review the clinical reports previously described in Portugal. In all of them was possible to identify risk exposition to pork. We alert to this microorganism's importance in Portugal where it is probably underdiagnosed.

  10. Abrogation of resistance to Theiler's virus-induced demyelination in C57BL mice by total body irradiation.

    PubMed

    Rodriguez, M; Patick, A K; Pease, L R

    1990-03-01

    Theiler's murine encephalitis virus (TMEV) produces an unusual biphasic disease in susceptible mice characterized by poliomyelitis with early viral replication in neurons, followed by chronic demyelination with viral antigen expression in spinal cord white matter. In addition, infectious virus persists in the central nervous system (CNS) throughout the chronic phase of disease. Previous studies have indicated an important role for major histocompatibility complex (MHC)-gene products in determining resistance/susceptibility to disease. In particular, certain class I gene products of the D region of the H-2 gene complex render mice of the C57BL lineage resistant to induction of demyelination. Intracerebral infection of B10.S(DS) mice results in demyelination in the spinal cord while infection of C57BL/10(Db) or B10.S(9R)(Dd) fails to produce white matter destruction. In this study we showed that immunosuppression with gamma irradiation renders normally resistant B10.S(9R) and C57BL/10 mice susceptible to TMEV-induced demyelination and allowed for increased viral replication. In addition, the majority of irradiated C57BL/10 mice infected with virus showed extensive areas of CNS remyelination by oligodendrocytes beginning at 63 days post-infection. In contrast, immunosuppression of normally susceptible B10.S mice resulted in acute disease and high mortality accompanied by overwhelming destruction of neurons. The study supports the hypothesis that MHC-conferred resistance in C57BL mice is associated with MHC D region products and indicate an important active role for the immune system early in infection in limiting vital infection during disease induction in nonimmunosuppressed mice.

  11. B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination

    PubMed Central

    Kothur, Kavitha; Wienholt, Louise; Tantsis, Esther M; Earl, John; Bandodkar, Sushil; Prelog, Kristina; Tea, Fiona; Ramanathan, Sudarshini; Brilot, Fabienne; Dale, Russell C.

    2016-01-01

    Background Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination. Aim To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS) and -negative (NEG) groups. Methods We measured 34 cytokines/chemokines using multiplex immunoassay in CSF collected from paediatric patients with serum MOG Ab POS [acute disseminated encephalomyelitis (ADEM = 8), transverse myelitis (TM = 2) n = 10] and serum MOG Ab NEG (ADEM = 5, TM = 4, n = 9) demyelination. We generated normative data using CSF from 20 non-inflammatory neurological controls. Results The CSF cytokine and chemokine levels were higher in both MOG Ab POS and MOG Ab NEG demyelination groups compared to controls. The CSF in MOG Ab POS patients showed predominant elevation of B cell related cytokines/chemokines (CXCL13, APRIL, BAFF and CCL19) as well as some of Th17 related cytokines (IL-6 AND G-CSF) compared to MOG Ab NEG group (all p<0.01). In addition, patients with elevated CSF MOG antibodies had higher CSF CXCL13, CXCL12, CCL19, IL-17A and G-CSF than patients without CSF MOG antibodies. Conclusion Our findings suggest that MOG Ab POS patients have a more pronounced CNS inflammatory response with elevation of predominant humoral associated cytokines/chemokines, as well as some Th 17 and neutrophil related cytokines/chemokines suggesting a differential inflammatory pathogenesis associated with MOG antibody seropositivity. This cytokine/chemokine profiling provides new insight into disease pathogenesis, and improves our ability to monitor inflammation and response to treatment. In addition, some of these molecules may represent potential immunomodulatory targets

  12. Bilateral demyelinating tumefactive lesions in three children with hemiparesis.

    PubMed

    Yapici, Zuhal; Eraksoy, Mefkure

    2002-09-01

    We present the results from the evaluations of three children ages of 2, 7, and 11 years with hemiparesis and multiple white-matter lesions on magnetic resonance images (MRIs). The initial symptoms were mainly acute/subacute hemiparesis in all and headache/vomiting in one of them. Before admission, one of them had a history of upper respiratory tract infection, whereas another had undergone urinary tract surgery, and the other reported no history of any infection or stress-related factor. In all of the children, MRI showed multiple superficial and deep white-matter hyperintensity in T2-weighted and proton density images with perifocal edema in the acute phase. During the symptomatic period, all of the patients underwent corticosteroid treatment. Whereas two of the patients demonstrated signs of recovery during the first week of treatment, the other patient demonstrated almost a full recovery with minimal neurologic sequela. Follow-up MRI demonstrated not only a remarkable decrease in the size and number of the lesions, with complete resolution for many of them, it also demonstrated a loss of contrast enhancement. None of these three patients, who had been followed up clinically and through MRI for 5 years, have shown either a clinical relapse or new lesions. The clinical pictures and MRI of the children were different in some aspects from acute multiple sclerosis and acute disseminated encephalomyelitis. Regarding both the clinical follow-up and treatment strategy, it is essential and interesting to state the fact that tumefactive lesions involving both hemispheres are likely to appear during the monitoring of the monophasic courses among inflammatory demyelinating diseases of childhood such as acute disseminated encephalomyelitis.

  13. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD, the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help clarifying the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  14. Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination.

    PubMed

    Ma, Jianmei; Tanaka, Kenji F; Shimizu, Takahiro; Bernard, Claude C A; Kakita, Akiyoshi; Takahashi, Hitoshi; Pfeiffer, Steven E; Ikenaka, Kazuhiro

    2011-05-01

    Demyelination coincides with numerous changes of gene expression in the central nervous system (CNS). Cystatin F, which is a papain-like lysosomal cysteine proteinase inhibitor that is normally expressed by immune cells and not in the brain, is massively induced in the CNS during acute demyelination. We found that microglia, which are monocyte/macrophage-lineage cells in the CNS, express cystatin F only during demyelination. By using several demyelinating animal models and the spinal cord tissues from multiple sclerosis (MS) patients, we examined spatiotemporal expression pattern of cystatin F by in situ hybridization and immunohistochemistry. We found that the timing of cystatin F induction matches with ongoing demyelination, and the places with cystatin F expression overlapped with the remyelinating area. Most interestingly, cystatin F induction ceased in chronic demyelination, in which remyelinating ability was lost. These findings demonstrate that the expression of cystatin F indicates the occurrence of ongoing demyelination/remyelination and the absence of cystatin F expression indicates the cessation of remyelination in the demyelinating area.

  15. Platelet-derived growth factor promotes repair of chronically demyelinated white matter.

    PubMed

    Vana, Adam C; Flint, Nicole C; Harwood, Norah E; Le, Tuan Q; Fruttiger, Marcus; Armstrong, Regina C

    2007-11-01

    In multiple sclerosis, remyelination becomes limited after repeated or prolonged episodes of demyelination. To test the effect of platelet-derived growth factor-A (PDGF-A) in recovery from chronic demyelination we induced corpus callosum demyelination using cuprizone treatment in hPDGF-A transgenic (tg) mice with the human PDGF-A gene under control of an astrocyte-specific promoter. After chronic demyelination and removal of cuprizone from the diet, remyelination and oligodendrocyte density improved significantly in hPDGF-A tg mice compared with wild-type mice. In hPDGF-A tg mice, oligodendrocyte progenitor density and proliferation values were increased in the corpus callosum during acute demyelination but not during chronic demyelination or the subsequent recovery period, compared with hPDGF-A tg mice without cuprizone or to treatment-matched wild-type mice. Proliferation within the subventricular zone and subcallosal zone was elevated throughout cuprizone treatment but was not different between hPDGF-A tg and wild-type mice. Importantly, hPDGF-A tg mice had reduced apoptosis in the corpus callosum during the recovery period after chronic demyelination. Therefore, PDGF-A may support oligodendrocyte generation and survival to promote remyelination of chronic lesions. Furthermore, preventing oligodendrocyte apoptosis may be important not only during active demyelination but also for supporting the generation of new oligodendrocytes to remyelinate chronic lesions.

  16. Clinicopathological and genetic study of early-onset demyelinating neuropathy.

    PubMed

    Parman, Yesim; Battaloglu, Esra; Baris, Ibrahim; Bilir, Birdal; Poyraz, Mürüvvet; Bissar-Tadmouri, Nisrine; Williams, Anna; Ammar, Nadia; Nelis, Eva; Timmerman, Vincent; De Jonghe, Peter; Najafov, Ayaz; Necefov, Ayaz; Deymeer, Feza; Serdaroglu, Piraye; Brophy, Peter J; Said, G

    2004-11-01

    Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene. PMID:15469949

  17. Acute promyelocytic leukemia: a curable disease.

    PubMed

    Lo Coco, F; Nervi, C; Avvisati, G; Mandelli, F

    1998-12-01

    The Second International Symposium on Acute Promyelocytic Leukemia (APL) was held in Rome in 12-14 November 1997. Clinical and basic investigators had the opportunity to discuss in this meeting the important advances in the biology and treatment of this disease achieved in the last 4 years, since the First Roman Symposium was held in 1993. The first part of the meeting was dedicated to relevant aspects of laboratory research, and included the following topics: molecular mechanisms of leukemogenesis and of response/resistance to retinoids, biologic and therapeutic effects of new agents such as arsenicals and novel synthetic retinoids; characterization of APL heterogeneity at the morphological, cytogenetic and immunophenotypic level. The updated results of large cooperative clinical trials using variable combinations of all-trans retinoic acid (ATRA) and chemotherapy were presented by the respective group chairmen, and formed the 'core' part of the meeting. These studies, which in most cases integrated the molecular assessment of response to treatment, provided a stimulating framework for an intense debate on the most appropriate frontline treatment options to be adopted in the future. The last day was dedicated to special entities such as APL in the elderly and in the child, as well as the role of bone marrow transplantation. The prognostic value of molecular monitoring studies was also discussed in the final session of the meeting. In this article, we review the major advances and controversial issues in APL biology and treatment discussed in this symposium and emerging from very recent publications. We would like to credit the successful outcome of this meeting to the active and generous input of all invited speakers and to participants from all over the world who provided constructive and fruitful discussions.

  18. Inflammatory demyelination and neurodegeneration in early multiple sclerosis.

    PubMed

    Charil, Arnaud; Filippi, Massimo

    2007-08-15

    A number of recent magnetic resonance imaging studies have challenged the classical view of multiple sclerosis (MS) as a "two-stage" disease where an early inflammatory demyelinating phase with focal macroscopic lesions formed in the white matter (WM) of the central nervous system is followed by a late neurodegenerative phase, which is believed to be a mere consequence of repeated inflammatory insults and irreversible demyelination. These studies have consistently shown the presence of diffuse normal-appearing WM damage, marked gray matter involvement and significant cortical functional reorganization, as well as the occurrence of the neurodegenerative component of MS from the earliest clinical stages of the disease with only a partial relation to MRI markers of inflammatory demyelination. The present review argues that MS can no longer be viewed as a "two-stage" disease, which suggests that the two pathological components are dissociated in time, but rather as a "simultaneous two-component" disease, where the relative contributions of the various pathological processes of the disease to the development of "fixed" disability, their relationship and their evolution over time need to be clarified. This new view of MS should inform the development of future research protocols to define its actual physiopathology and prompt the institution of early treatment which should ideally target not only inflammatory demyelination, but also the neurodegenerative aspects of the disease, as well as promote neuroprotection and enhance reparative mechanisms and adaptive functional reorganization of the cortex. PMID:17397873

  19. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    NASA Astrophysics Data System (ADS)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  20. Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

    PubMed

    Das, H K; Das, D; Doley, R; Sahu, P P

    2016-01-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

  1. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    PubMed Central

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-01-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

  2. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  3. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  4. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  5. Psychiatric comorbidity in pediatric patients with demyelinating disorders.

    PubMed

    Weisbrot, Deborah M; Ettinger, Alan B; Gadow, Kenneth D; Belman, Anita L; MacAllister, William S; Milazzo, Maria; Reed, Michael L; Serrano, Daniel; Krupp, Lauren B

    2010-02-01

    Little is known about psychiatric aspects of pediatric demyelinating conditions. A total of 23 youths (6-17 years) with demyelinating conditions underwent semistructured psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Adolescents and parents completed the Child Symptom Inventory-4 and the Youth's Inventory-4. Fears and conceptions of their neurological problems were elicited. In all, 48% (n = 11) met criteria for current psychiatric diagnoses, including 27% (n = 3) with depressive disorders and 64% (n = 7) with anxiety disorders. Fears and conceptions of the illness were severe and diverse. Depressive and anxiety disorders are common in pediatric demyelinating disease. Clinicians should therefore screen for psychiatric comorbidity symptoms as part of the routine evaluation of such patients.

  6. Chronic inflammatory demyelinating polyradiculoneuropathy, in an 8-year-old girl, complicated by deafness and kidney fibrosis.

    PubMed

    Stojanovic, Vesna D; Doronjski, Aleksandra R; Spasojevic, Slobodan D; Pavlovic, Vesna S; Nikolic, Marko M; Kovacevic, Branka B

    2009-08-01

    Based on case history and clinical and electrophysiological examinations, the authors report on a case of an 8-year-old girl who was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy. The disease was complicated by deafness and kidney fibrosis. During treatment with methylprednisolone and intravenous immunoglobulin, followed by mycophenolate mofetil, prompt improvement of neurological findings occurred. The improvement of hearing was poor. Because the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy has still not been clear, and on the grounds of several cases of chronic inflammatory demyelinating polyradiculoneuropathy conjoined with the kidney disease described in literature (glomerulopathy, interstitial nephritis), every patient with chronic inflammatory demyelinating polyradiculoneuropathy needs to undergo the urinalyses.

  7. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  8. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Lehmann, Helmar C; Hughes, Richard A C; Hartung, Hans-Peter

    2013-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a sporadically occurring, acquired neuropathic condition of autoimmune origin with chronic progressive or relapsing-remitting disease course. CIDP is a treatable disorder; a variety of immunosuppressive and immunomodulatory agents are available to modify, impede, and even reverse the neurological deficits and sequelae that manifest in the course of the disease. However, in many cases CIDP is not curable. Challenges that remain in the treatment of CIDP patients are well recognized and include a remarkably individual heterogeneity in terms of disease course and treatment response as well as a lack of objective and feasible measures to predict and monitor the responsiveness to the available therapies. In this chapter an overview of the currently used drugs in the treatment of CIDP patients is given and some important and controversial issues that arise in the context of care for CIDP patients are discussed.

  9. Influence of laser irradiation on demyelination of nervous fibers

    NASA Astrophysics Data System (ADS)

    Melnik, Nataly O.; Plaksij, Yu. S.; Mamilov, Serge A.

    2000-11-01

    Problem demyelinating diseases from actual in modern of neurology. Main disease of this group - multiple sclerosis, which morphological manifestation is the process demyelineation - disintegration of myelin, which covers axial cylinders of nervous filaments. The outcome of such damage is violation of realization of nervous impulses, dissonance of implement and coordination functions. Most typical the feature of a multiple sclerosis is origin of repeated remissions, which compact with indication remyelination. In development of disease the large role is played by modifications of immunological of a reactivity of an organism. The purpose of the title is development of new methods of treatment of a multiple sclerosis because of lasertherapy. For thsi purpose the influence of a laser exposure on demyelination and remyelination processes will be investigated, is investigated pathological fabrics at microscopic and submicroscopic levels. The study of proceses demyelination and remyelination will be conducted on experimental animals (rats), which are sick experimental allergic encephalomyelitis (EAE), that is the most adequate model of a multiple sclerosis. The patients' EAE animals will be subjected to treatment by a laser exposure. For want of it there will be determinate optimum lengths of waves, dozes and modes of laser radiation.

  10. Pathological heterogeneity of idiopathic central nervous system inflammatory demyelinating disorders.

    PubMed

    Lucchinetti, C

    2008-01-01

    The last decade has seen a resurgence of interest in MS neuropathology. This resurgence was partly fueled by the development of new molecular and histochemical tools to examine the MS lesion microscopically, as well as technological advances in neuroimaging, which permit a dynamic assessment of lesion formation and disease progression. The heterogeneous pathology of MS in relation to stage of lesion activity, phase of disease, and clinical course is discussed. Pathological studies reveal that the immune factors associated with multiple different effector mechanisms contribute to the inflammation, demyelination, and tissue injury observed in MS lesions. While many agree that pathological heterogeneity exists in white matter demyelinated lesions, it is uncertain whether these observations are patient-dependent and reflect pathogenic heterogeneity or, alternatively, are stage-dependent with multiple mechanisms occurring sequentially within a given patient. Evidence supporting both concepts is presented. Remyelination is present in MS lesions; however, the factors contributing to the extent of repair and oligodendrocyte survival differ depending on the disease phase. A variable and patient-dependent extent of remyelination is observed in chronic MS cases and will likely need to be considered when designing future clinical trials aimed to promote CNS repair. MS is one member of a spectrum of CNS idiopathic inflammatory demyelinating disorders that share the basic pathological hallmark of CNS inflammatory demyelination. Advances based on recent systematic clinicopathologic-serologic correlative approaches have led to novel insights with respect to the classification of these disorders, as well as a better understanding of the underlying pathogenic mechanisms.

  11. Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus.

    PubMed

    Dal Canto, M C; Lipton, H L

    1979-08-01

    A morphologic study of demyelination produced by Theiler's encephalomyelitis virus (TMEV) infection in C3H/He mice was performed. Demyelination in this strain of mouse was less intense and had a milder gliomesodermal response than that observed in SJL mice. As early as 80 days after infection numerous remyelinated axons were present in C3H/He mice, and later, extensive remyelination was observed and was mainly by Schwann cells. About one-third of remyelinated plaques showed recurrent demyelinating activity at 200 days. The best evidence of recurrent demyelination was the loss of myelin by abons which had been previously remyelinated by Schwann cells. In addition, acute areas of demyelination were also seen in spinal cords which contained chronic or quiescent plaques. The demonstration of recurrent demyelination in TMEV infection is important for it increases the relevance of this model to multiple sclerosis (MS). In addition TMEV infection of C3H/He mice appears to be an excellent model for further studies of Schwann cell remyelination and recurrent demyelination in the central nervous system (CNS).

  12. Family history of autoimmune thyroid disease and childhood acute leukemia.

    PubMed

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  13. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination.

    PubMed

    Hussain, Rashad; Ghoumari, Abdel M; Bielecki, Bartosz; Steibel, Jérôme; Boehm, Nelly; Liere, Philippe; Macklin, Wendy B; Kumar, Narender; Habert, René; Mhaouty-Kodja, Sakina; Tronche, François; Sitruk-Ware, Regine; Schumacher, Michael; Ghandour, M Said

    2013-01-01

    Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and these observations have spurred interest in the potential protective effects of androgens. Here, we demonstrate that testosterone treatment efficiently stimulates the formation of new myelin and reverses myelin damage in chronic demyelinated brain lesions, resulting from the long-term administration of cuprizone, which is toxic for oligodendrocytes. In addition to the strong effect of testosterone on myelin repair, the number of activated astrocytes and microglial cells returned to low control levels, indicating a reduction of neuroinflammatory responses. We also identify the neural androgen receptor as a novel therapeutic target for myelin recovery. After the acute demyelination of cerebellar slices in organotypic culture, the remyelinating actions of testosterone could be mimicked by 5α-dihydrotestosterone, a metabolite that is not converted to oestrogens, and blocked by the androgen receptor antagonist flutamide. Testosterone treatment also failed to promote remyelination after chronic cuprizone-induced demyelination in mice with a non-functional androgen receptor. Importantly, testosterone did not stimulate the formation of new myelin sheaths after specific knockout of the androgen receptor in neurons and macroglial cells. Thus, the neural brain androgen receptor is required for the remyelination effect of testosterone, whereas the presence of the receptor in microglia and in peripheral tissues is not sufficient to enhance remyelination. The potent synthetic

  14. Demyelination as a Rational Therapeutic Target for Ischemic or Traumatic Brain Injury

    PubMed Central

    Shi, Hong; Hu, Xiaoming; Leak, Rehana K.; Shi, Yejie; An, Chengrui; Suenaga, Jun; Chen, Jun; Gao, Yanqin

    2015-01-01

    Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients. PMID:25819104

  15. Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans.

    PubMed

    Serra-de-Oliveira, Nathalia; Boilesen, Sabine Nunes; Prado de França Carvalho, Carolina; LeSueur-Maluf, Luciana; Zollner, Ricardo de Lima; Spadari, Regina Célia; Medalha, Carla Cristina; Monteiro de Castro, Gláucia

    2015-01-01

    Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Further to the symptoms resulting from demyelination, new studies point to the involvement of neuroinflammation and white matter abnormalities in psychiatric disorders and neurodegenerative diseases. Cuprizone, a model of MS, produces consistent demyelination and elicits behavioural, morphological and inflammatory changes in animals that share some similarities with those observed in humans. In this study, we used the cuprizone model in Lewis rats to evaluate clinical signs triggered by the demyelination process which could be comparable with the symptoms seen in white matter abnormalities in human beings. To induce the demyelination process, 0.6% cuprizone was added to the Lewis rats' diet for 4 weeks. We proceeded with behavioural, morphological and immunological analyses. Animals fed with cuprizone exhibited behavioural changes: higher scores in the neurotoxicity test, reduced exploratory and locomotion behaviour, and also an increase of permanency in the closed arm of the elevated plus maze test, were observed. In these analyses, the animals showed motor coordination impairment and anxiety-like behaviour. Demyelination also triggered changes in discrimination of objects identified by an increase in the time spent close to a familiar object. These behavioural alterations were associated with a significant increase in the levels of TNF-alpha and corticosterone, consistent with the activation of microglia and astrocytes. Taken together, the results of this work show the cuprizone/Lewis rat model demyelination as an attractive paradigm for studying the correlation between white matter abnormalities and behaviour.

  16. Acute diarrhoeal disease in less developed countries

    PubMed Central

    Gordon, John E.; Guzmán, Miguel A.; Ascoli, Werner; Scrimshaw, Nevin S.

    1964-01-01

    A number of primary epidemiological characteristics are recognized as common to members of a syndrome designated “acute undifferentiated diarrhoeal disease”. This syndrome includes both specific and non-specific diarrhoeal disorders. Within the existing knowledge and with the facilities available in less developed countries, an epidemiological basis for control, directed against the syndrome as a whole, is presented as the practical approach to community management. Clinical and microbiological distinctions do not extend to the main bulk of the problem. Individual epidemiological patterns exist according to age and varying social and ecological conditions. Field study by periodic home visits over four years has defined these patterns in highland rural villages in Guatemala. The chief problem was weanling diarrhoea. PMID:14230899

  17. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

    PubMed Central

    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  18. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

  19. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  20. Mechanism of Theiler's virus-induced demyelination in nude mice.

    PubMed

    Rosenthal, A; Fujinami, R S; Lampert, P W

    1986-05-01

    In its natural murine host, infection with Theiler's murine encephalomyelitis virus (TMEV) produces a chronic, progressive demyelinating disease. To help elucidate the role of host immune mechanisms involved in demyelination, we studied TMEV infection in Nude mice. These animals demonstrated rising titers of infectious virus within the central nervous system and failed to produce anti-TMEV antibody. Neurologic signs including the development of severe hind limb paralysis were evident approximately 2 weeks postinfection with most animals succumbing within the first month. Immunoperoxidase studies demonstrated viral antigen in the cytoplasm of neurons and glial cells for the entire period of observation. Plaques of demyelination associated with scanty inflammatory infiltrates were present in the spinal cord by 14 days postinfection. Electron microscopic studies of the involved white matter revealed numerous degenerating glial cells, many of which contained paracrystalline arrays of picornavirus within their cytoplasm. Some of the infected glial cells were identified as oligodendrocytes by demonstrating their myelin-plasma membrane connections. The studies indicate that in Nude mice TMEV causes a lytic infection of oligodendrocytes producing demyelination independent of the T lymphocyte immune system.

  1. [Acute atrioventricular block in chronic Lyme disease].

    PubMed

    Wagner, Vince; Zima, Endre; Gellér, László; Merkely, Béla

    2010-09-26

    The tick bite transmitted Lyme disease is one of the most common antropozoonosis, about 10 000 new infections are reported in Hungary each year. The progress and clinical presentation can vary, and carditis can occur in later stages. A serologically verified Lyme disease caused third degree atrioventricular block in young male presenting with presyncope. Based on the tick-bites mentioned a few weeks prior to hospital admission, Lyme carditis was considered with the administration of antibiotics and monitor observation. Typical skin lesions were not recognized and laboratory findings showed no pathology. An electrophysiological study recorded a predominant supra-His atrioventricular block. Total regression of conduction could be detected later and the serological tests established an underlying Lyme disease. Currently no definite treatment recommendation is available for the potentially reversible Lyme carditis. The tick bite seemed to be the key on our way to diagnosis; however, serological tests proved the disease to be older than one year. A detailed medical history and serological tests are essential in identifying the cause and pacemaker implantation can be avoided.

  2. Acute graft-vs-host disease: pathobiology and management.

    PubMed

    Goker, H; Haznedaroglu, I C; Chao, N J

    2001-03-01

    Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD. PMID:11274753

  3. Demyelination increases axonal stationary mitochondrial size and the speed of axonal mitochondrial transport

    PubMed Central

    Kiryu-Seo, Sumiko; Ohno, Nobuhiko; Kidd, Grahame J.; Komuro, Hitoshi; Trapp, Bruce D.

    2010-01-01

    Axonal degeneration contributes to permanent neurological disability in inherited and acquired diseases of myelin. Mitochondrial dysfunction has been proposed as a major contributor to this axonal degeneration. It remains to be determined, however, if myelination, demyelination or remyelination alter the size and distribution of axonal mitochondrial stationary sites or the rates of axonal mitochondrial transport. Using live myelinated rat dorsal root ganglion (DRG) cultures, we investigated whether myelination and lysolecithin-induced demyelination affect axonal mitochondria. Myelination increased the size of axonal stationary mitochondrial sites by 2.3 fold. Following demyelination, the size of axonal stationary mitochondrial sites was increased by an additional 2.2 fold and the transport velocity of motile mitochondria was increased by 47%. These measures returned to the levels of myelinated axons following remyelination. Demyelination induced activating transcription factor (ATF) 3 in DRG neurons. Knockdown of neuronal ATF3 by shRNA abolished the demyelination-induced increase in axonal mitochondrial transport and increased nitrotyrosine immunoreactivity in axonal mitochondria, suggesting that neuronal ATF3 expression and increased mitochondrial transport protect demyelinated axons from oxidative damage. In response to insufficient ATP production, demyelinated axons increase the size of stationary mitochondrial sites and thereby balance ATP production with the increased energy needs of nerve conduction. PMID:20463228

  4. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases.

    PubMed

    Boucher, Richard C

    2015-11-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency.

  5. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases

    PubMed Central

    2015-01-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency. PMID:26595733

  6. Periaxin mutations cause a broad spectrum of demyelinating neuropathies.

    PubMed

    Takashima, Hiroshi; Boerkoel, Cornelius F; De Jonghe, Peter; Ceuterick, Chantal; Martin, Jean-Jacques; Voit, Thomas; Schröder, J-Michael; Williams, Anna; Brophy, Peter J; Timmerman, Vincent; Lupski, James R

    2002-06-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein. PMID:12112076

  7. Schwann cell remyelination and recurrent demyelination in the central nervous system of mice infected with attenuated Theiler's virus.

    PubMed

    Dal Canto, M C; Lipton, H L

    1980-01-01

    Theiler's murine encephalomyelitis virus (TMEV) infection produces a chronic demyelinating disease in mice, and myelin breakdown appears to be immune-mediated. By using an attenuated TMEC strain, WW virus, to infect mice, the course of the disease was slowed and the severity of the inflammatory and glial responses were reduced. In this circumstance, most of the demyelinating lesions showed extensive remyelination, predominantly by Schwann cells. In addition, it was demonstrated that there was recurrent demyelinating activity in the central nervous system (CNS) of infected animals. It is suggested that the rapidity and intensity of demyelinating lesions may influence the potential for remyelination and that Schwann cell participation may be a more important mechanism of myelin repair than it is now thought to be. The fact that there is a recurrent demyelination in TMEV infection increases its relevance as an experimental animal model for multiple sclerosis.

  8. Regional regulation of glutamate signaling during cuprizone-induced demyelination in the brain.

    PubMed

    Azami Tameh, Abolfazl; Clarner, Tim; Beyer, Cordian; Atlasi, Mohammad Ali; Hassanzadeh, Gholamreza; Naderian, Homayoun

    2013-10-01

    Glutamate excitotoxicity is associated with a wide range of neurodegenerative disorders and also seems to be involved in the pathology of demyelinating disorders such as multiple sclerosis (MS). Cuprizone-induced toxic demyelination shows clear characteristics of MS such as demyelination and axonal damage without the involvement of the innate immune system. In this study, we have evaluated glutamate signaling during cuprizone-induced demyelination in the white and gray matter of mouse brain by studying the expression of ionotropic and metabotropic glutamate-receptors and -transporters by Affymetrix gene array analysis, followed by real-time PCR and western blot analysis. Cellular localization of glutamate transporters was investigated by fluorescence double-labeling experiments. Comparing white and gray matter areas, the expression of glutamate receptors was region-specific. Among NMDA receptor subunits, NR2A was up-regulated in the demyelinated corpus callosum (CC), whereas the metabotropic glutamate receptor mGluR2 was down-regulated in demyelinated gray matter. Glutamate-aspartate transporter (GLAST) co-localizing with GFAP(+) astrocytes was increased in both demyelinated CC and telencephalic cortex, whereas Slc1a4 transporter was up-regulated only in CC. Our data indicate that cuprizone treatment affects glutamate-receptors and -transporters differently in gray and white matter brain areas revealing particularly regulation of GLAST and Slc1a4 compared with other genes. This might have an important influence on brain-region selective sensitivity to neurotoxic compounds and the progression of demyelination as has been reported for MS and other demyelinating neurological diseases. PMID:23711509

  9. Cuprizone-induced demyelination in CNP::GFP transgenic mice.

    PubMed

    Silvestroff, Lucas; Bartucci, Sandra; Soto, Eduardo; Gallo, Vittorio; Pasquini, Juana; Franco, Paula

    2010-06-15

    Cuprizone (bis-cyclohexanone oxaldihydrazone) was previously shown to induce demyelination in white matter enriched brain structures. In the present study we used the cuprizone demyelination model in transgenic mice expressing the enhanced green fluorescent protein (GFP) under the 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) promoter. The use of these particular transgenic mice allows easy detection of cells belonging to the entire oligodendroglial (OLG) lineage, ranging from OLG precursors to mature myelinating OLGs. We were able to evaluate the precise extent of oligodendroglial cell damage and recovery within the murine adult central nervous system (CNS) after inducing demyelination by acute cuprizone intoxication. A generalized loss of GFP+ cells was observed after cuprizone exposure and correlated with a decline in myelin basic protein (MBP) expression. OLGs were depleted in many brain areas that were previously thought to be unaffected by cuprizone treatment. Thus, in addition to the well-known cuprizone effects on the medial corpus callosum, we also found a loss of GFP+ cells in most brain structures, particularly in the caudatus putamen, cortex, anterior commissure, olfactory bulb, hippocampus, optic chiasm, brainstem, and cingulum. Loss of GFP+ cells was accompanied by extensive astrogliosis and microglial activation, although neurons were not affected. Interestingly, cuprizone-treated animals showed both activation of GFAP expression and a higher proliferation rate in subventricular zone cells. A week after cuprizone removal from the diet, GFP+ oligodendroglial cells began repopulating the damaged structures. GFP expression precedes that of MBP and allows OLG detection before myelin restoration.

