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Sample records for exacerbates cerebral amyloidosis

  1. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

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    Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

    2015-09-01

    To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

  2. Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly.

    Science.gov (United States)

    Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye Won; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Young

    2016-08-01

    Although many preclinical studies have suggested the possible linkage between dyslipidemia and cerebral amyloid deposition, the association between serum lipid measures and cerebral amyloid-beta (Aβ) deposition in human brain is still poorly known. We aimed to investigate the association in cognitively normal (CN) elderly individuals. Cross-sectional study. University hospital dementia clinic. 59 CN elderly. The study measures included comprehensive clinical and neuropsychological assessment based on the CERAD protocol, magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B positron emission tomography scans, and quantification for serum lipid biomarkers. Multiple linear regression analyses showed that a higher serum triglycerides level was associated with heavier global cerebral Aβ deposition even after controlling age, sex, and apolipoprotein E ε4 genotype. Serum apolipoprotein B also showed significant positive association with global cerebral Aβ deposition, but the significance disappeared after controlling serum triglycerides level. No association was found between other lipid measures and global cerebral Aβ deposition. The findings suggest that serum triglycerides are closely associated with cerebral amyloidosis, although population-based prospective studies are needed to provide further evidence of the causative effect of triglycerides on cerebral amyloidosis. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model

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    Teng Wei-Ping

    2010-11-01

    Full Text Available Abstract Background Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD, the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Results Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Conclusions Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

  4. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study

    NARCIS (Netherlands)

    Maat-Schieman, M. L.; Rozemuller, A. J.; van Duinen, S. G.; Haan, J.; Eikelenboom, P.; Roos, R. A.

    1994-01-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately

  5. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    International Nuclear Information System (INIS)

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-01-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related β-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of ∼ 4000 and its partial amino acid sequence to position 21 showed homology to the β-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of β-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both

  6. Peripherally applied synthetic peptide isoAsp7-Aβ(1-42) triggers cerebral β-amyloidosis.

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    Kozin, S A; Cheglakov, I B; Ovsepyan, A A; Telegin, G B; Tsvetkov, P O; Lisitsa, A V; Makarov, A A

    2013-10-01

    Intracerebral and intraperitoneal inoculation with β-amyloid-rich brain extracts originating from patients with Alzheimer's disease as well as intracerebral injection of aggregates composed of synthetic Aβ can induce cerebral β-amyloidosis, and associated cognitive dysfunctions in susceptible animal hosts. We have found that repetitive intravenous administration of 100 μg of synthetic peptide corresponding to isoAsp7-containing Aβ(1-42), an abundant age-dependent Aβ isoform present both in the pathological brain and in synthetic Aβ preparations, robustly accelerates formation of classic dense-core congophilic amyloid plaques in the brain of β-amyloid precursor protein transgenic mice. Our findings indicate this peptide as an inductive agent of cerebral β-amyloidosis in vivo.

  7. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis)

    OpenAIRE

    Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuro...

  8. Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

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    Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

    2016-07-01

    We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

  9. [A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

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    Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

    2009-08-01

    A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

  10. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis).

    Science.gov (United States)

    Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.

  11. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis

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    Mari Kantanen

    2014-07-01

    Full Text Available Hereditary gelsolin amyloidosis (AGel amyloidosis is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA. To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences.

  12. Cellular processing of the amyloidogenic cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Merz, G S; Schwenk, V

    1999-01-01

    of an amyloidogenic mutation on the intracellular processing of its protein product. The protein, a mutant of the cysteine protease inhibitor cystatin C, is the amyloid precursor protein in Hereditary Cerebral Hemorrhage with Amyloidosis--Icelandic type (HCHWA-I). The amyloid fibers are composed of mutant cystatin C...... (L68Q) that lacks the first 10 amino acids. We have previously shown that processing of wild-type cystatin C entails formation of a transient intracellular dimer that dissociates prior to secretion, such that extracellular cystatin C is monomeric. We report here that the cystatin C mutation engenders...

  13. Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

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    Bing Zhao

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

  14. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study.

    Science.gov (United States)

    Maat-Schieman, M L; Rozemuller, A J; van Duinen, S G; Haan, J; Eikelenboom, P; Roos, R A

    1994-09-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately associated with congophilic plaques in Alzheimer's disease (AD), but microglial involvement in diffuse plaque formation is controversial. Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD patients, one demented Down's syndrome (DS) patient and four non-demented controls were included for comparison. In controls and HCHWA-D patients ramified or "resting" microglia formed a reticular array in cortical gray and subcortical white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their normal regular spacing and ramified morphology. In AD/DS gray matter more microglial cells were stained than in controls and HCHWA-D patients. Intensely immunoreactive microglia with enlarged cell bodies and short, thick processes clustered in congophilic plaques. In contrast to the resting microglia, these "activated microglia" strongly expressed class II major histocompatibility complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support the view that microglia play a role in the formation of congophilic plaques but do not initiate diffuse plaque formation. Another finding in this study is the presence of strong monocyte/macrophage marker immunoreactivity in the wall of cortical congophilic blood vessels in HCHWA-D.

  15. Amyloidosis

    Science.gov (United States)

    ... is less common with modern dialysis techniques. Race. People of African descent appear to be at higher risk of carrying a genetic mutation associated with the type of amyloidosis that can harm the heart. Complications The potential complications of amyloidosis ...

  16. Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

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    Campanile, Alfonso; Sozzi, Fabiola B; Canetta, Ciro; Danzi, Gian Battista

    2013-01-01

    A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes.

  17. Overview of systemic and localized amyloidosis

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    Saulius Girnius

    2013-10-01

    Full Text Available Amyloidosis is a family of protein misfolding disorders, in which insoluble fibrillar proteins deposit extracellularly and cause end organ damage. Depending on the precursor protein, clinical manifestations in amyloidosis vary significantly. In systemic amyloidosis, the heart, kidneys, and nerves are most commonly affected, resulting in congestive heart failure, arrhythmia, nephrotic syndrome, renal failure, and peripheral and autonomic neuropathies. In localized amyloidosis, amyloid deposits at the site of production, so only one organ is disrupted. Once amyloidosis is confirmed histologically, the precursor subtype must be identified using immunohistochemistry, immunofixation, electron microscopy, or laser microdissection and mass spectrometry. Treatment should not be initiated prior to the identification of the type of amyloidosis. Currently, treatment focuses on the suppression of the precursor protein: in AL amyloidosis, chemotherapy or autologous stem cell transplants suppress production of immunoglobulin light chains; in AA amyloidosis, anti-microbial and anti-inflammatory agents suppress amyloid A production; and in AF amyloidosis, a liver transplantation removes the source of mutant transthyretin protein production. Newer drugs are being developed to target amyloidosis at an epigenetic level or stabilize folding intermediates, but there are currently in development.http://dx.doi.org/10.7175/rhc.v4i4.662

  18. Unique type of isolated cardiac valvular amyloidosis

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    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  19. AL Amyloidosis

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    Desport Estelle

    2012-08-01

    Full Text Available Abstract Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig light chains (LC (most commonly of lambda isotype usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and

  20. Amyloidosis and Kidney Disease

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    ... a fist. They are located just below the rib cage, one on each side of the spine. ... by dialysis-related amyloidosis can lead to bone fractures. Dialysis-related amyloidosis can also cause tears in ...

  1. Diagnostic studies in amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke Pier Cornelis

    2007-01-01

    In this thesis two diagnostic techniques are studied in amyloidosis. Systemic amyloidosis is characterized by deposition of amyloid fibrils (tiny fibres) throughout the body resulting in damage of vital organs. Amyloid can be detected in a tissue specimen stained with Congo red: red-stained amyloid

  2. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Localized Lymph Node Light Chain Amyloidosis

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    Binod Dhakal

    2015-01-01

    Full Text Available Immunoglobulin-derived light chain amyloidosis can occasionally be associated with localized disease. We present a patient with localized lymph node light chain amyloidosis without an underlying monoclonal protein or lymphoproliferative disorder and review the literature of lymph node amyloidosis discussing work-up and risk factors for systemic progression.

  4. Treatment of amyloidosis.

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    Tan, S Y; Pepys, M B; Hawkins, P N

    1995-08-01

    Amyloidosis is the extracellular deposition of normally soluble autologous protein in a characteristic abnormal fibrillar form. Systemic amyloidosis and some local forms are progressive, cause major morbidity, and are often fatal. No treatment specifically causes the resolution of amyloid deposits, but therapy that reduces the supply of amyloid fibril precursor proteins can improve survival and preserve organ function. Major regression of amyloid occurs in at least a proportion of such cases, suggesting that the clinical improvement reflects mobilization of amyloid. The clearest evidence for regression of amyloid has been obtained in juvenile rheumatoid arthritis patients with AA amyloidosis treated with chlorambucil. This drug suppresses the acute phase production of serum amyloid A protein, the precursor of AA amyloid fibrils, and is associated with remission of proteinuria and greatly improved survival. In many such patients, scintigraphy with serum amyloid P component shows major regression of amyloid over 12 to 36 months and frequently reveals a discrepancy between the local amyloid load and organ dysfunction. Measurement of target organ function is therefore not an adequate method for monitoring treatment aimed at promoting the resolution of amyloid. In monoclonal immunoglobulin light chain (AL) amyloidosis the aim of treatment is to suppress the underlying B-cell clone and, therefore, production of the amyloid fibril precursor protein. This can be difficult to achieve or sustain and, since the prognosis is so poor, many patients die before benefits of therapy are realized. A recent development has been the introduction of liver transplantation as treatment for familial amyloid polyneuropathy caused by transthyretin gene mutations. This leads to the disappearance of variant transthyretin from the plasma and halts progression of the neurologic disease. Features of autonomic neuropathy frequently ameliorate, and improvement in peripheral motor nerve function

  5. Dysphagia as initial presentation of primary amyloidosis

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    Piyush Ranjan

    2013-01-01

    Full Text Available Amyloidosis involves all parts of the gastrointestinal tract including the esophagus. The esophageal involvement in amyloidosis has been reported to vary from 13% in a radiology study to 22% in an autopsy series; however, such patients have symptoms of gastroesophageal reflux. Dysphagia is an uncommon presentation of amyloidosis. We report a 64-year-old patient who presented with progressive dysphagia of 4 months duration which was confirmed to be due to primary amyloidosis with multiple myeloma. The esophageal involvement by amyloidosis was confirmed by esophageal mucosal biopsies, and 22-channel high-resolution manometry.

  6. Macular Amyloidosis and Epstein-Barr Virus

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    Yalda Nahidi

    2016-01-01

    Full Text Available Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group. There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8% and control (23.8% groups (P=0.08. Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis.

  7. Incidence and survival in non-hereditary amyloidosis in Sweden

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    Hemminki Kari

    2012-11-01

    Full Text Available Abstract Background Amyloidosis is a heterogeneous disease caused by deposition of amyloid fibrils in organs and thereby interfering with physiological functions. Hardly any incidence data are available and most survival data are limited to specialist clinics. Methods Amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 2001 through 2008. Results The incidence of non-hereditary amyloidosis in 949 patients was 8.29 per million person-years and the diagnostic age with the highest incidence was over 65 years. Secondary systemic amyloidosis showed an incidence of 1 per million and a female excess and the largest number of subsequent rheumatoid arthritis deaths; the median survival was 4 years. However, as rheumatoid arthritis deaths also occurred in other diagnostic subtypes, the incidence of secondary systemic amyloidosis was likely to be about 2.0 per million. The median survival of patients with organ-limited amyloidosis was 6 years. Most myeloma deaths occurred in patients diagnosed with unspecified or ‘other’ amyloidosis. These subtypes probably accounted for most of immunoglobulin light chain (AL amyloidosis cases; the median survival time was 3 years. Conclusions The present diagnostic categorization cannot single out AL amyloidosis in the Swedish discharge data but, by extrapolation from myeloma cases, an incidence of 3.2 per million could be ascribed to AL amyloidosis. Similarly, based on rheumatoid arthritis death rates, an incidence of 2.0 could be ascribed to secondary systemic amyloidosis.

  8. New insights into systemic amyloidosis: primary amyloidosis associated with tubercular lymphadenitis

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    Shivraj Meena, Nirmal Ghati, Rita Sood, Naval Kishore Vikram

    2014-11-01

    Full Text Available Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine department of all India institute of medical sciences , New Delhi with on & off erythematous rashes over both eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1 month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon eyes, hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib and Dexamethasone based weekly chemotherapy.

  9. [Amyloidosis complicating spondyloarthropathies: Study of 15 cases].

    Science.gov (United States)

    Rodríguez-Muguruza, Samantha; Martínez-Morillo, Melania; Holgado, Susana; Saenz-Sarda, Xavier; Mateo, Lourdes; Tena, Xavier; Olivé, Alejandro

    2015-10-21

    Secondary amyloidosis (AA) is a rare complication of rheumatic diseases. The aim of this study was to determine the frequency of symptomatic amyloidosis AA in patients with spondyloarthropathy. Retrospective study (1984-2013). We reviewed the medical records of patients with spondyloarthropathy who had a histological diagnosis of amyloidosis AA (15 patients). We identified 1.125 patients with spondyloarthropathies. Fifteen (1.3%) patients with amyloidosis AA were recruited. It was suspected in 14 patients (93.3%) because of nephrotic syndrome in most of them: 14 were symptomatic (93.3%): 5 (33.3%) ankylosing spondylitis (AS), 5 (33.3%) spondylitis associated with inflammatory bowel diseases (IBD), 4 (26.7%) psoriatic arthritis, and one (6.7%) reactive arthritis. The mean disease duration was 23.9 years. Mortality after one and 5 years of follow-up was 30 and 50% respectively. The frequency of clinical amyloidosis AA in our patients was 1.3%. There was a marked male predominance, with AS or IBD. Clinical amyloidosis was diagnosed at a relatively late stage in spondyloarthropathy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

    Science.gov (United States)

    Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

    2018-03-01

    To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

  11. Mediastinal and bronchovascular amyloidosis

    International Nuclear Information System (INIS)

    Biggemann, M.; Hilweg, D.; Kappes, R.

    1990-01-01

    The clinical and radiographic aspects of an unusual case of mediastinal and bronchovascular amyloidosis are presented. Besides hilar and mediastinal lymphadenopathy, extensive amyloid deposition in the peribronchial and perivascular connective tissue sheats can be observed. Plain film radiographs and CT demonstrate an uncommon pattern of increased bronchovascular markings, which is discussed. Because of peribronchial amyloid deposits, bronchoscopy is of no help in demonstrating this special type of tracheobronchial amyloidosis. (orig.) [de

  12. [AA amyloidosis: a little-known complication of chronic leg ulcer].

    Science.gov (United States)

    Waton, J; Fays-Michel, S; Chandeclerc, M L; Corby, S; Cuny, J F; Barbaud, A; Schmutz, J-L

    2008-02-01

    AA amyloidosis, secondary to inflammatory chronic diseases like rheumatoid arthritis, is often complicated by renal failure. Chronic inflammatory dermatoses constitute rare causes of AA amyloidosis. We describe two cases of AA amyloidosis discovered after renal failure in patients presenting leg ulcers for several years. AL amyloidosis was suspected in both cases because of a history of monoclonal gammopathy in one patient and of plasmocytoma in the other. The diagnosis of AA amyloidosis was confirmed on renal histology through the detection of AA antibodies in amyloid deposits. No extrarenal amyloidosis was seen in either patient and there were no inflammatory diseases other than chronic leg ulcers. AA amyloidosis is caused by serum amyloid protein A (SAA), a reactive inflammatory protein. AA amyloidosis is thus caused by chronic inflammatory diseases, but only rarely by cutaneous inflammatory diseases. To our knowledge, the literature contains only seven other published cases of AA amyloidosis secondary to chronic leg ulcers. A review of the literature does not indicate whether cure of ulcers has any effect on the accompanying renal failure. We imagine that AA amyloidosis secondary to leg ulcer is in fact under-diagnosed. However, since the first specific treatment for AA amyloidosis is currently being evaluated by the Food and Drug Administration, it is essential that this serious complication of chronic leg ulcers be widely recognised.

  13. Primary (AL) amyloidosis with gastrointestinal involvement

    DEFF Research Database (Denmark)

    Madsen, Lone Galmstrup; Gimsing, Peter; Schiødt, Frank V

    2009-01-01

    OBJECTIVE: Immunoglobulin light-chain (AL) amyloidosis is a rare disease that can affect several organs. The aim of this study was to characterize patients with gastrointestinal manifestations of AL amyloidosis, in terms of symptoms, biochemistry, and outcome. MATERIAL AND METHODS: Retrospectivel...