  10. Cervical demyelinating lesion presenting with choreoathetoid movements and dystonia.

    PubMed

    de Pasqua, Silvia; Cevoli, Sabina; Calbucci, Fabio; Liguori, Rocco

    2016-09-15

    Pseudoathetosis and dystonia are rare manifestations of spinal cord disease that have been already reported in lesions involving the posterior columns at the cervical level. We report two patients with a cervical demyelinating lesion at C3-C4 level presenting with hand dystonia and pseudoathetoid movements. The movement disorder disappeared after steroid treatment. The cases we described highlight the importance of identifying secondary causes of movement disorders that can be reversible with appropriate therapy. PMID:27538633

  11. Managing acute and chronic renal stone disease.

    PubMed

    Moran, Conor P; Courtney, Aisling E

    2016-02-01

    Nephrolithiasis, or renal stone disease, is common and the incidence is increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a population level, the increase in stone incidence, erosion of gender disparity, and younger age of onset is likely to reflect increasing prevalence of obesity and a Western diet with a high intake of animal protein and salt. Stones can be detected by a variety of imaging techniques. The gold standard is a non-contrast CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones. CT KUB should be the primary mode of imaging for all patients with colic unless contraindicated. In such instances, or if a CT KUB is not available, an ultrasound KUB is an alternative. This has advantages in terms of radiation exposure and cost, but is limited in sensitivity, particularly for ureteric stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque stones. For most patients diclofenac is a reasonable first choice of analgesia, e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be less effective, but should be used if there is a contraindication to NSAIDs. A combination of diclofenac, paracetamol, and/or codeine regularly can provide adequate pain control in many cases. Failure of this analgesic combination should prompt consideration of secondary care support. If a ureteric stone < 5 mm in diameter is identified, the expectation is that this will pass without intervention. Initially medical management is still useful for stones between 5 and 10mm in diameter, but urology input is more likely to be necessary as up to 50% of these may require intervention. Stones that are >10 mm in diameter should be discussed with the urology service as they are unlikely to pass spontaneously.

  12. Interleukin‐10 is a critical regulator of white matter lesion containment following viral induced demyelination

    PubMed Central

    Puntambekar, Shweta S.; Hinton, David R.; Yin, Xinghua; Savarin, Carine; Bergmann, Cornelia C.; Trapp, Bruce D.

    2015-01-01

    Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti‐inflammatory cytokine IL‐10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL‐10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL‐10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL‐10 sufficient mice correlated with IL‐10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL‐10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106–2120 PMID:26132901

  13. Theiler's murine encephalomyelitis: a model of demyelination and persistence of virus.

    PubMed

    Rodriguez, M; Oleszak, E; Leibowitz, J

    1987-01-01

    Theiler's murine encephalomyelitis virus (TMEV) causes immune-mediated demyelination in susceptible mice which is similar to human demyelinating disorders such as multiple sclerosis. In addition, the picornavirus persists within the central nervous system throughout the course of the chronic demyelinating disease. This article reviews the neuropathology, virology, immunology, and molecular biology of the model system. We analyze the possible mechanisms by which this virus induces demyelination and persists in the nervous system. Finally, we provide a hypothesis that the specificity of primary white matter destruction in the TMEV model depends on immune-sensitized cells which interact with viral antigen plus major histocompatibility complex (MHC) antigens on the surfaces of oligodendrocytes or myelin sheaths.

  14. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  15. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  16. Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

    PubMed

    Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

    2016-01-01

    High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection.

  17. The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination

    PubMed Central

    Slowik, A; Schmidt, T; Beyer, C; Amor, S; Clarner, T; Kipp, M

    2015-01-01

    BACKGROUND AND PURPOSE Modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes within the lymph nodes. Here, we evaluated the potential of an agonist at this receptor, FTY720 (fingolimod), to activate the promyelinating pathways within the brain to encourage remyelination and neuroprotection. EXPERIMENTAL APPROACH In this study, we used the cuprizone model in male C57BL/6 mice and tested the promyelinating and neuroprotective effects of FTY720 after acute and chronic toxin-induced experimental demyelination. We used histological, immunohistochemical and gene expression methods. KEY RESULTS The midline of the corpus callosum was severely demyelinated after acute and chronic cuprizone-induced demyelination. Robust endogenous remyelination was evident after acute, but impaired after chronic, demyelination. FTY720 treatment modestly accelerated myelin recovery after acute but not chronic cuprizone exposure. Markers of gliosis (astrocyte and microglia activation) were not affected by FTY720 treatment. Remarkably, the accumulation of amyloid precursor protein-positive spheroids in axons was less distinct in FTY720-treated animals, indicating that this compound alleviated ongoing axonal damage. CONCLUSIONS AND IMPLICATIONS We show that even during endogenous remyelination, axonal degeneration continued at a low level, accumulating over time. This continuous neurodegenerative process was ameliorated by FTY720 treatment. FTY720 preserved CNS integrity by direct interaction with brain resident cells, the actions of which are still to be defined. PMID:25220526

  18. The origins of cachexia in acute and chronic inflammatory diseases.

    PubMed

    Delano, Matthew J; Moldawer, Lyle L

    2006-02-01

    The term cachexia originates from the Greek root kakos hexis, which translates into "bad condition," recognized for centuries as a progressive deterioration of body habitus. Cachexia is commonly associated with a number of disease states, including acute inflammatory processes associated with critical illness and chronic inflammatory diseases, such as cancer, congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and approximately 15% of the trauma deaths that occur from sepsis-induced organ dysfunction and malnutrition days to weeks after the initial traumatic event. The abnormalities associated with cachexia include anorexia, weight loss, a preferential loss of somatic muscle and fat mass, altered hepatic glucose and lipid metabolism, and anemia. Anorexia alone cannot fully explain the development of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism contribute to the severe tissue losses. Despite significant advances in our understanding of specific disease processes, the mechanisms leading to cachexia remain unclear and multifactorial. Although complex, increasing evidence from both animal models and clinical studies suggests that an inflammatory response, mediated in part by a dysregulated production of proinflammatory cytokines, plays a role in the genesis of cachexia, associated with both critical illness and chronic inflammatory diseases. These cytokines are further thought to induce an acute phase protein response (APR) and produce the alterations in lipid and carbohydrate metabolism identified as crucial markers of acute inflammation in states of malignancy and critical illness. Although much is still unknown about the etiology of cachexia, there is growing appreciation that cachexia represents the endproduct of an inappropriate interplay between multiple cytokines, neuropeptides, classic stress

  19. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  20. [Anesthetic Management of Three Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

    PubMed

    Maruyama, Naoko; Wakimoto, Mayuko; Inamori, Noriko; Nishimura, Shinya; Mori, Takahiko

    2015-08-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronically progressing or relapsing disease caused by immune-mediated peripheral neuropathy. We report the anesthetic management of three CIDP patients who underwent elective orthopedic surgeries. Owing to the risk of neuraxial anesthetics triggering demyelination, general anesthesia was selected to avoid epidural or spinal anesthesia or other neuraxial blockade. It was also judged prudent to avoid prolonged perioperative immobilization, which might compress vulnerable peripheral nerves. For Patient 1, general anesthesia was induced with propofol, remifentanil, and sevoflurane, and was maintained with sevoflurane and remifentanil. For Patients 2 and 3, general anesthesia was induced and maintained with propofol and remifentanil. For tracheal intubation, under careful monitoring with peripheral nerve stimulators, minimal doses of rocuronium (0.6-0.7 mg x kg(-1)) were administered. When sugammadex was administered to reverse the effect of rocuronium, all patients rapidly regained muscular strength. Postoperative courses were satisfactory without sequelae.

  1. Acute arthropathy in patients with rash diseases: a comparative study.

    PubMed

    de Oliveira, Solange Artimos; Bastos Camacho, Luiz Antonio; Fernandes Bruno, Letícia; de Gusmão, Rodrigo Coimbra; de Medeiros Pereira, Antonio Carlos; Coca Velarde, Luis Guillermo; Mendonça Siqueira, Marilda

    2009-09-01

    The aim of this study was to assess the association of acute arthropathy and selected clinical features in patients with acute rash diseases. Serum samples from 1,554 patients were tested for anti-measles, dengue, human parvovirus B19, and rubella virus IgM using enzyme immunoassay. Sera from children, in whom these infections were excluded, were studied for anti-human herpesvirus type 6 IgG antibodies using an indirect immunofluorescence test. Joint complaints occurred in 31.2% of the 862 patients with an etiologic diagnosis and were more frequently seen in adults than in children (OR 8.5). Among the adults, arthropathy prevailed in women compared to men (OR 1.8). Arthropathy was most frequently reported in rubella (41.2%) and in dengue fever cases (41.1%) than in the other rash diseases studied (p < 0.0001). Joint complaints were more frequently seen in patients with fever (OR 1.6) and with five or more days of onset of the disease (OR 1.6), regardless of serological diagnosis. Arthropathy appeared as a frequent condition in rash diseases, typically with low severity and no specific pattern of joint involvement.

  2. Nogo Receptor Inhibition Enhances Functional Recovery following Lysolecithin-Induced Demyelination in Mouse Optic Chiasm

    PubMed Central

    Pourabdolhossein, Fereshteh; Mozafari, Sabah; Morvan-Dubois, Ghislaine; Mirnajafi-Zadeh, Javad; Lopez-Juarez, Alejandra; Pierre-Simons, Jacqueline; Demeneix, Barbara A.; Javan, Mohammad

    2014-01-01

    Background Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR) that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm. Methodology/Principal Findings A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs). Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+) migrated away from this area as a function of time. Conclusions/Significance Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis. PMID:25184636

  3. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

    PubMed

    Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

    2016-03-01

    Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. PMID:26912645

  4. Thyroid hormones promote differentiation of oligodendrocyte progenitor cells and improve remyelination after cuprizone-induced demyelination.

    PubMed

    Franco, P G; Silvestroff, L; Soto, E F; Pasquini, J M

    2008-08-01

    In the present work we analyzed the capacity of thyroid hormones (THs) to improve remyelination using a rat model of cuprizone-induced demyelination previously described in our laboratories. Twenty one days old Wistar rats were fed a diet containing 0.6% cuprizone for two weeks to induce demyelination. After cuprizone withdrawal, rats were injected with triiodothyronine (T3). Histological studies carried out in these animals revealed that remyelination in the corpus callosum (CC) of T3-treated rats improved markedly when compared to saline treated animals. The cellular events occurring in the CC and in the subventricular zone (SVZ) during the first week of remyelination were analyzed using specific oligodendroglial cell (OLGc) markers. In the CC of saline treated demyelinated animals, mature OLGcs decreased and oligodendroglial precursor cells (OPCs) increased after one week of spontaneous remyelination. Furthermore, the SVZ of these animals showed an increase in early progenitor cell numbers, dispersion of OPCs and inhibition of Olig and Shh expression compared to non-demyelinated animals. The changes triggered by demyelination were reverted after T3 administration, suggesting that THs could be regulating the emergence of remyelinating oligodendrocytes from the pool of proliferating cells residing in the SVZ. Our results also suggest that THs receptor beta mediates T3 effects on remyelination. These results support a potential role for THs in the remyelination process that could be used to develop new therapeutic approaches for demyelinating diseases.

  5. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

    PubMed

    Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

    2016-03-01

    Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies.

  6. Noninvasive imaging in acute coronary disease. A clinical perspective

    SciTech Connect

    Gersh, B.J. )

    1991-09-01

    Numerous highly complex and sensitive noninvasive imaging techniques have enhanced the care of patients with acute myocardial infarction. Optimum use requires specific objectives to be defined in advance, including a review of the potential impact of the test on subsequent decisions. An additional issue that is subject to scrutiny in the current climate of cost containment relates to the incremental value of a specific examination. The imaging modality to be used will partially depend on other issues, including accessibility, cost, and interindividual or institutional expertise with a particular technique. Major applications in noninvasive imaging in the acute coronary syndromes include the following: (1) diagnosis, including identification of associated diseases and contraindications for acute reperfusion; (2) evaluation and management of complications ; (3) determination of prognosis (both early and late); (4) estimation of myocardial viability; (5) assessment of therapeutic efficacy; (6) investigational approaches, including 99mTc-sestamibi tomographic imaging, ultrafast cine computed tomographic scanning, and nuclear magnetic resonance imaging. Previous studies in the prethrombolytic era have documented the powerful impact of radionuclide stress testing on prognosis, but this needs to be reevaluated in the light of the changing current population undergoing stress testing. Preliminary data imply that the prognostic accuracy of stress testing after thrombolytic therapy is diminished. Moreover, the role of the open infarct-related artery in traditional estimates of prognosis requires further study. Noninvasive imaging has multiple applications in the diagnosis and management of patients with acute coronary disease, but the decision to use a specific technology in a particular circumstance mandates good clinical judgment and selectivity. 82 references.

  7. Acute acalculous cholecystitis and cardiovascular disease: a land of confusion.

    PubMed

    Tana, Marco; Tana, Claudio; Cocco, Giulio; Iannetti, Giovanni; Romano, Marcello; Schiavone, Cosima

    2015-12-01

    Acute acalculous cholecystitis (AAC) can be defined as acute inflammatory disease of the gallbladder without evidence of gallstones. The first case was reported in 1844 by Duncan et al.; however, some cases may have been missed previously in view of the complexity of the diagnosis. Several risk factors have been identified, and cardiovascular disease (CVD), in view of its multiple mechanisms of action, seems to play a key role. Atypical clinical onset, paucity of symptoms, overlap with comorbidities, and lack of robust, controlled trials result often in under or misdiagnosed cases. Moreover, laboratory results may be negative or not specific in the late stage of the disease, when a surgical treatment cannot be longer helpful if complications arise. A rapid diagnosis is therefore essential to achieve a prompt treatment and to avoid further clinical deterioration. In this short review, we would present the current evidence regarding epidemiology, pathophysiology, and clinical presentation of the complex relation between AAC and CVD. Then, we fully emphasize the role of ultrasound to achieve an early diagnosis and an appropriate treatment in suspected cases, reducing mortality and complications rates.

  8. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  9. A Rare Sequela of Acute Disseminated Encephalomyelitis

    PubMed Central

    Kodadhala, Vijay; Kurukumbi, Mohankumar; Jayam-Trouth, Annapurni

    2014-01-01

    Acute disseminated encephalomyelitis is a demyelinating disease, typically occurring in children following a febrile infection or a vaccination. Primary and secondary immune responses contribute to inflammation and subsequent demyelination, but the exact pathogenesis is still unknown. Diagnosis of acute disseminated encephalomyelitis is strongly suggested by temporal relationship between an infection or an immunization and the onset of neurological symptoms. Biopsy is definitive. In general, the disease is self-limiting and the prognostic outcome is favorable with anti-inflammatory and immunosuppressive agents. Locked-in syndrome describes patients who are awake and conscious but have no means of producing limb, speech, or facial movements. Locked-in syndrome is a rare complication of acute disseminated encephalomyelitis. We present a case of incomplete locked-in syndrome occurring in a 34-year-old male secondary to acute disseminated encephalomyelitis. Our case is unique, as acute disseminated encephalomyelitis occurred in a 34-year-old which was poorly responsive to immunosuppression resulting in severe disability. PMID:24977089

  10. Guillain-Barré syndrome (demyelinating) six weeks after bariatric surgery: A case report and literature review.

    PubMed

    Ishaque, Noman; Khealani, Bhojo A; Shariff, Amir H; Wasay, Muhammad

    2015-01-01

    Obesity is a major health problem worldwide. Bariatric surgery has been increasingly used to manage obesity. Many acute as well as chronic neurological complications have been reported after bariatric surgery including Guillain-Barré syndrome (GBS). An autoimmune process has been postulated as the underlying pathophysiology. Most of the reported cases of GBS after bariatric surgery are of the axonal variety. Here, we report a case of a demyelinating variety of GBS in a young woman who presented with acute onset of progressive weakness and paresthesia of all limbs within six weeks after bariatric surgery. She was treated with intravenous immunoglobulin (IVIG) and rehabilitation. She had complete recovery on follow-up. We believe that onset of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is demyelinating variety of GBS, is associated with changes in immune system after bariatric surgery.

  11. Epidemiology of coronary heart disease and acute coronary syndrome

    PubMed Central

    Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-01-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  12. Epidemiology of coronary heart disease and acute coronary syndrome.

    PubMed

    Sanchis-Gomar, Fabian; Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-07-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  13. Myelinating and demyelinating phenotype of Trembler-J mouse (a model of Charcot-Marie-Tooth human disease) analyzed by atomic force microscopy and confocal microscopy.

    PubMed

    Rosso, Gonzalo; Negreira, Carlos; Sotelo, José R; Kun, Alejandra

    2012-05-01

    The accumulation of misfolded proteins is associated with various neurodegenerative conditions. Mutations in PMP-22 are associated with the human peripheral neuropathy, Charcot-Marie-Tooth Type 1A (CMT1A). PMP-22 is a short-lived 22 kDa glycoprotein, which plays a key role in the maintenance of myelin structure and compaction, highly expressed by Schwann cells. It forms aggregates when the proteasome is inhibited or the protein is mutated. This study reports the application of atomic force microscopy (AFM) as a detector of profound topographical and mechanical changes in Trembler-J mouse (CMT1A animal model). AFM images showed topographical differences in the extracellular matrix and basal lamina organization of Tr-J/+ nerve fibers. The immunocytochemical analysis indicated that PMP-22 protein is associated with type IV collagen (a basal lamina ubiquitous component) in the Tr-J/+ Schwann cell perinuclear region. Changes in mechanical properties of single myelinating Tr-J/+ nerve fibers were investigated, and alterations in cellular stiffness were found. These results might be associated with F-actin cytoskeleton organization in Tr-J/+ nerve fibers. AFM nanoscale imaging focused on topography and mechanical properties of peripheral nerve fibers might provide new insights into the study of peripheral nervous system diseases.

  14. Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

    PubMed Central

    Sasagawa, Emi; de Aguilar, Ana Vilma Guevara; de Ramírez, Marta Alicia Hernández; Chévez, José Eduardo Romero; Nakagawa, Jun; Cedillos, Rafael Antonio; Kita, Kiyoshi

    2014-01-01

    Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole. PMID:24676660

  15. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  16. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  17. Crohnic Kidney Disease: Recurrent Acute Kidney Failure in a Patient With Crohn's Disease

    PubMed Central

    Demir, Mehmet Emin; Ercan, Zafer; Karakas, Emel Yigit; Ulas, Turgay; Buyukhatipoglu, Hakan

    2014-01-01

    Context: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. Case Report: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. Conclusion: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome. PMID:25599054

  18. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

  19. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  20. MRI of diffuse liver disease: characteristics of acute and chronic diseases.

    PubMed

    Chundru, Surya; Kalb, Bobby; Arif-Tiwari, Hina; Sharma, Puneet; Costello, James; Martin, Diego R

    2014-01-01

    Diffuse liver disease, including chronic liver disease, affects tens of millions of people worldwide, and there is a growing need for diagnostic evaluation as treatments become more readily available, particularly for viral liver diseases. Magnetic resonance imaging (MRI) provides unique capabilities for noninvasive characterization of the liver tissue that rival or surpass the diagnostic utility of liver biopsies. There has been incremental improvement in the use of standardized MRI sequences, acquired before and after administration of a contrast agent, for the evaluation of diffuse liver disease and the study of the liver parenchyma and blood supply. More recent developments have led to methods for quantifying important liver metabolites, including lipids and iron, and liver fibrosis, the hallmark of chronic liver disease. Here, we review the MRI techniques and diagnostic features associated with acute and chronic liver disease. PMID:24808418

  1. Detection of acute hepatopancreatic necrosis disease (AHPND) in Mexico.

    PubMed

    Nunan, Linda; Lightner, Donald; Pantoja, Carlos; Gomez-Jimenez, Silvia

    2014-08-21

    Acute hepatopancreatic necrosis disease (AHPND), which has also been referred to as early mortality syndrome (EMS), initially emerged as a destructive disease of cultured shrimp species in Asia in 2009. The pathogen associated with the disease, Vibrio parahaemolyticus, subsequently spread to the Western Hemisphere and emerged in Mexico in early 2013. The spread to the Western Hemisphere is a major concern to shrimp producers in the region. To date, the only peer-reviewed published method for determining whether mortalities are due to AHPND is through histological examination. A novel PCR detection method was employed to assess samples from Mexico in order to confirm the presence of the pathogen in this country. This manuscript details the detection methods used to confirm the presence of AHPND in Mexico. Both immersion and per os challenge studies were used to expose the Penaeus vannamei to the bacteria in order to induce the disease. Histological analysis confirmed AHPND status following the challenge studies. Also provided are the details of the molecular test by PCR that was used for screening candidate V. parahaemolyticus isolates. A rapid PCR assay for detection of AHPND may help with early detection and help prevent the spread of AHPND to other countries.

  2. The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes in Cuprizone Model of Demyelination.

    PubMed

    Vakilzadeh, Gelareh; Khodagholi, Fariba; Ghadiri, Tahereh; Ghaemi, Amir; Noorbakhsh, Farshid; Sharifzadeh, Mohammad; Gorji, Ali

    2016-09-01

    Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The protective effects of melatonin (MLT) on various neurodegenerative diseases, including MS, have been suggested. In the present study, we examined the effect of MLT on demyelination, apoptosis, inflammation, and behavioral dysfunctions in the cuprizone toxic model of demyelination. C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of cuprizone diet. Administration of MLT improved motor behavior deficits induced by cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition, MLT significantly enhanced nuclear factor-κB activation and decreased heme oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein production. Our data revealed that MLT improved neurological deficits and enhanced cell survival but was not able to initiate myelin production in the cuprizone model of demyelination. These findings may be important for the design of potential MLT therapy in demyelinating disorders, such as MS. PMID:26310973

  3. Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination.

    PubMed

    Evonuk, Kirsten S; Baker, Brandi J; Doyle, Ryan E; Moseley, Carson E; Sestero, Christine M; Johnston, Bryce P; De Sarno, Patrizia; Tang, Andrew; Gembitsky, Igor; Hewett, Sandra J; Weaver, Casey T; Raman, Chander; DeSilva, Tara M

    2015-07-15

    T cell infiltration into the CNS is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. Several lines of evidence suggest that glutamate dysregulation in the CNS is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. A major source of glutamate release during oxidative stress is the system Xc(-) transporter; however, this mechanism has not been tested in animal models of autoimmune inflammatory demyelination. We find that pharmacological and genetic inhibition of system Xc(-) attenuates chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Remarkably, pharmacological blockade of system Xc(-) 7 d after induction of EAE attenuated T cell infiltration into the CNS, but not T cell activation in the periphery. Mice harboring a Slc7a11 (xCT) mutation that inactivated system Xc(-) were resistant to EAE, corroborating a central role for system Xc(-) in mediating immune cell infiltration. We next examined the role of the system Xc(-) transporter in the CNS after immune cell infiltration. Pharmacological inhibitors of the system Xc(-) transporter administered during the first relapse in a SJL animal model of relapsing-remitting EAE abrogated clinical disease, inflammation, and myelin loss. Primary coculture studies demonstrate that myelin-specific CD4(+) Th1 cells provoke microglia to release glutamate via the system Xc(-) transporter, causing excitotoxic death to mature myelin-producing oligodendrocytes. Taken together, these studies support a novel role for the system Xc(-) transporter in mediating T cell infiltration into the CNS as well as promoting myelin destruction after immune cell infiltration in EAE.

  4. Inhibition of system xc− transporter attenuates autoimmune inflammatory demyelination1

    PubMed Central

    Doyle, Ryan E.; Moseley, Carson E.; Sestero, Christine M.; Johnston, Bryce P.; De Sarno, Patrizia; Tang, Andrew; Gembitsky, Igor; Hewett, Sandra J.; Weaver, Casey T.; Raman, Chander; DeSilva, Tara M.

    2015-01-01

    T cell infiltration into the central nervous system (CNS) is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. Several lines of evidence suggest that glutamate dysregulation in the CNS is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. A major source of glutamate release during oxidative stress is the system xc− transporter, however, this mechanism has not been tested in animal models of autoimmune inflammatory demyelination. We find that pharmacological and genetic inhibition of system xc− attenuates chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Remarkably, pharmacological blockade of system xc− seven days after induction of EAE attenuated T cell infiltration into the CNS, but not T cell activation in the periphery. Mice harboring a Slc7a11 (xCT) mutation that inactivated system xc− were resistant to EAE, corroborating a central role for system xc− in mediating immune cell infiltration. We next examined the role of the system xc− transporter in the CNS after immune cell infiltration. Pharmacological inhibitors of the system xc− transporter administered during the first relapse in a SJL animal model of relapsing-remitting EAE abrogated clinical disease, inflammation, and myelin loss. Primary co-culture studies demonstrate that myelin-specific CD4+ T helper type 1 (Th1) cells provoke microglia to release glutamate via the system xc− transporter causing excitotoxic death to mature myelin-producing OLs. Taken together these studies support a novel role for the system xc− transporter in mediating T cell infiltration into the CNS as well as promoting myelin destruction after immune cell infiltration in EAE. PMID:26071560

  5. Primary Epstein-Barr-virus infections in acute neurologic diseases.

    PubMed

    Grose, C; Henle, W; Henle, G; Feorino, P M

    1975-02-20

    Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

  6. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease

    PubMed Central

    Silva-dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  7. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    PubMed

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  8. CT appearance of acute inflammatory disease of the renal interstitium

    SciTech Connect

    Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

    1983-08-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious.

  9. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease.

    PubMed

    Coentre, Ricardo; Silva-Dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  10. Invasive fungal diseases in patients with acute lymphoid leukemia.

    PubMed

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  11. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome.

  12. Refsum's disease may mimic familial Guillain Barre syndrome.

    PubMed

    Verny, Christophe; Prundean, Adriana; Nicolas, Guillaume; Pautot, Vivien; Maugin, Dominique; Levade, Thierry; Bonneau, Dominique; Dubas, Frederic

    2006-11-01

    Refsum's disease is a rare autosomal recessive disorder with clinical features including retinitis pigmentosa, anosmia, deafness, chronic sensory-motor neuropathy, ataxia and the accumulation of phytanic acid in blood plasma and body tissues. We report the occurrence of Refsum's disease in two sisters, both presenting with acute demyelinating polyneuropathy mimicking the familial Guillain Barre syndrome. Thus, when GBS is suspected, particularly in cases of familial recurrence as well as in atypical cases of acute polyneuropathy, the diagnosis of Refsum's disease should be considered, looking for other features of the disease and, if appropriate, testing plasma phytanic acid levels.

  13. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin.

    PubMed

    Rodriguez, M; Dunkel, A J; Thiemann, R L; Leibowitz, J; Zijlstra, M; Jaenisch, R

    1993-07-01

    Intracerebral infection of susceptible strains of mice with Theiler's virus, a picornavirus, results in central nervous system demyelination, which is similar to multiple sclerosis. Immunogenetic experiments indicate that the MHC (H-2) and, in particular, the D region that controls class I-restricted immune responses, is an important determinant to development of demyelination. We tested whether disruption of beta 2-microglobulin (beta 2-m) would abrogate resistance to demyelinating disease normally observed in H-2b mice. All (C57BI/6 x 129)F3 mice transgenic for homozygous beta 2-m gene disruption (-/-) developed chronic demyelination after Theiler's murine encephalomyelitis virus infection, whereas none of the infected littermates with normal expression of class I MHC (beta 2-m, +/+) developed demyelination. Demyelinated lesions showed class II MHC expression, macrophages, and TNF but no class I MHC expression or CD8+ T cells. No correlation was observed between development of demyelination and delayed-type hypersensitivity responses to virus Ag. Despite the presence of demyelinating lesions, none of the infected beta 2-m (-/-) mice developed neurologic deficits. Infectious virus and virus Ag persisted in the central nervous systems of infected beta 2-m (-/-) mice but not in beta 2-m (+/+) mice. These experiments support the hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus-induced demyelination. Development of chronic neurologic deficits as observed in immunocompetent susceptible strains of mice may be dependent on the presence of class I MHC and CD8+ T cells.

  14. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  15. Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology.

    PubMed

    Kobayashi, Masaki; Shimizu, Yuko; Shibata, Noriyuki; Uchiyama, Shinichiro

    2014-10-01

    Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.

  16. Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord.

    PubMed

    Jeffery, N D; Crang, A J; O'leary, M T; Hodge, S J; Blakemore, W F

    1999-05-01

    Glial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam-walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X-irradiation; in the other, male glial cells were transplanted into nonirradiated female recipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal. PMID:10215903

  17. Childhood chronic inflammatory demyelinating polyradiculoneuropathy: combined analysis of a large cohort and eleven published series.

    PubMed

    McMillan, Hugh J; Kang, Peter B; Jones, H Royden; Darras, Basil T

    2013-02-01

    The clinical presentation, disease course, response to treatment, and long-term outcome of thirty childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients are presented representing the largest cohort reported to date. Most children (60%) presented with chronic (>8-weeks) symptom-onset while a smaller proportion showed sub-acute (4-8 weeks) or acute (''GBS-like''; <4 weeks) onset of disease. No gender predilection was observed. The majority of patients had a relapsing (70%) versus a monophasic (30%) temporal profile. Most received initial IVIG monotherapy; 80% showing a good response. Long-term follow-up (mean=3.8 years) was available for 23 patients; 45% were off all immunomodulatory medications, demonstrating no detectable (55%) or minimal (43%) clinical deficits. Our data were compared with 11 previously published childhood CIDP series providing a comprehensive review of 143 childhood CIDP cases. The combined initial or first-line treatment response across all studies was favourable for IVIG (79% patients) and corticosteroids (84% patients). Response to first-line plasma exchange was poor (only 14% patients improved) although it may offer some transient or partial benefit as an adjuvant or temporary therapy for selected patients. The combined long-term outcome of our cohort and the literature reveals a favourable prognosis for most patients. The combined modified Rankin scale decreased from 3.7 (at presentation) to 0.7 (at last follow-up). This review provides important data pertaining to clinical course, treatment response and long-term outcome of this relatively uncommon paediatric autoimmune disease.

  18. A Case Report of Post Rabipur (Purified Chick Embryo Rabies Vaccine) Acute Disseminated Encephalomyelitis.

    PubMed

    Kumar, Rajesh; Singh, A K Bishorjit; Pradhan, R N; Pathak, Vipin Kumar

    2015-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease that typically occurs following a viral infection or vaccination. The incidence of ADEM following vaccination has become very low since introduction of non-neural rabies vaccine and only few cases had been reported due to pure chick embryo derived rabies vaccine (PCERV). Here we are reporting a rare case of delayed post vaccinal ADEM. PMID:26591130

  19. Unusual basal ganglia lesions in a diabetic uraemic patient proven to be demyelination: first pathological observation

    PubMed Central

    Tajima, Yasutaka; Mito, Yasunori; Yanai, Mituru; Fukazawa, Yu-ichiro

    2012-01-01

    A 64-year-old man suffering from diabetes mellitus and chronic renal failure was admitted to our hospital because of consciousness disturbance and parkinsonism. Cranial MRI showed very characteristic features involving the bilateral basal ganglia. Subsequent postmortem examinations demonstrated demyelination in the affected areas. These myelin destruction patterns were quite similar to those of central pontine myelinolysis. However, rapid correction of hyponatraemia was ruled out in this patient. Therefore, a new demyelinating brain disease associated with diabetes mellitus and chronic renal failure was suggested. PMID:22948993

  20. Demyelinating lesions due to Theiler's virus are associated with ongoing central nervous system infection.

    PubMed

    Chamorro, M; Aubert, C; Brahic, M

    1986-03-01

    We used in situ hybridization and immunocytochemistry to look for a correlation between virus expression and white matter lesions during late demyelinating disease due to persistent Theiler's virus infection. We found the following. (i) Tissue lesions developed at the site of virus infection. This correlation was not explained by infection of lymphocytes and macrophages. (ii) Large differences in the extent of pathology existed between mice. The amount of inflammation paralleled the number of cells containing viral RNA or viral capsid antigens. (iii) C57BL/6 mice, which are resistant to demyelination, were able to eradicate the infection. Our results are strongly in favor of a mechanism of demyelination in which viral gene products play a central role.