  14. Laryngeal Amyloidosis Mimicking Glottic Cancer: A Case Report

    International Nuclear Information System (INIS)

    Lee, Sun Jin; Kim, Jee Young; Ahn, Kook Jin; Kim, Bum Soo; Park, Young Hak

    2010-01-01

    Amyloidosis is a slowly progressive, benign disease that is characterized by the extracellular deposition of fibrillar proteins in many different tissues and organs throughout the body. Primary amyloidosis can be subdivided into the systemic and localized forms. The localized form is less common than the systemic form and the larynx is the most frequently affected site. The importance of laryngeal amyloidosis lies in its possible confusion with glottic cancer because of the clinical feature. We report here on a case of laryngeal amyloidosis in a 47-year-old man who suffered from progressive dyspnea

  15. Laryngeal Amyloidosis Mimicking Glottic Cancer: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Jin; Kim, Jee Young; Ahn, Kook Jin; Kim, Bum Soo [The Catholic University of Korea, Seoul (Korea, Republic of); Park, Young Hak [St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2010-08-15

    Amyloidosis is a slowly progressive, benign disease that is characterized by the extracellular deposition of fibrillar proteins in many different tissues and organs throughout the body. Primary amyloidosis can be subdivided into the systemic and localized forms. The localized form is less common than the systemic form and the larynx is the most frequently affected site. The importance of laryngeal amyloidosis lies in its possible confusion with glottic cancer because of the clinical feature. We report here on a case of laryngeal amyloidosis in a 47-year-old man who suffered from progressive dyspnea.

  16. An interesting case of renal amyloidosis

    Directory of Open Access Journals (Sweden)

    A Hajra

    2016-01-01

    Full Text Available In amyloidosis, there is an extracellular deposition of beta-sheet fibrils. Over 25 proteins have been demonstrated to form amyloid. One of them is Ig amyloid light (AL chains. We are presenting a 40-year-old female who presented with progressive kyphoscoliosis for last 2 years following a minor trauma and bilateral pedal edema for last 3 months. On further investigation, we found that she had a biclonal variety of MM with amyloidosis of kidney leading to massive proteinuria. Very few case reports are available where patient with biclonal variety of MM develop renal amyloidosis.

  17. [Value of aspiration biopsy of subcutaneous fat in amyloidosis].

    Science.gov (United States)

    Ponce, P; Carvalho, F; Coelho, A

    1986-01-01

    Fine-needle aspiration of subcutaneous fat (FNAF) was performed in 24 patients, 12 with previously diagnosed amyloidosis presenting with proteinuria or nephrotic syndrome, and 12 presenting a nephrotic syndrome without amyloidosis on renal biopsy. FNAF was positive in 10 of 12 patients with amyloidosis (sensitivity: 83%) and negative in 12 of 12 patients with non-amyloid nephrotic syndrome (specificity: 100%). Considering a 2.5 to 10% prevalence of amyloidosis in adult patients with proteinuria or nephrotic syndrome, a positive FNAF is diagnostic of amyloidosis, and a negative FNAF rules out the diagnosis with a probability of 98 to 99%. FNAF is a simple and safe method which can be useful in patients who cannot undergo a renal biopsy.

  18. Amyloidosis of the thyroid gland: ultrasonographic aspect

    International Nuclear Information System (INIS)

    Moya, M.I.; Vilas, I.; Menargues, M.A.; Hernandez, M.

    1998-01-01

    Subclinical amyloid infiltration of the thyroid gland is very common. However, amyloidosis rarely provokes thyroid symptoms. We describe a case of goiter due to secondary amyloidosis and review the characteristic ultrasound findings associated with this condition. (Author) 6 refs

  19. Lichen amyloidosis in an unusual location.

    Science.gov (United States)

    Jhingan, A; Lee, J S S; Kumarasinghe, S P W

    2007-06-01

    We report lichen amyloidosis occurring on the upper lip and nasolabial folds of a 61-year-old woman from Singapore. She had a past history of systemic lupus erythematosus, which was in remission for three years. There had been no lesions of lupus erythematosus in this area. Clinically, the lesions were skin-coloured, firm papules and our differential diagnoses included trichoepithelioma, papular sarcoid or lupus miliaris disseminatus faciei. Skin biopsy from one of the lesions showed amyloid deposits in the dermis which were Congo red stain positive. These deposits also showed apple green birefringence. Immunohistochemical staining of the amyloid deposits stained positive for cytokeratins (CK) 5 and 6, and negative for CK 14. The kappa and lambda stains were equivocal. Further investigations, including multiple myeloma screen and rectal biopsy, ruled out systemic amyloidosis. There was no other evidence of cutaneous amyloidosis on her limbs or trunk. She refused treatment for her lesions. This case highlights the commonly-seen form of primary localised cutaneous amyloidosis in an unusual location.

  20. Heat stress exacerbates the reduction in middle cerebral artery blood velocity during prolonged self-paced exercise.

    Science.gov (United States)

    Périard, J D; Racinais, S

    2015-06-01

    This study examined the influence of hyperthermia on middle cerebral artery mean blood velocity (MCA Vmean). Eleven cyclists undertook a 750 kJ self-paced time trial in HOT (35 °C) and COOL (20 °C) conditions. Exercise time was longer in HOT (56 min) compared with COOL (49 min; P blood flow, and heart rate were higher throughout HOT compared with COOL (P blood pressure and oxygen uptake were lower from 50% of work completed onward in HOT compared with COOL (P heat appears to have exacerbated the reduction in MCA Vmean, in part via increases in peripheral blood flow and a decrease in arterial blood pressure. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Spontaneous, Experimentally Induced, and Transmissible AA Amyloidosis in Japanese Quail ( Coturnix japonica).

    Science.gov (United States)

    Nakayama, Yumi; Kamiie, Junichi; Watanabe, Gen; Suzuki, Kazuhiko; Murakami, Tomoaki

    2017-11-01

    The authors describe a spontaneous case of amyloid A (AA) amyloidosis in an adult female Japanese quail ( Coturnix japonica). The bird developed AA amyloidosis secondary to chronic peritonitis caused by a Gram-negative bacillus infection. Mild amyloid deposition was also identified in the intestinal tract of apparently healthy adult individuals, suggesting that quail may develop intestinal amyloidosis with age. Based on these observations, it was hypothesized that quail can develop AA amyloidosis following inflammatory stimulation with lipopolysaccharide (LPS). Therefore, adult quail were repeatedly injected with LPS and the development of AA amyloidosis was confirmed. The amyloid deposition in this model increased when quail amyloid was intravenously injected as an amyloid-enhancing factor. The experiments were repeated with young quail, but amyloid deposits were not observed following LPS injections. However, AA amyloidosis did develop when quail amyloid was injected in addition to LPS. These results indicated that adult quail develop AA amyloidosis after inflammatory stimulation with LPS. Furthermore, quail AA amyloidosis was shown to have transmissibility regardless of age. Interestingly, the authors found that administration of chicken amyloid fibrils also induced AA amyloidosis in young quail. This is the first report of cross-species transmission of avian AA amyloidosis.

  2. Amyloidosis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Braconi, Daniela; Bernardini, Giulia; Lupetti, Pietro; Rovensky, Josef; Ranganath, Lakshminaryan; Santucci, Annalisa

    2015-09-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces an HGA-melanin ochronotic pigment, of hitherto unknown composition. Besides the accumulation of HGA, the potential role and presence of unidentified proteins has been hypothesized as additional causal factors involved in ochronotic pigment deposition. Evidence has been provided on the presence of serum amyloid A (SAA) in several AKU tissues, which allowed classifying AKU as a novel secondary amyloidosis. In this paper, we will briefly review all direct and indirect lines of evidence related to the presence of amyloidosis in AKU. We also report the first data on abnormal SAA serum levels in a cohort of AKU patients.

  3. Amyloidosis of the renal pelvis presenting as flank pain

    Directory of Open Access Journals (Sweden)

    Rachel Shikhman, D.O.

    2018-02-01

    Full Text Available Amyloidosis is a rare disease defined by accumulation of extracellular amyloid systemically or within a specific organ. Localized amyloidosis of the genitourinary system is extremely rare, with the predominate location being the bladder. The imaging findings are often nonspecific and mimic urothelial carcinoma. We present a 49-year-old woman with a chief complaint of flank pain. A filling defect was discovered on radiological imaging. The defect was subsequently biopsied and proven to be a primary amyloidosis of the renal pelvis. We then review the radiological findings of amyloidosis of the genitourinary system.

  4. NUCLEAR IMAGING IN THE DIAGNOSIS OF CARDIAC AMYLOIDOSIS

    Directory of Open Access Journals (Sweden)

    V. B. Sergienko

    2018-01-01

    Full Text Available Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis but has its limitations. Accordingly, there is a need for noninvasive techniques to cardiac amyloidosis diagnostics. Echocardiography and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Recently, new opportunities of nuclear imaging in risk stratification and assessment of prognosis for patients with cardiac amyloidosis have appeared. During the last two decades different classes of radiopharmaceuticals have been developed based on compounds tropic to the components of amyloid infiltrates. In this paper we describe the current possibilities and perspectives of nuclear medicine techniques in patients with cardiac amyloidosis, including osteotropic and neurotropic scintigraphy, single-photon and positron emission tomography

  5. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  6. Characteristics of AA amyloidosis patients in San Francisco.

    Science.gov (United States)

    Lejmi, Hiba; Jen, Kuang-Yu; Olson, Jean L; James, Sam H; Sam, Ramin

    2016-04-01

    AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco. Here, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further. All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable. AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high. © 2015 Asian Pacific Society of Nephrology.

  7. Diagnostic and therapeutic approach of systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, BPC; van Gameren, [No Value; Bijzet, J; Jager, PL; van Rijswijk, MH

    Amyloidosis is a group of diseases, all characterised by deposition of protein fibrils with a beta-sheet structure. This structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. Three types of systemic amyloidosis are important for the clinician: AA (related to

  8. Clinical approach of patients with systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke

    2011-01-01

    Amyloidosis is the name of diseases characterised by deposition of protein fibrils with a beta-sheet structure. This beta-sheet structure generates affinity of amyloid for Congo red dye and is resistant to proteolysis. The main three types of systemic amyloidosis are AA (related to underlying

  9. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Fac. de Medicina. Instituto do Coracao. Servico de Medicina Nuclear e Imagem Molecular

    2008-07-01

    Full text: Introduction: Amyloidosis is a rare disease, characterized by extracellular deposition of insoluble amyloid fibrils in organs and tissues. It may affect virtually any system, preferably heart, kidneys and liver. The cardiac involvement produces a spectrum of clinical features, usually with progressive dysfunction. Early diagnosis is important for institution of appropriate therapy. Case report: Male patient, 75 years old, with diagnosed congestive heart failure functional class III and Mobitz II second-degree atrial-ventricular block, was hospitalized for implantation of definitive cardiac pacemaker. Patient mentioned history of worsening effort dyspnoea over a one-month period, progressing to minimum effort, orthopnea, paroxysmal nocturnal dyspnoea and paroxysms of dry cough, and swelling of lower limbs. Echocardiography showed diffuse hypertrophy of left ventricle (LV), with systolic dysfunction due to diffuse hypokinesia and hyperrefringent aspect in the septum. It was questioned a cardiac infiltrating process. Cardiac amyloidosis was considered as a diagnostic hypothesis. The patient underwent a pyrophosphate-{sup 99m}Tc scintigraphy, which showed abnormal tracer uptake in the heart projection, with diffuse pattern on the left ventricle walls, compatible with the clinical suspicion cardiac amyloidosis, which was later confirmed by endomyocardial biopsy. Discussion: In this case report, the patient had clinical and other auxiliary examinations, such as electrocardiography and Doppler echocardiography, compatible with cardiac amyloidosis, which led to implementation with pyrophosphate-{sup 99m}Tc scintigraphy and later endomyocardial biopsy. Cardiac amyloidosis occurs in about half the cases of primary amyloidosis (AL) and is rare in secondary amyloidosis (AA). Its clinical presentation is polymorphic and it can be classified into four distinctive types: restrictive cardiomyopathy, systolic dysfunction, postural hypotension and conduction disorders

  10. Cardiac amyloidosis detection with pyrophosphate-99mTc scintigraphy

    International Nuclear Information System (INIS)

    Souza, D.S.F.; Ichiki, W.A.; Coura Filho, G.B.; Izaki, M.; Giorgi, M.C.P.; Soares Junior, J; Meneghetti, J.C.

    2008-01-01

    Full text: Introduction: Amyloidosis is a rare disease, characterized by extracellular deposition of insoluble amyloid fibrils in organs and tissues. It may affect virtually any system, preferably heart, kidneys and liver. The cardiac involvement produces a spectrum of clinical features, usually with progressive dysfunction. Early diagnosis is important for institution of appropriate therapy. Case report: Male patient, 75 years old, with diagnosed congestive heart failure functional class III and Mobitz II second-degree atrial-ventricular block, was hospitalized for implantation of definitive cardiac pacemaker. Patient mentioned history of worsening effort dyspnoea over a one-month period, progressing to minimum effort, orthopnea, paroxysmal nocturnal dyspnoea and paroxysms of dry cough, and swelling of lower limbs. Echocardiography showed diffuse hypertrophy of left ventricle (LV), with systolic dysfunction due to diffuse hypokinesia and hyperrefringent aspect in the septum. It was questioned a cardiac infiltrating process. Cardiac amyloidosis was considered as a diagnostic hypothesis. The patient underwent a pyrophosphate- 99m Tc scintigraphy, which showed abnormal tracer uptake in the heart projection, with diffuse pattern on the left ventricle walls, compatible with the clinical suspicion cardiac amyloidosis, which was later confirmed by endomyocardial biopsy. Discussion: In this case report, the patient had clinical and other auxiliary examinations, such as electrocardiography and Doppler echocardiography, compatible with cardiac amyloidosis, which led to implementation with pyrophosphate- 99m Tc scintigraphy and later endomyocardial biopsy. Cardiac amyloidosis occurs in about half the cases of primary amyloidosis (AL) and is rare in secondary amyloidosis (AA). Its clinical presentation is polymorphic and it can be classified into four distinctive types: restrictive cardiomyopathy, systolic dysfunction, postural hypotension and conduction disorders. Cardiac

  11. Oral purpura as the first manifestation of primary systemic amyloidosis.

    Science.gov (United States)

    McCormick, Robert Stuart; Sloan, Philip; Farr, David; Carrozzo, Marco

    2016-07-01

    Oral blood blisters and purpura are rare features of primary systemic amyloidosis (amyloid light-chain (AL) amyloidosis). We report a case in which these unusual presentations led to a diagnosis of amyloidosis, which enabled effective treatment before organ failure. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. [Amyloidosis maculosa: diagnosis in primary care].

    Science.gov (United States)

    Toribio da Pena, S R; Olmos, O; Borbujo, J; Bastos Amigo, J A; Jiménez-Sánchez, F; Alonso, A

    1990-01-01

    Amyloidosis maculosa is a clinical entity with low incidence factor in our medium, which basically affects middle-aged women. The lesion is characterised by the presence of poorly defined, hyperpigmented, brownish or greyish maculae that converge and focus basically on the upper back and shoulders, usually accompanied by pruritus. Three patients were erroneously catalogued for years as having pityriasis versicolor. Two of these patients presented a typical clinical amyloidosis maculosa, and the third presented a less common manifestation of the disease: a single, well-defined lesion in the subscapular region. We believe that the approach to the diagnosis of pityriasis versicolor with hyperpigmented lesions that do not respond to specific treatment should be revised. Although amyloidosis maculosa has a low incidence in our medium, it is an entity which should not be discarded in these cases.

  13. The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China.

    Science.gov (United States)

    Huang, Xiang-Hua; Liu, Zhi-Hong

    2016-04-01

    Amyloidosis includes a group of diseases characterized by the extracellular deposition of various fibrillary proteins that can autoaggregate in a highly abnormal fibrillary conformation. The amyloid precursor protein of systemic light-chain (AL) amyloidosis is comprised of monoclonal light chains that are due to plasma cell dyscrasia. The clinical presentation of patients with AL amyloidosis varies from patient to patient. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains. Recent advances in therapy have helped many patients with AL amyloidosis achieve hematologic and organ responses. AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The clinical presentation of AL amyloidosis is variable, and the median overall survival was found to be 36.3 months. The disease prognosis and risk stratification are linked to serialized measurement of cardiac biomarkers and free light chains. The treatment of AL amyloidosis is mainly based on chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). The use of novel agents (thalidomide, lenalidomide, and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The lack of prospective clinical trials using the current therapies is a challenge for evidence-based decision making concerning the treatment of AL amyloidosis. (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At

  14. Primary Systemic Amyloidosis Presenting as Swollen Dense Breast: A Case Report

    International Nuclear Information System (INIS)

    Lee, Byung Hoon; Kim, Mi Young; Kim, Su Young; Hwang, Yoon Joon; Han, Yoon Hee; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee

    2006-01-01

    Breast involvement of primary systemic amyloidosis is rare. This is a rare case of breast amyloidosis presenting as a diffuse infiltrative lesion. We present the mammographic, ultrasound, and MR findings of a systemic primary amyloidosis involving the breast with diffuse infiltrative pattern

  15. Dysautonomias in Amyloidosis: : Need for an interdisciplinary approach

    NARCIS (Netherlands)

    Hazenberg, B. P. C.