  1. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

    PubMed

    Miura, Yumako; Devaux, Jérôme J; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi; Yuki, Nobuhiro

    2015-06-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

  2. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia

    PubMed Central

    Miura, Yumako; Devaux, Jérôme J.; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi

    2015-01-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option. PMID:25808373

  3. [Acute encephalic manifestations in Senegalese children with sickle cell disease].

    PubMed

    Diagne, I; Diagne-Guèye, N R; Fall, L; Ndiaye, O; Camara, B; Diouf, S; Signate-Sy, H; Kuakuvi, N

    2001-01-01

    The course of sickle cell disease (SCD) may be complicated by neurologic events, mainly bactérial meningitidis and stroke. We retrospectively studied all cases with acute encephalic manifestations (AEM) in a cohort of 461 children and adolescents with SCD followed at Albert Royer Children Hospital of Dakar (Senegal) from january 1991 to december 2000 (ten years). Among them 438 had sickle cell anemia (SCA), 19 SC disease and 4 S-beta thalassemia (3 S-beta+, 1 S-beta0). Seven patients, all with SCA, presented antecedents of AEM revealed by flacid and proportionnal hemiplegia evoking stroke. Prevalence of these AEM was 1.5 per cent among patients with SCD and 1.6 per cent among those with SCA. They were 4 girls and 3 boys (sex ratio = 0.75) aged 4 to 8.5 years when occurred the first accident. We observed no clinical or biological distinctive characteristic of SCA in these patients compared to those without crebrovascular accident. Recurrence was observed once in a boy after a 12 months interval and twice in a girl after 20 and 60 months intervals successively. No transfusionnal program was applied to prevent recurrent stroke because of insufficient conditions for long-term transfusion. Stroke appears to be rare in senegalese children with SCD. However it poses in our context the major problem of applicability of transfusionnal program which constitute the only therapy universally recognised to be effective to prevent recurrence. Nevertheless hydroxyurea could be a satisfactory alternative.

  4. Computer Models of Stress, Allostasis, and Acute and Chronic Diseases

    PubMed Central

    Goldstein, David S.

    2009-01-01

    The past century has seen a profound shift in diseases of humankind. Acute, unifactorial diseases are being replaced increasingly by multifactorial disorders that arise from complex interactions among genes, environment, concurrent morbidities and treatments, and time. According to the concept of allostasis, there is no single, ideal set of steady-state conditions in life. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators “homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by a comparator thermostat (homeostat). Stress might exert adverse health consequences via allostatic load. This presentation describes models of homeostatic systems that incorporate negative feedback regulation, multiple effectors, effector sharing, environmental influences, intrinsic obsolescence, and destabilizing positive feedback loops. These models can be used to predict effects of environmental and genetic alterations on allostatic load and therefore on the development of multi-system disorders and failures. PMID:19120114

  5. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

  6. MINIMAL RESIDUAL DISEASE QUANTITATION IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Shook, David; Coustan-Smith, Elaine; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Campana, Dario

    2009-01-01

    The prognosis for patients with acute myeloid leukemia (AML) is heterogeneous. A minority of patients has clinical and biologic features that are associated with a very high risk of relapse. For the remaining patients no clear prognostic factors can be identified at diagnosis. The degree of treatment response is likely to be an informative predictor of outcome for these patients. Modern assays to detect AML cells that are undetectable by conventional morphologic techniques, i.e. minimal residual disease (MRD), can potentially improve measurements of treatment response. It is plausible that modifications to treatment based on the results of these assays will improve clinical management and ultimately increase cure rates. Established MRD assays for AML are based on either polymerase chain reaction (PCR) amplification of genetic abnormalities or flow cytometric detection of abnormal immunophenotypes. Residual disease and treatment response can be measured by these assays in a manner that is much more sensitive and objective than that afforded by conventional morphologic examination. The expanding use of MRD testing is beginning to change the definition of treatment response and of remission. Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents. PMID:19778853

  7. [Acute diarrheal disease caused by enteropathogenic Escherichia coli in Colombia].

    PubMed

    Gómez-Duarte, Oscar G

    2014-10-01

    Intestinal Escherichia coli pathogens are leading causes of acute diarrheal disease in children less than 5 years in Latin America, Africa and Asia and a leading cause of death in children living in poorest communities in Africa and South East Asia. Studies on the role of E. coli pathogens in childhood diarrhea in Colombia and other countries in Latin America are limited due to the lack of detection assays in clinical laboratories at the main urban medical centers. Recent studies report that enterotoxigenic E. coli is the most common E. coli pathogens associated with diarrhea in children less than 5 years of age. Other E. coli pathotypes have been detected in children with diarrhea including enteropathogenic, enteroaggregative, shiga-toxin producing and diffusely adherent E. coli. It was also found that meat and vegetables at retail stores are contaminated with Shiga-toxin producing E. coli and enteroaggregative E. coli, suggesting that food products are involved in transmission and infection of the susceptible host. More studies are necessary to evaluate the mechanisms of transmission, the impact on the epidemiology of diarrheal disease, and management strategies and prevention of these pathogens affecting the pediatric population in Colombia.

  8. Glatiramer acetate, an anti-demyelination drug, reduced rats' epileptic seizures induced by pentylenetetrazol via protection of myelin sheath.

    PubMed

    You, Yu; Zhao, Yaqun; Bai, Hui; Liu, Zhiliang; Meng, Fanxin; Zhang, Hua; Xu, Ruxiang

    2013-06-14

    Glatiramer acetate (GA) is a clinically prescribed immunomodulator drug used to treat demyelinating disease like multiple sclerosis (MS). Persistent down-regulation in the expression of myelin sheath proteins has been observed in both rats with pentylenetetrazol (PTZ) induced chronic epilepsy and some clinical epilepsy patients. Hypothetically, protection of myelin sheath by pharmaceutical means in the process of epilepsy might, to some extent, be helpful to control epileptic seizures. Therefore, we tried to use GA to treat PTZ-induced epilepsy rats. GA treatment successfully protected rats' myelin sheath from demyelination in the process of PTZ-induced epileptic seizures. Notably, electroencephalogram (EEG) monitoring demonstrated that GA-treated epilepsy rats showed significantly lowered epileptiform discharges. Correspondingly, behavioral recording showed reduced frequency of seizures in GA-treated epilepsy rats. The results indicate that epilepsy associated demyelination may be a contributing factor in seizures behavior, and early intervention with anti-demyelination drugs may be beneficial to reduce the severity of seizures behavior.

  9. In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

    SciTech Connect

    Armstrong, R.; Friedrich, V.L. Jr.; Holmes, K.V.; Dubois-Dalcq, M. )

    1990-09-01

    A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with (3H)thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.

  10. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease.

    PubMed

    Long, Simon Y; Latimer, Erin M; Hayward, Gary S

    2016-01-01

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  11. Pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimp.

    PubMed

    Lai, Hung-Chiao; Ng, Tze Hann; Ando, Masahiro; Lee, Chung-Te; Chen, I-Tung; Chuang, Jie-Cheng; Mavichak, Rapeepat; Chang, Sheng-Hsiung; Yeh, Mi-De; Chiang, Yi-An; Takeyama, Haruko; Hamaguchi, Hiro-o; Lo, Chu-Fang; Aoki, Takashi; Wang, Han-Ching

    2015-12-01

    Acute hepatopancreatic necrosis disease (AHPND), also called early mortality syndrome (EMS), is a recently emergent shrimp bacterial disease that has resulted in substantial economic losses since 2009. AHPND is known to be caused by strains of Vibrio parahaemolyticus that contain a unique virulence plasmid, but the pathology of the disease is still unclear. In this study, we show that AHPND-causing strains of V. parahaemolyticus secrete the plasmid-encoded binary toxin PirAB(vp) into the culture medium. We further determined that, after shrimp were challenged with AHPND-causing bacteria, the bacteria initially colonized the stomach, where they started to produce PirAB(vp) toxin. At the same early time point (6 hpi), PirB(vp) toxin, but not PirA(vp) toxin, was detected in the hepatopancreas, and the characteristic histopathological signs of AHPND, including sloughing of the epithelial cells of the hepatopancreatic tubules, were also seen. Although some previous studies have found that both components of the binary PirAB(vp) toxin are necessary to induce a toxic effect, our present results are consistent with other studies which have suggested that PirB(vp) alone may be sufficient to cause cellular damage. At later time points, the bacteria and PirA(vp) and PirB(vp) toxins were all detected in the hepatopancreas. We also show that Raman spectroscopy "Whole organism fingerprints" were unable to distinguish between AHPND-causing and non-AHPND causing strains. Lastly, by using minimum inhibitory concentrations, we found that both virulent and non-virulent V. parahaemolyticus strains were resistant to several antibiotics, suggesting that the use of antibiotics in shrimp culture should be more strictly regulated. PMID:26549178

  12. Multifocal CNS demyelination following peripheral inoculation with herpes simplex virus type 1.

    PubMed

    Kastrukoff, L F; Lau, A S; Kim, S U

    1987-07-01

    The peripheral inoculation of herpes simplex virus type 1 (HSV 1) in experimental animals induces central nervous system (CNS) demyelinating lesions, but the potential relevance of this model to multiple sclerosis is lessened by the unifocal nature of the lesion. In this study, inbred strains of mice were selected on the basis of varying resistance to mortality following lip inoculation with virus. A spectrum of CNS pathology was observed, ranging from focal collections of inflammatory cells at the trigeminal root entry zone in resistant strains (C57BL/6J), to unifocal demyelinating lesions in moderately resistant strains (BALB/cByJ), to multifocal demyelinating lesions throughout the brain in susceptible strains (A/J). Findings from viral titration studies of the CNS support a direct cytolytic effect of virus in the development of demyelinating lesions at the trigeminal root entry zone but cannot exclude an immune-mediated component. Furthermore, 50% tissue-culture-infective doses, immunofluorescence, and electron microscopic studies of primary cultures of oligodendrocytes, derived from the three strains of adult mice, identify differences in resistance to HSV 1 infection in vitro, suggesting that differences at this level may also contribute to the pathological appearance. Multifocal lesions in A/J mice were first observed when the infectious virus could no longer be isolated from the CNS and may be the result of an immune-mediated process "triggered" by the acute CNS infection in susceptible strains of mice.

  13. Axonal pathology precedes demyelination in a mouse model of X-linked demyelinating/type I Charcot-Marie Tooth neuropathy.

    PubMed

    Vavlitou, Natalie; Sargiannidou, Irene; Markoullis, Kyriaki; Kyriacou, Kyriacos; Scherer, Steven S; Kleopa, Kleopas A

    2010-09-01

    The X-linked demyelinating/type I Charcot-Marie-Tooth neuropathy (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the gene that encodes the gap junction protein connexin32. Connexin32 is expressed by myelinating Schwann cells and forms gap junctions in noncompact myelin areas, but axonal involvement is more prominent in X-linked compared with other forms of demyelinating Charcot-Marie-Tooth disease. To clarify the cellular and molecular mechanisms of axonal pathology in CMT1X, we studied Gjb1-null mice at early stages (i.e. 2-4 months old) of the neuropathy, when there is minimal or no demyelination. The diameters of large myelinated axons were progressively reduced in Gjb1-null mice compared with those in wild-type littermates. Furthermore, neurofilaments were relatively more dephosphorylated and more densely packed starting at 2 months of age. Increased expression of β-amyloid precursor protein, a marker of axonal damage, was also detected in Gjb1-null nerves. Finally, fast axonal transport, assayed by sciatic nerve ligation experiments, was slower in distal axons of Gjb1-null versus wild-type animals with reduced accumulation of synaptic vesicle-associated proteins. These findings demonstrate that axonal abnormalities including impaired cytoskeletal organization and defects in axonal transport precede demyelination in this mouse model of CMT1X. PMID:20720503

  14. Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations without Conduction Block

    PubMed Central

    Daskalova, M. S.; Alexandrov, A. S.

    2006-01-01

    The membrane properties (intracellular, extracellular, electrotonic potentials, strength-duration time constants, rheobasic currents and recovery cycles), which can now be measured in healthy subjects and patients with demyelinating neuropathies, are investigated in simulated cases of focal reduction (70%) of the myelin sheath in one, two and three successive internodal segments along the length of human motor fibres. The internodally focally demyelinated cases (termed as IFD1, IFD2 and IFD3, respectively) are simulated using our previous double cable model of the fibres. The results show that the intracellular potentials are with reduced amplitude and slowed conduction velocity in the vicinity of demyelinated segments, however the segmental conduction block is not achieved. The radial decline of the extracellular potential amplitudes slightly increases with the increase of the radial distance and demyelination. In contrast, the electrotonic potentials, strength-duration time constants and rheobases are normal. In the recovery cycles, the refractoriness, supernormality and less late subnormality are close to the normal, showing that the pathology is relatively minor. The obtained abnormalities in the potentials and excitability properties provide new information about the pathophysiology of the demyelinated human motor axons and can be observed in vivo in patients with acquired demyelinating neuropathies. PMID:19669452

  15. Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

    PubMed Central

    Daskalova, M. S.; Alexandrov, A. S.

    2006-01-01

    The aim of this study is to investigate the membrane properties (potentials and axonal excitability indices) in the case of myelin wrap reduction (96%) in one, two and three consecutive internodes along the length of human motor nerve fibre. The internodally focally demyelinated cases (termed as IFD1, IFD2 and IFD3, respectively, with one, two and three demyelinated internodes are simulated using our previous double cable model of the fibre. The progressively greater increase of focal loss of myelin lamellae blocks the invasion of the intracellular potentials into the demyelinated zones. For all investigated cases, the radial decline of the extracellular potential amplitudes increases with the increase of the radial distance and demyelination, whereas the electrotonic potentials show a decrease in the slow part of the depolarizing and hyperpolarizing responses. The time constants are shorter and the rheobases higher for the IFD2 and IFD3 cases than for the normal case. In the recovery cycles, the same cases have less refractoriness, greater supernormality and less late subnormality than the normal case. The simulated membrane abnormalities can be observed in vivo in patients with demyelinating forms of Guillain-Barré syndrome. The study provides new information about the pathophysiology of acquired demyelinating neuropathies. PMID:19669456

  16. Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection.

    PubMed

    Song, Eunkyung; Kajon, Adriana E; Wang, Huanyu; Salamon, Doug; Texter, Karen; Ramilo, Octavio; Leber, Amy; Jaggi, Preeti

    2016-03-01

    Incidental adenovirus detection in Kawasaki disease (KD) is important to differentiate from acute adenovirus disease. Twenty-four of 25 children with adenovirus disease and mimicking features of KD had <4 KD-like features, predominance of species B or E, and higher viral burden compared with those with KD and incidental adenovirus detection. PMID:26707621

  17. Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice.

    PubMed

    Jia, Jie; Conlon, Thomas M; Ballester Lopez, Carolina; Seimetz, Michael; Bednorz, Mariola; Zhou-Suckow, Zhe; Weissmann, Norbert; Eickelberg, Oliver; Mall, Marcus A; Yildirim, Ali Önder

    2016-09-01

    Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls. Interestingly, wild-type and β-ENaC-transgenic mice demonstrated epithelial airway and vascular remodeling following CS exposure. Morphometric analysis of lung sections revealed that CS exposure caused increased mucus accumulation in the airway lumen of neonatal β-ENaC-transgenic mice compared with wild-type controls, which was accompanied by an increase in the number of goblet cells and Muc5ac upregulation. We conclude that short-term CS exposure 1) induces acute airway disease with airway epithelial and vascular remodeling in neonatal wild-type mice; and 2) exacerbates airway inflammation, mucus hypersecretion, and mucus plugging in neonatal β-ENaC-transgenic mice with chronic lung disease. Our results in neonatal mice suggest that young children may be highly susceptible to develop airway disease in response to tobacco smoke exposure, and that adverse effects may be aggravated in children with underlying chronic lung diseases. PMID:27448665

  18. Promotion of Remyelination by Sulfasalazine in a Transgenic Zebrafish Model of Demyelination.

    PubMed

    Kim, Suhyun; Lee, Yun-Il; Chang, Ki-Young; Lee, Dong-Won; Cho, Sung Chun; Ha, Young Wan; Na, Ji Eun; Rhyu, Im Joo; Park, Sang Chul; Park, Hae-Chul

    2015-11-01

    Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

  19. Promotion of Remyelination by Sulfasalazine in a Transgenic Zebrafish Model of Demyelination

    PubMed Central

    Kim, Suhyun; Lee, Yun-Il; Chang, Ki-Young; Lee, Dong-Won; Cho, Sung Chun; Ha, Young Wan; Na, Ji Eun; Rhyu, Im Joo; Park, Sang Chul; Park, Hae-Chul

    2015-01-01

    Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS. PMID:26549504

  20. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. PMID:21983132

  1. Acute respiratory disease in Spain: seven years of experience.

    PubMed

    Tellez, A; Perez-Breña, P; Fernandez-Patiño, M V; León, P; Anda, P; Nájera, R

    1990-01-01

    The clinical and epidemiologic features of viral and nonviral pathogens involved in acute respiratory diseases are described in the context of cases of infection (especially atypical pneumonia and bronchiolitis) studied at the Centro Nacional de Microbiología, Virología e Immunología Sanitarias in Madrid during a 7-year period (1979-1986). These etiologies were demonstrated in 1,637 (36.2%) of 4,521 cases. Among viruses, respiratory syncytial virus most frequently infected children; influenza virus showed the same pattern of circulation as in other European countries. Of nonviral agents, Mycoplasma pneumoniae and C. burnetii were most often involved in lower respiratory tract infections, with a variable predominance in patients of different ages. A high proportion of cases of M. pneumoniae infection occurred in infants and children aged less than 1 year, and most of these cases occurred during spring and summer. The majority of Q fever cases, including those observed in two outbreaks, occurred in the northern region.

  2. Direct micromethod for diagnosis of acute and congenital Chagas' disease.

    PubMed Central

    Feilij, H; Muller, L; Gonzalez Cappa, S M

    1983-01-01

    A microhematocrit concentration method (MH) for immediate diagnosis of Chagas' disease during the acute stage or in congenital cases was standardized. Parasitemia as low as 1,000 parasites per ml was detected, after centrifugation of six 50-microliters capillary tubes, by 10-min microscopic observation of each buffy coat spread between slide and cover glass. Operator's time was reduced by at least one-third when compared with a fresh blood observation (FB). In 12 of the 15 patients studied, diagnosis was performed in 4.9 +/- 3.08 min with MH, whereas 27.0 +/- 12.1 min were necessary when FB was used. In the three remaining patients whose FB results were negative, MH became positive after 13, 16, and 40 min. In our experience, FB proved to be more sensitive than previously reported. Suckling mouse inoculation also proved to be sensitive but, as in xenodiagnosis and in hemoculture, the delay in getting the final result was a limiting factor. PMID:6413530

  3. White Matter Diseases with Radiologic-Pathologic Correlation.

    PubMed

    Sarbu, Nicolae; Shih, Robert Y; Jones, Robert V; Horkayne-Szakaly, Iren; Oleaga, Laura; Smirniotopoulos, James G

    2016-01-01

    White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease). Infectious processes include Lyme disease (neuroborreliosis), progressive multifocal leukoencephalopathy, and human immunodeficiency virus (HIV) encephalopathy. Vascular processes include different types of small-vessel disease: arteriolosclerosis, cerebral amyloid angiopathy, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), primary angiitis of the central nervous system, Susac syndrome, and neurolupus. Toxic-metabolic processes include osmotic myelinolysis, methotrexate leukoencephalopathy, and posterior reversible encephalopathy syndrome. The imaging spectrum can vary widely from small multifocal white matter lesions to confluent or extensive white matter involvement. Understanding the pathologic substrate is fundamental for understanding the radiologic manifestations, and a systematic approach to the radiologic findings, in correlation with clinical and laboratory data, is crucial for narrowing the differential diagnosis. (©)RSNA, 2016. PMID:27618323

  4. The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination.

    PubMed Central

    Bostock, H; Sears, T A

    1978-01-01

    1. Longitudinal action currents were recorded from single undissected myelinated nerve fibres in intact, perfused ventral roots of normal rats and ones treated with diphtheria toxin to produce demyelination. 2. Closely spaced recording electrodes (120 micron), signal averaging and the use of a calibrating current throught the root permitted membrane currents to be determined over 240 micron lengths of nerve. Contour plotting was used to plot membrane current density as a function of space and time. 3. The previous result of Rasminsky & Sears (1972) of delayed saltation in demyelinated nerve fibres was confirmed. 4. In addition a new phenomenon of continuous conduction was observed, along distances of up to 1 1/2 times the afferent internodal distance. The continuous spatial distribution of inward current in these cases showed that electrical excitability was distributed along the internodes. 5. Internodal excitability was also revealed in demyelinated fibres by extra foci of inward current judged to be internodal on the basis of the spacing of the other (nodal) foci. 6. Continuous conduction occurred at velocities in the range of 1.1-2.3 m/sec or roughly 1/20th-1/40th of the velocities expected for normal stretches of the same fibres. 7. The continuous conduction was attributed to conduction along lengths of demyelinated axon. This was supported by estimates of 0.86 and 1.5 muF/cm2 for membrane capacity from the foot of a continuously conducted action potential. 8. The implications of internodal electrical excitability in demyelinated nerve fibres are discussed in relation to (a) recent estimates of the density of sodium channels in intact and homogenized normal nerves, (b) the pathophysiology of demyelinating disease. PMID:690876

  5. Intravenous Administration of Human ES-derived Neural Precursor Cells Attenuates Cuprizone-induced CNS Demyelination

    PubMed Central

    Crocker, Stephen J.; Bajpai, Ruchi; Moore, Craig S.; Frausto, Ricardo F.; Brown, Graham D.; Pagarigan, Roberto R.; Whitton, J. Lindsay; Terskikh, Alexey V.

    2011-01-01

    Aims Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods C57Bl/6 mice were fed cuprizone (0.2%) for two weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional two weeks of dietary cuprizone treatment, CNS tissues were analyzed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, GFAP. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. Conclusions These findings indicated that systemically-administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and (c) the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells. PMID:21276029

  6. Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination.

    PubMed

    Rodriguez, M; Nickerson, C; Patick, A K; David, C S

    1991-04-15

    Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse.

  7. Susceptibility to Theiler's virus-induced demyelination. Mapping of the gene within the H-2D region.

    PubMed

    Rodriguez, M; Leibowitz, J; David, C S

    1986-03-01

    Demyelination induced by Theiler's virus was examined in mouse strains with congeneic recombinant haplotypes. Light and electron microscopy of spinal cord sections from mice with s, q, v, p, and f H-2D alleles showed perivascular inflammation and primary demyelination. The presence of susceptible haplotypes in the K or I region did not correlate with pathologic abnormalities. The Qa, Tla, PgK, and UpG genes did not appear to be critical in determining susceptibility to disease. However, mutation in the H-2D genes altered the susceptibility to virus-induced demyelination. B10.D2dm1 mice, which have deletions in the 3' end of Dd and the 5' end of Ld, showed prominent demyelination and clinical deficits. In contrast, BALB/c-dm2, which have a deletion of the entire L gene, showed no pathologic changes. Central nervous system virus titers correlated with susceptibility to demyelination; both resistant and susceptible strains had a strong humoral immune response to the virus. The findings in the congeneic recombinant mice and in mice mutant in the H-2D region strongly suggest that at least one of the genes critical for determining virus-induced demyelination maps to the 3' end of the H-2D gene.

  8. Neuro-oncology dilemma: Tumour or tumefactive demyelinating lesion.

    PubMed

    Abdoli, Mohammad; Freedman, Mark S

    2015-11-01

    Tumefactive demyelinating lesions (TDLs) are not an uncommon manifestation of demyelinating disease but can pose diagnostic challenges in patients without a pre-existing diagnosis of multiple sclerosis (MS) as well as in known MS patients. Brain tumours can also arise in MS patients and can be seen in chronic MS patients as co-morbidities. Delayed diagnosis or unnecessary intervention or treatment will affect the ultimate prognosis of these patients. In this article, we will review some typical cases illustrating the dilemma and review the information that helps to differentiate the two conditions. The intention is not to present an extensive differential diagnosis of both entities, but to examine some typical examples when the decision arises to decide between the two. We take a somewhat different approach, by presenting the cases in "real time", allowing the readers to consider in their own minds which diagnosis they favour, discussing in detail some of the pertinent literature, then revealing later the actual diagnosis. We would urge readers to consider re-visiting their first thoughts about each case after reading the discussion, before reading the follow-up of each case. The overall objective is to highlight the real possibility of being forced to decide between these two entities in clinical practise, present a reasonable approach to help differentiate them and especially to focus on the possibility of TDLs in order to avoid unnecessary biopsy.

  9. Clinical trials in CIDP and chronic autoimmune demyelinating polyneuropathies.

    PubMed

    Dalakas, Marinos C

    2012-05-01

    The main chronic autoimmune neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy. On the basis of randomized controlled studies, corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis provide short-term benefits in CIDP. MMN responds only to IVIg. Because in MMN and CIDP, IVIg infusions are required every 3-6 weeks to sustain benefits or long-term remissions, there is a need for "IVIg-sparing" agents. In CIDP, immunosuppressive drugs, such as azathioprine, cyclosporine, methotrexate, mycophenolate, and cyclophosphamide, are used, but controlled trials have not shown that they are effective. Controlled trials have also not shown benefit to any agents in anti-MAG neuropathy. However, clinicians use many immunosuppressive drugs in both settings, but all have potentially serious side effects and are only effective in some patients. Thus, there is a need for new therapies in the inflammatory and paraproteinemic neuropathies. New agents targeting T cells, B cells, and transmigration and transduction molecules are discussed as potential treatment options for new trials. The need for biomarkers that predict therapeutic responses or identify patients with active disease is emphasized, and the search for better scoring tools that capture meaningful changes after response to therapies is highlighted.

  10. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients. PMID:27606147

  11. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients.

  12. Expansile, enhancing cervical cord lesion with an associated syrinx secondary to demyelination. Case report and review of the literature.

    PubMed

    Waziri, Allen; Vonsattel, Jean-Paul; Kaiser, Michael G; Anderson, Richard C E

    2007-01-01

    The authors describe the case of a patient with an enhancing, intramedullary cervical spinal cord lesion and associated syrinx. Biopsy sampling of the cervical lesion was performed, and the histological findings were consistent with a demyelinating process supporting the diagnosis of multiple sclerosis (MS). Syrinx formation associated with demyelinating disease has only been described in isolated cases, almost exclusively in Japanese patients with MS. A 22-year-old woman of Caribbean descent presented with a subacute, progressive myelopathy including symptoms of pain and weakness in all extremities, bladder incontinence, and the inability to ambulate. Magnetic resonance imaging of the brain and spinal cord demonstrated an enlarged cervical cord with enhancement and central cavitation consistent with a syrinx. The patient underwent a C3-7 laminoplasty and placement of a dural graft for cord decompression as well as fenestration of the central syrinx. Biopsy sampling of the lesion was performed, and the histopathological analysis, in conjunction with subsequent laboratory and diagnostic testing, supported the diagnosis of demyelinating disease. After treatment with a course of high-dose dexamethasone and inpatient rehabilitation therapy, the patient demonstrated significant clinical improvement. Spinal cord involvement is not uncommon in patients with demyelinating disease; however, enhancing lesions associated with extensive tissue loss and syrinx formation have rarely been reported. For the consulting neurological surgeon, demyelinating disease should be included in the differential diagnosis of such lesions given the level of complexity and risk to the patient associated with open biopsy of the spinal cord. PMID:17233291

  13. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice.

    PubMed

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Baron-Van Evercooren, Anne

    2015-09-01

    Induced pluripotent stem cell-derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it is not clear if these induced pluripotent-derived cells have the same reparative capacity as physiologically committed CNS-derived precursors. Here, we performed a side-by-side comparison of CNS-derived and skin-derived neural precursors in culture and following engraftment in murine models of adult spinal cord demyelination. Grafted induced neural precursors exhibited a high capacity for survival, safe integration, migration, and timely differentiation into mature bona fide oligodendrocytes. Moreover, grafted skin-derived neural precursors generated compact myelin around host axons and restored nodes of Ranvier and conduction velocity as efficiently as CNS-derived precursors while outcompeting endogenous cells. Together, these results provide important insights into the biology of reprogrammed cells in adult demyelinating conditions and support use of these cells for regenerative biomedicine of myelin diseases that affect the adult CNS.

  14. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype.

    PubMed

    Mathey, Emily K; Park, Susanna B; Hughes, Richard A C; Pollard, John D; Armati, Patricia J; Barnett, Michael H; Taylor, Bruce V; Dyck, P James B; Kiernan, Matthew C; Lin, Cindy S-Y

    2015-09-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.

  15. Chronic inflammatory demyelinating polyradiculoneuropathy associated intracranial hypertension.

    PubMed

    Altinkaya, Ayca; Topcular, Baris; Sakalli, Nazan Karagoz; Kuscu, Demet Yandim; Kirbas, Dursun

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated demyelinating neuropathy. In this report, we detail the course of a 58-year-old male patient who had headache and double vision followed by progressive paresthesia and difficulty in walking. The patient had bilateral papilledema and mild leg weakness, absent ankle jerks and loss of sensation in distal parts of his lower and upper extremities. His electromyography (EMG) was concordant with CIDP and lumbar puncture revealed high opening pressure. The polyradiculoneuropathy as well as the papilledema and elevated cerebrospinal fluid (CSF) pressure improved under steroids. The improvement in intracranial hypertension (IHT) and papilledema under steroid treatment suggests that the IHT in this patient might be associated with CIDP.

  16. [Current treatment and management of the acute phase of Peyronies's disease].

    PubMed

    Vanni, Alex J; Bennett, Nelson E

    2009-10-01

    The true pathophysiologic nature of Peyronie's disease continues to evolve. This pathology often results in a penile plaque(s), penile deformity, curvature, pain, and erectile dysfunction. Clinically, there are two distinct phases, acute and chronic. The focus of this review will center on the management of the acute phase of Peyronie's disease. While little data exists demonstrating disease resolution, disease stabilization is an important clinical goal for patients as this often allows acceptable sexual function. Thus, medical management during the acute phase of Peyronie's disease is aimed at limiting and stabilizing the degree of penile fibrosis, decreasing penile curvature, and reducing penile pain. In this manuscript we explain different therapies; oral, topical, intralesional injection and others like extracorporeal shockwave (ESWT), radiation and penile traction for acute phase of Peyronie's disease. Although no consensus exists for the treatment of acute phase Peyronie's disease, a majority of patients can achieve stabilization and in some cases regression of their disease with proper medical therapy. The goals of therapy should be discussed extensively with each patient, noting that erectile function will be likely despite some degree of curvature.

  17. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  18. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

    PubMed Central

    2016-01-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  19. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  20. CXCR4 Signaling Regulates Remyelination by Endogenous Oligodendrocyte Progenitor Cells in a Viral Model of Demyelination

    PubMed Central

    CARBAJAL, KEVIN S.; MIRANDA, JUAN L.; TSUKAMOTO, MICHELLE R.; LANE, THOMAS E.

    2016-01-01

    Following intracranial infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV), susceptible mice will develop widespread myelin destruction that results in pathological and clinical outcomes similar to those seen in humans with the demyelinating disease Multiple Sclerosis (MS). Partial remyelination and clinical recovery occurs during the chronic phase following control of viral replication yet the signaling mechanisms regulating these events remain enigmatic. Here we report the kinetics of proliferation and maturation of oligodendrocyte progenitor cells (OPCs) within the spinal cord following JHMV-induced demyelination and that CXCR4 signaling contributes to the maturation state of OPCs. Following treatment with AMD3100, a specific inhibitor of CXCR4, mice recovering from widespread demyelination exhibit a significant (P < 0.01) increase in the number of OPCs and fewer (P < 0.05) mature oligodendrocytes compared with HBSS-treated animals. These results suggest that CXCR4 signaling is required for OPCs to mature and contribute to remyelination in response to JHMV-induced demyelination. To assess if this effect is reversible and has potential therapeutic benefit, we pulsed mice with AMD3100 and then allowed them to recover. This treatment strategy resulted in increased numbers of mature oligodendrocytes, enhanced remyelination, and improved clinical outcome. These findings highlight the possibility to manipulate OPCs in order to increase the pool of remyelination-competent cells that can participate in recovery. PMID:21830237

  1. Promoting remyelination: utilizing a viral model of demyelination to assess cell-based therapies

    PubMed Central

    Marro, Brett S; Blanc, Caroline A; Loring, Jeanne F; Cahalan, Michael D; Lane, Thomas E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS. While a broad range of therapeutics effectively reduce the incidence of focal white matter inflammation and plaque formation for patients with relapse-remitting forms of MS, a challenge within the field is to develop therapies that allow for axonal protection and remyelination. In the last decade, growing interest has focused on utilizing neural precursor cells (NPCs) to promote remyelination. To understand how NPCs function in chronic demyelinating environments, several excellent pre-clinical mouse models have been developed. One well accepted model is infection of susceptible mice with neurotropic variants of mouse hepatitis virus (MHV) that undergo chronic demyelination exhibiting clinical and histopathologic similarities to MS patients. Combined with the possibility that an environmental agent such as a virus could trigger MS, the MHV model of demyelination presents a relevant mouse model to assess the therapeutic potential of NPCs transplanted into an environment in which inflammatory-mediated demyelination is established. PMID:25245576

  2. Oligodendrocyte Lineage Cells in Chronic Demyelination of Multiple Sclerosis Optic Nerve.

    PubMed

    Jennings, Alison Ruth; Carroll, William M

    2015-09-01

    Reports that chronically demyelinated multiple sclerosis brain and spinal cord lesions contained immature oligodendrocyte lineage cells have generated major interest aimed at the potential for promotion of endogenous repair. Despite the prominence of the optic nerve as a lesion site and its importance in clinical disease assessment, no detailed studies of multiple sclerosis-affected optic nerve exist. This study aims to provide insight into the cellular pathology of chronic demyelination in multiple sclerosis through direct morphological and immunohistochemical analysis of optic nerve in conjunction with observations from an experimental cat optic nerve model of successful remyelination. Myelin staining was followed by immunohistochemistry to differentially label neuroglia. Digitally immortalized sections were then analyzed to generate quantification data and antigenic phenotypes including maturational stages within the oligodendrocyte lineage. It was found that some chronically demyelinated multiple sclerosis optic nerve lesions contained oligodendroglial cells and that heterogeneity existed in the presence of myelin sheaths, oligodendrocyte maturational stages and extent of axonal investment. The findings advance our understanding of oligodendrocyte activity in chronically demyelinated human optic nerve and may have implications for studies aimed at enhancement of endogenous repair in multiple sclerosis.

  3. Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Rajabally, Yusuf A

    2015-05-01

    Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first-line, high-dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long-term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy.

  4. Axonal Pathology Precedes Demyelination in a Mouse Model of X-Linked Demyelinating/ Type I Charcot-Marie Tooth (CMT1X) Neuropathy

    PubMed Central

    Vavlitou, Natalie; Sargiannidou, Irene; Markoullis, Kyriaki; Kyriacou, Kyriacos; Scherer, Steven S.; Kleopa, Kleopas A.

    2010-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the gene that encodes the gap junction protein connexin32 (Cx32). Cx32 is expressed by myelinating Schwann cells and forms gap junctions in non-compact myelin areas but axonal involvement is more prominent in X-linked compared to other forms of demyelinating Charcot-Marie-Tooth disease. To clarify the cellular and molecular mechanisms of axonal pathology in CMT1X, we studied Gjb1-null mice at early stages (i.e. 2- to 4-month-old) of the neuropathy, when there is minimal or no demyelination. The diameters of large myelinated axons were progressively reduced in Gjb1-null mice compared to those in wild type littermates. Furthermore, neurofilaments were relatively more dephosphorylated and more densely packed starting at 2 months of age. Increased expression of β-amyloid precursor protein, a marker of axonal damage, was also detected in Gjb1-null nerves. Finally, fast axonal transport, assayed by sciatic nerve ligation experiments, was slower in distal axons of Gjb1-null vs. wild type animals with reduced accumulation of synaptic vesicle-associated proteins. These findings demonstrate that axonal abnormalities including impaired cytoskeletal organization and defects in axonal transport precede demyelination in this mouse model of CMT1-X. PMID:20720503

  5. [On the mechanisms and diagnosis of conduction disturbances due to demyelination with special reference to multifocal demyelinating neuropathy (Lewis-Sumner)].

    PubMed

    Kaji, R; Kimura, J

    1991-12-01

    Multifocal demyelinating neuropathy with persistent conduction block can mimic motor neuron disease, but is potentially reversible. Its diagnosis rests upon electrophysiological demonstration of focal conduction block at multiple sites. Conduction block is the most important mechanism causing clinical symptoms in peripheral nerve demyelination. On the other hand, conduction slowing is not always associated with clinical symptoms. In 2 out of 9 patients with multifocal demyelinating motor neuropathy, MRI showed focal swelling of the nerve at the site of conduction block. Both of them had elevated titers of anti-GM1 antibodies. In one, we biopsied a portion of the medial pectoral nerve, which was adjacent to the focal swelling, at surgical exploration. Pathological findings included very thin myelin associated with large diameter fibers and small onion bulb formation, suggesting that remyelinative process is abortive in this disease leading to persistent conduction block. Anti-GM1 antibodies bound to the denuded axoplasmic membrane may interfere with the process by masking the cell surface markers. The reason why the sensory fibers are spared is unclear, but it may be possible that GM1 in sensory axons have less affinity to the antibody than that in motor fibers. PMID:1817801

  6. Acute abdomen in adult Celiac disease: an intestinal intussusception case.

    PubMed

    Makay, Ozer; Kazimi, Mircelal; Doğanavşargil, Başak; Osmanoğlu, Necla; Yilmaz, Mustafa

    2007-06-01

    It is well known that half of the cases admitted to hospital emergency services complain of abdominal pain and that nearly half of these cases are diagnosed with nonspecific abdominal pain. The population of patients with celiac sprue is rarely encountered at the emergency room. Although acute abdominal pain is rarely seen in adult celiac sprue, it should be added to the differential diagnosis. It should also be remembered that acute abdominal pain in these patients could be originating from perforation, intussusceptions and/or intestinal lymphoma. Herein we report a case of adult celiac sprue where successful surgical exploration was carried out because of entero-enteral intussusception. PMID:17602358

  7. Demyelination induces transport of ribosome-containing vesicles from glia to axons: evidence from animal models and MS patient brains.

    PubMed

    Shakhbazau, Antos; Schenk, Geert J; Hay, Curtis; Kawasoe, Jean; Klaver, Roel; Yong, V Wee; Geurts, Jeroen J G; van Minnen, Jan

    2016-06-01

    Glial cells were previously proven capable of trafficking polyribosomes to injured axons. However, the occurrence of such transfer in the general pathological context, such as demyelination-related diseases, needs further evidence. Since this may be a yet unidentified universal contributor to axonal survival, we study putative glia-axonal ribosome transport in response to demyelination in animal models and patients in both peripheral and central nervous system. In the PNS we investigate whether demyelination in a rodent model has the potential to induce ribosome transfer. We also probe the glia-axonal ribosome supply by implantation of transgenic Schwann cells engineered to produce fluorescent ribosomes in the same demyelination model. We furthermore examine the presence of axonal ribosomes in mouse experimental autoimmune encephalomyelitis (EAE), a well-established model for multiple sclerosis (MS), and in human MS autopsy brain material. We provide evidence for increased axonal ribosome content in a pharmacologically demyelinated sciatic nerve, and demonstrate that at least part of these ribosomes originate in the transgenic Schwann cells. In the CNS one of the hallmarks of MS is demyelination, which is associated with severe disruption of oligodendrocyte-axon interaction. Here, we provide evidence that axons from spinal cords of EAE mice, and in the MS human brain contain an elevated amount of axonal ribosomes compared to controls. Our data provide evidence that increased axonal ribosome content in pathological axons is at least partly due to glia-to-axon transfer of ribosomes, and that demyelination in the PNS and in the CNS is one of the triggers capable to initiate this process. PMID:27115494

  8. The long-term prognosis of acute kidney injury: acute renal failure as a cause of chronic kidney disease.

    PubMed

    Basile, Carlo

    2008-01-01

    There is a widespread opinion that acute kidney injury (AKI) is a rather harmless complication and that survival is determined not by renal dysfunction per se, but by the severity of the underlying disease. This opinion is in sharp contrast to evidence from several recent experimental and clinical investigations indicating that AKI is a condition which exerts a fundamental impact on the course of the disease, the evolution of associated complications and on prognosis, independently from the type and severity of the underlying condition. In conclusion, severe AKI in the critically ill patient is associated with high rates of morbidity, mortality and consumption of health care resources.

  9. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  10. Relationship between haze and acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing.

    PubMed

    Zhang, Jin-Jun; Cui, Meng-Meng; Fan, Da; Zhang, De-Shan; Lian, Hui-Xin; Yin, Zhao-Yin; Li, Jin

    2015-03-01

    Haze is an atmospheric phenomenon in which dry particulate pollutants obscure the sky. Haze has been associated with chronic diseases, but its relationship with acute diseases is less clear. We aimed to determine the association between haze and acute cardiovascular, cerebrovascular, and respiratory diseases, in order to determine the influence of haze on human health. We compared the number of cases of acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing Emergency Center between 2006 and 2013, with haze data from Beijing Observatory. The relationship between the number of hazy days and the number of cases of the above types of diseases was analyzed using univariate analyses. Both the number of cases and the number of hazy days showed a rising trend. The average number of cases per day for all three diseases was higher on hazy days than on non-hazy days. There was a positive correlation between the number of hazy days and the number of cases, and this correlation showed a hysteretic quality. Haze has an influence on acute cardiovascular (CVDs), cerebrovascular (CBDs), and respiratory system (RSDs) diseases. Haze seems to have an additive effect, since the associations between haze and number of cases were stronger in the following month than in the preceding month. The increasing trend in the number of hazy days might worsen the problem of haze-related diseases.

  11. Management of Acute Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease in the Emergency Department.

    PubMed

    Suau, Salvador J; DeBlieux, Peter M C

    2016-02-01

    Acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations are the most common respiratory diseases requiring emergent medical evaluation and treatment. Asthma and COPD are chronic, debilitating disease processes that have been differentiated traditionally by the presence or absence of reversible airflow obstruction. Asthma and COPD exacerbations impose an enormous economic burden on the US health care budget. In daily clinical practice, it is difficult to differentiate these 2 obstructive processes based on their symptoms, and on their nearly identical acute treatment strategies; major differences are important when discussing anatomic sites involved, long-term prognosis, and the nature of inflammatory markers. PMID:26614239

  12. Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system.

    PubMed

    Zhang, Jing; Zhang, Zheng Gang; Li, Yi; Lu, Mei; Zhang, Yi; Elias, Stanton B; Chopp, Michael

    2016-04-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). No effective remyelination therapies are in use. We hypothesized that thymosin beta4 (Tβ4) is an effective remyelination treatment by promoting differentiation of oligodendrocyte progenitor cells (OPCs), and that the epidermal growth factor receptor (EGFR) signaling pathway contributes to this process. Two demyelination animal models were employed in this study: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated daily for 30days, with Tβ4 or saline treatment initiated on the day of EAE onset; and 2) cuprizone diet model, a non-inflammatory demyelination model. The mice were treated daily for 4weeks with Tβ4 or saline after fed a cuprizone diet for 5weeks. Immunofluorescent staining and Western blot were performed to measure the differentiation of OPCs, myelin and axons, respectively. To obtain insight into mechanisms of action, the expression and activation of the EGFR pathway was measured. AG1478, an EGFR inhibitor, was employed in a loss-of-function study. Data revealed that animals in both demyelination models exhibited significant reduction of myelin basic protein (MBP(+)) levels and CNPase(+) oligodendrocytes. Treatment of EAE mice with Tβ4 significantly improved neurological outcome. Double immunofluorescent staining showed that Tβ4 significantly increased the number of newly generated oligodendrocytes identified by BrdU(+)/CNPase(+) cells and MBP(+) mature oligodendrocytes, and reduced axonal damage in the EAE mice compared with the saline treatment. The newly generated mature oligodendrocytes remyelinated axons, and the increased mature oligodendrocytes significantly correlated with functional improvement (r=0.73, p<0.05). Western blot analysis revealed that Tβ4 treatment increased expression and activation of the EGFR pathway. In the cuprizone demyelination model, Tβ4 treatment was confirmed that significantly

  13. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease

    PubMed Central

    Squiers, John J.; Edwards, Anthony G.; Parra, Alberto; Hofmann, Sandra L.

    2016-01-01

    A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined. PMID:27047980

  14. FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL

    PubMed Central

    SANGENIS, Luiz Henrique Conde; DE SOUSA, Andréa Silvestre; SPERANDIO DA SILVA, Gilberto Marcelo; XAVIER, Sérgio Salles; MACHADO, Carolina Romero Cardoso; BRASIL, Patrícia; DE CASTRO, Liane; DA SILVA, Sidnei; GEORG, Ingebourg; SARAIVA, Roberto Magalhães; do BRASIL, Pedro Emmanuel Alvarenga Americano; HASSLOCHER-MORENO, Alejandro Marcel

    2015-01-01

    SUMMARY Chagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro. PMID:26422165

  15. Tumefactive demyelination-an unusual neurological presentation of HIV.

    PubMed

    Uriel, Alison; Stow, Rachael; Johnson, Leann; Varma, Anoop; du Plessis, Daniel; Gray, Francois; Herwadkar, Amit; Holland, Jeremy; Lewthwaite, Penny; Wilkins, Ed

    2010-11-15

    We describe 3 individuals infected with human immunodeficiency virus with unusual focal brain syndromes; magnetic resonance imaging revealed "open-ring" pattern space occupying lesions. After deterioration while the patients were receiving anti-Toxoplasma therapy, brain biopsy was performed, which revealed aggressive demyelination consistent with tumefactive demyelination. Treatment with high-dose steroids resulted in complete recovery in all cases.

  16. Asymmetric type F botulism with cranial nerve demyelination.

    PubMed

    Filozov, Alina; Kattan, Jessica A; Jitendranath, Lavanya; Smith, C Gregory; Lúquez, Carolina; Phan, Quyen N; Fagan, Ryan P

    2012-01-01

    We report a case of type F botulism in a patient with bilateral but asymmetric neurologic deficits. Cranial nerve demyelination was found during autopsy. Bilateral, asymmetric clinical signs, although rare, do not rule out botulism. Demyelination of cranial nerves might be underrecognized during autopsy of botulism patients.

  17. Chronic inflammatory demyelinating polyradiculoneuropathy with cholesterol deposits in a dog.

    PubMed

    Piñeyro, Pablo; Sponenberg, D Philip; Pancotto, Theresa; King, Rosalind H M; Jortner, Bernard S

    2015-11-01

    Chronic inflammatory demyelinating polyradiculoneuropathy occurred in an 11-year-old Labrador Retriever dog. Spinal cord compression resulted from massive radiculitis with prominent cholesterol granulomas. Cholesterol deposition and associated granuloma formation is unique in chronic inflammatory demyelinating polyradiculoneuropathy, in both its human and canine expressions.

  18. Demyelinating Guillain-Barré syndrome recurs more frequently than axonal subtypes.

    PubMed

    Notturno, Francesca; Kokubun, Norito; Sekiguki, Yukari; Nagashima, Takahide; De Lauretis, Angelo; Yuki, Nobuhiro; Kuwabara, Satoshi; Uncini, Antonino

    2016-06-15

    Guillain-Barré syndrome (GBS) is considered a monophasic disorder yet recurrences occur in up to 6% of patients. We retrospectively studied an Italian-Japanese population of 236 GBS and 73 Miller Fisher syndrome (MFS) patients and searched for factors which may be associated with recurrence. A recurrent patient was defined as having at least two episodes that fulfilled the diagnostic criteria for GBS and MFS with an identifiable recovery after each episode and a minimum of 2months between episodes. Preceding Campylobacter jejuni (C. jejuni) infection and antiganglioside antibodies were also assessed. Seven (3%) recurrent GBS and one (1.4%) recurrent MFS patients were identified. In the individual patient the clinical features during episodes were usually similar varying in severity whereas the preceding infection differed. None of the patients had GBS in one episode and MFS in the recurrence or vice versa. Recurrent GBS patients, compared with monophasic GBS, did not have preceding diarrhea at the first episode and considering the electrophysiological subtypes, acute inflammatory demyelinating polyneuropathies recurred more frequently than axonal GBS (6.5% vs 0.9%, p=0.04). In conclusion in a GBS population with a balanced number of demyelinating and axonal subtypes less frequent diarrhea and demyelination at electrophysiology were associated with recurrence.

  19. Newer therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Kuitwaard, Krista; van Doorn, Pieter A

    2009-05-29

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder with variable symptoms and severity that can be difficult to diagnose. Intravenous immunoglobulin, plasma exchange and corticosteroids have all been proven to be beneficial in randomized controlled trials, although the proof for corticosteroids is less clear. Although these treatments are likely to be similar in efficacy, they differ in terms of their cost, availability and adverse effects. These characteristics should be taken into account when deciding which treatment to offer a patient. If there is no response to the first treatment option, one of the other treatments should be tried. Patients with a pure motor CIDP may deteriorate after corticosteroid treatment. Some patients do not respond or become refractory or intolerant to these conventional treatments. Those who become unresponsive to therapy should be checked again for the appearance of a monoclonal protein or other signs of malignancy. Over the years, small non-randomized studies have reported possible beneficial effects of various immunosuppressive agents. A Cochrane review concluded that currently there is insufficient evidence to decide whether these immunosuppressive drugs are beneficial in CIDP. When giving immunosuppressive drugs, one should be aware that some might even cause demyelinating disease. It is difficult to prove beneficial effects of these newer treatments since they have only been used in small groups of patients, who are refractory to other treatments, and often in combination with other treatments. CIDP patients can deteriorate during or after infections or improve spontaneously, making it more difficult to judge treatment efficacy. Various treatments for CIDP are described such as azathioprine, ciclosporin, cyclophosphamide, interferons, methotrexate, mycophenolate mofetil, rituximab and etanercept. An overview of these newer treatments, their mode of action, adverse effects and

  20. Consensus definitions for pediatric MS and other demyelinating disorders in childhood.

    PubMed

    Tardieu, Marc; Banwell, Brenda; Wolinsky, Jerry S; Pohl, Daniela; Krupp, Lauren B

    2016-08-30

    In light of the published 2012 International Pediatric Multiple Sclerosis Group definitions for pediatric multiple sclerosis (MS) and related disorders and given that pediatric-onset MS is now formally included in the 2010 McDonald criteria for MS, we sought to review these criteria and summarize their application in children with acquired CNS demyelination. In addition, proposals are made for definitions of no evidence of disease activity and inadequate treatment response that are important because of new therapeutic options and trials.

  1. Laparoscopic appendectomy in a pediatric patient with type 1 Charcot-Marie-Tooth disease.

    PubMed

    Heller, Joshua A; Marn, Richard Y

    2015-12-01

    A pediatric patient with type 1 Charcot-Marie-Tooth disease-a disorder associated with a demyelinating polyneuropathy-presented for laparoscopic appendectomy in the setting of acute appendicitis. Induction and maintenance of anesthesia were successfully managed without the use of any depolarizing or nondepolarizing neuromuscular blocking agents. The patient was successfully extubated at the completion of the procedure without any respiratory or neuromuscular sequelae, with excellent pain control and no postoperative nausea or vomiting.

  2. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    PubMed

    Rath, Eva; Zandieh, Shahin; Löckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed.

  3. Paraneoplastic tumefactive demyelination with underlying combined germ cell cancer.

    PubMed

    Broadfoot, Jack R; Archer, Hilary A; Coulthard, Elizabeth; Appelman, Auke P A; Sutak, Judit; Braybrooke, Jeremy P; Love, Seth

    2015-12-01

    Paraneoplastic demyelination is a rare disorder of the central nervous system. We describe a 60-year-old man with tumefactive demyelination who had an underlying retroperitoneal germ cell cancer. He presented with visuospatial problems and memory loss and had a visual field defect. His MRI was interpreted as a glioma but stereotactic biopsy showed active demyelination. Investigation for multiple sclerosis was negative but CT imaging showed retroperitoneal lymphadenopathy, and nodal biopsy confirmed a combined germ cell cancer. He responded poorly to corticosteroid treatment, and his visual field defect progressed. However, 6 months after plasma exchange and successful chemotherapy, he has partially improved clinically and radiographically. Tumefactive demyelination is typically associated with multiple sclerosis but may be paraneoplastic. It is important to recognise paraneoplastic tumefactive demyelination early, as the neurological outcome relies on treating the associated malignancy. PMID:26088612

  4. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

    PubMed

    Kobayashi, Masatake; Nanri, Kazunori; Taguchi, Takeshi; Ishiko, Tomoko; Yoshida, Masaharu; Yoshikawa, Noriko; Sugisaki, Kentaro; Tanaka, Nobuyuki

    2015-02-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

  5. CNS demyelination in fibrodysplasia ossificans progressiva.

    PubMed

    Kan, Lixin; Kitterman, Joseph A; Procissi, Daniele; Chakkalakal, Salin; Peng, Chian-Yu; McGuire, Tammy L; Goldsby, Robert E; Pignolo, Robert J; Shore, Eileen M; Kaplan, Frederick S; Kessler, John A

    2012-12-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder of progressive heterotopic ossification (HO) caused by a recurrent activating mutation of ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. FOP is characterized by progressive HO, which is associated with inflammation in the setting of dysregulated BMP signaling, however, a variety of atypical neurologic symptoms are also reported by FOP patients. The main objective of this study is to investigate the potential underlying mechanism that is responsible for the observed atypical neurologic symptoms. We evaluated two mouse models of dysregulated BMP signaling for potential CNS pathology through non-invasive magnetic resonance imaging (MRI) studies and histological and immunohistochemical approaches. In one model, BMP4 is over-expressed under the control of the neuron-specific enolase promoter; the second model is a knock-in of a recurrent FOP mutation of ACVR1/ALK2. We also retrospectively examined MRI scans of four FOP patients. We consistently observed demyelinated lesions and focal inflammatory changes of the CNS in both mouse models but not in wild-type controls, and also found CNS white matter lesions in each of the four FOP patients examined. These findings suggest that dysregulated BMP signaling disturbs normal homeostasis of target tissues, including CNS where focal demyelination may manifest as the neurologic symptoms frequently observed in FOP.

  6. MRI demyelination pattern and clinical course in a child with cerebral X-linked adrenoleukodystrophy (X-ALD)

    PubMed Central

    Löbel, Ulrike; Wölfl, Matthias; Schlegel, Paul-Gerhardt; Warmuth-Metz, Monika

    2015-01-01

    The clinical spectrum in boys with X-linked adrenoleukodystrophy (X-ALD) ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. In the individual case, the disease course still remains unpredictable. Research findings suggest an important role of brain magnetic resonance imaging (MRI) lesion patterns as prognostic markers for X-ALD. Hence, familiarity with imaging features of childhood X-ALD in combination with clinical manifestation is required in order to stratify affected patients for therapy. We report on MRI findings and clinical course of cerebral X-ALD in a young boy with a rare subtype of white matter demyelination. PMID:25848550

  7. MRI demyelination pattern and clinical course in a child with cerebral X-linked adrenoleukodystrophy (X-ALD).

    PubMed

    Nowak, Johannes; Löbel, Ulrike; Wölfl, Matthias; Schlegel, Paul-Gerhardt; Warmuth-Metz, Monika

    2015-04-01

    The clinical spectrum in boys with X-linked adrenoleukodystrophy (X-ALD) ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. In the individual case, the disease course still remains unpredictable. Research findings suggest an important role of brain magnetic resonance imaging (MRI) lesion patterns as prognostic markers for X-ALD. Hence, familiarity with imaging features of childhood X-ALD in combination with clinical manifestation is required in order to stratify affected patients for therapy. We report on MRI findings and clinical course of cerebral X-ALD in a young boy with a rare subtype of white matter demyelination.

  8. Atypical presentation of acute and chronic coronary artery disease in diabetics

    PubMed Central

    Khafaji, Hadi AR Hadi; Suwaidi, Jassim M Al

    2014-01-01

    In patients with diabetes mellitus, cardiovascular disease is the principal cause of mortality and chest pain is the most frequent symptom in patients with stable and acute coronary artery disease. However, there is little knowledge concerning the pervasiveness of uncommon presentations in diabetics. The symptomatology of acute coronary syndrome, which comprises both pain and non-pain symptoms, may be affected by traditional risk factors such as age, gender, smoking, hypertension, diabetes, and dyslipidemia. Such atypical symptoms may range from silent myocardial ischemia to a wide spectrum of non-chest pain symptoms. Worldwide, few studies have highlighted this under-investigated subject, and this aspect of ischemic heart disease has also been under-evaluated in the major clinical trials. The results of these studies are highly diverse which makes definitive conclusions regarding the spectrum of atypical presentation of acute and even stable chronic coronay artery disease difficult to confirm. This may have a significant impact on the morbidity and mortality of coronary artery disease in diabetics. In this up-to-date review we will try to analyze the most recent studies on the atypical presentations in both acute and chronic ischemic heart disease which may give some emphasis to this under-investigated topic. PMID:25228959

  9. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-07-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348.

  10. Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring

    PubMed Central

    Gaffney, D; Fell, G; O'Reilly, D

    2000-01-01

    Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition. Key Words: Wilson's disease • copper • diagnosis PMID:11127261

  11. Outcomes before and after the Implementation of a Critical Pathway for Patients with Acute Aortic Disease

    PubMed Central

    Shin, Kyu Chul; Lee, Hye Sun; Park, Joon Min; Joo, Hyun-Chel; Ko, Young-Guk; Park, Incheol

    2016-01-01

    Purpose Acute aortic diseases, such as aortic dissection and aortic aneurysm, can be life-threatening vascular conditions. In this study, we compared outcomes before and after the implementation of a critical pathway (CP) for patients with acute aortic disease at the emergency department (ED). Materials and Methods This was a retrospective observational cohort study. The CP was composed of two phases: PRE-AORTA for early diagnosis and AORTA for prompt treatment. We compared patients who were diagnosed with acute aortic disease between pre-period (January 2010 to December 2011) and post-period (July 2012 to June 2014). Results Ninety-four and 104 patients were diagnosed with acute aortic disease in the pre- and post-periods, respectively. After the implementation of the CP, 38.7% of acute aortic disease cases were diagnosed via PRE-AORTA. The door-to-CT time was reduced more in PRE-AORTA-activated patients [71.0 (61.0, 115.0) min vs. 113.0 (56.0, 170.5) min; p=0.026]. During the post-period, more patients received emergency intervention than during the pre-period (22.3% vs. 36.5%; p=0.029). Time until emergency intervention was reduced in patients, who visited the ED directly, from 378.0 (302.0, 489.0) min in the pre-period to 200.0 (170.0, 299.0) min in the post-period (p=0.001). The number of patients who died in the ED declined from 11 to 4 from the pre-period to the post-period. Hospital mortality decreased from 26.6% to 14.4% in the post-period (p=0.033). Conclusion After the implementation of a CP for patients with acute aortic disease, more patients received emergency intervention within a shorter time, resulting in improved hospital mortality. PMID:26996561

  12. Acute myopericarditis associated with cat scratch disease in an adolescent.

    PubMed

    Barson, William J; Honegger, J Robert; Texter, Karen

    2014-09-01

    Cat scratch disease is generally characterized by a self-limited chronic regional lymphadenopathy, but numerous other clinical manifestations involving a variety of organ systems have been reported. Cardiac involvement is unusual and when reported, it has been associated with culture-negative endocarditis in adults. We present the case of an adolescent male with typical cat scratch disease and associated myopericarditis.

  13. Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

    ClinicalTrials.gov

    2014-01-23

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  14. Acute aortic syndrome: A systems approach to a time-critical disease.

    PubMed

    Kawabori, Masashi; Kaneko, Tsuyoshi

    2016-09-01

    Acute aortic syndrome represents a group of potentially lethal aortic diseases, including classic acute aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. Among these conditions, type A aortic dissection is the most common acute presentation. Only surgical interventions are recommended in guidelines as lifesaving procedures for type A dissection. Despite new diagnostic imaging methods, advanced surgical strategy, and improved postoperative management in the over 250-year history of aortic dissection, in-hospital mortality and morbidity rates still remain high. Recently, several new system-based approaches, such as implementation of multidisciplinary experienced high-volume centers and establishment of regional systematic management flow have been reported to improve the outcome. Here, we will describe the pathophysiology, diagnosis, and treatment as well as the new systematic approach to treat acute aortic syndrome. PMID:27650339

  15. Acute myocardial infarction following scorpion sting in a case with obstructive coronary artery disease.

    PubMed

    Patra, Soumya; Satish, K; Singla, Vivek; Ravindranath, K S

    2013-01-01

    The occurrence of an acute myocardial infarction (MI) following a scorpion sting has been very rarely reported in the previous literature. Possible pathogenetic mechanisms include severe hypotension due to hypovolaemic shock and coronary spasm with subsequent thrombosis of coronary vessels developed after the release of vasoactive, inflammatory and thrombogenic substances contained in the scorpion venom. All of the previously reported cases had normal coronary angiogram. We report a case of a 65-year-old woman who presented with severe scorpion sting and was treated with prazosin. But a few hours later, she developed acute anterior wall MI. Coronary angiogram revealed the presence of significant stenosis in coronary arteries. As acute MI owing to significant coronary artery disease can be evident after severe scorpion envenomation, so every case of acute coronary syndrome following scorpion sting needs early diagnosis, thorough cardiovascular evaluation and appropriate treatment. PMID:23715842

  16. Intestinal Schistosomiasis as Unusual Aetiology for Acute Appendicitis, Nowadays a Rising Disease in Western Countries

    PubMed Central

    López de Cenarruzabeitia, I.; Landolfi, S.; Armengol Carrasco, M.