    2013-01-01

    Systemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary

  16. The Prevalence and Management of Systemic Amyloidosis in Western Countries.

    Science.gov (United States)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    2016-04-01

    Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secondary, and familial amyloidosis. All types of amyloid are secondary to some underlying precursor-producing process: each type is caused by a misfolded soluble precursor protein that becomes deposited as insoluble amyloid fibrils. The incidence of amyloidosis is not well documented, but probably falls between 5 and 13 per million per year. Prevalence data are scarce, but one UK study indicates about 20 per million inhabitants. Amyloidosis can be localized (amyloid deposited in the organ or tissue of precursor production) or systemic (amyloid at one or more sites distant from the site of precursor production). The major systemic types of amyloidosis are AL (associated with a light chain-producing plasma cell dyscrasia), AA (associated with longstanding inflammation), wild-type ATTR (associated with normal transthyretin and old age), and hereditary ATTR (associated with a transthyretin mutation) amyloidosis. Imaging techniques, such as cardiac ultrasound, magnetic resonance imaging, bone scintigraphy, and serum amyloid P component scintigraphy, are useful both for diagnosing amyloidosis and for assessing disease severity. Serologic markers are useful for detecting organ disease and disease monitoring during follow-up. Current treatment modalities are directed against the ongoing supply of precursor proteins and thereby aim to stop further accumulation of amyloid. Novel treatment modalities, such as interference with amyloid formation and even removal of amyloid, are being studied. A well-thought and planned monitoring during follow-up helps to assess the effect of treatment and to early detect possible progression of amyloidosis. Clinical management comprises histologic proof of amyloid

  17. Iodine-123-labelled serum amyloid P component scintigraphy in amyloidosis

    International Nuclear Information System (INIS)

    Saile, R.; Deveaux, M.; Marchandise, X.; Duquesnoy, B.

    1993-01-01

    This study describes the results of scintigraphy with iodine-123-labelled serum amyloid P component (SAP) as a means of establishing the distribution of organ involvement in amyloidosis. The significance of 123 I-SAP scans obtained in 15 patients with biopsy-proven AA or AL amyloidosis is discussed. Biopsy-proven amyloidosis was typically confirmed by scintigraphy, though such confirmation was not obtained in the kidneys in six patients with histological proof of extensive renal amyloid deposition. This lack of uptake may have been due to the accumulation of a major part of the 123 I-SAP in the spleen and/or liver. Twenty-four hour whole-body retention of 123 I-SAP was higher in patients with amyloidosis than in controls. Twenty-four hour tracer accumulation of the radioactivity in the extravascular compartment was notably greater in patients than in controls and appeared to be a good diagnostic criterion. We conclude that 123 I-SAP scintigraphy may be helpful for the evaluation of organ involvement not only in patients with biopsy-proven amyloidosis but also when a biopsy cannot be performed or when a strong suspicion of amyloidosis exists in spite of repeated negative biopsises. (orig.)

  18. AA amyloidosis complicating the hereditary periodic fever syndromes.

    Science.gov (United States)

    Lane, Thirusha; Loeffler, Jutta M; Rowczenio, Dorota M; Gilbertson, Janet A; Bybee, Alison; Russell, Tonia L; Gillmore, Julian D; Wechalekar, Ashutosh D; Hawkins, Philip N; Lachmann, Helen J

    2013-04-01

    AA amyloidosis is a life-threatening complication of the hereditary periodic fever syndromes (HPFS), which are otherwise often compatible with normal life expectancy. This study was undertaken to determine the characteristics, presentation, natural history, and response to treatment in 46 patients who had been referred for evaluation at the UK National Amyloidosis Centre. Disease activity was monitored by serial measurement of serum amyloid A. Renal function was assessed by measurement of serum creatinine and albumin levels, the estimated glomerular filtration rate, and proteinuria from 24-hour urine collections. The amyloid load was measured by serum amyloid P scintigraphy. Twenty-four patients had familial Mediterranean fever, 12 patients had tumor necrosis factor receptor-associated periodic syndrome, 6 patients had cryopyrin-associated periodic syndromes, and 4 patients had mevalonate kinase deficiency. The median age at onset of HPFS was 5 years; median age at presentation with AA amyloidosis was 38 years. Diagnosis of an HPFS had not been considered prior to presentation with AA amyloidosis in 23 patients (50%). Eleven patients (24%) had end-stage renal failure (ESRF) at presentation; of these, 3 had received transplants prior to referral. A further 13 patients developed ESRF over the followup period, with 10 undergoing renal transplantation. The median time to progression to ESRF from onset of AA amyloidosis was 3.3 years (interquartile range [IQR] 2-8), with a median time to transplant of 4 years (IQR 3-6). Eleven patients (24%) died. The median survival in the entire cohort was 19 years from diagnosis of AA amyloidosis. Of the 37 patients who were treated successfully, or in whom at least partial suppression of the underlying HPFS was achieved, 17 (46%) showed amyloid regression, 14 (38%) showed a stable amyloid load, and 2 (5%) showed increased amyloid deposition over the followup period. AA amyloidosis remains a challenging and serious late complication

  19. Primary Hepatic Amyloidosis: Report of an Unusual Case Presenting as a Mass

    International Nuclear Information System (INIS)

    Son, Rak Chae; Chang, Jae Chun; Choi, Joon Hyuk

    2011-01-01

    Hepatic involvement of amyloidosis is common. Diffuse infiltration with hepatomegaly is a usual radiologic finding of hepatic amyloidosis. To our knowledge, this is the first case of amyloidosis involving the liver that presented as a mass.

  20. SECONDARY AMYLOIDOSIS WITH LUNG INVOLVEMENT INA FEMALE PATIENT WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Irina Mikhailovna Marusenko

    2009-01-01

    Full Text Available The paper considers the problem of secondary amyloidosis that more frequently occurs in patients with various arthritides, both seropositive and seronegative. According to the data available in the literature, the most common manifestations of secondary amyloidosis are involvements of the kidney, liver, nervous system, and, less frequently, the lung. The authors describe their own observation of secondary amyloidosis in rheumatoid arthritis, which is accompanied by the involvement of the lung, kidney, and intestine, resulting in fatal outcome. The lifetime diagnosis of amyloidosis was histologically verified.

  1. Systemic amyloidosis due to unknown multiple myeloma in small bowel pseudo-obstruction: case report

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    Giuseppe Caparrotti

    2016-03-01

    Full Text Available Amyloidosis is a pathologic diagnosis characterized by extracellular deposition of insoluble protein fibrils in various organs and tissues. There are two main forms of amyloidosis, primary amyloidosis, and secondary amyloidosis. Gastrointestinal involvement is common in both amyloidosis forms. We describe the case of a 78-year-old woman taken to the operating room for small bowel obstruction, found to have pseudo-obstruction and enteritis. Exploratory laparotomy revealed gastric mass and histological examen showed extensive amyloid deposition consistent with amyloidosis. Hematological evaluation revealed unknown multiple myeloma. This case report and literature data suggest to perform a hematological examination in patients with amyloidosis diagnosis to exclude a multiple myeloma or other plasma cell disorders

  2. Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.

    Science.gov (United States)

    Halushka, Marc K; Eng, George; Collins, A Bernard; Judge, Daniel P; Semigran, Marc J; Stone, James R

    2015-06-01

    Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping.

  3. Amyloidosis diagnosed in cytology specimen of pleural effusion: A case report.

    Science.gov (United States)

    Manur, Rashmi; Lamzabi, Ihab

    2018-06-01

    Amyloidosis is a rare condition resulting from extracellular deposition of amyloid, a fibrillary material derived from various precursor proteins. Involvement of the pleura by amyloidosis is a rare but serious complication. Pleural amyloidosis is primarily diagnosed by identifying amyloid deposition by histology on pleural biopsy specimens. Hereby, we report a case of systemic amyloidosis where we were able to identify amyloid in a pleural effusion specimen sent for cytopathology evaluation. A 59-year-old male with newly diagnosed multiple myeloma and systemic amyloidosis underwent therapeutic thoracentesis. The H&E stained cell block sections revealed a single, less than one millimeter focus of waxy material surrounded by a rim of reactive mesothelial cells suspicious for amyloid deposit in a background of fibrin, lymphocytes, and reactive mesothelial cells. The focus stained salmon pink with Congo-red special stain and showed apple-green birefringence under polarized light. Our finding suggests that pleural involvement in patients with systemic amyloidosis can be identified on effusion specimens and avert the need for more invasive procedures like pleural or pulmonary parenchymal biopsies. © 2017 Wiley Periodicals, Inc.

  4. Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage

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    Bárbara Corrêa

    Full Text Available Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

  5. Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

    Directory of Open Access Journals (Sweden)

    Jinze Qian

    2010-05-01

    Full Text Available Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II deposits as amyloid fibrils (AApoAII and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(cTg(+/- and normal R1.P1-Apoa2(c mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

  6. Amyloidosis cutis dyschromica: A rare reticulate pigmentary dermatosis

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    Shyam Verma

    2015-01-01

    Full Text Available We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling-Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica.

  7. Renal amyloidosis: a synopsis of its clinical presentation, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Elena V. Zakharova

    2015-04-01

    Full Text Available Amyloidosis is a heterogeneous group of hereditary and acquired diseases in which normally soluble plasma proteins are deposited in the extracellular and/or intracellular space in abnormal, insoluble, fibrillar form. Renal damage is one of the most common features of systemic amyloidosis, and the presentation is most commonly due to the consequences of renal involvement, with proteinuria and progressive renal decline. Progression to end-stage renal failure is common. Early diagnosis of systemic amyloidosis is difficult. Renal amyloidosis typically presents with nephrotic syndrome and/or renal failure. Treatment of AL amyloidosis aims to reduce production of the monoclonal immunoglobulin precursor via chemotherapy. Current options for treatment include melphalan+dexamethasone or cyclophosphamide-bortezomib-dexamethasone regimens, or in selected patients, high-dose melphalan with autologous stem cell transplantation. The focus of current research is on pharmacological therapy to solubilize amyloid fibrils and increase tissue catabolism of amyloid deposits.

  8. Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma

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    Mihajlo Gjeorgjievski

    2015-01-01

    Full Text Available Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS, smoldering multiple myeloma (SMM, and multiple myeloma (MM. This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda- type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment.

  9. Generalised pustular psoriasis, psoriatic arthritis and nephrotic syndrome associated with systemic amyloidosis.

    Science.gov (United States)

    David, M; Abraham, D; Weinberger, A; Feuerman, E J

    1982-09-01

    The case report is presented of a psoriatic patient with arthropathy, generalised pustular psoriasis and nephrotic syndrome, in whom systemic amyloidosis developed. The literature reports 13 cases of psoriasis associated with amyloidosis, 3 of whom suffered from pustular psoriasis as does our case. With the addition of our case, 12 of these 14 had concomitant arthropathy. This seems to suggest that arthritis is an important factor in the appearance of amyloidosis. Rectal biopsy and/or renal biopsy may be helpful in establishing the diagnosis of amyloidosis relatively early in patients with psoriatic arthritis.

  10. Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis. Case report and literature review

    International Nuclear Information System (INIS)

    Luo, Ming; Peng, Gang; Shi, Liangliang; Li, Zhenyu; Fei, Shijiang; Ding, Qian; Cheng, Jing; Ming, Xing

    2016-01-01

    Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1-year follow-up. Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case. (orig.) [de

  11. Surgical management of advanced ocular adnexal amyloidosis.

    Science.gov (United States)

    Patrinely, J R; Koch, D D

    1992-06-01

    Ocular adnexal amyloidosis is characterized by amyloid deposition within the deep connective tissue layers of the eyelids, conjunctiva, and anterior orbit. Management of advanced cases has traditionally been unsatisfactory, with either no surgery offered because of fear of hemorrhage or an en bloc resection performed of the entire involved area. We present two cases of advanced periorbital amyloidosis successfully managed by preserving the anatomic planes of the eyelids and meticulously debulking the deposits with a spooned curette. Lax eyelid tendons and aponeuroses were simultaneously repaired, and no sacrifice of eyelid tissues was necessary. One patient remained asymptomatic for 2 years after surgery before developing early reaccumulation in the lower eyelids. The other patient required additional eyelid debulking and ptosis revision 8 months after surgery, but was in stable condition at follow-up 2 years after surgery. This technique offers safe, easily repeatable, nondestructive treatment for advanced periocular amyloidosis.

  12. Autologous Stem Cell Transplant for AL Amyloidosis

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    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  13. Recent Insights into the Pathogenesis of Type AA Amyloidosis

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    J. C. H. van der Hilst

    2011-01-01

    Full Text Available The amyloidoses are a group of life-threatening diseases in which fibrils made of misfolded proteins are deposited in organs and tissues. The fibrils are stable, insoluble aggregates of precursor proteins that have adopted an antiparallel β-sheet structure. In type AA, or reactive, amyloidosis, the precursor protein of the fibrils is serum amyloid A (SAA. SAA is a 104-amino-acid protein that is produced in the liver in response to proinflammatory cytokines. Although the protein that is produced by the liver contains 104 amino acids, only the N-terminal 66–76 amino acids are found in amyloid fibrils. Furthermore, SAA has been shown to have an α-helical structure primarily. Thus, for SAA to be incorporated into an amyloid fibril, two processes have to occur: C-terminal cleavage and conversion into a β-sheet. Only a minority of patients with elevated SAA levels develop amyloidosis. Factors that contribute to the risk of amyloidosis include the duration and degree of SAA elevation, polymorphisms in SAA, and the type of autoinflammatory syndrome. In the Hyper-IgD syndrome, amyloidosis is less prevalent than in the other autoinflammatory diseases. In vitro work has shown that the isoprenoid pathway influences amyloidogenesis by farnesylated proteins. Although many proteins contain domains that have a potential for self-aggregation, amyloidosis is only a very rare event. Heat shock proteins (HSPs are chaperones that assist other proteins to attain, maintain, and regain a functional conformation. In this review, recent insights into the pathogenesis of amyloidosis are discussed, in addition to a new hypothesis for a role of HSPs in the pathogenesis of type AA.

  14. Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis

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    Faust Dominik

    2009-01-01

    Full Text Available Background. Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and γ-glutamyl transferase. Case report. The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and γ-glutamyl transferase, and their general status significantly improved. Conclusion. Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

  15. Long-term follow-up after surgery in localized laryngeal amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Hazenberg, Bouke P. C.; Dikkers, Frederik G.

    2016-01-01

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence

  16. Long-term follow-up after surgery in localized laryngeal amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Aldert J. C.; Hazenberg, Bouke P. C.; Dikkers, Frederik G.

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence

  17. Frictional amyloidosis in Oman - A study of ten cases

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    Mysore Venkataram

    2002-01-01

    Full Text Available Macular amyloidosis is an important cause for cutaneous pigmentation, the aetiology of which is poorly understood. Friction has recently been implicated the causation of early lesions, referred to as frictional amyloidosis. Confirmation of diagnosis by the detect on of amyloid using histochemical stains is inconsistent. Ten patients with pigmentation suggestive of macular amyloidosis were studied with detailed history, clinical examination, biopsy for histochemistry and electron microscopy. Nine out of ten patients had a history of prolonged friction with various objects such as bath sponges, brushes, towels, plant sticks and leaves. Amyloid was demonstrated by histochemical staining in only six out of ten cases. In the remaining four cases, amyloid was detected by electron microscopy. These consisted of aggregates of non-branching, extracellular, intertwining fibres measuring between 200-500 nm in length and between 20-25 nm in diameter. The study confirms the role of friction in the causation of this condition. Histochemical stains are not always successful in the detection of amyloid and electron microscopy is helpful for confirming its presence. The term frictional amyloidosis aptly describes the condition.

  18. Inhibitory effect of propolis on the development of AA amyloidosis.

    Science.gov (United States)

    Harata, Daichi; Tsuchiya, Yuya; Miyoshi, Tomoyuki; Yanai, Tokuma; Suzuki, Kazuhiko; Murakami, Tomoaki

    2018-04-01

    In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.

  19. Lichen amyloidosis induced on the upper back by long-term friction with a nylon towel.

    Science.gov (United States)

    Yoshida, Aki; Takahashi, Kazuhiro; Tagami, Hachiro; Akasaka, Toshihide

    2009-01-01

    Primary localized cutaneous amyloidosis can take several clinical forms. In Asia, macular amyloidosis caused by prolonged friction from a rough nylon towel or brush is common, and macular amyloidosis and lichen amyloidosis occasionally occur together, as so-called biphasic amyloidosis. We report herein the case of an 83-year-old Japanese man with lichen amyloidosis caused by prolonged nylon towel friction. This patient presented with unique symmetrical papular lesions on the upper back and shoulders. Lesions comprised slightly shiny, brownish, fine uniform papules approximately 0.5 mm in diameter, showing a partially linear, annular or rippled arrangement. Although this case was caused by prolonged nylon towel friction, no coexisting macular lesions could be found. To the best of our knowledge, this represents the first case of lichen amyloidosis induced by nylon towel friction in the absence of the macular amyloidosis that is usually observed in such cases. We instructed the patient to stop the habit of nylon towel rubbing and prescribed a topical steroid ointment and cepharanthine. After 6 months of treatment, papular lesions became clearly flatter.