    2012-01-01

    Intestinal schistosomiasis as unusual aetiology for acute appendicitis, nowadays a rising disease in western countries. Recent changes in global migration has led to an immigration growth in our scenario, upsurging people coming from endemic areas of schistosomiasis. Schistosomal appendicitis, seldom reported in developed countries, is now an expected incrising entity in our hospitals during the near future. Due to this circumstances, we believe that schistosomiasis should be consider as a rising source for acute appendicitis in western countries. In order to illustrate this point, we present a case of a 45-years-old black man, from Africa, was admitted via A&E because of acute abdominal pain, located in right lower quadrant. Acute appendicitis was suspected, and he underwent laparotomy and appendectomy. Pathological study by microscope revealed a gangrenous appendix with abscesses and parasitic ova into the submucosal layer of the appendix, suggesting Schistosomiasis. PMID:22792502

  17. Oligodendrocyte death results in immune-mediated CNS demyelination

    PubMed Central

    Traka, Maria; Podojil, Joseph R; McCarthy, Derrick P; Miller, Stephen D; Popko, Brian

    2016-01-01

    Although multiple sclerosis is a common neurological disorder, the origin of the autoimmune response against myelin, which is the characteristic feature of the disease, remains unclear. To investigate whether oligodendrocyte death could cause this autoimmune response, we examined the oligodendrocyte ablation Plp1-CreERT;ROSA26-eGFP-DTA (DTA) mouse model. Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, DTA mice develop a fatal secondary disease characterized by extensive myelin and axonal loss. Strikingly, late-onset disease was associated with increased numbers of T lymphocytes in the CNS and myelin oligodendrocyte glycoprotein (MOG)-specific T cells in lymphoid organs. Transfer of T cells derived from DTA mice to naive recipients resulted in neurological defects that correlated with CNS white matter inflammation. Furthermore, immune tolerization against MOG ameliorated symptoms. Overall, these data indicate that oligodendrocyte death is sufficient to trigger an adaptive autoimmune response against myelin, suggesting that a similar process can occur in the pathogenesis of multiple sclerosis. PMID:26656646

  18. Oligodendrocyte death results in immune-mediated CNS demyelination.

    PubMed

    Traka, Maria; Podojil, Joseph R; McCarthy, Derrick P; Miller, Stephen D; Popko, Brian

    2016-01-01

    Although multiple sclerosis is a common neurological disorder, the origin of the autoimmune response against myelin, which is the characteristic feature of the disease, remains unclear. To investigate whether oligodendrocyte death could cause this autoimmune response, we examined the oligodendrocyte ablation Plp1-CreER(T);ROSA26-eGFP-DTA (DTA) mouse model. Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, DTA mice develop a fatal secondary disease characterized by extensive myelin and axonal loss. Strikingly, late-onset disease was associated with increased numbers of T lymphocytes in the CNS and myelin oligodendrocyte glycoprotein (MOG)-specific T cells in lymphoid organs. Transfer of T cells derived from DTA mice to naive recipients resulted in neurological defects that correlated with CNS white matter inflammation. Furthermore, immune tolerization against MOG ameliorated symptoms. Overall, these data indicate that oligodendrocyte death is sufficient to trigger an adaptive autoimmune response against myelin, suggesting that a similar process can occur in the pathogenesis of multiple sclerosis.

  19. A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias.

    PubMed

    Ventura, Paolo; Cappellini, Maria Domenica; Biolcati, Gianfranco; Guida, Claudio Carmine; Rocchi, Emilio

    2014-07-01

    Acute porphyrias are a heterogeneous group of metabolic disorders resulting from a variable catalytic defect of four enzymes out of the eight involved in the haem biosynthesis pathway; they are rare and mostly inherited diseases, but in some circumstances, the metabolic disturbance may be acquired. Many different environmental factors or pathological conditions (such as drugs, calorie restriction, hormones, infections, or alcohol abuse) often play a key role in triggering the clinical exacerbation (acute porphyric attack) of these diseases that may often mimic many other more common acute medical and neuropsychiatric conditions and whose delayed diagnosis and treatment may be fatal. In order to obtain an accurate diagnosis of acute porphyria, the knowledge and the use of appropriate diagnostic tools are mandatory, even in order to provide as soon as possible the more effective treatment and to prevent the use of potentially unsafe drugs, which can severely precipitate these diseases, especially in the presence of life-threatening symptoms. In this paper, we provide some recommendations for the diagnostic steps of acute porphyrias by reviewing literature and referring to clinical experience of the board members of the Gruppo Italiano Porfiria (GrIP).

  20. AFM combines functional and morphological analysis of peripheral myelinated and demyelinated nerve fibers.

    PubMed

    Heredia, Alejandro; Bui, Chin Chu; Suter, Ueli; Young, Peter; Schäffer, Tilman E

    2007-10-01

    Demyelination of the myelinated peripheral or central axon is a common pathophysiological step in the clinical manifestation of several human diseases of the peripheral and the central nervous system such as the majority of Charcot-Marie-Tooth syndromes and multiple sclerosis, respectively. The structural degradation of the axon insulating myelin sheath has profound consequences for ionic conduction and nerve function in general, but also affects the micromechanical properties of the nerve fiber. We have for the first time investigated mechanical properties of rehydrated, isolated peripheral nerve fibers from mouse using atomic force microscopy (AFM). We have generated quantitative maps of elastic modulus along myelinated and demyelinated axons, together with quantitative maps of axon topography. This study shows that AFM can combine functional and morphological analysis of neurological tissue at the level of single nerve fibers.

  1. A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Stübgen, Joerg-Patrick

    2013-03-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a group of idiopathic, acquired, immune-mediated inflammatory demyelinating diseases of the peripheral nervous system. A majority of patients with CIDP respond to "first-line" treatment with IVIG, plasmapheresis and/or corticosteroids. There exists insufficient evidence to ascertain the benefit of treatment with "conventional" immunosuppressive drugs. The inconsistent efficacy, long-term financial burden and health risks of non-specific immune altering therapy have drawn recurrent attention to the possible usefulness of a variety of biological agents that target key aspects in the CIDP immunopathogenic pathways. This review aims to give an updated account of the scientific rationale and potential use of biological therapeutics in patients with CIDP. No specific treatment recommendations are given. The discovery, development and application of biological markers by modern molecular diagnostic techniques may help identify drug-naïve or treatment-resistant CIDP patients most likely to respond to targeted immunotherapy.

  2. Multifocal inflammatory demyelination in a patient with rheumatoid arthritis and treatment complications.

    PubMed

    Lu, Jian-Qiang; Ringrose, Jennifer; Gross, Donald; Emery, Derek; Blevins, Gregg; Power, Christopher

    2016-08-15

    Rheumatoid arthritis (RA) and multiple sclerosis (MS) are both autoimmune diseases that share similar pathogenesis, but the development of MS in RA patients without the treatment of anti-tumor necrosis factor-alpha is rarely reported, which might be attributed to the use of other medications with potential immunosuppressive effects in the treatment of RA. Since MS can be clinically silent and autopsy examination of the central nervous system in RA patients is rarely described, the association of MS with RA may be possibly under-recognized. We report an autopsy case revealing multifocal inflammatory demyelination in a RA patient who had a prolonged use of methotrexate and hydroxychloroquine resulting in hydroxychloroquine-induced myopathies and heart failure. The neuropathological features of this case are consistent with MS, although there are some altered inflammatory demyelinating features such as relatively smaller lesions and less infiltration of inflammatory cells, particularly T-cells. Our present case, in combination with literature review, suggests that the RA treatment especially with hydroxychloroquine and methotrexate is likely to alter the characteristics of inflammatory demyelination and disease course. PMID:27423608

  3. Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats.

    PubMed

    Nichols, N L; Punzo, A M; Duncan, I D; Mitchell, G S; Johnson, R A

    2013-01-15

    Although respiratory complications are a major cause of morbidity/mortality in many neural injuries or diseases, little is known concerning mechanisms whereby deficient myelin impairs breathing, or how patients compensate for such changes. Here, we tested the hypothesis that respiratory and forelimb motor functions are impaired in a rat model of focal dorsolateral spinal demyelination (ethidium bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused dorsolateral demyelination at C2-C3 followed by significant spontaneous remyelination at 14 days post-EB. Although ventilation did not differ between groups, ipsilateral integrated phrenic nerve burst amplitude was significantly reduced versus SHAM during chemoreceptor activation at 7 days post-EB but recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude correlated with cross-sectional lesion area. This ratio was significantly reduced 7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14-day groups during chemoreceptor activation. Limb function ipsilateral to EB was impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a reversible model of focal, spinal demyelination, and may be a useful model to study mechanisms of functional impairment and recovery via motor plasticity, or the efficacy of new therapeutic interventions to reduce severity or duration of disease. PMID:23159317

  4. Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

    PubMed Central

    Cruz-Martinez, P; González-Granero, S; Molina-Navarro, M M; Pacheco-Torres, J; García-Verdugo, J M; Geijo-Barrientos, E; Jones, J; Martinez, S

    2016-01-01

    Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination. PMID:27171265

  5. Seasonal effects on the reported incidence of acute diarrhoeal disease in northeast Thailand.

    PubMed

    Pinfold, J V; Horan, N J; Mara, D D

    1991-09-01

    This paper examines the seasonal variation in the reported incidence of acute diarrhoea for selected areas in the northeast of Thailand. Charts are presented which show rainfall, temperature and reported incidence of acute diarrhoea for the period 1982 to 1987. Incidence of diarrhoea appears to be inversely related to a sharp decrease in temperature around January each year. Although rainfall does not appear to have a direct effect on the relative incidence of acute diarrhoea, there is always a consistent reduction during July or August, after the rains have begun. Seasonal changes in climate may be indirectly related to other factors which have an important bearing on diarrhoeal disease. Rainwater collection is an important water source in this region and the affect this has on water use is discussed in relation to faeco-oral disease transmission.

  6. Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art

    PubMed Central

    Sista, Akhilesh K.; Vedantham, Suresh; Kaufman, John A.

    2015-01-01

    The societal and individual burden caused by acute and chronic lower extremity venous disease is considerable. In the past several decades, minimally invasive endovascular interventions have been developed to reduce thrombus burden in the setting of acute deep venous thrombosis to prevent both short- and long-term morbidity and to recanalize chronically occluded or stenosed postthrombotic or nonthrombotic veins in symptomatic patients. This state-of-the-art review provides an overview of the techniques and challenges, rationale, patient selection criteria, complications, postinterventional care, and outcomes data for endovascular intervention in the setting of acute and chronic lower extremity deep venous disease. Online supplemental material is available for this article. © RSNA, 2015 PMID:26101920

  7. Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease

    SciTech Connect

    Joensuu, H.

    1989-02-01

    Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease.

  8. [McArdle disease presenting with rhabdomyolisis and acute kidney injury].

    PubMed

    Costa, Rui; Castro, Rui; Costa, Alexandre; Taipa, Ricardo; Vizcaíno, Ramon; Morgado, Teresa

    2013-01-01

    McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.

  9. [Acute respiratory distress syndrome caused by tropical eosinophilic lung disease: a case in Gabon].

    PubMed

    Chani, M; Iken, M; Eljahiri, Y; Nzenze, J R; Mion, G

    2011-04-01

    The purpose of this report is to describe the case of a 28-year-old woman in whom acute respiratory distress syndrome (ARDS) following cholecystectomy led to the discovery of eosinophilic lung disease. Outcome was favorable after oxygenotherapy and medical treatment using ivermectin and corticosteroids. The case shows that hypereosinophilic syndrome can be the underlying cause of ARDS. PMID:21695880

  10. Brief communication: Legionnaire's disease successfully treated in acute myelocytic leukemia during severe neutropenia.

    PubMed

    Guthrie, T H; Mahizhnan, P

    1983-01-01

    A patient with acute nonlymphocytic leukemia developed progressive lung infiltrates and unremitting fevers during a profound neutropenic state. Legionnaire's disease was diagnosed by simple immunologic studies and successfully treated with erythromycin. This index case alerts physicians toward a treatable infection which would not normally be susceptible to the empiric antibiotic regimens given neutropenic patients with fevers.

  11. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  12. [Prognostication of malignization and acute complications of gastric ulcer disease, using multiparametric neuronet clasterization].

    PubMed

    Dzyubanovskiy, I Ya; Selskiy, P R; Viytovych, L E

    2015-03-01

    Results of examination of 20 gastric ulcer disease patients were analyzed for delineation of a high risk group for an acute complications occurrence, and in whom the conduction of organ preserving preventive operative interventions is expedient. For prognostication such following indices were applied: quantity of cells-producents of various immunoglobulins, mitotic and apoptotic indices, relative volume of damaged epitheliocytes, the patients' age.

  13. Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination.

    PubMed

    Mikaeloff, Yann; Caridade, Guillaume; Assi, Saada; Tardieu, Marc; Suissa, Samy

    2007-04-01

    Public concern about possible increases in the risk of multiple sclerosis associated with hepatitis B vaccination has led to low vaccination coverage. We investigated whether this vaccination after a first episode of acute CNS inflammatory demyelination in childhood increased the risk of conversion to multiple sclerosis. We studied the French Kid Sclérose en Plaques (KIDSEP) neuropaediatric cohort of patients enrolled between 1994 and 2003 from their first episode of acute CNS inflammatory demyelination (inclusion in the cohort) until the occurrence of a second episode, up to 2005. A Cox proportional hazards model of time-dependent vaccine exposure was used to evaluate the effect of vaccination (hepatitis B, tetanus) during follow-up on the risk of second episode occurrence (conversion to multiple sclerosis). The cohort included 356 subjects with a mean follow-up of 5.8 years (SD 2.7). Relapse occurred in 146 (41%) subjects during follow-up; 33 subjects were exposed to hepatitis B vaccine and 28 to tetanus vaccine at some time during follow-up. The adjusted hazard ratio (HR) for relapse occurring within 3 years of hepatitis B vaccination was 0.78 (0.32-1.89) and during any time period was 1.09 (0.53-2.24). The adjusted HR for relapse occurring within 3 years of tetanus vaccination was 0.99 (0.58-1.67) and during any time period was 1.08 (0.63-1.83). We conclude that vaccination against hepatitis B or tetanus after a first episode of CNS inflammatory demyelination in childhood does not appear to increase the risk of conversion to multiple sclerosis, although the possibility of a small increase in risk cannot be excluded.

  14. Diagnostic challenges of Wilson's disease presenting as acute pancreatitis, cholangitis, and jaundice.

    PubMed

    Nussinson, Elchanan; Shahbari, Azmi; Shibli, Fahmi; Chervinsky, Elena; Trougouboff, Philippe; Markel, Arie

    2013-11-27

    Wilson's disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons's disease. Moreover, cases of Wilson's disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis, cholangitis, and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography. However, because of his long-term jaundice and the presence of pigmented gallstones, the patient underwent further evaluation for Wilson's disease, which was subsequently confirmed. This patient's unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson's disease and cholestasis, and the difficulties associated with their differentiation. It suggests that Wilson's disease should be considered in patients with pancreatitis, cholangitis, and severe protracted jaundice caused by pigmented gallstones.

  15. Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Gulcev, Makedonka; Reilly, Cavan; Griffin, Timothy J; Broeckling, Corey D; Sandri, Brian J; Witthuhn, Bruce A; Hodgson, Shane W; Woodruff, Prescott G; Wendt, Chris H

    2016-01-01

    Introduction Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). Methods We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry. We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired t-test to test for differences between days 0 and 30 in the AECOPD group. Results We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity. Conclusion Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity. PMID:27729784

  16. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  17. Acute thyroid eye disease (TED): principles of medical and surgical management.

    PubMed

    Verity, D H; Rose, G E

    2013-03-01

    The active inflammatory phase of thyroid eye disease (TED) is mediated by the innate immune system, and management is aimed at aborting this self-limited period of autoimmune activity. In most patients with TED, ocular and adnexal changes are mild and management involves controlling thyroid dysfunction, cessation of smoking, and addressing ocular surface inflammation and exposure. In patients with acute moderate disease, this being sufficient to impair orbital functions, immunosuppression reduces the long-term sequelae of acute inflammation, and adjunctive fractionated low-dose orbital radiotherapy is used as a steroid-sparing measure. Elective surgery is often required following moderate TED, be it for proptosis, diplopia, lid retraction, or to debulk the eyelid, and this should be delayed until the disease is quiescent, with the patient stable and weaned off all immunosuppression. Thus, surgical intervention during the active phase of moderate disease is rarely indicated, although clinical experience suggests that, where there is significant orbital congestion, early orbital decompression can limit progression to more severe disease. Acute severe TED poses a major risk of irreversible loss of vision due to marked exposure keratopathy, 'hydraulic' orbital congestion, or compressive optic neuropathy. If performed promptly, retractor recession with or without a suture tarsorrhaphy protects the ocular surface from severe exposure and, in patients not responding to high-dose corticosteroid treatment, decompression of the deep medial orbital wall and floor can rapidly relieve compressive optic neuropathy, as well as alleviate the inflammatory and congestive features of raised orbital pressure.

  18. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  19. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time.

  20. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time. PMID:21625092

  1. Dietary patterns and their association with acute coronary heart disease: Lessons from the REGARDS Study

    PubMed Central

    Al Suwaidi, Jassim

    2015-01-01

    Shikany et al used data from 17,418 participants in the REGARDS study, a national, population-based, longitudinal study of white and black adults aged ≥ 45 years, enrolled between 2003–2007. They examined 536 acute coronary heart disease events at follow-up (median 5.8 years) in relation to five dietary patterns (Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad). After adjustment for baseline variables, the highest consumers of the Southern pattern experienced a 56% higher hazard for acute CHD. PMID:26779528

  2. A rare cause of acute abdominal disease: two reports of caecal diverticulum perforation.

    PubMed

    Çiftci, Fatih; Abdurrahman, İbrahim; Eren, Abdülkadir

    2016-05-01

    Diverticulum of the caecum is a rare lesion. From a clinical point of view, the inflammation it causes can mimic symptoms of acute appendicitis, causing difficulties in diagnosis and thus prescription of appropriate treatment. It is almost impossible to differentiate this disease from acute appendicitis through physical examination alone, and radiological imaging may also prove insufficient. For this reason, it is common to perioperatively diagnose diverticula of the caecum. Two cases of patients who underwent surgery for perforated caecal diverticula are presently described. PMID:27598596

  3. How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver

    PubMed Central

    2016-01-01

    Treatment of acute graft-versus-host disease (GVHD) has evolved from a one-size-fits-all approach to a more nuanced strategy based on predicted outcomes. Lower and time-limited doses of immune suppression for patients predicted to have low-risk GVHD are safe and effective. In more severe GVHD, prolonged exposure to immunosuppressive therapies, failure to achieve tolerance, and inadequate clinical responses are the proximate causes of GVHD-related deaths. This article presents acute GVHD-related scenarios representing, respectively, certainty of diagnosis, multiple causes of symptoms, jaundice, an initial therapy algorithm, secondary therapy, and defining futility of treatment. PMID:26729898

  4. Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination.

    PubMed

    Haines, Jeffery D; Herbin, Olivier; de la Hera, Belén; Vidaurre, Oscar G; Moy, Gregory A; Sun, Qingxiang; Fung, Ho Yee Joyce; Albrecht, Stefanie; Alexandropoulos, Konstantina; McCauley, Dilara; Chook, Yuh Min; Kuhlmann, Tanja; Kidd, Grahame J; Shacham, Sharon; Casaccia, Patrizia

    2015-04-01

    Axonal damage has been associated with aberrant protein trafficking. We examined a newly characterized class of compounds that target nucleo-cytoplasmic shuttling by binding to the catalytic groove of the nuclear export protein XPO1 (also known as CRM1, chromosome region maintenance protein 1). Oral administration of reversible CRM1 inhibitors in preclinical murine models of demyelination significantly attenuated disease progression, even when started after the onset of paralysis. Clinical efficacy was associated with decreased proliferation of immune cells, characterized by nuclear accumulation of cell cycle inhibitors, and preservation of cytoskeletal integrity even in demyelinated axons. Neuroprotection was not limited to models of demyelination, but was also observed in another mouse model of axonal damage (that is, kainic acid injection) and detected in cultured neurons after knockdown of Xpo1, the gene encoding CRM1. A proteomic screen for target molecules revealed that CRM1 inhibitors in neurons prevented nuclear export of molecules associated with axonal damage while retaining transcription factors modulating neuroprotection.

  5. Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis.

    PubMed

    Totaro, Rocco; Di Carmine, C; Splendiani, A; Torlone, S; Patriarca, L; Carrocci, C; Sciamanna, S; Marini, C; Carolei, A

    2016-07-01

    Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan-Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

  6. A Unified Frequency Domain Model to Study the Effect of Demyelination on Axonal Conduction.

    PubMed

    Chaubey, Saurabh; Goodwin, Shikha J

    2016-01-01

    Multiple sclerosis is a disease caused by demyelination of nerve fibers. In order to determine the loss of signal with the percentage of demyelination, we need to develop models that can simulate this effect. Existing time-based models does not provide a method to determine the influences of demyelination based on simulation results. Our goal is to develop a system identification approach to generate a transfer function in the frequency domain. The idea is to create a unified modeling approach for neural action potential propagation along the length of an axon containing number of Nodes of Ranvier (N). A system identification approach has been used to identify a transfer function of the classical Hodgkin-Huxley equations for membrane voltage potential. Using this approach, we model cable properties and signal propagation along the length of the axon with N node myelination. MATLAB/Simulink platform is used to analyze an N node-myelinated neuronal axon. The ability to transfer function in the frequency domain will help reduce effort and will give a much more realistic feel when compared to the classical time-based approach. Once a transfer function is identified, the conduction as a cascade of each linear time invariant system-based transfer function can be modeled. Using this approach, future studies can model the loss of myelin in various parts of nervous system. PMID:27103847

  7. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system.

    PubMed

    Gonzalez, Ginez A; Hofer, Matthias P; Syed, Yasir A; Amaral, Ana I; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R N

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  8. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

    PubMed Central

    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  9. A Unified Frequency Domain Model to Study the Effect of Demyelination on Axonal Conduction

    PubMed Central

    Chaubey, Saurabh; Goodwin, Shikha J.

    2016-01-01

    Multiple sclerosis is a disease caused by demyelination of nerve fibers. In order to determine the loss of signal with the percentage of demyelination, we need to develop models that can simulate this effect. Existing time-based models does not provide a method to determine the influences of demyelination based on simulation results. Our goal is to develop a system identification approach to generate a transfer function in the frequency domain. The idea is to create a unified modeling approach for neural action potential propagation along the length of an axon containing number of Nodes of Ranvier (N). A system identification approach has been used to identify a transfer function of the classical Hodgkin–Huxley equations for membrane voltage potential. Using this approach, we model cable properties and signal propagation along the length of the axon with N node myelination. MATLAB/Simulink platform is used to analyze an N node-myelinated neuronal axon. The ability to transfer function in the frequency domain will help reduce effort and will give a much more realistic feel when compared to the classical time-based approach. Once a transfer function is identified, the conduction as a cascade of each linear time invariant system-based transfer function can be modeled. Using this approach, future studies can model the loss of myelin in various parts of nervous system. PMID:27103847

  10. Overlapping demyelinating syndromes and anti-NMDA receptor encephalitis

    PubMed Central

    Titulaer, Maarten J.; Höftberger, Romana; Iizuka, Takahiro; Leypoldt, Frank; McCracken, Lindsey; Cellucci, Tania; Benson, Leslie A.; Shu, Huidy; Irioka, Takashi; Hirano, Makito; Singh, Gagandeep; Calvo, Alvaro Cobo; Kaida, Kenichi; Morales, Pamela S.; Wirtz, Paul W.; Yamamoto, Tomotaka; Reindl, Markus; Rosenfeld, Myrna R.; Graus, Francesc; Saiz, Albert; Dalmau, Josep

    2014-01-01

    Objective To report the clinical, radiological, and immunological association of demyelinating disorders with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods Clinical and radiological analysis of a cohort of 691 patients with anti-NMDAR encephalitis. Determination of antibodies to NMDAR, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) was performed using brain immunohistochemistry and cell-based assays. Results Twenty-three of 691 patients with anti-NMDAR encephalitis had prominent MRI and/or clinical features of demyelination. Group 1 included 12 patients in whom anti-NMDAR encephalitis was preceded or followed by independent episodes of NMO-spectrum disorder (5 cases, 4 anti-AQP4-positive), or brainstem or multifocal demyelinating syndromes (7 cases, all anti-MOG-positive). Group 2 included 11 patients in whom anti-NMDAR encephalitis occurred simultaneously with MRI and symptoms compatible with demyelination (5 AQ4-positive, 2 MOG-positive). Group 3 (136 controls) included 50 randomly selected patients with typical anti-NMDAR encephalitis, 56 with NMO, and 30 with multiple sclerosis: NMDAR-antibodies were detected only in the 50 anti-NMDAR patients, MOG-antibodies in 3/50 anti-NMDAR and 1/56 NMO patients, and AQP4-antibodies in 48/56 NMO and 1/50 anti-NMDAR patients (p<0.0001 for all comparisons with Groups 1 and 2). Most patients improved with immunotherapy, but compared with anti-NMDAR encephalitis the demyelinating episodes required more intensive therapy and resulted in more residual deficits. Only 1/23 NMDAR patients with signs of demyelination had ovarian teratoma compared with 18/50 anti-NMDAR controls (p=0.011) Interpretation Patients with anti-NMDAR encephalitis may develop concurrent or separate episodes of demyelinating disorders, and conversely patients with NMO or demyelinating disorders with atypical symptoms (e.g., dyskinesias, psychosis) may have anti-NMDAR encephalitis. PMID:24700511

  11. Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside.

    PubMed

    Peltier, Amanda C; Donofrio, Peter D

    2012-07-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immunomodulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP.

  12. Chronic Inflammatory Demyelinating Polyradiculoneuropathy: From Bench to Bedside

    PubMed Central

    Peltier, Amanda C.; Donofrio, Peter D.

    2015-01-01

    Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immuno-modulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulins (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP. PMID:23117943

  13. Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

    PubMed Central

    Zhang, Mao; Zhan, Xiao L; Ma, Zi Y; Chen, Xing S; Cai, Qi Y

    2015-01-01

    Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS. PMID:25577802

  14. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  15. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  16. The Burden of Acute Disease in Mahajanga, Madagascar – A 21 Month Study

    PubMed Central

    Kannan, Vijay C.; Andriamalala, Clara N.; Reynolds, Teri A.

    2015-01-01

    Background Efforts to develop effective and regionally-appropriate emergency care systems in sub-Saharan Africa are hindered by a lack of data on both the burden of disease in the region and on the state of existing care delivery mechanisms. This study describes the burden of acute disease presenting to an emergency unit in Mahajanga, Madagascar. Methods and Findings Handwritten patient registries on all emergency department patients presenting between 1 January 2011 and 30 September 2012 were reviewed and data entered into a database. Data included age, sex, diagnosis, and disposition. We classified diagnoses into Clinical Classifications Software (CCS) multi-level categories. The population was 53.5% male, with a median age of 31 years. The five most common presenting conditions were 1) Superficial injury; contusion, 2) Open wounds of head; neck; and trunk, 3) Open wounds of extremities, 4) Intracranial injury, and 5) Unspecified injury and poisoning. Trauma accounted for 48%, Infectious Disease for 15%, Mental Health 6.1%, Noncommunicable 29%, and Neoplasms 1.2%. The acuity seen was high, with an admission rate of 43%. Trauma was the most common reason for admission, representing 19% of admitted patients. Conclusions This study describes the burden of acute disease at a large referral center in northern Madagascar. The Centre Hôpitalier Universitaire de Mahajanga sees a high volume of acutely ill and injured patients. Similar to other reports from the region, trauma is the most common pathology observed, though infectious disease was responsible for the majority of adult mortality. Typhoid fever other intestinal infections were the most lethal CCS-coded pathologies. By utilizing a widely understood classification system, we are able to highlight contrasts between Mahajanga’s acute and overall disease burden as well as make comparisons between this region and the rest of the globe. We hope this study will serve to guide the development of context

  17. [Legionnaires' disease complicated by rhabdomyolysis and acute renal failure: about a case].

    PubMed

    Bac, Arnaud; Ramadan, Ahmed Sabry; Youatou, Pierre; Mols, Pierre; Cerf, Dominique; Ngatchou, William

    2016-01-01

    Legionnaires' disease is a bacterial disease of the respiratory system caused by a gram-negative germ whose clinical manifestation can be benign limiting to flu-like syndrome or can be more severe being characterized by pneumonia which may be complicated by multisystem disease that can lead to death. We report the case of a 48 year-old patient with rhabdomyolysis complicated by acute renal failure following Legionella pneumophila pneumonia. We here highlight the pathophysiological aspects and treatment of this rare complication during Legionella infection. PMID:27642464

  18. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  19. Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

    PubMed

    Tanaka, Ryota; Maruyama, Hiroshi; Tomidokoro, Yasushi; Yanagiha, Kumi; Hirabayashi, Takumi; Ishii, Akiko; Okune, Mari; Inoue, Sae; Sekine, Ikuo; Tamaoka, Akira; Fujimoto, Manabu

    2016-09-01

    Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.

  20. [The particularities of acute surgical diseases treatment of abdominal cavity organs in patients with haemophilia].

    PubMed

    Shutov, S A; Karagiulia, S R; Danishian, K I; Zorenko, V Iu; Grzhimolovskiĭ, A V; Polianskaia, T Iu; Shulutko, E M; Galstian, G M

    2014-01-01

    The experience of treatment of 366 patients with haemophilia who were urgently hospitalized in hеmatological Scientific Center over the last 10 years is presented in the article. There were 114 (31.1%) patients with acute diseases of abdominal cavity organs, 150 (41%) patients with bleeding from upper gastrointestinal tract, 102 (27.9%) patients with acute hematomas of retroperitoneal space. Urgent operations were performed in 48 (22.2%) patients who were hospitalized with clinical symptoms of acute abdomen syndrome. It was developed the criteria of diagnosis and choice of treatment tactic on the basis of the received results. Application of presented algorithms led to improve the quality of urgent surgical care to patients with haemophilia.

  1. [Acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult - 2014 AS SMC Guidelines on the classification and diagnosis of aortic diseases].

    PubMed

    Gavorník, Peter; Dukát, Andrej; Gašpar, Ľudovít

    2015-01-01

    In addition to organovascular arterial ischemic diseases (cardiovascular, vasculovascular, neurovascular, extre-mitovascular, renovascular, genitovascular, bronchopulmovascular, mesenteriovascular, osteoarthromusculovascular, dermovascular, oculovascular, otovascular, stomatovascular etc.), aortic diseases contribute to the wide spectrum of arterial diseases: aortic aneurysms (AA), acute aortic syndromes (AAS) including aortic dissection (AD), intramural haematoma (IMH), penetrating atherosclerotic ulcer (PAU) and traumatic aortic injury (TAI), pseudoaneurysm, aortic rupture, atherosclerosis, vasculitis as well as genetic diseases (e.g. Turner syndrome, Marfan syndrome, Ehlers-Danlos syndrome) and congenital abnormalities including the coarctation of the aorta (CoA). Similarly to other arterial diseases, aortic diseases may be diagnosed after a long period of subclinical development or they may have an acute presentation. Acute aortic syndrome is often the first sign of the disease, which needs rapid diagnosis and decisionmaking to reduce the extremely poor prognosis. Key clinical-etiology-anatomy-patophysiology (CEAP) diagnostic aspects of aortic diseases are discussed in this document (project Vessels).