  20. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

    Science.gov (United States)

    Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

    2014-05-01

    Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

  1. Myocardial 99mTc-MDP uptake on the bone scintigraphy in the hemodialysis-associated amyloidosis: a case report

    International Nuclear Information System (INIS)

    Fard Esfahani, A.; Assadi, M.; Eftekhari, M.; Fallahi Sichani, B.; Beiki, D.; Akbarpour, S.; Mohammadian, M.

    2005-01-01

    Amyloidosis is characterized by an abnormal extracellular deposition of amyloid in different organs, where it usually causes some type of dysfunction. Its cause is unknown. Five different types of amyloidosis have been described according to the underlying disease; immunoglobulin amyloidosis, ,familial amyloidosis, senile systemic amyloidosis, secondary amyloidosis and hemodialysis-associated amyloidosis. We report a case of hemodialysis-associated amyloidosis in a 56-year-old man that radionuclide imaging demonstrated intense uptake of Tc-99m MDP within the myocardium. The diagnosis of amyloidosis was established by analysis of aspirated abdominal fat, although other non- invasive modalities didn't reveal any positive findings. The,first clue to the possible presence of amyloidosis in this case was provided by the radionuclide bone scan performed, which revealed intense tracer uptake in the heart suggesting amyloid deposit. We conclude that in cases of extraosseous accumulation of' Tc-99 MDP especially as a diffuse pattern of myocardial uptake, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting

  2. The Prevalence and Management of Systemic Amyloidosis in Western Countries

    NARCIS (Netherlands)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    BACKGROUND: Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary,

  3. What is the role of giant cells in AL-amyloidosis?

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Sandgren, O

    1999-01-01

    of some cases of systemic AL-amyloidosis. Based on these findings and electron microscopic studies, it is discussed whether the giant cells actively participate in amyloid fibril formation by uptake and modification of the precursor protein or the giant cells are part of a foreign body reaction. Included....... In this work it is shown that that there is a difference between localized and systemic amyloidosis in respect to accompanying giant cells which constantly are found associated with amyloid deposits in localized AL-amyloidosis. In addition, giant cells were found together with amyloid deposits in lymph nodes...

  4. Breast amyloidosis in a female patient with multiple myeloma: Ultrasonographic and mammographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Ah Rhm; Kim, Joon Mee; Nam, Se Jin [Inha University Hospital, Incheon (Korea, Republic of)

    2017-05-15

    Amyloidosis is a rare disease characterized by pathological protein deposits in organs or tissues. Breast involvement by amyloidosis is rare. We report a female patient with amyloidosis in the breast, with underlying multiple myeloma, which presents as a focal asymmetry on a screening mammogram and a low suspicious mass lesion by ultrasonography.

  5. Renal failure due to primary amyloidosis: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Ramon Andrade Bezerra de Mello

    Full Text Available CONTEXT: Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal immunoglobulin that settle in tissues in the form of insoluble amyloid fibrils. The aim of this study was to report a case of primary amyloidosis with renal failure, diagnosed in Hospital São João, Porto, Portugal, focusing on the diagnostic difficulties and presenting a literature review. CASE REPORT: A 68-year-old Caucasian man was admitted to the Internal Medicine Department of the hospital with a condition of anasarca and nephrotic syndrome. After performing a renal biopsy that tested positive using Congo red and immunohistochemistry, lambda light chain amyloidosis was diagnosed. This evolved into terminal renal disease, which led to hemodialysis and several episodes of urinary and catheter infections. He was started on chemotherapy, consisting of bortezomib 0.7 mg/m² and dexamethasone 40 mg in six cycles. This led to clinical improvement, stabilization of the illness and good tolerance of the treatment. CONCLUSION: Amyloidosis is a rare entity that is difficult to diagnose. This is because of the unspecific early clinical manifestations of the disease. The hypothesis of amyloidosis is only considered when specific organ failure occurs. This case consisted of primary amyloidosis with involvement of the kidneys as an initial presentation of the disease and its difficulties were shown, going from the clinical approach to the final diagnosis.

  6. Abdominal fat pad excisional biopsy for the diagnosis and typing of systemic amyloidosis.

    Science.gov (United States)

    Garcia, Yessica; Collins, A Bernard; Stone, James R

    2018-02-01

    In the past, the diagnosis and typing of amyloidosis often required an invasive biopsy of an internal organ, such as the heart or kidneys. Abdominal fat pad excisional biopsy (FPEB) offers a less invasive approach, but the sensitivity of this technique has been unclear. To determine the sensitivity of FPEB for immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, we performed a retrospective clinicopathologic analysis of 97 patients who had undergone FPEB, of which 16 were positive for amyloid. The most significant pretest feature predicting a positive FPEB was a serum free light chain κ/λ ratio less than .5, and in this group of patients the probability of a positive biopsy was dependent on the size of the biopsy (P=.004). In FPEBs, the amyloid was present in multiple distinct patterns: pericellular, septal, medium-sized vessel, small vessel, and nodular. For patients with AL amyloidosis for which direct typing was attempted using the FPEB tissue, the amyloid was successfully typed in the FPEB in 90% of cases. The overall sensitivity of FPEB was 79% for AL amyloidosis and 12% for ATTR amyloidosis (P=.0003). In patients with AL amyloidosis, the sensitivity of FPEB was dependent on biopsy size, with small biopsies (≤700 mm 3 ) having a sensitivity of ~50%, and large biopsies (>700 mm 3 ) having a sensitivity of ~100%. This study demonstrates that FPEB has high sensitivity for AL amyloidosis, and can be routinely used to type the amyloid. However, FPEB has low sensitivity for ATTR amyloidosis in our patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Clinical outcomes and survival in AA amyloidosis patients

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    Yavuz Ayar

    Full Text Available Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6% had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2% and rheumatoid arthritis (10.6% in the good outcome group and malignancy (20% in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively. Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006 and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027 were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted

  8. Ventricular fibrillation after bortezomib therapy in a patient with systemic amyloidosis

    Directory of Open Access Journals (Sweden)

    Satoshi Yamasaki

    2013-09-01

    Full Text Available A 64-year-old female was diagnosed with systemic amyloidosis associated with multiple myeloma. Bortezomib and dexamethasone-therapy was initiated; however, she developed lethal ventricular fibrillation (VF and cardiac arrest after 84 hours of therapy. Cardiopulmonary resuscitation using direct current shocks with epinephrine and amiodarone was initiated but failed to receive cardiac function. Although her arterial pulsations recovered immediately after the injection of vasopressin, she died of heart failure 8 hours after the onset of VF. Cardiac amyloidosis was verified by autopsy. Although the direct association of bortezomib with lethal VF remained to be clarified in our patient, the current report emphasizes on bortezomib as a substantial risk factor for cardiomyocyte damage. The potential risk of lethal events associated with cardiac amyloidosis should be carefully considered during bortezomib treatment for patients with AL amyloidosis.

  9. Systemic AA amyloidosis in the red fox (Vulpes vulpes).

    Science.gov (United States)

    Rising, Anna; Cederlund, Ella; Palmberg, Carina; Uhlhorn, Henrik; Gaunitz, Stefan; Nordling, Kerstin; Ågren, Erik; Ihse, Elisabet; Westermark, Gunilla T; Tjernberg, Lars; Jörnvall, Hans; Johansson, Jan; Westermark, Per

    2017-11-01

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model. © 2017 The Protein Society.

  10. Efficacy of etanercept in patients with AA amyloidosis secondary to rheumatoid arthritis.

    Science.gov (United States)

    Nakamura, T; Higashi, S; Tomoda, K; Tsukano, M; Baba, S

    2007-01-01

    The efficacy of biological therapies in rheumatoid arthritis (RA) is well known, but their hypothetical benefit in amyloid A (AA) amyloidosis secondary to RA still remains to be considered. We evaluated the efficacy and safety of etanercept in serum amyloid A (SAA) 1.3 allele Japanese patients with AA amyloidosis secondary to RA. Seven RA patients with histologically confirmed AA amyloidosis and renal involvement who were treated with etanercept were enrolled. They all had the SAA1.3 allele, which has been shown to be a risk factor not only for the association of AA amyloidosis but also for a poor prognosis in Japanese RA patients. Efficacy was assessed as a sustained decrease in RA inflammation and an amelioration of renal function. RA inflammation and AA amyloidosis were improved and stabilized after 43.4 +/- 16.5 weeks. At week 20 the number of tender (p = 0.017) and swollen (p = 0.017) joints, and levels of serum C-reactive protein (p = 0.018) and albumin (p = 0.045) had improved. The values for SAA, serum creatinine, calculated creatinine clearance, and proteinuria also ameliorated. No severe adverse events were observed. One patient eventually had to go on hemodialysis but her tolerance of etanercept remained stable. Etanercept can be used safely and effectively in AA amyloidosis secondary to RA with renal involvement, and is of clinical benefit in the short-term, even in patients on hemodialysis. It appears that SAA1.3 allele may be used as a clinical parameter for the introduction of etanercept in Japanese RA with AA amyloidosis.

  11. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease

    Science.gov (United States)

    Zhang, Beiru; Une, Yumi; Fu, Xiaoying; Yan, Jingmin; Ge, FengXia; Yao, Junjie; Sawashita, Jinko; Mori, Masayuki; Tomozawa, Hiroshi; Kametani, Fuyuki; Higuchi, Keiichi

    2008-01-01

    AA amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, but little is known about the underlying mechanisms. Given the transmissible characteristics of AA amyloidosis, transmission between captive cheetahs may be a possible mechanism involved in the high incidence of AA amyloidosis. In this study of animals with AA amyloidosis, we found that cheetah feces contained AA amyloid fibrils that were different from those of the liver with regard to molecular weight and shape and had greater transmissibility. The infectious activity of fecal AA amyloid fibrils was reduced or abolished by the protein denaturants 6 M guanidine·HCl and formic acid or by AA immunodepletion. Thus, we propose that feces are a vehicle of transmission that may accelerate AA amyloidosis in captive cheetah populations. These results provide a pathogenesis for AA amyloidosis and suggest possible measures for rescuing cheetahs from extinction. PMID:18474855

  12. Amyloidosis Associated with Neoplastic Diseases

    African Journals Online (AJOL)

    1974-09-21

    Sep 21, 1974 ... adrenals, pancreas, a salivary gland, in a small scar in the myocardium, and in .... Biopsy specimens obtained through colonoscopy de- monstrated the ... cancer, found amyloidosis in 16, establishing an in- cidence of 0,4%.

  13. Isolated Light Chain Amyloidosis Involving the Parotid Gland: A Case Report.

    Science.gov (United States)

    Gareb, Barzi; Perry, Michael; Tadrous, Paul Joseph

    2018-03-08

    Amyloidosis in the parotid gland is rare and is usually associated with systemic amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. We present a case of localized light chain amyloidosis of the parotid gland without systemic involvement. A 70-year-old woman presented with an asymptomatic swelling of the right parotid region. The findings of a physical examination, hematologic and biochemical investigations, imaging, and cytology were inconclusive. The patient underwent an extracapsular dissection of the right parotid gland. Histologic analysis showed that the tissue of the right parotid gland mostly consisted of amyloid deposition. The amyloid stained with antibodies to lambda light chains. Additional investigations showed no systemic involvement. The patient is asymptomatic 5 months after surgery. Clinicians should be aware of the possibility of localized amyloid light chain amyloidosis in the parotid gland, especially if magnetic resonance imaging, computed tomography imaging, and ultrasound findings are inconclusive, and they should recognize, evaluate, and treat it accordingly. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. All rights reserved.

  14. Long-term mortality outcome in patients with reactive amyloidosis associated with rheumatoid arthritis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Harada, Takashi; Murakami, Syuichi; Hasegawa, Hisashi; Sakatsume, Minoru; Nakano, Masaaki; Gejyo, Fumitake

    2006-07-01

    It is well established that amyloidosis is a serious clinical complication that can influence the prognosis of patients with rheumatoid arthritis (RA). The purpose of the study was to obtain information on the survival and the hemodialysis (HD) of patients with amyloidosis. Eighty patients (9 men and 71 women) who were diagnosed with amyloidosis by biopsy and definite or classical RA were studied retrospectively. The average duration of RA prior to the diagnosis of amyloidosis was 15.4+/-9.4 years. The average period from the diagnosis of amyloidosis to death was 67.4 months. Forty-nine patients died of the disease (32 cases with HD and 17 cases without HD). Thirty-one patients lived (7 cases with HD and 24 cases without HD). Regarding the survival of these patients, 49 (61.3%) of the 80 patients have died. Survival rate at 28 months was 75%; at 67 months, it was 50%; and at 111 months, it was down to 25%. Mortality rate was 11.9% per year. Survival rate in dialysis at 9.8 months was 75%; at 60.6 months, it dropped to 50%; and at 100.0 months, to 25%. As for patients' survival, high onset age of amyloidosis was the major determining factor for poor survival in these patients (ppatients also had poor survival (p=0.07). The long-term results were very encouraging to initiate HD in patients with end-stage renal disease due to reactive amyloidosis associated with RA.

  15. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Directory of Open Access Journals (Sweden)

    Ling-Chao Meng

    2015-01-01

    Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

  16. [Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

    Science.gov (United States)

    Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

    2003-01-01

    The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

  17. Diagnosis of secondary amyloidosis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Lupetti, Pietro; Perfetto, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2014-09-26

    Alkaptonuria (AKU) is an inborn error of catabolism due to a deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a severe arthropathy, cardiovascular and kidney disease but other organs are affected, too. We found secondary amyloidosis as a life-threatening complication in AKU, thus opening new perspectives for its treatment. We proved that methotrexate and anti-oxidants have an excellent efficacy to inhibit the production of amyloid in AKU model chondrocytes. Owing to the progressive and intractable condition, it seems important to detect amyloid deposits at an early phase in AKU and the choice of specimens for a correct diagnosis is crucial. Ten AKU subjects were examined for amyloidosis; abdominal fat pad aspirates, labial salivary gland, cartilage and synovia specimens were analysed by CR, Th-T, IF, TEM. Amyloid was detected in only one abdominal fat pad specimen. However, all subjects demonstrated amyloid deposition in salivary glands and in other organ biopsies, indicating salivary gland as the ideal specimen for early amyloid detection in AKU. This is, at the best of our knowledge, the first report providing correct indications on the diagnosis of amyloidosis in AKU, thus offering the possibility of treatment of such co-morbidity to AKU patients. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_185.

  18. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics.

    Science.gov (United States)

    Vrana, Julie A; Theis, Jason D; Dasari, Surendra; Mereuta, Oana M; Dispenzieri, Angela; Zeldenrust, Steven R; Gertz, Morie A; Kurtin, Paul J; Grogg, Karen L; Dogan, Ahmet

    2014-07-01

    Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. Copyright© Ferrata Storti Foundation.

  19. Outcomes after Bronchoscopic Procedures for Primary Tracheobronchial Amyloidosis: Retrospective Study of 6 Cases

    Directory of Open Access Journals (Sweden)

    Ihsan Alloubi

    2012-01-01

    Full Text Available Respiratory amyloidosis is a rare disease which refers to localized aberrant extracellular protein deposits within the airways. Tracheobronchial amyloidosis (TBA refers to the deposition of localized amyloid deposits within the upper airways. Treatments have historically focused on bronchoscopic techniques including debridement, laser ablation, balloon dilation, and stent placement. We present the outcomes after rigid bronchoscopy to remove the amyloid protein causing the airway obstruction in 6 cases of tracheobronchial amyloidosis. This is the first report of primary diffuse tracheobronchial amyloidosis in our department; clinical features, in addition to therapy in the treatment of TBA, are reviewed. This paper shows that, in patients with TBA causing airway obstruction, excellent results can be obtained with rigid bronchoscopy and stenting of the obstructing lesion.

  20. Outcomes after bronchoscopic procedures for primary tracheobronchial amyloidosis: retrospective study of 6 cases.

    Science.gov (United States)

    Alloubi, Ihsan; Thumerel, Matthieu; Bégueret, Hugues; Baste, Jean-Marc; Velly, Jean-François; Jougon, Jacques

    2012-01-01

    Respiratory amyloidosis is a rare disease which refers to localized aberrant extracellular protein deposits within the airways. Tracheobronchial amyloidosis (TBA) refers to the deposition of localized amyloid deposits within the upper airways. Treatments have historically focused on bronchoscopic techniques including debridement, laser ablation, balloon dilation, and stent placement. We present the outcomes after rigid bronchoscopy to remove the amyloid protein causing the airway obstruction in 6 cases of tracheobronchial amyloidosis. This is the first report of primary diffuse tracheobronchial amyloidosis in our department; clinical features, in addition to therapy in the treatment of TBA, are reviewed. This paper shows that, in patients with TBA causing airway obstruction, excellent results can be obtained with rigid bronchoscopy and stenting of the obstructing lesion.