  2. Acute Disseminated Encephalomyelitis after Oral Therapy with Herbal Extracts: A Case Report

    PubMed Central

    Kaymakamzade, Bahar; Karabudak, Rana; Kurne, Aslı Tuncer; Nurlu, Gülay

    2016-01-01

    Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. Case Report: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. Conclusion: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions. PMID:27308086

  3. Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure

    PubMed Central

    Vergani, D; Massironi, L; Lombardi, F; Fiorentini, C

    1998-01-01

    A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide—a somatostatin analogue—followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, non-metastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

 Keywords: carcinoid heart disease;  ovarian tumour;  acute pericarditis;  heart failure PMID:10065036

  4. [Acute encephalopathy due to late-onset maple syrup urine disease in a school boy].

    PubMed

    Qu, Su-Qing; Yang, Li-Cai; Luan, Zuo; Du, Kan; Yang, Hui

    2012-03-01

    Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

  5. Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Guimarães-Costa, R; Iancu Ferfoglia, R; Viala, K; Léger, J-M

    2014-10-01

    Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.

  6. Class I-deficient resistant mice intracerebrally inoculated with Theiler's virus show an increased T cell response to viral antigens and susceptibility to demyelination.

    PubMed

    Pullen, L C; Miller, S D; Dal Canto, M C; Kim, B S

    1993-09-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination in susceptible mouse strains. The histology of TMEV-induced demyelination is similar to that seen in patients suffering from multiple sclerosis. It was previously shown that the susceptibility of mice to TMEV-induced demyelination in certain strain combinations is closely associated with the major histocompatibility complex (MHC) class I locus. Here we examine disease susceptibility of beta 2-microglobulin (beta 2M)-deficient transgenic mice lacking class I expression and functional CD8+ T cells. In contrast to TMEV-infected parental C57BL/6 mice, the transgenics develop high levels of virus-specific DTH and T cell proliferation accompanied by an increased frequency of central nervous system (CNS) demyelinating lesions. However, clinical signs of demyelination were not noted. Neither antibody titer nor viral persistence were significantly affected in the beta 2M-deficient mice. These results suggest that in the absence of functional class I/CD8+ cells, the class II-restricted T cell response to TMEV is enhanced and CNS pathogenesis is heightened, although the level is not severe enough to result in clinical disease. When the TMEV-infected mice were subcutaneously immunized with virus, however, the beta 2M-deficient mice displayed clinical symptoms. Therefore, our results strongly suggest that CD8+ T cells do not directly contribute to CNS demyelination. In contrast, such T cells appear to be primarily involved in down-regulation of a potentially damaging CD4+ T cell response in resistant animals, although some of the T cells may play a role in clearing viral persistence in the CNS, resulting in the protection of the host from viral demyelination.

  7. Acute Pelvic Inflammatory Disease in Cameroon: A Cross Sectional Descriptive Study.

    PubMed

    Nkwabong, Elie; Dingom, Madye A N

    2015-12-01

    This cross-sectional descriptive study, aimed at identifying the sociodemographic characteristics of women diagnosed with acute pelvic inflammatory disease (PID), as well as the microorganisms isolated, was carried out between October 1st, 2013 and March 31st, 2014 in two major hospitals in Yaoundé, Cameroon. Seventy women diagnosed with acute PID were recruited. The main variables recorded were maternal age, occupation, marital status, number of current sexual partners, the clinical presentation at admission and the microorganisms identified. Data were analyzed using SPSS 20.0. Mean maternal age was 29.0 ± 7.7 years. Students were more represented (37.1%), 58.6 % were single, 64.3% had ≥ 2 sexual partners. The most frequent signs and symptoms were abnormal vaginal discharge (100%), adnexal tenderness (97.1%), cervical motion tenderness (94.3%) and fever ≥ 38.3 degrees C (82.9%). No microorganism was isolated in 20% of cases, especially among women who underwent intra-uterine procedures. The most frequent microorganisms were genital tract mycoplasmas (54.3%). Acute PID is common among young, single women with multiple sexual partners. The micro-organisms frequently responsible for acute PID were genital tract mycoplasmas, whose identification should be included among routine tests for women with suspected acute PID in the hospitals. PMID:27337857

  8. Epidemiology of acute infections among patients with chronic kidney disease.

    PubMed

    Dalrymple, Lorien S; Go, Alan S

    2008-09-01

    The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity. PMID:18650409

  9. [Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm].

    PubMed

    Legnani, Delfino

    2009-07-01

    The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression. PMID:19696555

  10. Management of acute painful crises in sickle cell disease.

    PubMed

    Kotila, T R

    2005-08-01

    Pain is a common mode of manifestation of sickle cell disease (SCD) but there is limited information on pain management in this disorder. This study examines the use of opioids and non-opioid analgesia in the management of painful crisis in adult SCD patients; the routine use of antimalarials and antibiotics as adjunct therapy was also examined. A total of 87% of the patients had had a form of analgesics before presentation, 20% of which had parenteral analgesia. Ten per cent had not used any form of medication while another 10% used non-steroidal anti-inflammatory drugs. When asked, 59% of the patients desired oral non-opioid analgesics while 31% were not concerned about the type of analgesic given. Only 8% requested opioids. Hospital admission was not necessary in 65% of the patients; they were observed in the day-care unit and allowed home within 24 h. Sixty per cent did not have a test for malaria; 66% of those who had the test performed were negative, 35% of those whose thick film for malaria was negative had antimalarials prescribed. Only five patients (7%) were febrile at presentation. Thirty-four per cent had antibiotics prescribed, a third of these parenterally. Thirty-nine per cent had no fever but received antibiotics.

  11. The role of multiparametric flow cytometry in the detection of minimal residual disease in acute leukaemia.

    PubMed

    Lee, Denise; Grigoriadis, George; Westerman, David

    2015-12-01

    Flow cytometry is the most accessible method for minimal residual disease (MRD) detection due to its availability in most haematological centres. Using a precise combination of different antibodies, immunophenotypic detection of MRD in acute leukaemia can be performed by identifying abnormal combinations or expressions of antigens on malignant cells at diagnosis, during and post treatment. These abnormal phenotypes, referred to as leukaemia-associated immunophenotypes (LAIPs) are either absent or expressed at low frequency in normal bone marrow (BM) cells and are used to monitor the behaviour and quantitate the amount of residual disease following treatment. In paediatric acute lymphoblastic leukaemia (ALL), the level of MRD by multiparametric flow cytometry (MPFC) during therapy is recognised as an important predictor of outcome. Although less extensively studied, adult ALL and adult and paediatric acute myeloid leukaemia (AML) have also demonstrated similar findings. The challenge now is incorporating this information for risk-stratification so that therapy can be tailored individually and ultimately improve outcome while also limiting treatment-related toxicity. In this review we will elaborate on the current and future role of MPFC in MRD in acute leukaemia while also addressing its limitations.

  12. Acute Q fever: an emerging and endemic disease in southern Taiwan.

    PubMed

    Lai, Chung-Hsu; Huang, Chun-Kai; Chin, Chuen; Chung, Hsing-Chun; Huang, Wu-Shiung; Lin, Chih-Wen; Hsu, Chuan-Yuan; Lin, Hsi-Hsun

    2008-01-01

    Acute Q fever is a worldwide zoonosis caused by Coxiella burnetii infection. In Taiwan, cases of acute Q fever increased during 3 y of observation, especially at Kaohsiung County and City in southern Taiwan. From 15 April 2004 to 15 April 2007, a total of 67 cases of acute Q fever were identified at E-Da hospital located at Kaohsiung County. 19 (28.4%) patients had a history of travel in rural areas and only 1 had been outside southern Taiwan. 21 (31.3%) patients had a history of animal contact. 20 (30.8%) of the 65 examined patients had underlying chronic hepatitis B or hepatitis C virus infection. Fever (98.5%), chills (79.1%), headache (79.1%), relative bradycardia (44.8%), elevated aminotransferases (100%), and thrombocytopenia (74.6%) were common manifestations. 12 (19.0%) cases had abnormal findings on chest X-ray. Fatty liver (50.0%) and hepatomegaly and/or splenomegaly (41.9%) were found by abdominal image examinations. 42 (76.4%) of 55 cases had defervescence within 3 d after treatment, whereas 4 (7.3%) had spontaneous remission. Acute Q fever is an endemic infectious disease with hepatitis rather than pneumonia as the major presentation in southern Taiwan and the emergence of Q fever is due to increased alertness for the disease by physicians. PMID:17852909

  13. Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease

    SciTech Connect

    LeBoit, P.E.

    1989-02-01

    The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens.

  14. Acute Schistosomiasis in Brazilian Traveler: The Importance of Tourism in The Epidemiology of Neglected Parasitic Diseases

    PubMed Central

    Guiguet Leal, Diego Averaldo; Franco, Regina Maura Bueno; Neves, Maria Francisca; Simões, Luciana Franceschi; Bastos, Letícia Aparecida Duart; Allegretti, Silmara Marques; Zanotti-Magalhães, Eliana Maria; Magalhães, Luiz Augusto

    2012-01-01

    Parasitic infectious diseases acquired in tourist areas may pose a challenge to physicians and to travel medicine practitioners. Acute schistosomiasis may be seen in returning travelers and migrants after primary infection. This form of schistosomiasis is frequently misdiagnosed due to its temporal delay and its nonspecific presentation and might occur even in countries where the disease is endemic, such as in Brazil. The patient developed the acute phase of schistosomiasis with severe clinical manifestations. The quantitative analysis revealed the presence of 240 eggs per gram of stool. The treatment was administered with oxamniquine, and the control of cure of the patient was monitored and was favorable. The present paper aims to emphasize the importance of a detailed clinical history including information regarding travel history. PMID:22844623

  15. Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease

    PubMed Central

    Atwal, P.S.; Macmurdo, C.; Grimm, P.C.

    2015-01-01

    Acute metabolic decompensation in maple syrup urine disease can occur during intercurrent illness and is a medical emergency. A handful of reports in the medical literature describe the use of peritoneal dialysis and haemodialysis as therapeutic inventions. We report the only patient from our centre to have haemodialysis performed in this setting. Combined with dietary BCAA restriction and calorific support, haemodialysis allows rapid reduction in plasma leucine concentrations considerably faster than conservative methods. PMID:26937409

  16. Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease.

    PubMed

    Atwal, P S; Macmurdo, C; Grimm, P C

    2015-09-01

    Acute metabolic decompensation in maple syrup urine disease can occur during intercurrent illness and is a medical emergency. A handful of reports in the medical literature describe the use of peritoneal dialysis and haemodialysis as therapeutic inventions. We report the only patient from our centre to have haemodialysis performed in this setting. Combined with dietary BCAA restriction and calorific support, haemodialysis allows rapid reduction in plasma leucine concentrations considerably faster than conservative methods. PMID:26937409

  17. Percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with coronary aneurysm and stenosis due to Kawasaki disease.

    PubMed

    Drossner, David M; Chappell, Clay; Rab, Tanveer; Kim, Dennis

    2012-06-01

    We report the case of an acutely ill 3-year-old female, with a previous medical history of Kawasaki disease, who presented to care with an acute myocardial infarction. We describe the coordinated therapies employed by pediatric and adult cardiologists aimed to establish coronary revascularization.

  18. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans

    PubMed Central

    Chua, Kaw Bing; Crameri, Gary; Hyatt, Alex; Yu, Meng; Tompang, Mohd Rosli; Rosli, Juliana; McEachern, Jennifer; Crameri, Sandra; Kumarasamy, Verasingam; Eaton, Bryan T.; Wang, Lin-Fa

    2007-01-01

    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named “Melaka virus”) isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms ≈1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house ≈1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans. PMID:17592121

  19. Major comorbid disease processes associated with increased incidence of acute kidney injury

    PubMed Central

    Farooqi, Salwa; Dickhout, Jeffrey G

    2016-01-01

    Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS). This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including: Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI. PMID:26981437

  20. [Acute painful crisis in a female Nigerian patient with sickle cell disease].

    PubMed

    Nin, Sayaka; Seki, Masanori; Maie, Koichiro; Kuroda, Akihiro; Miyamoto, Kana; Ogawa, Shinichi; Ito, Yufu; Kurita, Naoki; Yokoyama, Yasuhisa; Sakata Yanagimoto, Mamiko; Obara, Naoshi; Hasegawa, Yuichi; Ogino, Yasuko; Ito, Takayoshi; Chiba, Shigeru

    2015-01-01

    We report a 38-year-old Nigerian woman with sickle cell disease. Sickle cell disease had been diagnosed when she experienced her first sickle cell crisis episode at age 8 years. Thereafter, she had infrequent minor episodes. She visited a hospital presenting with fever, anemia, jaundice, and systemic pain, and was then transferred to our hospital. Together with rehydration and red blood cell transfusion, analgesics and antibiotics were prescribed, and produced gradual improvement of all symptoms and signs. The patient was discharged on day 9 of hospitalization. Sickle cell crisis is an acute painful episode caused by occlusion of arterioles. The degree of pain and accompanying symptoms, as well as the frequencies of crises, are variable. Moreover, one third of individuals with sickle cell disease never experience a crisis. As our society becomes increasingly globalized, the probabilities of encountering sickle cell disease patients will be higher. PMID:25745965

  1. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*

    PubMed Central

    Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2014-01-01

    The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

  2. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  3. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.

    PubMed

    Laverdière, Isabelle; Guillemette, Chantal; Tamouza, Ryad; Loiseau, Pascale; Peffault de Latour, Regis; Robin, Marie; Couture, Félix; Filion, Alain; Lalancette, Marc; Tourancheau, Alan; Charron, Dominique; Socié, Gérard; Lévesque, Éric

    2015-02-01

    Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32-0.41; P=0.0009-0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of

  4. Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry.

    PubMed

    Reiber, Hansotto

    2016-04-01

    The analysis of intrathecal IgG, IgA and IgM synthesis in cerebrospinal fluid (CSF) and evaluation in combined quotient diagrams provides disease-related patterns. The compilation with complementary parameters (barrier function, i.e., CSF flow rate, cytology, lactate, antibodies) in a cumulative CSF data report allows a knowledge-based interpretation and provides analytical and medical plausibility for the quality assessment in CSF laboratories. The diagnostic relevance is described for neurological and psychiatric diseases, for which CSF analysis can't be replaced by other diagnostic methods without loss of information. Dominance of intrathecal IgM, IgA or three class immune responses give a systematic approach for Facial nerve palsy, Neurotrypanosomiasis, Opportunistic diseases, lymphoma, Neurotuberculosis, Adrenoleucodystrophy or tumor metastases. Particular applications consider the diagnostic power of the polyspecific antibody response (MRZ-antibodies) in multiple sclerosis, a CSF-related systematic view on differential diagnostic of psychiatric diseases and the dynamics of brain- derived compared to blood-derived molecules in CSF for localization of paracytes. PMID:27097008

  5. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    PubMed

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF.

  6. Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute Chagas' disease.

    PubMed

    Wen, Jian-Jun; Bhatia, Vandanajay; Popov, Vsevolod L; Garg, Nisha Jain

    2006-12-01

    In this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium. The antioxidant phenyl-alpha-tert-butyl nitrone (PBN) arrested the oxidative damage-mediated loss in mitochondrial membrane integrity, preserved redox potential-coupled mitochondrial gene expression, and improved respiratory complex activities (47 to 95% increase) and cardiac ATP level (>or=40% increase) in infected myocardium. Importantly, PBN resulted twofold decline in mitochondrial reactive oxygen species production rate in infected myocardium. Taken together, our data demonstrate the pathological significance of oxidative stress in metabolic decay and energy homeostasis in acute chagasic myocarditis and further suggest that oxidative injuries affecting mitochondrial integrity-dependent expression and activity of the respiratory complexes initiate a feedback cycle of electron transport chain inefficiency, increased reactive oxygen species production, and energy homeostasis in acute chagasic hearts. PBN and other mitochondria-targeted antioxidants may be useful in altering mitochondrial decay and oxidative pathology in Chagas' disease.

  7. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  8. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders. PMID:24152019

  9. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.

  10. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia.

  11. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female.

    PubMed

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke; Imashuku, Shinsaku

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  12. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  13. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis

    PubMed Central

    Seehusen, Frauke; Al-Azreg, Seham A.; Raddatz, Barbara B.; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease. PMID:27441688

  14. Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

    PubMed

    Cortese, A; Franciotta, D; Alfonsi, E; Visigalli, N; Zardini, E; Diamanti, L; Prunetti, P; Osera, C; Gastaldi, M; Berzero, G; Pichiecchio, A; Piccolo, G; Lozza, A; Piscosquito, G; Salsano, E; Ceroni, M; Moglia, A; Bono, G; Pareyson, D; Marchioni, E

    2016-04-15

    Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

  15. Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination

    PubMed Central

    Marro, Brett S.; Grist, Jonathan J.

    2016-01-01

    The functional role of the ELR+ chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein–positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G+CD11b+ neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease. PMID:26773148

  16. [Mathematical analysis of complicated course of acute surgical diseases of abdominal cavity organs].

    PubMed

    Vozniuk, S M; Pol'ovyĭ, V P; Sydorchuk, R I; Palianytsia, A S

    2013-03-01

    In this paper we analyze the results of diagnosis and treatment of 130 patients with acute surgical diseases of the abdominal cavity, complicated by peritonitis. We proposed the method of estimating the severity of the patients using a coefficient of status severity (C(SS)), developed a scale for prediction of complicated outcomes of acute surgical pathology of the abdominal cavity and abdominal sepsis, which is adapted to the working conditions of local clinics. Using the C(SS) and the scale prediction, allowed timely identification of patients' risk group with possible complicated course, assign adequate treatment, reduce postoperative complications by 5%, relaparotomies by 4.4%, decrease postoperative mortality by 3.9%.

  17. Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Reddy, Raghu M; Guntupalli, Kalpalatha K

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD. PMID:18268918

  18. Management of chronic obstructive pulmonary disease patients after hospitalization for acute exacerbation.

    PubMed

    Osthoff, Mirjam; Leuppi, Jörg D

    2010-01-01

    The objective of this review is to sum up the literature regarding the management of patients with chronic obstructive pulmonary disease (COPD) after hospitalization for an acute exacerbation. Guidelines recommend a follow-up 4-6 weeks after hospitalization to assess coping strategies, inhaler technique, the need for long-term oxygen therapy and the measurement of FEV(1). This review discusses the follow-up of patients with exacerbations of COPD, the use and value of spirometry in their further management, the potential benefit of home monitoring, the value of long-term oxygen therapy, the value of self-management programs including the use of action plans, the potential benefit of noninvasive ventilation as well as the value of early rehabilitation. There is not enough literature to allow specific recommendations and to define components of a care plan after hospitalization for an acute exacerbation; however, early rehabilitation should be included.

  19. Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

    PubMed

    Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

    2014-03-01

    Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis.

  20. Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin

    PubMed Central

    Keough, Michael B.; Jensen, Samuel K.; Yong, V. Wee

    2015-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system characterized by plaque formation containing lost oligodendrocytes, myelin, axons, and neurons. Remyelination is an endogenous repair mechanism whereby new myelin is produced subsequent to proliferation, recruitment, and differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes, and is necessary to protect axons from further damage. Currently, all therapeutics for the treatment of multiple sclerosis target the aberrant immune component of the disease, which reduce inflammatory relapses but do not prevent progression to irreversible neurological decline. It is therefore imperative that remyelination-promoting strategies be developed which may delay disease progression and perhaps reverse neurological symptoms. Several animal models of demyelination exist, including experimental autoimmune encephalomyelitis and curprizone; however, there are limitations in their use for studying remyelination. A more robust approach is the focal injection of toxins into the central nervous system, including the detergent lysolecithin into the spinal cord white matter of rodents. In this protocol, we demonstrate that the surgical procedure involved in injecting lysolecithin into the ventral white matter of mice is fast, cost-effective, and requires no additional materials than those commercially available. This procedure is important not only for studying the normal events involved in the remyelination process, but also as a pre-clinical tool for screening candidate remyelination-promoting therapeutics. PMID:25867716

  1. Child neurology: chronic inflammatory demyelinating polyradiculoneuropathy in children.

    PubMed

    Markowitz, Jennifer A; Jeste, Shafali S; Kang, Peter B

    2008-12-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder characterized by patchy demyelination of nerve roots and distal nerves. The course may be monophasic progressive or relapsing-remitting. CIDP is less common in children than in adults. As in adults, children with CIDP present with proximal and distal weakness and loss of deep tendon reflexes. Children are most often brought to medical attention due to gait disturbance and falling. As in adults, immunomodulatory treatment is the mainstay of therapy. Based on the small number of case series available, children with CIDP seem have a more favorable long-term course than adults.

  2. Characteristic MRI features of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Abe, Yuichi; Terashima, Hiroshi; Hoshino, Hideki; Sassa, Kaori; Sakai, Tetsuro; Ohtake, Akira; Kubota, Masaya; Yamanouchi, Hideo

    2015-10-01

    We present characteristic magnetic resonance imaging (MRI) features in a pediatric female patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Muscle weakness developed at 8 years old and fluctuated during the clinical course over 7 years. Electrophysiological studies showed a demyelination pattern with moderately delayed nerve conduction velocity, as well as dispersion phenomenon. MRI showed marked changes in thickening of the spinal nerve roots and their peripheral nerves in the lumber and brachial plexuses, as well as in the bilateral trigeminal nerves. It is suggested that these MRI features are characteristic and strongly supportive of the diagnosis of CIDP with a prolonged clinical course.

  3. The acute haemolytic syndrome in Wilson's disease--a review of 22 patients.

    PubMed

    Walshe, J M

    2013-11-01

    An analysis of 321 case notes of patients with Wilson's disease seen between 1955 and 2000 and one case seen in 1949 has revealed that 22 patients presented with a haemolytic crisis. This study was not a specific research project but a retrospective analysis of 321 patients with Wilson's disease seen between 1949 and 2000. All investigations were carried out in the best interests of diagnosis and management of patients referred to my clinic. The delay in diagnosis in 18 cases resulted in progression to severe hepatic disease in 14 cases and to neurological disease in 4 cases. One patient had no symptoms at the time her sister's illness was diagnosed as Wilson's disease. In a second patient, with liver disease, the diagnosis was also made when a sister was found to have Wilson's disease. There was a female to male ratio of 15:7. The average age of onset was 12.6 years and the incidence 6.9%. Delay in diagnosis resulted in nine deaths. Three patients, late in the series, were admitted in the acute phase, two female and one male; of these two responded to chelation therapy, the third required liver transplantation. Haemolysis appeared to be extravascular, and possible mechanisms of the haemolysis are discussed.

  4. Diagnostic challenges of Wilson’s disease presenting as acute pancreatitis, cholangitis, and jaundice

    PubMed Central

    Nussinson, Elchanan; Shahbari, Azmi; Shibli, Fahmi; Chervinsky, Elena; Trougouboff, Philippe; Markel, Arie

    2013-01-01

    Wilson’s disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons’s disease. Moreover, cases of Wilson’s disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis, cholangitis, and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography. However, because of his long-term jaundice and the presence of pigmented gallstones, the patient underwent further evaluation for Wilson’s disease, which was subsequently confirmed. This patient’s unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson’s disease and cholestasis, and the difficulties associated with their differentiation. It suggests that Wilson’s disease should be considered in patients with pancreatitis, cholangitis, and severe protracted jaundice caused by pigmented gallstones. PMID:24303094

  5. Health-related QOL in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease: a review of the literature.

    PubMed

    Doll, Helen; Miravitlles, Marc

    2005-01-01

    There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research.A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George's Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1-12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute

  6. Legionnaire's disease and acute renal failure: a case report and literature review.

    PubMed

    Boucree, M C

    1988-10-01

    A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad.

  7. Anti-GBM Disease in Pregnancy: Acute Renal Failure Resolved After Plasma Exchange, Hemodialysis, and Steroids.

    PubMed

    Adnan, Mohammed Muqeet; Morton, Jordan; Hashmi, Syed; Abdul Mujeeb, Sufyan; Kern, William; Cowley, Benjamin D

    2016-01-01

    Antiglomerular basement membrane (GBM) disease presenting during pregnancy is uncommon. We present a case of a pregnant female who presented with acute renal failure requiring dialysis due to anti-GBM disease. She responded well to plasma exchange, high-dose steroids, and hemodialysis. Cyclophosphamide was discussed but not given at the patient's request due to concerns for the well-being of the fetus. Unfortunately, she suffered a spontaneous abortion in her eighth week of pregnancy. Subsequently, she had progressive improvement in her renal function and became hemodialysis independent at 2 weeks after diagnosis. Her renal function returned to baseline 3 months after diagnosis. We present this case in detail and review the literature regarding anti-GBM disease in pregnancy. PMID:26788531

  8. Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies.

    PubMed

    Ommen, Hans Beier

    2016-02-01

    Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon.

  9. Severe demyelinating hypertrophic polyneuropathy caused by a de novo frameshift mutation within the intracellular domain of myelin protein zero (MPZ/P0).

    PubMed

    Zschüntzsch, Jana; Dibaj, Payam; Pilgram, Sara; Kötting, Judith; Gerding, Wanda M; Neusch, C

    2009-06-15

    Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A with an underlying duplication in the gene coding for the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P(0)) account for demyelinating CMT1B, Dejerine-Sottas syndrome (DSS), or congenital hypomyelinating neuropathy (CHN). Here, we report a patient with a severe, early-onset hypertrophic and dysmyelinating neuropathy. The patient exhibits a novel frameshift mutation with an insertion of a single T-nucleotide on position c.618_619 of the MPZ gene resulting in a premature stop M207fsX38. PMID:19344920

  10. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  11. Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease

    PubMed Central

    Shi, Patricia Ann; Manwani, Deepa; Olowokure, Olugbenga; Nandi, Vijay

    2014-01-01

    Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory pattern of LDF has probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed. PMID:24857171

  12. Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

    PubMed

    Shi, Patricia Ann; Manwani, Deepa; Olowokure, Olugbenga; Nandi, Vijay

    2014-12-01

    Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory patterns of LDF have probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed.

  13. Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center

    PubMed Central

    Naqvi, Rubina; Mubarak, Muhammed; Ahmed, Ejaz; Akhtar, Fazal; Bhatti, Sajid; Naqvi, Anwar; Rizvi, Adib

    2015-01-01

    Introduction: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. Objectives: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. Patients and Methods: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. Results: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. Conclusion: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome. PMID:26693497

  14. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    ClinicalTrials.gov

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; 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); Recurrent Adult Acute Myeloid Leukemia

  15. IgG4-related disease manifesting as an acute gastric-pericardial fistula.

    PubMed

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-11-28

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  16. IgG4-related disease manifesting as an acute gastric-pericardial fistula

    PubMed Central

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-01-01

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  17. Morphologic, immunologic, and cytogenetic characteristics of secondary acute unclassifiable leukemia in Hodgkin's disease.

    PubMed

    Orazi, A; Cattoretti, G; Sozzi, G; Miozzo, M; Polli, N; Delia, D; Viviani, S; Negretti, E; Della Porta, G; Rilke, F

    1988-08-31

    Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.

  18. Unusual presentation of Erdheim-Chester disease in a child with acute lymphoblastic leukemia

    PubMed Central

    Vallonthaiel, Archana George; Mridha, Asit Ranjan; Gamanagatti, Shivanand; Jana, Manisha; Sharma, Mehar Chand; Khan, Shah Alam; Bakhshi, Sameer

    2016-01-01

    Erdheim-Chester disease (ECD) is an uncommon, non-familial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense 99mTechnetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of “coated aorta” or “hairy kidneys”. ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia.

  19. Unusual presentation of Erdheim-Chester disease in a child with acute lymphoblastic leukemia.

    PubMed

    Vallonthaiel, Archana George; Mridha, Asit Ranjan; Gamanagatti, Shivanand; Jana, Manisha; Sharma, Mehar Chand; Khan, Shah Alam; Bakhshi, Sameer

    2016-08-28

    Erdheim-Chester disease (ECD) is an uncommon, non-familial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense (99m)Technetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of "coated aorta" or "hairy kidneys". ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia. PMID:27648170

  20. The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies.

    PubMed

    de Thé, Hugues; Le Bras, Morgane; Lallemand-Breitenbach, Valérie

    2012-07-01

    Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.

  1. Endothelial-cell injury in cutaneous acute graft-versus-host disease.

    PubMed Central

    Dumler, J. S.; Beschorner, W. E.; Farmer, E. R.; Di Gennaro, K. A.; Saral, R.; Santos, G. W.

    1989-01-01

    The presence of an erythematous skin rash and hemorrhagic complications in acute graft-versus-host disease (GVHD) suggest that the vasculature may be involved in the immunopathologic process. We reviewed endothelial and vascular histopathologic changes on light microscopy and on immunoperoxidase stained sections of skin biopsies obtained from 41 HLA-identical allogeneic marrow transplant recipients with at least grade 2 GVHD. Biopsies taken from 14 allogeneic HLA-identical bone marrow transplant recipients who never developed GVHD were used as controls. Sections were evaluated for evidence of immunologic vascular injury using the rank file analysis of histologic features, expression of HLA-DR antigen, and the distribution of fibrin and factor VIII-related antigen (F VIII RAg). Patients with acute GVHD had significantly greater intimal lymphocytic infiltrates, perivascular nuclear dust deposition, perivascular F VIII Rag extravasation and deposition and vascular proliferation than controls. We find significantly greater endothelial injury in GVHD patients, which may represent primary immunologic injury to the vasculature. The clinical findings in acute GVHD probably result from cumulative endothelial as well as epithelial injury. Images Figure 1 Figure 2 Figure 3 PMID:2596572

  2. The Role of Purine Metabolites as DAMPs in Acute Graft-versus-Host Disease

    PubMed Central

    Apostolova, Petya; Zeiser, Robert

    2016-01-01

    Acute graft-versus-host disease (GvHD) causes high mortality in patients undergoing allogeneic hematopoietic cell transplantation. An early event in the classical pathogenesis of acute GvHD is tissue damage caused by the conditioning treatment or infection that consecutively leads to translocation of bacterial products [pathogen-associated molecular patterns (PAMPs)] into blood or lymphoid tissue, as well as danger-associated molecular patterns (DAMPs), mostly intracellular components that act as pro-inflammatory agents, once they are released into the extracellular space. A subtype of DAMPs is nucleotides, such as adenosine triphosphate released from dying cells that can activate the innate and adaptive immune system by binding to purinergic receptors. Binding to certain purinergic receptors leads to a pro-inflammatory microenvironment and promotes allogeneic T cell priming. After priming, T cells migrate to the acute GvHD target organs, mainly skin, liver, and the gastrointestinal tract and induce cell damage that further amplifies the release of intracellular components. This review summarizes the role of different purinergic receptors in particular P2X7 and P2Y2 as well as nucleotides in the pathogenesis of GvHD.

  3. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    PubMed Central

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  4. Methanobactin reverses acute liver failure in a rat model of Wilson disease.

    PubMed

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Kabiri, Yaschar; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K; Schirmacher, Peter; DiSpirito, Alan A; Bandow, Nathan; Baral, Bipin S; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A; Adamski, Jerzy; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H J; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz; Zischka, Hans

    2016-07-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  5. Early Diagnosis and Management of Acute Vertigo from Vestibular Migraine and Ménière's Disease.

    PubMed

    Seemungal, Barry; Kaski, Diego; Lopez-Escamez, Jose Antonio

    2015-08-01

    Vestibular migraine is the most common cause of acute episodic vestibular symptoms after benign paroxysmal positional vertigo. In contrast, Ménière's disease is an uncommon disorder. For both conditions, early and accurate diagnosis (or its exclusion) enables the correct management of patients with acute episodic vestibular symptoms. Long-term management of migraine requires changes in lifestyle to avoid triggers of migraine and/or prophylactic drugs if attacks become too frequent. The long-term management of Ménière's disease also involves lifestyle changes (low salt diet), medications (betahistine, steroids), and ablative therapy applied to the diseased ear (eg, intratympanic gentamicin).