  1. Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanya L. Poshusta

    2013-11-01

    Full Text Available Light chain (AL amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.

  2. Symptomatic Primary (AL Amyloidosis of the Stomach and Duodenum

    Directory of Open Access Journals (Sweden)

    Reidar Fossmark

    2013-01-01

    Full Text Available Primary (AL amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.

  3. Cancer-testis antigen expression and immunogenicity in AL amyloidosis

    International Nuclear Information System (INIS)

    Rosenzweig, M A; Landau, H; Seldin, D; O'Hara, C; Girnius, S; Hanson, N; Frosina, D; Sedrak, C; Arcila, M; Comenzo, R L; Giralt, S; Gnjatic, S; Jungbluth, A A; Koehne, G

    2012-01-01

    Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted

  4. Evaluation of 61 Secondary Amyloidosis Patients: A Single-Center Experience from Turkey

    Directory of Open Access Journals (Sweden)

    Can Huzmeli

    2016-09-01

    Full Text Available Aim: To evaluate demographic,clinical and laboratory characteristics, causes, MEFV gene mutations, and mortality rates of patients with secondary amyloidosis. Material and Method: 61 patients who had been diagnosed with secondary amyloidosis by renal and rectal biopsy between 2007 and 2013 in the nephrology clinic of Cumhuriyet University, Faculty of Medicine, were included in the study. Demographic characteristics, causes of secondary amyloidosis, MEFV gene mutations, end-stage renal failure (ESRF, renal transplantation, and mortality rates were examined retrospectively. Results: In etiological terms, Familial Mediterranean Fever (FMF occurrence was 62.2% (38, bronchiectasis and emphysema 9.8% (6, tuberculosis 4.9% (3, coexistence of FMF and ankylosing spondylitis 3.2% (2, coexistence of FMF and rheumatoid arthritis 1.6% (1, coexistence of FMF and systemic lupus erythematosus (SLE 1.6% (1, osteomyelitis 1.6% (1, septic arthritis 1.6% (1, Crohn%u2019s disease 1.6% (1, colon cancer 1.6% (1, coexistence of bronchiectasis and tuberculosis 1.6% (1, rheumatoid arthritis 1.6% (1, and idiopathic cases 6.5% (4. Proteinuria was determined at nephrotic level among 68% (32 of 47 patients who had secondary amyloidosis. MEFV gene mutation of 45 patients with secondary amyloidosis was assessed. Most patients had M694V gene mutation. Surprisingly, we detected heterozygous E148Q mutation in 3 cases. 12 cases died; of these, 9 had ESRF. Five cases with ESRF underwent renal transplantation. Discussion: We found FMF as the most common cause for secondary AA amyloidosis in this study. Further studies should be done with larger or multicenter cohorts.

  5. Senile amyloidosis and neuron binding antibody in the aging Syrian hamster

    International Nuclear Information System (INIS)

    Blumenthal, H.T.; Musacchia, X.J.

    1985-01-01

    The effects of age, sex, and irradiation on the genesis of amyloidosis, neuron-binding antibody (NBA), and the concomitant appearance of these two phenomena were studied in a colony of Syrian hamsters. In nonirradiated controls amyloidosis increased in prevalence with age after 12 months, and prevalence was higher in females than in males. Irradiation had the effect of advancing the appearance of amyloidosis to the 7-12 months group but did not intensify the amyloidotic process. IgG binding to the nucleus or cytoplasm of neurons was rare, and, despite the fact that IgM and IgA binding to these structures was present in about one-third of the animals, there was neither an aging nor an irradiation effect. The only statistically significant findings with respect to the concomitant occurrence of amyloid and NBA were negative correlations between nuclear IgM and IgA binding and amyloidosis. Of the various species thus far studied, the hamster is the first in which there has been no aging effect in respect to NBA

  6. Purpuric halo around hemangioma as a clue for primary systemic amyloidosis: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yin-Shuo Chang

    2018-03-01

    Full Text Available Mucocutaneous lesion appears in up to 40% of patients with primary systemic amyloidosis (AL amyloidosis. The cutaneous signs may be co-expressed with other organ involvement or even solely presented as the first clue. We reported a case of systemic AL amyloidosis who was initially presented as a solitary hemangioma with a purpuric halo. Excisional biopsy revealed a hemangioma with amyloid deposited in thickened vascular walls. Systemic AL amyloidosis was diagnosed after thorough survey. The stage of disease at the time of initial treatment is the greatest prognostic factor. To our knowledge, this is the first case of systemic AL amyloidosis initially presented as a purpuric halo around hemangioma in Taiwan. This target-like lesion should be linked to systemic AL amyloidosis and early diagnosis is extraordinary important.

  7. Long-term TNF-alpha blockade in patients with amyloid A amyloidosis complicating rheumatic diseases.

    Science.gov (United States)

    Fernández-Nebro, Antonio; Olivé, Alejandro; Castro, María Carmen; Varela, Angela Herranz; Riera, Elena; Irigoyen, Maria V; García de Yébenes, María Jesús; García-Vicuña, Rosario

    2010-05-01

    To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection. Copyright 2010 Elsevier Inc. All rights reserved.

  8. A Concise Review of Amyloidosis in Animals

    Directory of Open Access Journals (Sweden)

    Moges Woldemeskel

    2012-01-01

    Full Text Available Amyloidosis refers to a group of protein misfolding diseases characterized by deposition of a particular amyloid protein in various organs and tissues of animals and humans. Various types and clinical forms of amyloidosis, in which the pathology and pathogenesis is diverse depending upon the underlying causes and species affected, are reported in domestic and wild animals. The clinical findings are also quite variable consequent to the variation of the tissues and organs involved and the extent of functional disruption of the affected organs in various animal species. The affected organs may be enlarged and exhibit variable pallor grossly, or the amyloid deposit may be discernible only after microscopic examination of the affected tissues. Amyloid appears as a pale eosinophilic homogenous extracellular deposit in tissues. However, microscopic examination and Congo red staining with green birefringence under polarized light are needed to confirm amyloid and differentiate it from other apparently similar extracellular deposits such as collagen and fibrin. Identifying the type of amyloid deposit needs immunohistochemical staining, ultrastructural characterization of the amyloid fibril, and if feasible also genetic studies of the involved species for clinical and prognostic purposes. This paper provides a concise review of the occurrence of amyloidosis in domestic and wild animals.

  9. Renal amyloidosis in a child with sickle cell anemia.

    Science.gov (United States)

    Simşek, Behçet; Bayazit, Aysun K; Ergin, Melek; Soran, Mustafa; Dursun, Hasan; Kilinc, Yurdanur

    2006-06-01

    The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

  10. Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

    Science.gov (United States)

    Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

    2006-08-01

    We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

  11. {sup 18}F-FDG PET/CT in Primary AL Hepatic Amyloidosis Associated with Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Son, Youn Mi; Bak, Cheol Hee [Seoul Medical Center, Seoul (Korea, Republic of); Choi, Joon Young; Cheon, Mi Ju; Kim, Young Eun; Lee, Kyung Han; Kim, Byung Tae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-10-15

    We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased {sup 18}F-FDG uptake in the liver. Although there have been several case studies showing positive {sup 18}F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the {sup 18}F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously.

  12. {sup 123}I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Noordzij, Walter; Glaudemans, Andor W.J.M.; Rheenen, Ronald W.J. van; Dierckx, Rudi A.J.O.; Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Hazenberg, Bouke P.C. [University of Groningen, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands)

    2012-10-15

    Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. {sup 123}I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and {sup 123}I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 {+-} 0.75, and the mean wash-out rate was 8.6 {+-} 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 {+-} 0.70 versus 2.8 {+-} 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 {+-} 9.9 % vs. 17 {+-} 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 {+-} 0.59 vs. 2.9 {+-} 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, {sup 123}I-MIBG scintigraphy can detect cardiac denervation in

  13. Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

    Science.gov (United States)

    McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

    2013-12-17

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

  14. Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

    Science.gov (United States)

    Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

    2018-02-23

    Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; Pvalue in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

  15. 18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

    Directory of Open Access Journals (Sweden)

    Tawada A

    2014-06-01

    Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

  16. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January

  17. Silicone Stent Placement for Primary Tracheal Amyloidosis Accompanied by Cartilage Destruction

    OpenAIRE

    Ryu, Duck Hyun; Eom, Jung Seop; Jeong, Ho Jung; Kim, Jung Hoon; Lee, Ji Eun; Jun, Ji Eun; Song, Dae Hyun; Han, Joungho; Kim, Hojoong

    2014-01-01

    Primary tracheal amyloidosis (PTA) can lead to airway obstructions, and patients with severe PTA should undergo bronchoscopic interventions in order to maintain airway patency. Focal airway involvements with amyloidosis can only be treated with mechanical dilatation. However, the PTA with diffused airway involvements and concomitant cartilage destructions requires stent placement. Limited information regarding the usefulness of silicone stents in patients with PTA has been released. Therefore...

  18. Primary localized amyloidosis of the eyelid

    DEFF Research Database (Denmark)

    Olsen, K E; Sandgren, O; Sletten, K

    1996-01-01

    Primary localized amyloidosis has been described in many different organs in the body. Studies by immunohistochemical techniques have suggested an immunoglobulin light chain origin of the amyloid material. Only in a limited number of cases has the amyloid protein been characterized by amino acid...

  19. Anxiety and depression among amyloid light-chain cardiac amyloidosis patients: The role of life satisfaction.

    Science.gov (United States)

    Smorti, Martina; Guarnieri, Silvia; Bergesio, Franco; Perfetto, Federico; Cappelli, Francesco

    2016-06-01

    The present study aimed to provide a contribution to the study of a rare disease, amyloid light-chain (AL) cardiac amyloidosis, which is the most common type of systemic amyloidosis. In AL amyloidosis prognosis is determined by cardiac involvement. Although the association between psychological distress (e.g. anxiety and depression) and AL cardiac amyloidosis is documented, very little is known about the psychosocial variables that may mediate the association. The aim of the study is therefore to examine the potential mediating role of life satisfaction in the relationship between cardiac symptom severity (independent variable) and anxious and depressive symptoms (dependent variables) in AL patients. Forty-three AL amyloidosis patients (57.1% males) with cardiac amyloidosis were administered the Satisfaction with Life Scale, the State-Trait Anxiety Inventory and the Centre for Epidemiological Study-Depression Scale. Clinical variables such as months since cardiac symptom onset and cardiac symptom severity were collected. Findings showed significant relationships between symptom severity and psychological disorders (e.g. anxiety and depression) and these were mediated by life satisfaction. Overall, findings highlight the importance of subjective well-being (e.g. life satisfaction) to reduce anxious and depressive symptoms and to improve general health in AL patients. © The European Society of Cardiology 2015.

  20. AL Amyloidosis Complicated by Persistent Oral Bleeding

    Directory of Open Access Journals (Sweden)

    Luiz Antonio Liarte Marconcini

    2015-01-01

    Full Text Available A case of amyloid light chain (AL amyloidosis is presented here with uncontrolled bleeding after a nonsurgical dental procedure, most likely multifactorial in nature, and consequently treated with a multidisciplinary approach.

  1. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

  2. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy

    Directory of Open Access Journals (Sweden)

    Terry Golombick

    2015-01-01

    Full Text Available Multiple myeloma (MM, smoldering myeloma (SMM, and monoclonal gammopathy of undetermined significance (MGUS represent a spectrum of plasma cell dyscrasias (PCDs. Immunoglobulin light chain amyloidosis (AL falls within the spectrum of these diseases and has a mortality rate of more than 80% within 2 years of diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical benefit in some patients with PCDs. In addition to a clinical benefit in these patients, curcumin has been found to have a strong affinity for fibrillar amyloid proteins. We thus administered curcumin to a patient with laryngeal amyloidosis and smoldering myeloma and found that the patient has shown a lack of progression of his disease for a period of five years. This is in keeping with our previous findings of clinical benefits of curcumin in patients with plasma cell dyscrasias. We recommend further evaluation of curcumin in patients with primary AL amyloidosis.

  3. Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre.

    Science.gov (United States)

    Lane, Thirusha; Pinney, Jennifer H; Gilbertson, Janet A; Hutt, David F; Rowczenio, Dorota M; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Youngstein, Taryn; Quarta, Candida C; Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N; Lachmann, Helen J

    2017-09-01

    Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre. We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990-1997; C2: 1998-2006; C3: 2007-2014. Mean age at presentation increased from 46 in C1 to 56 in C3 (p AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.

  4. Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein

    Directory of Open Access Journals (Sweden)

    Dorota Rowczenio

    2017-05-01

    Discussion: We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.

  5. Amyloidosis involving the respiratory system: 5-year′s experience of a multi-disciplinary group′s activity

    Directory of Open Access Journals (Sweden)

    Raffaele Scala

    2015-01-01

    Full Text Available Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients′ clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma. It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

  6. Light-chain amyloidosis presenting with rapidly progressive submucosal hemorrhage of the stomach

    Directory of Open Access Journals (Sweden)

    Song-Yi Kim

    2016-04-01

    Full Text Available The gastrointestinal tract is frequently in involved light-chain (AL amyloidosis, but significant hemorrhagic complications are rare. A 71-year-old man presented to our hospital with dyspepsia and heartburn for 1 month. Gastroscopy revealed a large submucosal hematoma at the gastric fundus. Two days later, a follow-up gastroscopy indicated extensive expansion of the hematoma throughout the upper half of the stomach. The hematoma displayed ongoing expansion during the endoscopic examination, suggesting that rupture was imminent. Emergency total gastrectomy was performed, and amyloidosis was confirmed after examining the surgical specimen. Bone marrow examination revealed multiple myeloma, and serum immunoglobulin assay confirmed the diagnosis of myeloma-associated AL amyloidosis. At manuscript submission, the patient was doing well and was undergoing chemotherapy.

  7. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

    2014-01-01

    BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (Mit...... the ETBR mRNA and protein levels. It also significantly reduced the ETBR mediated cerebrovascular contractility. Detailed analysis indicated that ERK1/2 mediated phosphorylation of Sp1 might be essential for ETBR transcription. CONCLUSION: Transcription factor Sp1 regulates the ETBR mediated...

  8. Revisiting renal amyloidosis with clinicopathological characteristics, grading, and scoring: A single-institutional experience.

    Science.gov (United States)

    Kalle, Abhiram; Gudipati, Archana; Raju, Sree Bhushan; Kalidindi, Karthik; Guditi, Swarnalatha; Taduri, Gangadhar; Uppin, Megha S

    2018-01-01

    Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017. Light microscopic analysis; Congo red with polarization; IF; IHC for Amyloid A, kappa, and lambda; and bone marrow evaluation were done. Classification of glomerular amyloid deposition and scoring and grading are done as per the guidelines of Sen S et al . There are 40 cases of biopsy-proven renal amyloidosis with 12 primary and 23 secondary cases. Mean age at presentation was 42.5 years. Edema was the most common presenting feature. Secondary amyloidosis cases were predominant. Tuberculosis was the most common secondary cause. Multiple myeloma was detected in four primary cases. Grading of renal biopsy features showed a good correlation with the class of glomerular involvement. Clinical history, IF, and IHC are essential in amyloid typing. Grading helps provide a subtle guide regarding the severity of disease in the background of a wide range of morphological features and biochemical values. Typing of amyloid is also essential for choosing the appropriate treatment.

  9. MRI of pathology-proven peripheral nerve amyloidosis

    International Nuclear Information System (INIS)

    McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D.

    2017-01-01

    To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

  10. MRI of pathology-proven peripheral nerve amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D. [Mayo Clinic, Department of Musculoskeletal Radiology, Rochester, MN (United States)

    2017-01-15

    To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

  11. Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Hasegawa, Eriko; Wakamatsu, Ayako; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Ito, Yumi; Imai, Naofumi; Ueno, Mitsuhiro; Nakano, Masaaki; Narita, Ichiei

    2017-06-01

    The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log 10 %amyloid). The results of sex-, age-, and Log 10 %amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and

  12. Guideline of transthyretin-related hereditary amyloidosis for clinicians

    Directory of Open Access Journals (Sweden)

    Ando Yukio

    2013-02-01

    Full Text Available Abstract Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis—and, specifically, familial amyloidotic polyneuropathy—so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials.