  6. Kallikrein 6 Regulates Early CNS Demyelination in a Viral Model of Multiple Sclerosis

    PubMed Central

    Scarisbrick, Isobel A.; Yoon, Hyesook; Panos, Michael; Larson, Nadya; Blaber, Sachiko I.; Blaber, Michael; Rodriguez, Moses

    2012-01-01

    Kallikrein 6 (Klk6) is a secreted serine protease that is elevated in active multiple sclerosis lesions and patient sera. To further evaluate the involvement of Klk6 in chronic progressive demyelinating disease, we determined its expression in the brain and spinal cord of SJL mice infected with Theiler’s murine encephalomyelitis virus (TMEV) and assessed the effects of Klk6-neutralizing antibodies on disease progression. Klk6 RNA expression was elevated in the brain and spinal cord by 7 days post-infection (dpi). Thereafter, Klk6 expression persisted primarily in the spinal cord reaching a peak of 5-fold over controls at mid-chronic stages (60–120 dpi). Significant elevations in Klk6 RNA were also induced in splenocytes stimulated with viral capsid proteins in vitro and in activated THP-1 monocytes. Klk6-neutralizing antibodies reduced TMEV-driven brain and spinal cord pathology and DTH responses when examined at early chronic time points (40 dpi). Reductions in spinal cord pathology included a decrease in activated monocytes/microglia and reductions in the loss of myelin basic protein (MBP). By 180 dpi, pathology scores no longer differed between groups. These findings point to regulatory activities for Klk6 in the development and progression of CNS inflammation and demyelination that can be effectively targeted through the early chronic stages with neutralizing antibody. PMID:22335454

  7. Altered transition metal homeostasis in the cuprizone model of demyelination.

    PubMed

    Moldovan, Nataliya; Al-Ebraheem, Alia; Lobo, Lianne; Park, Raina; Farquharson, Michael J; Bock, Nicholas A

    2015-05-01

    In the cuprizone model of demyelination, the neurotoxin cuprizone is fed to mice to induce a reproducible pattern of demyelination in the brain. Cuprizone is a copper chelator and it has been hypothesized that it induces a copper deficiency in the brain, which leads to demyelination. To test this hypothesis and investigate the possible role of other transition metals in the model, we fed C57Bl/6 mice a standard dose of cuprizone (0.2% dry chemical to dry food weight) for 6 weeks then measured levels of copper, manganese, iron, and zinc in regions of the brain and visceral organs. As expected, this treatment induced demyelination in the mice. We found, however, that while the treatment significantly reduced copper concentrations in the blood and liver in treated animals, there was no significant difference in concentrations in brain regions relative to control. Interestingly, cuprizone disrupted concentrations of the other transition metals in the visceral organs, with the most notable changes being decreased manganese and increased iron in the liver. In the brain, manganese concentrations were also significantly reduced in the cerebellum and striatum. These data suggest a possible role of manganese deficiency in the brain in the cuprizone model. PMID:25749275

  8. Late central demyelination after Fischer's syndrome: MRI studies.

    PubMed Central

    Ferrer, X; Ellie, E; Larrivière, M; Deleplanque, B; Lagueny, A; Julien, J

    1993-01-01

    The case of a patient who presented with clinical, electrophysiological, and MRI evidence of central demyelination is described. The patient had been admitted to hospital for Fischer's syndrome a few years previously. The association of these two events suggests that central and peripheral myelinopathy may be related in Fischer's syndrome. PMID:8509787

  9. [The combined treatment of acute suppurative diseases of the fingers and hand using decamethoxin].

    PubMed

    Fishchenko, A Ia; Paliĭ, G K; Kravets, V P

    1992-03-01

    The authors discuss the results of complex treatment of 286 patients with acute pyoinflammatory diseases of the fingers and hand with the use of a new Soviet-produced antiseptic decametoxin. Panaris was diagnosed in 196 (68.5%), phlegmons and abscesses in 82 (29.7%), furuncle in 6 (2.1%) and carbuncle in 2 (0.7%) patients. 224 (78.4%) patients received out-patient and 62 (21.6%) in-patient treatment. The authors established that as the result of the applied complex treatment with the use of various antiseptic compositions containing decametoxin the mean duration of treatment was 7.8 days. The article discusses the causes of the disease, the methods of operative treatment, and management of patients in the postoperative period.

  10. Quantitative assessment of relative roles of drivers of acute respiratory diseases

    NASA Astrophysics Data System (ADS)

    Goswami, Prashant; Baruah, Jurismita

    2014-10-01

    Several thousands of people, including children, suffer from acute respiratory disease (ARD) every year worldwide. Pro-active planning and mitigation for these diseases require identification of the major drivers in a location-specific manner. While the importance of air pollutants in ARD has been extensively studied and emphasized, the role of weather variables has been less explored. With Delhi with its large population and pollution as a test case, we examine the relative roles of air pollution and weather (cold days) in ARD. It is shown that both the number of cold days and air pollution play important roles in ARD load; however, the number of cold days emerges as the major driver. These conclusions are consistent with analyses for several other states in India. The robust association between ARD load and cold days provides basis for estimating and predicting ARD load through dynamical model, as well as impact of climate change.

  11. [Acute conditions after kidney transplantation in patients with autosomal dominant polycystic kidney disease].

    PubMed

    Bujdák, P; Pribylincová, V; Reznícek, J; Miklosi, M; Breza, J

    2003-05-01

    There is a high risk of severe complications after kidney transplantation. In patients with autosomal dominant polycystic kidney disease (AD-PKD) the incidence of complications like ischaemic cardiac disease, acute myocardial infarction, pulmonary embolism, perforation of colonic diverticulosis is especially higher. The authors want to indicate another specific complication, rupture of the cyst of own polycystic kidney with retroperitoneal haemorrhage. Within the group of 658 patients who underwent kidney transplantation between January 1981 and January 2000 there were 54 (8.2%) patients with AD-PKD. Four patients with severe retroperitoneal haemorrhage due to rupture of the cyst of own polycystic kidney we present in a short case reports. All cases were fatal. Expect morphologic and functional follow up of the graft it is necessary to follow up polycystic kidney and indicate urgent nephrectomy in the case of any change.

  12. Plasma exchange for hemolytic crisis and acute liver failure in Wilson disease.

    PubMed

    Verma, Nishant; Pai, Gautham; Hari, Pankaj; Lodha, Rakesh

    2014-05-01

    Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.

  13. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases.

    PubMed

    Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting; Yuan, Shu

    2016-01-01

    Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders.

  14. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

  15. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  16. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  17. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases

    PubMed Central

    Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting; Yuan, Shu

    2016-01-01

    Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders. PMID:26649144

  18. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases.

    PubMed

    Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting; Yuan, Shu

    2016-01-01

    Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders. PMID:26649144

  19. The formation of inflammatory demyelinated lesions in cerebral white matter

    PubMed Central

    Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

    2016-01-01

    Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

  20. A Puzzle of Vestibular Physiology in a Meniere's Disease Acute Attack

    PubMed Central

    Martinez-Lopez, Marta; Manrique-Huarte, Raquel; Perez-Fernandez, Nicolas

    2015-01-01

    The aim of this paper is to present for the first time the functional evaluation of each of the vestibular receptors in the six semicircular canals in a patient diagnosed with Meniere's disease during an acute attack. A 54-year-old lady was diagnosed with left Meniere's disease who during her regular clinic review suffers an acute attack of vertigo, with fullness and an increase of tinnitus in her left ear. Spontaneous nystagmus and the results in the video head-impulse test (vHIT) are shown before, during, and after the attack. Nystagmus was initially left beating and a few minutes later an upbeat component was added. No skew deviation was observed. A decrease in the gain of the vestibuloocular reflex (VOR) and the presence of overt saccades were observed when the stimuli were in the plane of the left superior semicircular canal. At the end of the crisis nystagmus decreased and vestibuloocular reflex returned to almost normal. A review of the different possibilities to explain these findings points to a hypothetical utricular damage. PMID:26167320

  1. [Acute epidural hematoma of the posterior fossa in a case of von Willebrand's disease].

    PubMed

    Takenaka, N; Mine, T; Ikeda, E; Iwai, H; Kusano, S

    1988-01-01

    A rare case of acute epidural hematoma of the posterior fossa associated with von Willebrand's disease is reported. A 9-year-old boy fell down and hit his occipital region against a floor. Soon after he came home and slept, but three hours later he began to vomit and became drowsiness. He visited our hospital and his Glasgow Coma Scale showed 13 points. CT scan on admission showed acute epidural hematoma of left posterior fossa and contusional hematoma in the right temporal lobe. The bleeding time was over 18 minutes. He had been suspected to be suffering from von Willebrand's disease two years ago. Then fresh blood, fresh frozen plasma and anti-hemophilic globulin were prepared. Ten hours after injury, the operation was begun. Fresh epidural hematoma existed as a clot beyond transverse sinus. During the procedure of dural tenting suture, diffuse bleeding from bone, muscle, subcutaneous tissue and dura occurred and it was difficult to stop the bleeding. By using fresh blood and anti-hemophilic globulin, the bleeding was controlled, and then the operation was achieved. In the postoperative course a new epidural hematoma was found in the left temporal region and a new but asymptomatic retinal hemorrhage was found in his right eye. He was discharged without any neurological deficits 25 days after operation.

  2. Primary percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with giant coronary aneurysm due to Kawasaki disease.

    PubMed

    Mongiovì, Maurizio; Alaimo, Annalisa; Vernuccio, Federica; Pieri, Daniele

    2014-01-01

    We report a case of acute myocardial infarction in an 8-year-old boy with a history of Kawasaki disease and giant coronary aneurysms in the right and left coronary arteries. We performed coronary angiography and percutaneous coronary intervention 4 hours after the onset of symptoms. This case suggests that primary percutaneous coronary intervention might be safe and effective in the long-term treatment of acute myocardial infarction due to coronary sequelae of Kawasaki.

  3. Follicular Mucinosis in a Male Adolescent with a History of Acute Myelogenous Leukemia and Graft-versus-Host Disease.

    PubMed

    Jefferson, Julie; Taube, Janis; Grossberg, Anna

    2016-01-01

    Although many cases of follicular mucinosis are idiopathic, numerous others are associated with mycosis fungoides or, rarely, other neoplastic or inflammatory disorders. There are only three reported cases, all in adults, of follicular mucinosis arising in association with acute myelogenous leukemia, two of which involved mycosis fungoides-associated follicular mucinosis, including one case in which the patient had a preceding bone marrow transplant. We present the first reported case of follicular mucinosis arising in an adolescent with acute myelogenous leukemia and acute graft-versus-host disease after an allogeneic bone marrow transplantation. PMID:26645410

  4. Similarities between inherited demyelinating neuropathies and Wallerian degeneration: an old repair program may cause myelin and axon perturbation under nonlesion conditions.

    PubMed

    Martini, Rudolf; Klein, Dennis; Groh, Janos

    2013-09-01

    Wallerian degeneration (WD) and inherited demyelinating neuropathies of the Charcot-Marie-Tooth type 1 (CMT1) appear to represent completely distinct events. CMT1-like diseases are chronic disorders of peripheral nerves that are genetically caused and lead to secondary neurodegenerative events, resulting in usually non-treatable disabilities, whereas WD is an acute, usually transient, reaction on injuries, aiming to allow peripheral nerve regeneration. Despite these differences, there are some striking similarities regarding molecular characteristics of neural cells in the affected peripheral nerves. The most conspicuous similarities might comprise the inflammatory component in both situations, as identified in appropriate mouse models. However, although inflammation is a beneficial component in WD, leading to removal of regrowth-repellent myelin debris, inflammation in CMT1 mouse models causes damage of initially intact nerve fibers. We hypothesize that, in CMT1 models, molecular pathways are activated that are shared with an important repair program after peripheral nerve injury, but lead to neural perturbation when activated under nonlesion conditions, as is the case in CMT1. These novel insights into the pathogenesis of CMT1 might be instrumental for the development of new therapeutic options in humans.

  5. Behçet's Disease Presenting with Acute Transverse Myelitis: MRI Findings and Review of the Nosology. A Case Report.

    PubMed

    Sanal, H T; Bulakbasi, N; Kocaoglu, M; Tayfun, C

    2007-04-30

    Spinal cord involvement, either isolated or together with brain, in Behçet's disease (BD) has been reported. In these cases the existence of the disease was previously known or the classical triad of disease such as oral and genital ulcers with uveitis/iritis was present. Here we describe a 22-year-old man in whom acute transverse myelitis diagnosed with MRI was the first finding of BD. PMID:24299651

  6. Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by next-generation sequencing.

    PubMed

    Salipante, Stephen J; Fromm, Jonathan R; Shendure, Jay; Wood, Brent L; Wu, David

    2014-11-01

    Detection of minimal residual disease predicts adverse outcome in patients with acute myeloid leukemia. Currently, minimal residual disease may be detected by RQ-PCR or flow cytometry, both of which have practical and diagnostic limitations. Here, we describe a next-generation sequencing assay for minimal residual disease detection in NPM1-mutated acute myeloid leukemia, which encompasses ∼60% of patients with normal karyotype acute myeloid leukemia. Exon 12 of NPM1 was PCR amplified using sequencing adaptor-linked primers and deep sequenced to enable detection of low-prevalence, acute myeloid leukemia-specific activating mutations. We benchmarked our results against flow cytometry, the standard of care for acute myeloid leukemia minimal residual disease diagnosis at our institution. The performance of both approaches was evaluated using defined dilutions of an NPM1 mutation-positive cell line and longitudinal clinical samples from acute myeloid leukemia patients. Using defined control material, we found this assay sensitive to approximately 0.001% mutant cells, outperforming flow cytometry by an order of magnitude. Next-generation sequencing was precise and semiquantitative over four orders of magnitude. In 22 longitudinal samples from six acute myeloid leukemia patients, next-generation sequencing detected minimal residual disease in all samples deemed negative by flow cytometry. Further, in one-third of patients, sequencing detected alternate NPM1 mutations in addition to the patient's index mutation, consistent with tumor heterogeneity. Next-generation sequencing provides information without prior knowledge of NPM1 mutation subtype or validation of allele-specific probes as required for RQ-PCR assays, and without generation and interpretation of complex multidimensional flow cytometry data. This approach may complement current technologies to enhance patient-specific clinical decision-making.

  7. Original Research: Acute chest syndrome in sickle cell disease: Effect of genotype and asthma

    PubMed Central

    Pahl, Kristy

    2016-01-01

    Sickle cell disease is a severe hemoglobinopathy caused by mutations in the beta globin genes. The disorder has protean manifestations and leads to severe morbidity and early mortality. Acute chest syndrome (ACS) is a common complication and in the USA is the leading cause of death in patients with sickle cell disease. Care of patients with sickle cell disease is complex and typically involves both primary care physicians and hematology subspecialists. The purpose of this study was first to attempt to validate in a pediatric sickle cell patient cohort associations between ACS and sickle cell disease genotype and between ACS and asthma as a comorbidity. The second purpose of the study was to study in a typical community the frequency with which asthma associated with ACS was addressed in terms of electronic medical record integration, pulmonary subspecialty consultation for management of asthma, and completion of pulmonary function testing (PFTs). A retrospective study of the electronic medical record of a children’s hospital that provides most of the medical care for children in a portion of western New York state was performed. We found that ACS was more common in the sickle cell disease genotypes SS and S/beta-thalassemia-null, and that ACS was more frequent in patients treated for asthma. We also found that despite the use of a comprehensive electronic medical record, there was poor documentation of ACS and asthma episodes in the problem lists of patients with sickle cell disease, and that most patients with sickle cell disease with ACS or asthma failed to receive formal consultation services from pediatric pulmonary subspecialists. PMID:26936083

  8. Original Research: Acute chest syndrome in sickle cell disease: Effect of genotype and asthma.

    PubMed

    Pahl, Kristy; Mullen, Craig A

    2016-04-01

    Sickle cell disease is a severe hemoglobinopathy caused by mutations in the beta globin genes. The disorder has protean manifestations and leads to severe morbidity and early mortality. Acute chest syndrome (ACS) is a common complication and in the USA is the leading cause of death in patients with sickle cell disease. Care of patients with sickle cell disease is complex and typically involves both primary care physicians and hematology subspecialists. The purpose of this study was first to attempt to validate in a pediatric sickle cell patient cohort associations between ACS and sickle cell disease genotype and between ACS and asthma as a comorbidity. The second purpose of the study was to study in a typical community the frequency with which asthma associated with ACS was addressed in terms of electronic medical record integration, pulmonary subspecialty consultation for management of asthma, and completion of pulmonary function testing (PFTs). A retrospective study of the electronic medical record of a children's hospital that provides most of the medical care for children in a portion of western New York state was performed. We found that ACS was more common in the sickle cell disease genotypes SS and S/beta-thalassemia-null, and that ACS was more frequent in patients treated for asthma. We also found that despite the use of a comprehensive electronic medical record, there was poor documentation of ACS and asthma episodes in the problem lists of patients with sickle cell disease, and that most patients with sickle cell disease with ACS or asthma failed to receive formal consultation services from pediatric pulmonary subspecialists.

  9. Acute coronary syndrome (ACS) registry--leading the charge for National Cardiovascular Disease (NCVD) Database.

    PubMed

    Chin, S P; Jeyaindran, S; Azhari, R; Wan Azman, W A; Omar, I; Robaayah, Z; Sim, K H

    2008-09-01

    Coronary artery disease is one of the most rampant non-communicable diseases in the world. It begins indolently as a fatty streak in the lining of the artery that soon progresses to narrow the coronary arteries and impair myocardial perfusion. Often the atherosclerotic plaque ruptures and causes sudden thrombotic occlusion and acute ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina (UA). This phenomenon is called acute coronary syndrome (ACS) and is the leading cause of death not only in Malaysia but also globally. In order for us to tackle this threat to the health of our nation we must arm ourselves with reliable and accurate information to assess current burden of disease resources available and success of current strategies. The acute coronary syndrome (ACS) registry is the flagship of the National Cardiovascular Disease Database (NCVD) and is the result of the dedicated and untiring efforts of doctors and nurses in both public and private medical institutions and hospitals around the country, ably guided and supported by the National Heart Association, the National Heart Foundation, the Clinical Research Centre and the Ministry of Health of Malaysia. Analyses of data collected throughout 2006 from 3422 patients with ACS admitted to the 12 tertiary cardiac centres and general hospitals spanning nine states in Malaysia in this first report has already revealed surprising results. Mean age of patients was 59 years while the most consistent risk factor for STEMI was active smoking. Utilization of medications was high generally. Thirty-day mortality for STEMI was 11%, for NSTEMI 8% and UA 4%. Thrombolysis (for STEMI only) reduced in-hospital and 30-day mortality by nearly 50%. Percutaneous coronary intervention or PCI also reduced 30-day mortality for patients with non-ST elevation MI and unstable angina. The strongest determinants of mortality appears to be Killip Class and age of the patient. Fewer women received

  10. Acute responses to exercise training and relationship with exercise adherence in moderate chronic obstructive pulmonary disease.

    PubMed

    Rizk, Amanda K; Wardini, Rima; Chan-Thim, Emilie; Bacon, Simon L; Lavoie, Kim L; Pepin, Véronique

    2015-11-01

    The objectives of our study were to (i) compare, in chronic obstructive pulmonary disease (COPD) patients, acute responses to continuous training at high intensity (CTHI), continuous training at ventilatory threshold (CTVT) and interval training (IT); (ii) examine associations between acute responses and 12-week adherence; and (iii) investigate whether the relationship between acute responses and adherence is mediated/moderated by affect/vigour. Thirty-five COPD patients (forced expiratory volume in 1 second = 60.2 ± 15.8% predicted), underwent baseline assessments, were randomly assigned to CTHI, CTVT or IT, were monitored throughout about before training, and underwent 12 weeks of exercise training during which adherence was tracked. Compared with CTHI, CTVT was associated with lower respiratory exchange ratio, heart rate and respiratory rate (RR), while IT induced higher [Formula: see text], [Formula: see text]maximal voluntary ventilation, RR and lower pulse oxygen saturation. From pre- to post-exercise, positive affect increased (F = 9.74, p < 0.001) and negative affect decreased (F = 6.43, p = 0.005) across groups. CTVT reported greater end-exercise vigour compared to CTHI (p = 0.01) and IT (p = 0.02). IT exhibited lowest post-exercise vigour (p = 0.04 versus CTHI, p = 0.02 versus CTVT) and adherence rate (F = 6.69, p = 0.004). Mean [Formula: see text] (r = -0.466, p = 0.007) and end-exercise vigour (r = 0.420, p = 0.017) were most strongly correlated with adherence. End-exercise vigour moderated the relationship between [Formula: see text] and adherence (β = 2.74, t(32) = 2.32, p = 0.03). In summary, CTHI, CTVT and IT improved affective valence from rest to post-exercise and induced a significant 12-week exercise training effect. However, they elicited different acute physiological responses, which in turn were associated with differences in 12-week adherence to the target training intensity. This association was moderated by acute end-exercise vigour.

  11. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-05-23

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms.

  12. Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Sivagnanalingam, Umayal; Balys, Marlene; Eberhardt, Allison; Wang, Nancy; Myers, Jason R.; Ashton, John M.; Becker, Michael W.; Calvi, Laura M.; Mendler, Jason H.

    2015-01-01

    Cytogenetically normal acute myeloid leukemia (CN-AML) patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH). Tail vein injection of CG-SH into NOD scid gamma mice led to leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks. Treatment of leukemic mice with anthracycline/cytarabine-based chemotherapy resulted in clearance of disease from the spleen and peripheral blood, but persistence of disease in the bone marrow as assessed by flow cytometry and secondary transplantation. Whole exome sequencing of CG-SH revealed mutations in ASXL1, CEBPA, GATA2, and SETBP1, not previously reported. We conclude that CG-SH xenografts are a robust, reproducible in vivo model of CN-AML in which to explore mechanisms of chemotherapy resistance and novel therapeutic approaches. PMID:26177509

  13. Nephropathy in dietary hyperoxaluria: A potentially preventable acute or chronic kidney disease

    PubMed Central

    Glew, Robert H; Sun, Yijuan; Horowitz, Bruce L; Konstantinov, Konstantin N; Barry, Marc; Fair, Joanna R; Massie, Larry; Tzamaloukas, Antonios H

    2014-01-01

    Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma, profound tubular damage and interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to end-stage renal disease (ESRD). This sequence of events, well recognized in the past in primary and enteric hyperoxalurias, has also been documented in a few cases of dietary hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide, thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions. Studies addressing this question have the potential of improving population health and should be undertaken, alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate, and into the mechanisms of development of oxalate-induced renal parenchymal disease. Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies. PMID:25374807

  14. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-01-01

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms. PMID:27323085

  15. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

    PubMed Central

    2009-01-01

    Background Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients. Methods One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT). Results Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO. Conclusion SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors. PMID:19643023

  16. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review

    PubMed Central

    Molnár, Gergő A.; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

    2016-01-01

    Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + ortho-tyrosine)/para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases. PMID:26785996

  17. Determining the community prevalence of acute gastrointestinal illness and gaps in surveillance of acute gastroenteritis and foodborne diseases in Guyana.

    PubMed

    Persuad, Shamdeo; Mohamed-Rambaran, Pheona; Wilson, Alexis; James, Colin; Indar, Lisa

    2013-12-01

    Guyana is an English-speaking country in South America and, culturally, it is part of the Caribbean. Objective of this study was to determine the community prevalence and true burden and economic impact of acute gastroenteritis (AGE) and foodborne diseases (FBDs) in Guyana. A cross-sectional population-based survey was conducted in 7 of the 10 regions in Guyana during August and November 2009 to capture the high- and low-AGE season respectively. Overall, 1,254 individual surveys were administered at a response rate of 96.5%. The overall monthly prevalence of self-reported cases of AGE was 7.7% (97 cases) (95% CI 6.3-9.3), and the yearly incidence was 1.0 episodes per person-year. The highest monthly prevalence of AGE was observed in region 4 (8.9%) and in children aged 1-4 year(s) (12.7%). Of the 97 AGE cases, 23% sought medical care; 65% reported spending time at home due to their illness [range 1-20 day(s), mean 2.7 days], of whom 51% required other individuals to look after them while ill. The maximum number of stools per 24 hours ranged from 3 to 9 (mean 4.5), and number of days an individual suffered from AGE ranged from 1 to 21 day(s) (mean 2.7 days). The burden of syndromic AGE cases in the population for 2009 was estimated to be 131,012 cases compared to the reported 30,468 cases (76.7% underreporting), which implies that, for every syndromic case of AGE reported, there were additional 4.3 cases occurring in the community. For every laboratory-confirmed case of FBD/AGE pathogen reported, it was estimated that approximately 2,881 more cases were occurring in the population. Giardia was the most common foodborne pathogen isolated. The minimum estimated annual cost associated with the treatment for AGE was US$ 2,358,233.2, showing that AGE and FBD pose a huge economic burden on Guyana. Underreporting of AGE and foodbome pathogens, stool collection, and laboratory capacity were major gaps, affecting the surveillance of AGE in Guyana.

  18. TREM2 regulates microglial cell activation in response to demyelination in vivo

    PubMed Central

    Cantoni, Claudia; Bollman, Bryan; Licastro, Danilo; Xie, Mingqiang; Mikesell, Robert; Schmidt, Robert; Yuede, Carla M.; Galimberti, Daniela; Olivecrona, Gunilla; Klein, Robyn S.; Cross, Anne H.; Otero, Karel; Piccio, Laura

    2015-01-01

    Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2−/−) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2−/− microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2−/− microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage. PMID:25631124

  19. Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect.

    PubMed

    Salem, Neveen A; Assaf, Naglaa; Ismail, Manal F; Khadrawy, Yasser A; Samy, Mohga

    2016-08-01

    Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1β, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone. PMID:26467344

  20. A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

    PubMed Central

    Hyun, Young Se; Kwak, Geon; Choi, Yu-Ri; Yeo, Ha Kyung; Jwa, Dong Hwan; Kim, Eun Ja; Mo, Won Min; Nam, Soo Hyun; Kim, Sung Min; Yoo, Jeong Hyun; Koo, Heasoo; Park, Hwan Tae; Chung, Ki Wha; Choi, Byung-Ok

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy. PMID:26828946

  1. Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ceuppens, Ruben; Dumont, Debora; van Brussel, Leen; van de Plas, Babs; Daniels, Ruth; Noben, Jean-Paul; Verhaert, Peter; van der Gucht, Estel; Robben, Johan; Clerens, Stefan; Arckens, Lutgarde

    2007-02-01

    One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases.

  2. [Demyelinating diseases in the southern regions of Uzbekistan].

    PubMed

    Alaev, B A; Samibaev, M Kh; Umanskiĭ, K G

    1983-01-01

    Examination of the clinical archives for 1931-1980, epidemiological survey of the Samarkand and Kashka-Darya regions as well as clinical examination of 49 patients showed disseminated sclerosis to occur more rarely among the aboriginal population (26,8%) than among newcomers (73,2%). General morbidity was 1.7: 100.000 population; this made it possible to attribute the region under study to a low risk zone. The debut, clinical picture and clinical course of disseminated sclerosis in three groups of patients (aboriginal population, persons born in other Uzbekistan regions and newcomers) were similar and did not differ from classical descriptions by European authors.

  3. [Relationship between child day-care attendance and acute infectious disease. A systematic review].

    PubMed

    Ochoa Sangrador, Carlos; Barajas Sánchez, M Verisima; Muñoz Martín, Beatriz

    2007-01-01

    Child day-care attendance is considered to be an acute early childhood disease risk factor, the studies available however not affording the possibility of fully quantifying this risk. A systematic review of clinical trials and cohort studies was conducted, in which the effects child day-care attendance had on the health of young children based on the Cochrane Collaboration, PubMed and Spanish Medical Index databases, without any time or language-related limits, were analyzed and rounded out with analyses of referenced works and an additional EMBASE search. The methodological quality was evaluated by means of personalized criteria. Pooling measures (relative risks, incidence density ratios and weighted mean differences) were calculated with their confidence intervals, assuming random effects models. A significant increase was found to exist of a risk consistent over time and among different social and geographical environments. Considering the most methodologically-stringent studies with adjusted effect estimates, child day-care attendance was related to an increased risk of upper respiratory tract infection (RR=1,88), acute otitis media (RR=1,58), otitis media with fluid draining (RR=2,43), lower respiratory tract infections (overall RR=210; acute pneumonia RR=1.70; broncholitis RR=1,80; bronchitis RR=2,10) and gastroenteritis (RR=1,40). Child day-care attendance could be responsible for 33%-50% of the episodes of respiratory infection and gastroenteritis among the exposed population. In conclusion, it can be said that the risk for childhood health attributable to the child day-care attendance is discreet but of high-impact. This information has some major implications for research, clinical practice, healthcare authorities and society as a whole.

  4. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  5. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease

    PubMed Central

    Seliger, Stephen L.; Zhang, Amy D.; Weir, Matthew R.; Walker, Loreen; Hsu, Van Doren; Parsa, Afshin; Diamantidis, Clarissa; Fink, Jeffrey C.

    2013-01-01

    Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). However, a recent trial in diabetic CKD patients suggested a greater stroke risk associated with full correction of anemia using ESAs. We performed a case-control study examining the association of incident ESA use with acute stroke in CKD patients, using national Veterans Affairs data. Patients with eGFR<60 cc/min/1.73m2 and outpatient hemoglobin (Hb)<12g/dL were included. Acute hospitalized stroke cases (N=2071) were identified using diagnosis codes and matched 1:5 to controls without stroke. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use (N=1026, 8.3%) was associated with 30% greater odds of stroke (odds ratio[OR]=1.30, 95% confidence interval[CI]: 1.06, 1.58). There was significant interaction (p=.015) between ESA use and cancer; ESA use was associated with 85% greater odds of stroke in cancer patients (95% CI: 1.26, 2.65), but not associated with stroke in patients without cancer (OR=1.07, 95% CI: 0.85, 1.35). ESA-treated patients with cancer received a median initial dose 2.5 to 4 times greater than ESA patients without cancer, but pre-ESA Hb and rate of Hb change did not differ between groups. Among a large national sample of anemic CKD patients, ESA treatment is associated with an increased risk of acute stroke, with the greatest effect among patients with cancer. PMID:21389972

  6. Hemidystonia secondary to cervical demyelinating lesions.

    PubMed

    Yücesan, C; Tuncel, D; Akbostanci, M C; Yücemen, N; Mutluer, N

    2000-09-01

    Hemidystonia is usually associated with a structural lesion in the contralateral basal ganglia. We report a patient with definite multiple sclerosis, according to Poser's criteria, presenting with an acute-onset sustained left hemidystonia. Cranial T2-weighted magnetic resonance imaging (MRI) showed several hyperintense lesions in the centri semiovali and in the periventricular area without basal ganglia involvement. Moreover cervical spinal cord T2-weighted MRI showed two hyperintense lesions in the left posterolateral spine at C2 and C3, and one lesion in the right posterolateral spine at C4 levels. The hemidystonia improved completely after daily treatment with 1000 mg of methylprednisolone, and cervical MRI was performed after the improvement which showed that the lesions had become smaller and less intense. Finally we consider that the hemidystonia may be caused by the cervical spinal cord lesions of multiple sclerosis. PMID:11054144

  7. [Aeromonas spp asociated to acute diarrheic disease in Cuba: case-control study].