  13. MRI in cardiac sarcoidosis and amyloidosis; MRT bei kardialer Sarkoidose und Amyloidose

    Energy Technology Data Exchange (ETDEWEB)

    Bauner, K.U. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Wintersperger, B. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

    2013-01-15

    Sarcoidosis and amyloidosis are both multisystem disorders, which may involve the heart; however, isolated cardiac disease is rare. Diagnosis of cardiac sarcoidosis and amyloidosis is crucial because the patient prognosis is dependent on cardiac involvement and early treatment. Echocardiography is the first line imaging modality in the diagnostic work-up of both diseases, possibly giving hints towards the correct diagnosis. Besides myocardial biopsy and radionuclide studies cardiac magnetic resonance imaging (MRI) is routinely performed in patients suspect of having infiltrative cardiomyopathy. The T1 mapping procedure is currently being evaluated as a new technique for detection and quantification of global myocardial enhancement, as seen in cardiac amyloidosis. Sensitivities and specificities for detection of cardiac sarcoidosis and amyloidosis can be significantly improved by MRI, especially with late gadolinium enhancement (LGE) imaging. In cardiac sarcoidosis the use of LGE is outcome-related while in amyloidosis analysis of T1-mapping may be of prognostic value. If cardiac involvement in sarcoidosis or amyloidosis is suspected cardiac MRI including LGE should be performed for establishing the diagnosis. (orig.) [German] Die Sarkoidose und Amyloidose sind Multisystemerkrankungen, in deren Verlauf es zu einer kardialen Beteiligung kommen kann. Bildgebend wird als primaeres Verfahren die Echokardiographie eingesetzt. Zur weiteren Diagnostik wird neben der Biopsie und nuklearmedizinischen Verfahren v. a. die MRT herangezogen. Als neuere Technik zur Darstellung globaler diffuser Kontrastmittelanreicherungen, wie sie im Rahmen der Amyloidose vorkommen, wird z. Z. das T1-Mapping evaluiert. Durch den Einsatz der MRT, insbesondere des Late-Gadolinium-Enhancements (LGE), koennen die Sensitivitaet und Spezifitaet in der Diagnostik der kardialen Sarkoidose und Amyloidose entscheidend verbessert werden. Bei der Sarkoidose stellt das Vorhandensein eines LGE einen

  14. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  15. Cardiac amyloidosis

    International Nuclear Information System (INIS)

    Marin, Jorge E; Duque, Mauricio; Medina, Luis E; Uribe, William; Velasquez, Jorge E

    2005-01-01

    Amyloidosis is an infiltrative systemic disease that may involve the heart. it has a genetic etiology and is an important cause of restrictive cardiomyopathy. It may involve all heart structures but has a great affinity for myocardial tissue. Diastolic dysfunction is the most early and frequent manifestation, although due to myocardial infiltration, it may progress to systolic dysfunction, resulting in a rigid heart syndrome. There is also an involvement of the conducting system. The condition may be suspected in any patient with cardiomegalia of unexplained cause. Among the diagnostic tools, the voltage/mass relation may be kept in mind. endomyocardial biopsy is useful although it is not always positive through histological verification. The treatment consists of supportive measures and selected cases may benefit with hepatic transplantation

  16. Profile of renal AA amyloidosis in older and younger individuals: a single-centre experience.

    Science.gov (United States)

    Erdogmus, Siyar; Kendi Celebi, Zeynep; Akturk, Serkan; Kumru, Gizem; Duman, Neval; Ates, Kenan; Erturk, Sehsuvar; Nergizoglu, Gokhan; Kutlay, Sim; Sengul, Sule; Keven, Kenan

    2018-05-18

    In epidemiological studies of amyloid A (AA) amyloidosis from Turkey, the most frequently cause was familial Mediterranean fever (FMF) and it occurs generally in young age population. However, there are no sufficient data regarding aetiology, clinical presentation and prognosis of renal AA amyloidosis in advanced age patients. In this study, we aimed to investigate demographic, clinical presentation, aetiology and outcomes of adults aged 60 years or older patients with biopsy-proven renal AA amyloidosis. This is a retrospective study involving 53 patients who were diagnosed with AA amyloidosis by kidney biopsy from 2006 to 2016. In all patients, kidney biopsies were performed due to asymptomatic proteinuria, nephrotic syndrome and/or renal insufficiency. The patients were separated into two groups on the basis of age (group I: ≥60 years and group II: AA amyloidosis were as follows: FMF 16 (50%), bronchiectasis 7 (23%), chronic osteomyelitis 2 (6%), inflammatory bowel disease 2 (6%), rheumatoid arthritis 2 (6%), ankylosing spondylitis 1 (3%) and unknown aetiology 2 (6%). The underlying disorders of AA amyloidosis in group II patients were as follows: FMF 17 (81%), Behcet's disease 1 (5%) and unknown aetiology 3 (14%). No statistically significant differences were detected between two groups with regard to systolic and diastolic blood pressures, albumin, proteinuria and lipids. The combination of chronic kidney disease and nephrotic syndrome was the most common clinical presentation in group I (73%) and group II (43%) (p = .05). Compared to the group II, estimated glomerular filtration rate was significantly lower in group I at the time of kidney biopsy (p = .003). At 12-month follow-up, 61% of the group I and 33% of the group II developed end-stage kidney disease requiring dialysis, while 11% of the group I died. Our results indicated that renal AA amyloidosis is a rare disease in advanced age patients. At baseline and follow-up period, advanced age

  17. Anakinra induces complete remission of nephrotic syndrome in a patient with familial mediterranean fever and amyloidosis.

    Science.gov (United States)

    Sevillano, Ángel M; Hernandez, Eduardo; Gonzalez, Esther; Mateo, Isabel; Gutierrez, Eduardo; Morales, Enrique; Praga, Manuel

    2016-01-01

    Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1β inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Cemal Selçuk İşoğlu

    2015-06-01

    Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

  19. Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis.

    Science.gov (United States)

    Rowczenio, Dorota; Tennent, Glenys A; Gilbertson, Janet; Lachmann, Helen J; Hutt, David F; Bybee, Alison; Hawkins, Philip N; Gillmore, Julian D

    2014-12-01

    The clinical features of hereditary gelsolin (AGel) amyloidosis include corneal lattice dystrophy, distal sensorimotor, cranial neuropathy and cutis laxa. To date, four mutations of the gelsolin (GSN) gene encoding the following variants have been identified as the cause of this malady; p.D214N, p.D214Y, p.G194R and p.N211K (this nomenclature includes the 27-residue signal peptide). Interestingly, the latter two variants are associated exclusively with a renal amyloidosis phenotype. Here we report the clinical features in 10 patients with AGel amyloidosis associated with the p.D214N mutation, all of whom underwent whole body (123)I-SAP scintigraphy and were followed up in a single UK Centre for a prolonged period. Two patients, from the same kindred presented with proteinuria; eight subjects had a characteristic AGel amyloidosis phenotype including cranial neuropathy and/or corneal lattice dystrophy. (123)I-SAP scintigraphy revealed substantial renal amyloid deposits in all 10 patients, including those with preserved renal function, and usually without tracer uptake into other visceral organs. (123)I-SAP scintigraphy is a non-invasive technique that aids early diagnosis of patients with this rare disease, especially those who lack a family history and/or present with an unusual clinical phenotype.

  20. Laryngeal amyloidosis with laryngocele: MRI and CT

    International Nuclear Information System (INIS)

    Arslan, A.; Ceylan, N.; Cetin, A.; Demirci, A.

    1998-01-01

    A case of laryngeal amyloidosis associated with a laryngocele is reported. Preoperative CT showed diffuse thickening of the epiglottis, aryepiglottic folds and false vocal cords with well-defined calcific foci. MRI revealed contrast enhancement and increased signal intensity on T2-weighted images. (orig.)

  1. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

    Science.gov (United States)

    Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2014-12-01

    Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

  2. Cerebral blood flow variations in CNS lupus

    International Nuclear Information System (INIS)

    Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.

    1990-01-01

    We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery

  3. An Incidental Finding of AL-associated Amyloidosis Presenting as Gastric Ulcers

    Directory of Open Access Journals (Sweden)

    Nadia Huq

    2018-01-01

    Full Text Available Gastrointestinal tract amyloidosis has been reported in rare instances and related symptoms are usually nonspecific to the disease process. We present a patient who initially had melena on anticoagulation and endoscopy revealed a bleeding gastric ulcer. Hemostasis was achieved. The patient had a recurrence of symptoms despite being off anticoagulation months later and at that time repeat endoscopy showed multiple gastric ulcers with surrounding friable mucosa. Biopsy results were significant for light chain associated-amyloidosis. This case represents a rare cause of gastric ulcer.

  4. Drawing attention to a neglected injecting-related harm: a systematic review of AA amyloidosis among people who inject drugs.

    Science.gov (United States)

    Harris, Magdalena; Brathwaite, Rachel; Scott, Jenny; Gilchrist, Gail; Ciccarone, Dan; Hope, Vivian; McGowan, Catherine R

    2018-04-26

    Chronic skin and soft tissue infections (SSTI) among people who inject drugs (PWID) can lead to AA amyloidosis: a serious, yet neglected, multi-organ disease. We aim to synthesize findings on the epidemiology, risk factors, clinical outcomes, screening recommendations and challenges to treatment for AA amyloidosis among PWID. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the following bibliographic databases in July 2017: CINAHL Plus, Embase, Global Health, MEDLINE, PsycEXTRA, PsycINFO and SCOPUS. Studies were included if they investigated AA amyloidosis in PWID. Studies were not restricted to location, study type, year or language of publication. Study heterogeneity precluded meta-analysis; we present a narrative review of the literature. Thirty-seven papers from eight countries met inclusion criteria. A total of 781 PWID are reported on, of whom 177 had AA amyloidosis. Where disease causality is established, it is attributed to chronic inflammation caused by injecting-related SSTIs. Most (88.7%) PWID with AA amyloidosis had SSTIs. The proportion of PWID with AA amyloidosis at post-mortem ranged from 1.6% (Germany) to 22.5% (Serbia). Biopsy studies reported from 5.26% (Portugal) to 50% (Germany) of AA amyloidosis in PWID with suspected or known kidney disease. Following diagnosis, the typical trajectory for PWID with AA amyloidosis was rapid deterioration of renal function requiring haemodialysis. Treatment difficulties, end-stage renal failure and premature death from sepsis were observed. Good outcomes, including reversibility of AA amyloidosis, are attributed to rapid treatment of the underlining inflammation and injecting cessation. Notably, given the population in question, no studies were published in addiction or harm reduction journals; most (92%) appeared in specialist nephrology and medical journals. There is strong evidence of an association between skin

  5. 'Care and Prevent': rationale for investigating skin and soft tissue infections and AA amyloidosis among people who inject drugs in London.

    Science.gov (United States)

    Harris, M; Brathwaite, R; McGowan, Catherine R; Ciccarone, D; Gilchrist, G; McCusker, M; O'Brien, K; Dunn, J; Scott, J; Hope, V

    2018-05-08

    Skin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID. Care and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study. We are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening

  6. Amyloidosis in association with spontaneous feline immunodeficiency virus infection.

    Science.gov (United States)

    Asproni, Pietro; Abramo, Francesca; Millanta, Francesca; Lorenzi, Davide; Poli, Alessandro

    2013-04-01

    Tissues from 34 naturally feline immunodeficiency virus (FIV)-infected cats, 13 asymptomatic cats and 21 cats with signs of feline acquired immunodeficiency syndrome (F-AIDS), and 35 FIV-seronegative subjects were examined to determine the presence of amyloid deposits. Twenty experimentally FIV-infected cats and five specific pathogen-free (SPF) control cats were also included in the study. Paraffin-embedded sections from kidney and other organs were submitted to histological and histochemical analysis. Amyloid deposits were identified by a modified Congo red stain and confirmed by electron microscopy to demonstrate the presence of amyloid fibrils in amyloid positive glomeruli. In all positive cases, secondary amyloidosis was identified with potassium permanganate pretreatment and amyloid type was further characterised by immunohistochemistry using primary antibodies against human AA and feline AL amyloids. Amyloid deposits were present in different tissues of 12/34 (35%) naturally FIV-infected cats (seven presenting F-AIDS and five in asymptomatic phase) and in 1/30 FIV-seronegative cats. All the experimentally FIV-infected and SPF subjects showed no amyloid deposits. Amyloidosis has been reported in human lentiviral infections, and the data reported here demonstrate the need, in naturally FIV-infected cats, to consider the presence of amyloidosis in differential diagnosis of hepatic and renal disorders to better assess the prognosis of the disease.

  7. [A review for recent advances in AA amyloid research and therapeutic approach to AA amyloidosis complicating rheumatoid arthritis].

    Science.gov (United States)

    Tamura, Hiroaki; Hasegawa, Kiminori

    2009-02-01

    AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis. It has been demonstrated biochemically that amyloidosis resulted from abnormal folding of proteins, which are deposited as insoluble fibrils in extracellular tissue, leading to the disruption of their normal function. In this regard, amyloidosis has been recognized as a conformation disorder. Interestingly, genetic polymorphisms of amyloid precursor protein (SAA) have been reported to associate with increased risk for AA amyloidosis. Also recent biochemical research revealed that SAA is synthesized under the influence of the proinflammatory cytokines, such as IL-6, TNF-alpha, IL-1. Additionally, it was suggested that amyloid deposits in extracellular tissue could reflect to the serum level of SAA in the reversible fashion, leading to the hypothesis that the control of the SAA synthesis could be beneficial to the treatment of amyloidosis. In this context, anti-cytokine therapies may be most effective. Especially the inhibition of IL-6 is critical to suppression of SAA production, so treatment with a humanized monoclonal antibody against human IL-6 receptor may not only ameliorate RA disease activity but also pave the way for the treatment of AA amyloidosis.

  8. IgG,kappa monoclonal gammopathy of unknown significance with AL amyloidosis simulating giant cell arteritis

    Directory of Open Access Journals (Sweden)

    Pompilian Valer Mihai

    2017-09-01

    Full Text Available Monoclonal gammopathies complicated by AL amyloidosis can mimic giant cell arteritis (GCA. We hereby present the case of a 63 year old woman in whom symptoms consistent with GCA were the first manifestations of a monoclonal gammopathy of unknown significance (MGUS associated with amyloidosis. A 63 year old woman was admitted for temporal headache, maseterine claudication, neck and shoulder stiffness. She was recently diagnosed with carpal tunnel syndrome. On physical examination she had prominent temporal arteries, macroglosia and orthostatic hypotension. Muscular strength was normal. She had high ESR and CRP; in this clinical context, GCA was suspected. A gamma spike on serum protein electrophoresis raised the suspicion of monoclonal gammopathy (MG. Immunoelectrophoresis revealed monoclonal bands for IgG and kappa chains. Massive deposits of amyloid and no inflammation were found on temporal artery biopsy. Multiple myeloma and lymphoma were ruled out. A diagnosis of AL amyloidosis complicating MGUS was formulated. She did well on therapy with bortezomib, cyclophosphamide and dexamethasone. Cases published in medical literature reveal amyloidosis mimicking GCA in the setting of established MGUS. As far as we know, this is the first case of MGUS with IgG and kappa chains in which a GCA-like picture induced by amyloidosis was present from the very onset.

  9. Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis. Case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ming [Hubei University of Medicine, Department of Clinical Oncology, Taihe Hospital, Shiyan, Hubei (China); Peng, Gang; Shi, Liangliang; Li, Zhenyu; Fei, Shijiang; Ding, Qian; Cheng, Jing [HuaZhong University of Science and Technology, Cancer Center, Union Hospital, Tongji Medical College, Wuhan (China); Ming, Xing [Hubei University of Medicine, Department of infection control and prevention, Taihe Hospital, Shiyan, Hubei (China)

    2016-12-15

    Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1-year follow-up. Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case. (orig.) [German] Die primaere lokalisierte Amyloidose ist durch die Ablagerung von Amyloidproteinen gekennzeichnet, die sich auf ein Organ beschraenkt, also nicht systemisch ist. Eine primaere Amyloidose im Nasen-Rachen-Raum ist ausserordentlich selten, bisher gibt es keine Standardtherapie. Ihre anatomische Position bedeutet eine Herausforderung, nur selten resultiert eine chirurgische Intervention in einer vollstaendigen Resektion der lokalisierten Amyloidose. Daher ist die Beteiligung mehrerer Disziplinen fuer eine optimale Behandlung von besonderer

  10. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography

    International Nuclear Information System (INIS)

    Dorbala, Sharmila; Vangala, Divya; Semer, James; Strader, Christopher; Bruyere, John R.; Moore, Stephen C.; Di Carli, Marcelo F.; Falk, Rodney H.

    2014-01-01

    Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of 18 F-florbetapir for imaging cardiac amyloidosis. We performed a pilot study of cardiac 18 F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of 18 F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A 18 F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. Left and right ventricular myocardial uptake of 18 F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min -1 , IQR 0.034 - 0.051 min -1 , vs. 0.023 min -1 , IQR 0.015 - 0.025 min -1 , P = 0.002; TBR 1.84, 1.64 - 2.50, vs. 1.26, IQR 0.91 - 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 - 5.65, vs. 1.35, IQR 1.17 - 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 - 1.64, vs. 0.18, IQR 0.15 - 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. 18 F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied. (orig.)

  11. Silicone stent placement for primary tracheal amyloidosis accompanied by cartilage destruction.

    Science.gov (United States)

    Ryu, Duck Hyun; Eom, Jung Seop; Jeong, Ho Jung; Kim, Jung Hoon; Lee, Ji Eun; Jun, Ji Eun; Song, Dae Hyun; Han, Joungho; Kim, Hojoong

    2014-06-01

    Primary tracheal amyloidosis (PTA) can lead to airway obstructions, and patients with severe PTA should undergo bronchoscopic interventions in order to maintain airway patency. Focal airway involvements with amyloidosis can only be treated with mechanical dilatation. However, the PTA with diffused airway involvements and concomitant cartilage destructions requires stent placement. Limited information regarding the usefulness of silicone stents in patients with PTA has been released. Therefore, we report a case of diffused PTA with tracheomalacia causing severe cartilage destruction, which is being successfully managed with bronchoscopic interventions and silicone stent placements.

  12. Imaging findings and literature review of 18F-FDG PET/CT in primary systemic AL amyloidosis

    International Nuclear Information System (INIS)

    Lee, Joo Hee; Lee, Ga Yeon; Kim, Seok Jin; Kim, Ki Hyun; Jeon, Eun Seok; Lee, Kyung Han; Kim, Byung Tae; Choi, Joon Young

    2015-01-01

    Although several case reports and case series have described 18 F-FDG PET/CT in amyloidosis, the value of 18 F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of 18 F-FDG PET/CT in patients with primary systemic AL amyloidosis. Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment 18 F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on 18 F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis. F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUV max  = 7.0 ± 3.2, range 2.1–14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal 18 F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). 18 F-FDG uptake was negative for pancreas and gastric lesions. Although 18 F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of 18 F-FDG PET/CT in amyloidosis will be warranted

  13. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis

    DEFF Research Database (Denmark)

    Nelson, Lærke Marie; Gustafsson, Finn; Gimsing, Peter

    2015-01-01

    Background/Aims: Immunoglobulin light-chain (AL) amyloidosis is a systemic disorder that causes progressive organ dysfunction. The optimal treatment strategy requires accurate patient stratification with an emphasis on the extent of cardiac involvement. Reports on its prognosis are sparse...... and predominantly originate from highly selected centers. We aimed to evaluate patient characteristics and outcomes in a cohort treated at a single center. Methods: This is a single-center retrospective study of 63 consecutive patients diagnosed with AL amyloidosis between January 2000 and December 2012. Patients...... were evaluated by treatment strategy and cardiac involvement. Results: The mean age at diagnosis was 61.4 years (±8.9), and 39 patients (62%) were male. Thirty-two (51%) patients presented with cardiac amyloid involvement (CA) and the remaining 31 (49%) had noncardiac amyloidosis (NCA). The median...

  14. Churg-Strauss syndrome associated with AA amyloidosis: a case report.

    Science.gov (United States)

    Maamar, Mouna; Tazi-Mezalek, Zoubida; Harmouche, Hicham; El Hamany, Zitouna; Adnaoui, Mohammed; Aouni, Mohammed

    2012-01-01

    Churg Strauss syndrome is a rare systemic and pulmonary vasculitis exceptionally associated with AA amyloidosis. We report the case of a 65-year old woman with past medical history of asthma. She developed polyarthralgia, headache and purpura. A laboratory workout found hypereosinophilia (1150/µL), positive p-ANCA, microscopic haematuria and proteinuria at 2g/day. A diagnosis of Churg-Strauss syndrome was established based on five criteria of the American College of Rheumatology (ACR). Renal biopsy showed an important type AA amyloid deposit. The patient was treated with steroids with a good response of the vasculitis and amyloidosis with disappearance of the proteinuria.

  15. Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    2012-07-01

    Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

  16. Longitudinal study of experimental induction of AA amyloidosis in mice seeded with homologous and heterologous AA fibrils.

    Science.gov (United States)

    Muhammad, Naeem; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-09-01

    To investigate pathogenesis and kinetics of experimentally induced murine AA amyloidosis seeded with homologous (murine) and heterologous (bovine) AA fibrils. Experimental AA amyloidosis was induced by administration of inflammatory stimulus and preformed AA fibrils to a total of 111 female C57/Black mice. In this longitudinal study, heterologous (bovine) as well as homologous (murine) AA fibrils were injected intraperitoneally to mice in various combinations. Re-stimulation was done at 120 or 300 days post first inoculation. To analyze the intensity of amyloid depositions in mice organs, immunohistochemical techniques and image J software were used. Assessment of cytokines level in sera was done using a Mouse Th1/Th2/Th17 Cytokine CBA Kit. Incidence and severity of AA amyloidosis were quite low in mice inoculated with heterologous bovine AA fibrils than homologous murine one. Homologous AA fibrils administration at first and second inoculation caused maximum amount of amyloid depositions and severe systemic form of amyloidosis. Increase in the level of pro-inflammatory cytokine IL-6 was observed after first inoculation, while second inoculation caused a further increase in the level of anti-inflammatory cytokine IL-10. AA amyloidosis can be induced by heterologous as well as homologous AA fibrils. Severity of AA amyloidosis induced with homologous AA fibrils is higher compared to heterologous AA fibrils.

  17. Bilateral optic neuropathy and intraretinal deposits after pars plana vitrectomy in amyloidosis

    Directory of Open Access Journals (Sweden)

    Rossetti Alberto

    2015-01-01

    Full Text Available Pathological examination of material from a nonextensive pars plana vitrectomy (PPV in the right eye provided a diagnosis of nonfamilial amyloidosis in a 68-year-old woman, who presented with bilateral glass wool-like vitreous opacities. Genetic testing revealed a Tyr114Cys mutation in the transthyretin gene. Six months after PPV, perimetry showed intense constriction with a temporal island and central scotoma in the right eye. An extensive PPV was performed in the left eye. Spectral domain optical coherence tomography evidenced bilateral epimacular amyloid deposits and unreported reflective spots within the inner retina. One year later, visual acuity had decreased to 20/400 in the left eye, with mild vitreous opacity, pale cupped optic disc and inferior altitudinal field defect. Bilateral diurnal intraocular pressure, transiently increased after PPV, never exceeded 16 mmHg with medication. Our patient presented optic nerve blood supply impairment, due to amyloidosis, which caused optic atrophy. Epiretinal and intraretinal deposit detection could aid in diagnosing patients with suspected amyloidosis.

  18. Oral involvement in a case of AA amyloidosis: a case report

    Directory of Open Access Journals (Sweden)

    Yıldız Levent

    2010-06-01

    Full Text Available Abstract Introduction Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein causes systemic amyloidosis, a serious inflammatory disorder. We document a male patient who developed reactive amyloidosis (AA type, most likely secondary to his long standing periodontitis. Case presentation A 67-year-old Turkish man complained of pain in his oral cavity (burning mouth especially on the tongue, and had difficulty chewing and swallowing foods. A careful dental/periodontal examination was performed, including assessment of plaque, gingival condition and periodontal probing depths on all his remaining teeth. Prosthetic rehabilitation was provided three months after the completion of his periodontal and surgical therapy. The concentration of serum inflammatory markers including erythrocyte sedimentation rate, white blood cell count, fibrinogen and high sensitive C-reactive protein were measured at baseline, at the second and sixth weeks, and at three and six months after the periodontal and surgical therapy. Conclusions Oral examination revealed a few papules on the dorsum of the tongue with two slightly painful, small ulcers, localized on the vestibule of the mouth. The mean probing depth was 9.10 ± 0.84 mm. Biopsies of the tongue, buccal mucosa and retromolar trigone were performed and amyloid deposits were found. The serum inflammatory markers improved more dramatically at the second week of periodontal therapy than any other time intervals. Amyloidosis may manifest as periodontal destruction that leads to severe chronic periodontitis. Proper periodontal treatment may alleviate systemic inflammatory mediators caused by the amyloidosis.

  19. Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

    Science.gov (United States)

    Uwumugambi, Nsabimana A; Sanchorawala, Vaishali; Shelton, Anthony C; Stern, Lauren; Gordon, Craig E

    2017-02-01

    Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  20. Surgical management of macroglossia secondary to amyloidosis.

    Science.gov (United States)

    Gadiwalla, Yusuf; Burnham, Richard; Warfield, Adrian; Praveen, Prav

    2016-04-11

    The authors report a case of amyloidosis-induced macroglossia treated with surgical reduction of the tongue using a keyhole to inverted T method with particular emphasis on the postoperative sequelae. Significant tongue swelling persisted for longer than anticipated requiring tracheostomy to remain in situ for 14 days. 2016 BMJ Publishing Group Ltd.

  1. The Hidden Cost of Untreated Paragangliomas of the Head and Neck: Systemic Reactive (AA Amyloidosis

    Directory of Open Access Journals (Sweden)

    Erkan Dervisoglu

    2015-01-01

    Full Text Available We report a case of a 51-year-old man who was diagnosed with systemic reactive (AA amyloidosis in association with untreated glomus jugulare and glomus caroticum tumors. He refused radiotherapy and renal replacement therapy. Paragangliomas, although rare, should be considered one of the tumors that can result in AA amyloidosis.

  2. Imaging findings and literature review of {sup 18}F-FDG PET/CT in primary systemic AL amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Hee; Lee, Ga Yeon; Kim, Seok Jin; Kim, Ki Hyun; Jeon, Eun Seok; Lee, Kyung Han; Kim, Byung Tae; Choi, Joon Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-09-15

    Although several case reports and case series have described {sup 18}F-FDG PET/CT in amyloidosis, the value of {sup 18}F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of {sup 18}F-FDG PET/CT in patients with primary systemic AL amyloidosis. Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment {sup 18}F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on {sup 18}F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis. F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUV{sub max} = 7.0 ± 3.2, range 2.1–14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal {sup 18}F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). {sup 18}F-FDG uptake was negative for pancreas and gastric lesions. Although {sup 18}F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of {sup 18}F-FDG PET/CT in amyloidosis will be warranted.

  3. LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

    Science.gov (United States)

    Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

    2016-06-01

    This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component

    International Nuclear Information System (INIS)

    Hawkins, P.N.; Lavender, J.P.; Pepys, M.B.

    1990-01-01

    In systemic amyloidosis the distribution and progression of disease have been difficult to monitor, because they can be demonstrated only by biopsy. Serum amyloid P component (SAP) is a normal circulating plasma protein that is deposited on amyloid fibrils because of its specific binding affinity for them. We investigated whether labeled SAP could be used to locate amyloid deposits. Purified human SAP labeled with iodine-123 was given intravenously to 50 patients with biopsy-proved systemic amyloidosis--25 with the AL (primary) type and 25 with the AA (secondary) type--and to 26 control patients with disease and 10 healthy subjects. Whole-body images and regional views were obtained after 24 hours and read in a blinded fashion. In the patients with amyloidosis the 123I-SAP was localized rapidly and specifically in amyloid deposits. The scintigraphic images obtained were characteristic and appeared to identify the extent of amyloid deposition in all 50 patients. There was no uptake of the 123I-SAP by the control patients and the healthy subjects. In all patients with AA amyloidosis the spleen was affected, whereas the scans showed uptake in the heart, skin, carpal region, and bone marrow only in patients with the AL type. Positive images were seen in six patients in whom biopsies had been negative or unsuccessful; in all six, amyloid was subsequently found on biopsy or at autopsy. Progressive amyloid deposition was observed in 9 of 11 patients studied serially. Scintigraphy after the injection of 123I-SAP can be used for diagnosing, locating, and monitoring the extent of systemic amyloidosis

  5. Cardiac amyloidosis induces up-regulation of Deleted in Malignant Brain Tumors 1 (DMBT1)

    DEFF Research Database (Denmark)

    Müller, Hanna; Renner, Marcus; Bergmann, Frank

    2013-01-01

    Amyloidosis is a life-threatening protein misfolding disease and affects cardiac tissue, leading to heart failure, myocardial ischemia and arrhythmia. Amyloid deposits result in oxidative stress, inflammation and apoptosis. The purpose of this study was to examine the role of innate defense compo...... components, i.e., Deleted in Malignant Brain Tumors 1 (DMBT1) and the complement system, in different types of cardiac amyloidosis....

  6. Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report

    Directory of Open Access Journals (Sweden)

    Kamata Tsugumasa

    2012-08-01

    Full Text Available Abstract Introduction Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach. Case presentation A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis. Conclusions We report an unusual case of primary amyloidosis of the stomach

  7. Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

    International Nuclear Information System (INIS)

    Benson, M.D.; Cohen, A.S.

    1979-01-01

    Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease

  8. Focal Amyloidosis of the Orbit Presenting as a Mass: MRI and CT Features

    International Nuclear Information System (INIS)

    Yerli, Hasan; Aydin, Erdinc; Avci, Suat; Haberal, Nihan; Oto, Sibel

    2011-01-01

    Focal orbital amyloidosis is a rare entity and little is known about its magnetic resonance imaging (MRI) features. In this case report, imaging features of a case of focal orbital amyloidosis presenting as a mass have been documented together with its histopathological findings. On MRI, a well-defined mass was seen as isointense with rectus muscle on T1-weighted images and heterogeneously hypointense on T2-weighted images. Punctuate calcifications were observed on the computerized tomography (CT) examination

  9. Etanercept In the treatment of AA-amyloidosis in juvenile rheumatoid arthritis

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    H Mihels

    2004-01-01

    Full Text Available Objective. To study effect of etanercept, an antagonist of serum A amyloid production in the AA amyloidosis treatment in juvenile idiopathic arthritis (JIA. Material and methods. Etanercept was administered to all pts with AA amyloidosis admitted to Garmisch-Paterkirchen pediatric rheumatological clinic beginning with 2000. C-reactive protein (CRP, degree of proteinuria and serum creatinin were used as preliminary outcome measures. Results. 11 pts with seronegative JIA (6 boys and 5 girls were included in the study. Mean follow up duration was l,9±l.01 years. 8 children had systemic, 2 - olygoarticular and one - polyarticular disease onset. Before the study all pts had CRP level elevation (1,03-8,29 mg/dl, mean 4,53 mg/dl. 8 from 11 had marked proteinuria (364-7400 mg/24 hours, mean 1186 mg/24 hours. 2 from 11 had serum creatinin elevation. During etanercept treatment CRP level normalized in 2 and significantly decreased in 4 pts. Proteinuria decreased in 4 from 8 pts. Significant change of creatinin level was not achieved. One girl who did not have improvement during etanercept treatment showed CRP normalization and decrease of proteinuria when the drug was changed to infliximab. Conclusion. Treatment with etanercept provided improvement in almost 2/3 from 11 pts with JIA and AA amyloidosis. Etanercept may be the drug of choice in pts with normal creatinine level in the absence of proteinuria. When it fails another tumor necrosis factor antagonist such as infliximab should be used. It is necessary to extend volume and duration of the study to get more reliable data on etanercept efficacy in JIA pts with AA amyloidosis.

  10. Proteomic analysis of highly prevalent amyloid A amyloidosis endemic to endangered island foxes.

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    Patricia M Gaffney

    Full Text Available Amyloid A (AA amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA. Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34% in a genetically isolated population of island foxes (Urocyon littoralis with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%, spleen (58%, oral cavity (45%, and vasculature (44% and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤ 0.05. Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins.

  11. Independent Prognostic Value of Stroke Volume Index in Patients With Immunoglobulin Light Chain Amyloidosis.

    Science.gov (United States)

    2018-05-01

    Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37-3.66), 2.36 (1.96-2.85), and 2.32 (1.91-2.80). For the subset that had left ventricular strain performed, the prognostic cut point was -14% (hazard ratios, 2.70; 95% confidence intervals, 1.84-3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients. © 2018 American Heart Association, Inc.

  12. Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

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    Masaru Matsui

    2014-01-01

    Full Text Available Systemic reactive AA amyloidosis is a life-threatening complication of chronic inflammatory diseases. Anti-interleukin-6 receptor, tocilizumab (TCZ, has been shown to improve clinical symptoms of patients with AA amyloidosis, accompanied with regression of the amyloid deposition. We report a case of AA amyloidosis evaluated by histology of multiple organs before and after TCZ treatment. A woman in her 60s with rheumatoid arthritis was referred to our hospital because of cardiac and renal dysfunction. A gastric and renal biopsy revealed the deposition of AA amyloid, and echocardiography revealed concentric left ventricular hypertrophy. Her estimated glomerular filtration rate was decreased to 8.6 mL/min/1.73 m2, and B-type natriuretic peptide, C-reactive protein, and serum amyloid A protein were significantly elevated. TCZ treatments markedly decreased her serum amyloid A protein and C-reactive protein levels, but hemodialysis was required 1 year later. Endoscopic gastric rebiopsy 3 years after initiation of TCZ treatments revealed the regression of amyloid deposition and echocardiography revealed improvement of her left ventricular hypertrophy. However, a renal rebiopsy revealed that the amyloid deposition had not regressed. In conclusion, these observations suggest that the therapeutic effects of TCZ can vary among organs in patients with AA amyloidosis.