    PubMed

    Bravo, Laura; Fernández, Anabel; Núñez, Fidel Á; Rivero, Luis A; Ramírez, Margarita; Aguila, Adalberto; Ledo, Yudith; Cruz, Yanaika; Hernández, Jenny

    2012-02-01

    The members of the genus Aeromonas are currently considered important gastrointestinal pathogens in different geographical areas. From February 1985 to January 2005 several case-control studies were coordinated by the National Reference Laboratory for Diarrheal Diseases from the Pedro Kouri Institute. The study purpose was to analyze a possible pathogenic role for Aeromonas spp in Cuban children with acute diarrhea. In that period 2,322 children less than 5 years old with acute diarrhea were studied for diarhoeal pathogens and another group of 2,072 non hospitalized children without diarrhea during the similar time from the same geographical areas and matched by ages were recruited. In the group of children with diarrheas (cases), Aeromonas spp. was isolated in 166 (7.15%) and in the control group the microorganism was found in only 35 (1.76%). When Aeromonas isolation rates were compared between both groups, we found that probability to isolate this specie was significantly higher in cases than in controls (OR = 4.48, 95% IC: 3.05-6.60; P < 0.001). The Aeromonas species more frequently isolated were A. caviae, A. hydrophila, and A. veronii bv sobria. Other enteric pathogens detected in children with diarrhea were: Shigella spp in 418 (18%) (P < 0.0001), Salmonella spp in 53 (2.3%) (P < 0.01), and enteropathogenic E. coli in 58 (2.49%) (P < 0.05).

  8. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    PubMed

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD.

  9. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    PubMed

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD. PMID:25455279

  10. Gentle Massage Improves Disease- and Treatment-Related Symptoms in Patients with Acute Myelogenous Leukemia

    PubMed Central

    Taylor, Ann Gill; Snyder, Audrey E; Anderson, Joel G; Brown, Cynthia J; Densmore, John J; Bourguignon, Cheryl

    2014-01-01

    Objective Cancer treatment is reported to be stressful, and patients diagnosed with hematologic cancers often exhibit higher levels of anxiety and emotional distress than individuals with other malignancies. Management of these symptoms in patients with hematologic cancer presents significant challenges, as many of them are in and out of the hospital while undergoing high dose chemotherapy. Oncology patients use complementary modalities such as therapeutic massage in an attempt to alleviate disease and treatment-related symptoms, including anxiety and emotional distress. In the current study, the feasibility of a novel massage intervention delivered over the continuum of care, as well as assessment of the immediate and cumulative effects of massage, was examined in patients with acute myelogenous leukemia. Methods A mixed-methods, unmasked, prospective, randomized study was conducted with two groups: a usual care alone control group and a massage therapy intervention plus usual care group. Results Significant improvements in levels of stress and health-related quality of life were observed in the massage therapy group versus the usual care alone group, after adjusting for anxiety level, including both immediate and cumulative effects of massage. Conclusions While the findings of the current study regarding acceptability, feasibility, and potential efficacy of therapeutic massage as a complementary health-enhancing intervention in patients diagnosed with acute myelogenous leukemia are very promising, the relatively small size of the study sample limits generalizability. PMID:25530922

  11. Significance of murine retroviral mutagenesis for identification of disease genes in human acute myeloid leukemia.

    PubMed

    Erkeland, Stefan J; Verhaak, Roel G W; Valk, Peter J M; Delwel, Ruud; Löwenberg, Bob; Touw, Ivo P

    2006-01-15

    Retroviral insertion mutagenesis is considered a powerful tool to identify cancer genes in mice, but its significance for human cancer has remained elusive. Moreover, it has recently been debated whether common virus integrations are always a hallmark of tumor cells and contribute to the oncogenic process. Acute myeloid leukemia (AML) is a heterogeneous disease with a variable response to treatment. Recurrent cytogenetic defects and acquired mutations in regulatory genes are associated with AML subtypes and prognosis. Recently, gene expression profiling (GEP) has been applied to further risk stratify AML. Here, we show that mouse leukemia genes identified by retroviral insertion mutagenesis are more frequently differentially expressed in distinct subclasses of adult and pediatric AML than randomly selected genes or genes located more distantly from a virus integration site. The candidate proto-oncogenes showing discriminative expression in primary AML could be placed in regulatory networks mainly involved in signal transduction and transcriptional control. Our data support the validity of retroviral insertion mutagenesis in mice for human disease and indicate that combining these murine screens for potential proto-oncogenes with GEP in human AML may help to identify critical disease genes and novel pathogenetic networks in leukemia.

  12. Acute hepatopancreatic necrosis disease (AHPND) outbreaks in Penaeus vannamei and P. monodon cultured in the Philippines.

    PubMed

    de la Peña, Leobert D; Cabillon, Nikko Alvin R; Catedral, Demy D; Amar, Edgar C; Usero, Roselyn C; Monotilla, Wilberto D; Calpe, Adelaida T; Fernandez, Dalisay Dg; Saloma, Cynthia P

    2015-10-27

    Acute hepatopancreatic necrosis disease (AHPND) has recently emerged as a serious disease of cultured shrimp. It has also been described as early mortality syndrome (EMS) due to mass mortalities occurring within 20 to 30 d after stocking of ponds with postlarvae. Here, Penaeus vannamei and Penaeus monodon from shrimp farms in the Philippines were examined for the toxin-producing strain of Vibrio parahaemolyticus due to AHPND-like symptoms occurring in marketable size shrimp. In the P. vannamei, histology revealed typical AHPND pathology, such as sloughing of undifferentiated cells in the hepatopancreatic tubule epithelium. Analysis using the IQ2000 AHPND/EMS Toxin 1 PCR test generated 218 bp and 432 bp amplicons confirmative of the toxin-producing strain of V. parahaemolyticus among shrimp sampled from 8 of 9 ponds. In the P. monodon, histology revealed massive sloughing of undifferentiated cells of the hepatopancreatic tubule epithelium in the absence of basophilic bacterial cells. PCR testing generated the 2 amplicons confirmatory for AHPND among shrimp sampled from 5 of 7 ponds. This study confirms the presence of AHPND in P. vannamei and P. monodon farmed in the Philippines and suggests that the disease can also impact late-stage juvenile shrimp.

  13. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis. PMID:25830761

  14. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

  15. Air pollution and acute respiratory diseases in children: regression analysis of morbidity data.

    PubMed

    Biesiada, M; Zejda, J E; Skiba, M

    2000-01-01

    The aim of this study was to investigate the relationship between acute respiratory diseases and the air quality in the urban area of the Upper Silesian Industrial Zone during autumn and winter with special emphasis on temporal variability in the air concentrations of pollutants. The survey was carried out in 5 primary care units in Chorzów where the morbidity data on the selected respiratory diseases were collected from 1 November 1992 to 31 March 1993. The air pollution data were obtained from the monitoring station, being a part of the Sanitary and Epidemiological Station Network. Regression analysis with mean values of concentrations of air pollutants as explanatory variables revealed a positive effect of combined suspended particulate matter and SO2 concentration on the increased prevalence of bronchitis and bronchiolitis. Similar and even stronger effect was observed at the level of temporal variability coefficients of the air pollutants. A hypothesis that temporal variability of the air concentration of pollutants might be a more relevant factor for determining the prevalence of respiratory diseases than simple mean values of the pollutant concentrations is very interesting worthy of further investigations.

  16. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    PubMed

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

  17. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs.

  18. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  19. Rotavirus and acute diarrhoeal disease in children in a southern Indian coastal town*

    PubMed Central

    Paniker, C. K. J.; Mathew, S.; Mathan, M.

    1982-01-01

    Rotavirus was found by electron microscopy in the stools of 70.7% of a representative sample (368) of the 3355 children with acute diarrhoea admitted to hospital over a period of 16 months in Calicut on the west coast of India. The prevalence of the virus was high (nearly 100% of cases examined) in the period from November to January and lowest in May just before the onset of the monsoon. Prevalence was high (75.1%) in infants aged from 6 to 23 months, but was considerably lower in those under 6 months of age (34.8%). The management of cases and the planning of control measures for this disease are discussed in the light of knowledge of the high prevalence of rotavirus. PMID:6282478

  20. Rotavirus and acute diarrhoeal disease in children in a southern Indian coastal town.

    PubMed

    Paniker, C K; Mathew, S; Mathan, M

    1982-01-01

    Rotavirus was found by electron microscopy in the stools of 70.7% of a representative sample (368) of the 3355 children with acute diarrhoea admitted to hospital over a period of 16 months in Calicut on the west coast of India. The prevalence of the virus was high (nearly 100% of cases examined) in the period from November to January and lowest in May just before the onset of the monsoon. Prevalence was high (75.1%) in infants aged from 6 to 23 months, but was considerably lower in those under 6 months of age (34.8%). The management of cases and the planning of control measures for this disease are discussed in the light of knowledge of the high prevalence of rotavirus.

  1. Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report

    PubMed Central

    Xi, Xiao-Tu; Wang, Mao-Jie; Huang, Run-Yue; Ding, Bang-Han

    2016-01-01

    Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered. PMID:27588099

  2. Supplemental nasogastric feeding in cystic fibrosis patients during treatment for acute exacerbation of chest disease.

    PubMed

    Daniels, L; Davidson, G P; Martin, A J; Pouras, T

    1989-06-01

    The use of overnight, nasogastric, nutritional supplementation during hospitalization of children with cystic fibrosis (CF) receiving antibiotic therapy for acute exacerbations of respiratory disease was evaluated in 11 children (mean age = 7.75 years). Supplementary feeding significantly increased inpatient energy intake from 116 +/- 30% to 165 +/- 30% (P less than 0.001) of recommended dietary allowance with minimal effect on oral intake. It also resulted in significantly improved weight gains but neither increased energy intakes nor weights were sustained at short-term (mean = 5.7 weeks) or long-term (mean = 21.6 weeks) follow-up. The notion that short bursts of nasogastric feeding for inpatients with CF improve growth status is not supported. However, the study did show that treatment of chest infections alone does not positively affect spontaneous oral energy intake. PMID:2504140

  3. Unusual presentation of Erdheim-Chester disease in a child with acute lymphoblastic leukemia

    PubMed Central

    Vallonthaiel, Archana George; Mridha, Asit Ranjan; Gamanagatti, Shivanand; Jana, Manisha; Sharma, Mehar Chand; Khan, Shah Alam; Bakhshi, Sameer

    2016-01-01

    Erdheim-Chester disease (ECD) is an uncommon, non-familial, non-Langerhans cell histiocytosis, which involves skeletal system and soft tissue usually in middle aged and elderly patients. The characteristic radiologic features include bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal parts of the long bones, or bilateral symmetrically abnormal intense 99mTechnetium labelling of the metaphyseal-diaphyseal region of the long bones, and computed tomography scan findings of “coated aorta” or “hairy kidneys”. ECD in childhood with osteolytic lesion is extremely rare. We describe an unusual case with an expansile lytic bone lesion at presentation in a case of acute lymphoblastic leukemia. PMID:27648170

  4. ROLE OF MINIMAL RESIDUAL DISEASE MONITORING IN ADULT AND PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    SYNOPSIS Assays that measure minimal residual disease (MRD) can determine the response to treatment in patients with acute lymphoblastic leukemia (ALL) much more precisely than morphological screening of bone marrow smears. The clinical significance of MRD detected by flow cytometry or polymerase chain reaction-based methods in childhood ALL has been conclusively established. Hence, MRD is being used in several clinical trials to adjust treatment intensity. Similar findings have been gathered in adult patients with ALL, making MRD one of the most powerful and informative parameters to guide clinical management. This article discusses practical issues related to MRD methodologies and the evidence supporting the use of MRD for risk assignment in clinical trials. PMID:19825454

  5. Painful acute radiation thyroiditis induced by 131I treatment of Graves' disease.

    PubMed

    Shah, Kinjal K; Tarasova, Valentina; Davidian, Michael; Anderson, Robert J

    2015-01-01

    A 44-year-old woman, chronic smoker with Graves' disease was treated with radioactive iodine ablation (RAI). One week after the treatment, she presented with severe pain in the anterior neck with radiation to the angle of the jaw associated with fatigue, tremor and odynophagia. Physical examination demonstrated an asymmetric and exquisitely tender thyroid gland. There was no laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed. Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started initially were ineffective for pain control. Prednisone provided relief and was continued for 1 month with a tapering dose. Symptoms completely resolved after 1 month at which time the thyroid remained diffusely enlarged and non-tender. Three months following RAI ablation she developed hypothyroid symptoms. Levothyroxine was initiated. The patient has remained asymptomatic on continued follow-up care. PMID:25576511

  6. Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.

    PubMed

    Dehghan, Shoaleh; Liu, Elizabeth B; Seto, Jason; Torres, Sarah F; Hudson, Nolan R; Kajon, Adriana E; Metzgar, David; Dyer, David W; Chodosh, James; Jones, Morris S; Seto, Donald

    2012-01-01

    Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment. PMID:22158846

  7. [Differential diagnostics of acute inflammatory diseases and tumors of the neck].

    PubMed

    Vuĭtsik, N B; Butkevich, A Ts; Kuntsevich, G I; Zemlianoĭ, A B

    2008-01-01

    The purpose of the investigation was to assess the clinical significance of ultrasonography for differential diagnostics between acute inflammatory and tumorous lesions of the neck. One hundred and eighty-six patients with soft-tissue lesions of the neck aged 18 to 74 (mean age 31.45 +/- 8.39 years), 95 (51%) males and 91 (49%) females were examined. Basing on clinical and ultrasonographic examination, the patients were divided into two groups: 149 or 80% patients with acute inflammatory lesions (Group 1), and 37 or 20% patients with tumorous lesions (Group 2). Thirty-four of the 149 Group 1 patients (22.82%) had lymphadenitis, 30 (20.13%) had soft tissue infiltrates, 13 (8.72%) had abscesses, 19 (12.72%) had phlegmons, 32 (21.48%) had acute inflammatory changes in the major salivary glands, 3 (2.01%) had teratomas with signs of inflammation, and 17 (11.41%) patients had inflammatory changes in the tumors. Of 37 patients with tumorous lesions, 16 (43.2%) had salivary gland tumors, 12 (32.4%) had metastases in the lymphatic nodes, and 9 (24.3%) had neurofibromatosis. Soft tissue ultrasonography was performed using Sonos-5500 and Image-Point ultrasound scanners with 7.5 MHz sensors (Hewlett-Packard, USA), Logio-pro, Uoluson-730 Expert (General Electric, USA), and Premium Edition (ACUSON Antares, Siemens, Germany) with 5 to 13 MHz wide-frequency sensors. Visualization was performed in B-modes using tissue harmonics, color duplex scanning, Sie Scape panoramic visualization, contrast visualization and Sight 4D and 3D-Scape modes. The results of ultrasonography were analyzed taking into account additional methods such as computed and magnetic resonance tomography, intraoperative findings, the results of puncture biopsy, histological, morphological, and bacteriological studies. The study demonstrates that ultrasonography is the method of choice, which is in some cases enough to establish a diagnosis of an acute inflammatory disease or a tumorous formation of various

  8. Varicella-zoster virus encephalomyelitis with a prominent demyelinating component.

    PubMed

    Berth, Sarah; Carbunar, Olimpia; Yang, Ning Sarah; Fredericks, Brian; Lipton, Howard L; Valyi-Nagy, Tibor

    2015-12-01

    The histopathologic presentation of varicella-zoster virus (VZV) infection of the central nervous system is varied and is not well understood. Here we report a case of VZV encephalomyelitis with prominent demyelinating pathology in a patient with a history of follicular lymphoma treated with allogeneic stem cell transplantation. The patient presented with waxing and waning bilateral limb weakness and mental status changes. MRI showed leptomeningeal, peripheral spinal cord and periventricular cerebral white matter lesions in the brain, and polymerase chain reaction on cerebrospinal fluid detected VZV DNA. The patient expired from developing atrial fibrillation that rapidly progressed to ventricular fibrillation 10 days after admission to our hospital. Autopsy revealed macrophage-rich areas of demyelination in the spinal cord and cerebrum with relative preservation of axons associated with inclusion bodies and positive immunostaining for VZV. This case represents a rare example of VZV encephalomyelitis presenting with a predominantly demyelinating, "multiple sclerosis-like" pathology. The clinical and histopathologic findings and relevant literature are presented and discussed.

  9. Charcot-Marie-Tooth Disease

    MedlinePlus

    ... a different neuropathy distinct from CMT1A called hereditary neuropathy with predisposition to pressure palsy (HNPP) is caused ... PMP-22 gene result in episodic, recurrent demyelinating neuropathy. CMT1B is an autosomal dominant disease caused by ...

  10. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation.

  11. Transcranial near-infrared laser therapy applied to promote clinical recovery in acute and chronic neurodegenerative diseases

    PubMed Central

    Lapchak, Paul A

    2012-01-01

    One of the most promising methods to treat neurodegeneration is noninvasive transcranial near-infrared laser therapy (NILT), which appears to promote acute neuroprotection by stimulating mitochondrial function, thereby increasing cellular energy production. NILT may also promote chronic neuronal function restoration via trophic factor-mediated plasticity changes or possibly neurogenesis. Clearly, NILT is a treatment that confers neuroprotection or neurorestoration using pleiotropic mechanisms. The most advanced application of NILT is for acute ischemic stroke based upon extensive preclinical and clinical studies. In laboratory settings, NILT is also being developed to treat traumatic brain injury, Alzheimer’s disease and Parkinson’s disease. There is some intriguing data in the literature that suggests that NILT may be a method to promote clinical improvement in neurodegenerative diseases where there is a common mechanistic component, mitochondrial dysfunction and energy impairment. This article will analyze and review data supporting the continued development of NILT to treat neurodegenerative diseases. PMID:22145842

  12. Prolonged dysphagia due to Listeria-rhombencephalitis with brainstem abscess and acute polyradiculoneuritis.

    PubMed

    Smiatacz, Tomasz; Kowalik, Maciej Michal; Hlebowicz, Maria

    2006-06-01

    We report a case of previously healthy student with acute rhombencephalitis and brainstem abscess caused by Listeria monocytogenes. The disease begun with uncharacteristic prodromal symptoms of gastrointestinal infection followed by headache and vertigo. After hospital admission the patient rapidly deteriorated, presenting pronounced dysphagia and respiratory failure requiring mechanical ventilation. The diagnosis was established upon clinical symptoms of infection, brainstem involvement, typical MRI findings and positive for L. monocytogenes blood culture. Infection was complicated by acute, demyelinating neuropathy, diagnosed upon clinical symptoms of frail palsy confirmed by ENG. Initially introduced empirical doxycyclin/ceftriaxon treatment was subsequently changed to targeted ampicillin/gentamycin therapy, mechanical ventilation, intravenous human immunoglobulin treatment, tracheostomy and endoscopic gastrostomy. Prolonged dysphagia resolved after rehabilitation. After one year the patient remains well with only slight dysmetria. PMID:16260041

  13. [Fatal acute interstitial lung disease associated with docetaxel administration: about a case and review of the literature].

    PubMed

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

    2016-01-01

    Docetaxel is a chemotherapeutic agent belonging to the taxane family. This drug is widely used to treat cancers. Interstitial lung disease is a rare but serious toxicity due to the high mortality risk. We report a case of a patient with breast cancer who had fatal acute interstitial lung disease after auxiliary chemotherapy with docetaxel. The clinician should be aware of this risk and should consider it in differential diagnosis in patients with respiratory symptoms treated with docetaxel. PMID:27642457

  14. Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival

    PubMed Central

    Gordon, Stephen B.; Chaponda, Mas; Walsh, Amanda L.; Whitty, Christopher J.M.; Gordon, Melita A.; Machili, C. Edward; Gilks, Charles F.; Boeree, Martin J.; Kampondeni, Sam; Read, Robert C.; Molyneux, Malcolm E.

    2016-01-01

    Objective HIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed. We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease. Design, setting and patients Acute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S. pneumoniae in the blood or cerebrospinal fluid. Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome. Results A total of 217 patients with pneumococcal disease were studied over an 18-month period. Among these, 158 out of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17). Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors. Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period. Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient. Conclusion Most patients with pneumococcal disease in Malawi have HIV co-infection. They have severe disease with a high mortality rate. At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk. PMID:12131218

  15. Fingolimod Attenuates Splenocyte-Induced Demyelination in Cerebellar Slice Cultures

    PubMed Central

    Pritchard, Adam J.; Mir, Anis K.; Dev, Kumlesh K.

    2014-01-01

    The family of sphingosine-1-phosphate receptors (S1PRs) is G-protein-coupled, comprised of subtypes S1PR1-S1PR5 and activated by the endogenous ligand S1P. The phosphorylated version of Fingolimod (pFTY720), an oral therapy for multiple sclerosis (MS), induces S1PR1 internalisation in T cells, subsequent insensitivity to S1P gradients and sequestering of these cells within lymphoid organs, thus limiting immune response. S1PRs are also expressed in neuronal and glial cells where pFTY720 is suggested to directly protect against lysolecithin-induced deficits in myelination state in organotypic cerebellar slices. Of note, the effect of pFTY720 on immune cells already migrated into the CNS, prior to treatment, has not been well established. We have previously found that organotypic slice cultures do contain immune cells, which, in principle, could also be regulated by pFTY720 to maintain levels of myelin. Here, a mouse organotypic cerebellar slice and splenocyte co-culture model was thus used to investigate the effects of pFTY720 on splenocyte-induced demyelination. Spleen cells isolated from myelin oligodendrocyte glycoprotein immunised mice (MOG-splenocytes) or from 2D2 transgenic mice (2D2-splenocytes) both induced demyelination when co-cultured with mouse organotypic cerebellar slices, to a similar extent as lysolecithin. As expected, in vivo treatment of MOG-immunised mice with FTY720 inhibited demyelination induced by MOG-splenocytes. Importantly, in vitro treatment of MOG- and 2D2-splenocytes with pFTY720 also attenuated demyelination caused by these cells. In addition, while in vitro treatment of 2D2-splenocytes with pFTY720 did not alter cell phenotype, pFTY720 inhibited the release of the pro-inflammatory cytokines such as interferon gamma (IFNγ) and interleukin 6 (IL6) from these cells. This work suggests that treatment of splenocytes by pFTY720 attenuates demyelination and reduces pro-inflammatory cytokine release, which likely contributes to enhanced

  16. Minimal residual disease detection using flow cytometry: Applications in acute leukemia.

    PubMed

    Chatterjee, T; Mallhi, R S; Venkatesan, S

    2016-04-01

    Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia.

  17. Clinical features and outcome of acute exacerbation of interstitial pneumonia associated with connective tissue disease.

    PubMed

    Toyoda, Yuko; Hanibuchi, Masaki; Kishi, Jun; Kawano, Hiroshi; Morizumi, Shun; Sato, Seidai; Kondo, Mayo; Takikura, Terumi; Tezuka, Toshifumi; Goto, Hisatsugu; Nishioka, Yasuhiko

    2016-01-01

    Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p <0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated. J. Med. Invest. 63: 294-299, August, 2016. PMID:27644575

  18. Acute posterior fossa epidural hematoma in a newborn infant with Menkes disease.

    PubMed

    Takeuchi, Satoru; Horikawa, Masahiro; Wakamatsu, Hajime; Hashimoto, Jyunya; Nawashiro, Hiroshi

    2014-02-01

    Epidural hematoma (EDH) in newborn infants is rare compared with other types of intracranial hemorrhages. Furthermore, posterior fossa EDH is extremely rare. We present a case of posterior fossa EDH in an infant with Menkes disease with accessory bones in the occiput. A male infant with a condition diagnosed with Menkes disease by prenatal testing was born at 39 weeks via vacuum extraction. The patient presented with a mild tremor at 2 days after delivery. A brain computed tomography (CT) scan showed an acute EDH in the posterior fossa, extending into the occipitoparietal area. Three-dimensional CT and bone window CT scan revealed several accessory bones, diastasis of 1 accessory suture, a communicated fracture, and a linear fracture in the occipital bone. Furthermore, a bone fragment from a communicated fracture displaced toward the inside. The patient was treated conservatively for EDH because of his good general condition. The hematoma gradually resolved, and his tremor did not recur. We suggest the following mechanism of posterior fossa EDH development in our patient: (1) external force was applied to the occiput inside the birth canal during delivery, resulting in diastasis; (2) a communicated fracture occurred, and a bone fragment displaced toward the inside (linear fracture was caused indirectly by the force); (3) a transverse sinus was injured by the fragment; and (4) EDH developed in both the posterior fossa and supratentorial region. Copper deficiency can also cause fragility of connective tissues, vessels, and bones.

  19. Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease

    PubMed Central

    Lamarre, Yann; Romana, Marc; Waltz, Xavier; Lalanne-Mistrih, Marie-Laure; Tressières, Benoît; Divialle-Doumdo, Lydia; Hardy-Dessources, Marie-Dominique; Vent-Schmidt, Jens; Petras, Marie; Broquere, Cedric; Maillard, Frederic; Tarer, Vanessa; Etienne-Julan, Maryse; Connes, Philippe

    2012-01-01

    Background Little is known about the effects of blood rheology on the occurrence of acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia and hemoglobin SC disease. Design and Methods To address this issue, steady-state hemorheological profiles (blood viscosity, red blood cell deformability, aggregation properties) and hematologic parameters were assessed in 44 children with sickle cell anemia and 49 children with hemoglobin SC disease (8-16 years old) followed since birth. Clinical charts were retrospectively reviewed to determine prior acute chest syndrome or vaso-occlusive episodes, and rates of these complications were calculated. Results Multivariate analysis revealed that: 1) a higher steady-state blood viscosity was associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, but not in children with hemoglobin SC disease; 2) a higher steady-state red blood cell disaggregation threshold was associated with previous history of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. Conclusions Our results indicate for the first time that the red blood cell aggregation properties may play a role in the pathophysiology of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. In addition, whereas greater blood viscosity is associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, no association was found in children with hemoglobin SC disease, underscoring differences in the etiology of vaso-occlusive crises between sickle cell anemia and hemoglobin SC disease. PMID:22689686

  20. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil.

  1. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil. PMID:26670404

  2. Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

    PubMed

    Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu

    2016-06-01

    The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.

  3. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition.

    PubMed

    Vallat, Jean-Michel; Sommer, Claudia; Magy, Laurent

    2010-04-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic neuropathy of supposed immune origin. Understanding of its pathophysiology has recently improved, although its causes remain unclear. The classic presentation of CIDP includes sensory and motor symptoms in the distal and proximal segments of the four limbs with areflexia, evolving over more than 8 weeks. Raised protein concentrations in CSF and heterogeneous slowing of nerve conduction are typical of the condition. In addition to this usual phenotype, distribution of symptoms, disease course, and disability can be heterogeneous, leading to underdiagnosis of the disorder. Diagnosis is sometimes challenging and can require use of imaging and nerve biopsy. Steroids and intravenous immunoglobulin are effective, and plasma exchange can be helpful as rescue therapy. The usefulness of immunosuppressants needs to be established. The identification of specific diagnostic markers and new therapeutic strategies with conventional or targeted immunotherapy are needed to improve the outlook for patients with CIDP.

  4. Chronic inflammatory demyelinating polyradiculoneuropathy in a boy with systemic lupus erythematosus.

    PubMed

    Zoilo, Morel Ayala; Eduardo, Benadón; Enrique, Faugier; del Rocio, Maldonado V M

    2010-05-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy. Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease that can affect the central nervous system in about 40% of patients, with prevalence and incidence unknown in the pediatric population due to lack of multicenter studies. We report the case of a 13-year-old Mexican boy, diagnosed with CIDP at the onset of SLE, beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. The patient had positive ANA, antiDNAdc, antiBeta2glycoprotein, anti-cardiolipin, ANCA-C and X. He received intravenous immunoglobulin, cyclophosphamide, steroids, and azathioprine and showed clinical improvement. It is important to take into account the presence of peripheral neurological disorders in patients with pediatric SLE, considering CIDP as an uncommon presentation, making the diagnosis important for better treatment and evolution.

  5. Predicting mortality after acute coronary syndromes in people with chronic obstructive pulmonary disease

    PubMed Central

    Smeeth, Liam; Pearce, Neil; Herrett, Emily; Timmis, Adam; Hemingway, Harry; Wedzicha, Jadwiga; Quint, Jennifer K

    2016-01-01

    Objective To assess the accuracy of Global Registry of Acute Coronary Events (GRACE) scores in predicting mortality at 6 months for people with chronic obstructive pulmonary disease (COPD) and to investigate how it might be improved. Methods Data were obtained on 481 849 patients with acute coronary syndrome admitted to UK hospitals between January 2003 and June 2013 from the Myocardial Ischaemia National Audit Project (MINAP) database. We compared risk of death between patients with COPD and those without COPD at 6 months, adjusting for predicted risk of death. We then assessed whether several modifications improved the accuracy of the GRACE score for people with COPD. Results The risk of death after adjusting for GRACE score predicted that risk of death was higher for patients with COPD than that for other patients (RR 1.29, 95% CI 1.28 to 1.33). Adding smoking into the GRACE score model did not improve accuracy for patients with COPD. Either adding COPD into the model (relative risk (RR) 1.00, 0.94 to 1.02) or multiplying the GRACE score by 1.3 resulted in better performance (RR 0.99, 0.96 to 1.01). Conclusions GRACE scores underestimate risk of death for people with COPD. A more accurate prediction of risk of death can be obtained by adding COPD into the GRACE score equation, or by multiplying the GRACE score predicted risk of death by 1.3 for people with COPD. This means that one third of patients with COPD currently classified as low risk should be classified as moderate risk, and could be considered for more aggressive early treatment after non-ST-segment elevation myocardial infarction or unstable angina. PMID:27177534

  6. MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease.

    PubMed

    Zhao, Yulin; Schwartz, Evan A; Palmer, Gregory M; Zennadi, Rahima

    2016-03-01

    In sickle cell disease (SCD), treatment of recurrent vasoocclusive episodes, leading to pain crises and organ damage, is still a therapeutic challenge. Vasoocclusion is caused primarily by adherence of homozygous for hemoglobin S (SS) red blood cells (SSRBCs) and leukocytes to the endothelium. We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and humanized SCD mouse models of acute vasoocclusive episodes using intravital microscopy. Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-α-pretreated nude mice before human SSRBC infusion inhibited SSRBC adhesion in inflamed vessels, prevented the progression of vasoocclusion, and reduced SSRBC organ sequestration. By use of a more clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-α-pretreated nude mice after human SSRBC infusion and onset of vasoocclusion reversed SSRBC adhesion and vasoocclusion and restored blood flow. In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte adhesion after the inflammatory trigger of vasoocclusion and improved microcirculatory blood flow. Cell adhesion was reversed by shedding of endothelial E-selectin, P-selectin, and αvβ3 integrin, and leukocyte CD44 and β2 integrin. Thus, MEK1/2 inhibitors, by targeting the adhesive function of SSRBCs and leukocytes, could represent a valuable therapeutic intervention for acute sickle cell vasoocclusive crises.

  7. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    USGS Publications Warehouse

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  8. Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease.

    PubMed

    Shechter, Michael; Shalmon, Guy; Scheinowitz, Mickey; Koren-Morag, Nira; Feinberg, Micha S; Harats, Dror; Sela, Ben Ami; Sharabi, Yehonatan; Chouraqui, Pierre

    2011-05-01

    Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.

  9. Deep Vein Thrombosis in the Lower Extremities in Comatose Elderly Patients with Acute Neurological Diseases

    PubMed Central

    Tomita, Y