  13. Upregulation of NOX2 and NOX4 Mediated by TGF-β Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury

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    Zheng Lou

    2018-04-01

    Full Text Available Background/Aims: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX-derived reactive oxygen species (ROS play an important role in cerebral ischemia/reperfusion (I/R injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-β signals in ROS generation. Methods: Sprague–Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R and/or treated with activin receptor-like kinase (ALK5 inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-β and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. Results: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis, TGF-β signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3 and oxidative stress (upregulation of NOX2/4, rapid release of ROS [oxidative burst]. However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-β signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. Conclusions: Our studies demonstrated that TGF-β signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.

  14. Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial.

    Science.gov (United States)

    Beeh, Kai M; Glaab, Thomas; Stowasser, Susanne; Schmidt, Hendrik; Fabbri, Leonardo M; Rabe, Klaus F; Vogelmeier, Claus F

    2013-10-29

    Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival. NCT00563381; Study identifier: BI 205.389.

  15. Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis.

    Science.gov (United States)

    Sethi, Sanjeev; Vrana, Julie A; Theis, Jason D; Leung, Nelson; Sethi, Anjali; Nasr, Samih H; Fervenza, Fernando C; Cornell, Lynn D; Fidler, Mary E; Dogan, Ahmet

    2012-07-01

    Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008-2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell-derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.

  16. Dialysis-related amyloidosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Scarpioni R

    2016-12-01

    Full Text Available R Scarpioni, M Ricardi, V Albertazzi, S De Amicis, F Rastelli, L Zerbini Department of Nephrology and Dialysis, Azienda Unità Sanitaria Local (AUSL Hospital “Guglielmo da Saliceto”, Piacenza, Italy Abstract: Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2 microglobulins (β2M, in the osteoarticular structures and viscera. Most of the β2M is eliminated through glomerular filtration and subsequent reabsorption and catabolism by the proximal tubules. As a consequence, the serum levels of β2M are inversely related to the glomerular filtration rate; therefore, in end-stage renal disease patients, β2M levels increase up to 60-fold. Serum levels of β2M are also elevated in several pathological conditions such as chronic inflammation, liver disease, and above all, in renal dysfunction. Retention of amyloidogenic protein has been attributed to several factors including type of dialysis membrane, prolonged uremic state and/or decreased diuresis, advanced glycation end products, elevated levels of cytokines and dialysate. Dialysis treatment per se has been considered to be an inflammatory stimulus, inducing cytokine production (such as interleukin-1, tumor necrosis factor-α, interleukin-6 and complement activation. The released cytokines are thought to stimulate the synthesis and release of β2M by the macrophages and/or augment the expression of human leukocyte antigens (class I, increasing β2M expression. Residual renal function is probably the best determinant of β2M levels. Therefore, it has to be maintained as long as possible. In this article

  17. Solitary plasmacytoma of spine with amyloidosis

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    Cui-yun SUN

    2017-01-01

    Full Text Available Objective To report the diagnosis and treatment of one case of solitary plasmacytoma of spine with amyloidosis and investigate the clinicopathological features combined with literatures. Methods and Results The patient was a 46-year-old woman. She suffered from weakness of both lower limbs, unsteady gait and numbness of toes for 20 d. MRI examination revealed an irregular mass behind the spinal cord at T5-7 level and T6-7 vertebral body accessory. The enhanced MRI showed obvious heterogeneous enhancement. The border was clear and spinal dura mater was compressed to shift forward. During operation, T5-7 processus spinosus and vertebral laminae were eroded, and the cortex of bone showed "moth-eaten" erosion. The intraspinal and extradural lesion had rich blood supply, loose bone structure and intact spinal dura mater. Histologically, tumor cells were composed of intensive small cells, and focal plasmacytoid cells were seen. Flake pink staining substance was among them. Artificial cracks were common and multinuclear giant tumor cells were scatteredly distributed. Immunohistochemical analysis showed the cytoplasm of tumor cells were diffusely positive for CD138, CD38 and vimentin (Vim,scatteredly positive for leukocyte common antigen (LCA, and negative for immune globulin κ light chain(IgGκ and λ light chain (IgGλ, CD99, S-100 protein (S-100, pan cytokeratin (PCK, epithelial membrane antigen (EMA, HMB45 and CD34. The Ki-67 labeling index was 1.25%. Congo red staining showed the pink staining substance was brownish red. Hybridization in situ examination showed the DNA content of IgGκ was more than that of IgGλ. The final pathological diagnosis was solitary plasmacytoma of spine with amyloidosis. The patient was treated with postoperative chemotherapy, and there was no recurrence or metastasis during 18-month follow-up period. Conclusions Solitary plasmacytoma of spine with amyloidosis is a rare tumor. The imaging features can offer a few

  18. MRI and echocardiography in the diagnosis of cardiac amyloidosis

    International Nuclear Information System (INIS)

    Wang Jing; Kong Xiangquan; Zhou Guofeng; Xu Haibo; Chang Dandan; Feng Yiming; Liu Dingxi; Zhang Li; Xie Mingxing

    2010-01-01

    Objective: To assess the values of MRI and echocardiography for the diagnosis of cardiac amyloidosis (CA). Methods: Eleven cases with CA proved pathologically performed MRI and echocardiography, the findings were analyzed retrospectively. Results: The characteristic features of cardiac amyloidosis on MRI and echocardiography were: diffuse slight myocardial thickening of the left ventricular wall and interventricular septum (11 cases), slight myocardial thickening of the interatrial septum (5 cases), increased left ventricular mass (7 cases), enlarged left atrium (7 cases), impaired ventricular systolic and diastolic function (10 cases), pleural and pericardial effusions (11 and 9 cases). Echocardiography showed that myocardium was hyperechoic and presented as ground glass with some spotty hyperechoes in 6 cases. MRI revealed a distinct diffuse delayed enhancement of subendocardial and entire myocardium in 8 cases. Conclusion: Doppler echocardiography is the first-choice imaging technique and cardiac magnetic resonance imaging can provide more information for the diagnosis of CA. (authors)

  19. Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kenneth S. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI (United States); Holsbeeck, Marnix T. van [Wayne State School of Medicine, Department of Radiology, Henry Ford Hospital, Detroit, MI (United States); Abbud, Alexander [Wayne State School of Medicine, Department of Pathology, Henry Ford Hospital, Detroit, MI (United States)

    2010-01-15

    Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054-2058 and 2176-2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis - over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61-64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed. (orig.)

  20. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice

    NARCIS (Netherlands)

    van Gameren, Ingrid I.; Hazenberg, BPC; Bijzet, J.; van Rijswijk, M.H.

    Objective. Aspiration of subcutaneous abdominal fat is a simple and fast method for detecting systemic amyloidosis; however, the sensitivity of this approach remains undetermined. The aim of this study was to assess the accuracy of fat tissue aspiration for detecting systemic amyloidosis and the

  1. Exacerbation of radiation induced meningioma due to hemorrhage after cerebral angiography. A case report

    International Nuclear Information System (INIS)

    Yamaguchi, Shinya; Matsuo, Yoshihiro; Uesaka, Toshio; Matsukado, Koichiro; Suzuki, Satoshi O.; Iwaki, Toru

    2011-01-01

    We report the case of a 34-year-old woman who exhibited acute deterioration in her condition after cerebral angiography for evaluation of a large meningioma. She had undergone surgery and irradiation for a glioma in the right occipital lobe 23 years before this episode. She experienced incapacity at work. On CT and MRI, a large meningioma was detected on the left frontal convexity; this tumor was thought to be radiation-induced. Cerebral angiography was performed to assess the vascularization of the tumor. Her condition began to deteriorate 2.5 h after the cerebral angiography. CT revealed an increase in the mass of the tumor, and a high density area in the tumor. We immediately removed the tumor. Histopathological examinationrevealed the tumor to be a meningothelial meningioma. New hemorrhagic foci were identified in the tumor. In addition, macrophages containing hemosiderin were detected, and some of the tumor vessels exhibited hyaline degeneration. We suspected that angiography triggered bleeding in the meningioma, which was already predisposed to hemorrhage. (author)

  2. Pediatric Cerebral Palsy in Africa: Where Are We?

    Science.gov (United States)

    Donald, Kirsten A; Kakooza, Angelina M; Wammanda, Robinson D; Mallewa, Macpherson; Samia, Pauline; Babakir, Haydar; Bearden, David; Majnemer, Annette; Fehlings, Darcy; Shevell, Michael; Chugani, Harry; Wilmshurst, Jo M

    2015-07-01

    Cerebral palsy is the most common cause of physical disability in children worldwide. However, little is reported on this condition in the African context. Doctors from 22 countries in Africa, and representatives from a further 5 countries outside Africa, met to discuss the challenges in the evaluation and management of children with cerebral palsy in Africa and to propose service needs and further research. Basic care is limited by the poor availability of diagnostic facilities or medical personnel with experience and expertise in managing cerebral palsy, exacerbated by lack of available interventions such as medications, surgical procedures, or even regular therapy input. Relevant guidelines are lacking. In order to guide services for children with existing disabilities, to effectively target the main etiologies and to develop preventive strategies for the continent, research priorities must include multicenter collaborative studies looking at the prevalence, risk factors, and treatment of cerebral palsy. © The Author(s) 2014.

  3. Amiloidosis secundaria en la enfermedad inflamatoria intestinal Secondary amyloidosis in Chrohn's disease

    Directory of Open Access Journals (Sweden)

    S. Seijo Ríos

    2008-12-01

    Full Text Available La amiloidosis es una entidad clínica que se produce a consecuencia del depósito a nivel extracelular de un material proteico amorfo, causando una desorganización de la arquitectura normal de múltiples órganos y tejidos y, por tanto, una alteración funcional de los mismos. La amiloidosis secundaria es una complicación infrecuente pero muy grave que aparece en el contexto de neoplasias, enfermedades infecciosas e inflamatorias de curso crónico, como es el caso de la enfermedad inflamatoria intestinal, principalmente enfermedad de Crohn, ensombreciendo el pronóstico de estos pacientes. A continuación presentamos dos casos clínicos correspondientes a dos pacientes con enfermedad de Crohn que desarrollaron amiloidosis secundaria.Amyloidosis is a clinical entity that results from the deposition of an extracellular protein material that causes disruption in the normal architecture of multiple organs and tissues, and impairs their function. Secondary amyloidosis is a rare but serious complication that may worsen the prognosis of patients with cancer, infection or chronic inflammatory disease, including inflammatory bowel disease, particularly Crohn's disease. We report two cases of Crohn's disease associated with secondary amyloidosis.

  4. Estimation of Daily Proteinuria in Patients with Amyloidosis by Using the Protein-To-Creatinine ratio in Random Urine Samples.

    Science.gov (United States)

    Talamo, Giampaolo; Mir Muhammad, A; Pandey, Manoj K; Zhu, Junjia; Creer, Michael H; Malysz, Jozef

    2015-02-11

    Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria >500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr) in predicting 24 hour proteinuria in patient with amyloidosis. We compared results of random urine Pr/Cr ratio and concomitant 24-hour urine collections in 44 patients with amyloidosis. We found a strong correlation (Spearman's ρ=0.874) between the Pr/Cr ratio and the 24 hour urine protein excretion. For predicting renal involvement, the optimal cut-off point of the Pr/Cr ratio was 715 mg/g. The sensitivity and specificity for this point were 91.8% and 95.5%, respectively, and the area under the curve value was 97.4%. We conclude that the random urine Pr/Cr ratio could be useful in the screening of renal involvement in patients with amyloidosis. If validated in a prospective study, the random urine Pr/Cr ratio could replace the 24 hour urine collection for the assessment of daily proteinuria and presence of nephrotic syndrome in patients with amyloidosis.

  5. Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis

    OpenAIRE

    Kuroda, Takeshi; Tanabe, Naohito; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Kobayashi, Daisuke; Wada, Yoko; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    2016-01-01

    Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according ...

  6. Breast cancer and amyloid bodies: is there a role for amyloidosis in cancer-cell dormancy?

    Directory of Open Access Journals (Sweden)

    Mizejewski GJ

    2017-04-01

    Full Text Available Gerald J Mizejewski Wadsworth Center, New York State Department of Health, Albany, NY, USA Abstract: Breast cancer and Alzheimer’s disease (AD are major causes of death in older women. Interestingly, breast cancer occurs less frequently in AD patients than in the general population. Amyloidosis, the aggregation of amyloid proteins to form amyloid bodies, plays a central role in the pathogenesis of AD and other human neuropathies by forming intracellular fibrillary proteins. Contrary to popular belief, amyloidosis is a common occurrence in mammalian cells, and has recently been reported to be a natural physiological process in response to environmental stress stimulations (such as pH and temperature extremes, hypoxia, and oxidative stress. Many proteins contain an intrinsic “amyloid-converting motif”, which acts in conjunction with a specific noncoding RNA to induce formation of proteinaceous amyloid bodies that are stored in intracellular bundles. In cancer cells such as breast and prostate, the process of amyloidosis induces cells to enter a dormant or resting stage devoid of cell division and proliferation. Therefore, cancer cells undergo growth cessation and enter a dormant stage following amyloidosis in the cell; this is akin to giving the cell AD to cease growth. Keywords: α-fetoprotein, noncoding RNA, amyloid bodies, dormancy, breast cancer, Alzheimer’s disease

  7. Churg-Strauss syndrome associated with AA amyloidosis: a case ...

    African Journals Online (AJOL)

    Churg Strauss syndrome is a rare systemic and pulmonary vasculitis exceptionally associated with AA amyloidosis. We report the case of a 65-year old woman with past medical history of asthma. She developed polyarthralgia, headache and purpura. A laboratory workout found hypereosinophilia (1150/μL), positive ...

  8. Estimation of daily proteinuria in patients with amyloidosis by using the protein-to-creatinine ratio in random urine sample

    Directory of Open Access Journals (Sweden)

    Giampaolo Talamo

    2015-02-01

    Full Text Available Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria >500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr in predicting 24 hour proteinuria in patient with amyloidosis. We com- pared results of random urine Pr/Cr ratio and concomitant 24-hour urine collections in 44 patients with amyloidosis. We found a strong correlation (Spearman’s ρ=0.874 between the Pr/Cr ratio and the 24 hour urine protein excretion. For predicting renal involvement, the optimal cut-off point of the Pr/Cr ratio was 715 mg/g. The sensitivity and specificity for this point were 91.8% and 95.5%, respectively, and the area under the curve value was 97.4%. We conclude that the random urine Pr/Cr ratio could be useful in the screening of renal involvement in patients with amyloidosis. If validated in a prospective study, the random urine Pr/Cr ratio could replace the 24 hour urine collection for the assessment of daily proteinuria and presence of nephrotic syndrome in patients with amyloidosis.

  9. Thoracic and abdominal SPECT imaging in systemic amyloidosis in identifying multiorgan involvement

    International Nuclear Information System (INIS)

    Wellman, H.N.; Benson, M.D.; Park, H.M.; Siddiqui, A.R.; Krepshaw, J.D.

    1988-01-01

    Thirty-three patients with systemic amyloidosis have been studied. Thoracic single photon emission computed tomography (SPECT) for myocardial involvement and skeletal imaging were performed with Tc-99m PYP, and abdominal SPECT with TcS colloid. Myocardial wall involvement was easily discernible with SPECT in 17 cases, and in many with normal ultrasonography. PYP uptake was also observed in liver (five patients), kidneys (four patients), and soft tissues (two patients). Most patients had widespread degenerative joint disease. With TcS colloid, intrinsic liver abnormalities were found in four patients, hepatomegaly in seven, and splenic infiltration in two. Nuclear SPECT and planar imaging characterize the distribution of systemic amyloidosis in organs, distribution not readily identified with other diagnostic modalities

  10. Renal amyloid A amyloidosis as a complication of hidradenitis suppurativa

    DEFF Research Database (Denmark)

    Schandorff, Kristine D; Miller, Iben M; Krustrup, Dorrit

    2016-01-01

    Rheumatic disease is the dominant cause of amyloid A (AA) amyloidosis, but other chronic inflammatory diseases may have similar consequences. Hidradenitis suppurativa (HS) is a relatively common, but little known skin disease characterized by chronic inflammation. Here we present a case of chronic...

  11. Primary conjunctival amyloidosis

    Directory of Open Access Journals (Sweden)

    Chandana Chakraborti

    2014-01-01

    Full Text Available A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid.On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

  12. Amiloidosis bucal Oral amyloidosis

    Directory of Open Access Journals (Sweden)

    Isabella Lima Arrais Ribeiro

    2012-03-01

    , confirmado con la coloración del espécimen con el reactivo rojo congo. Los depósitos de amiloide fueron encontrados en el tejido conjuntivo, que con la luz polarizada presentó birrefringencia. Tal hallazgo fue preocupante, ya que la amiloidosis afecta diversos tejidos, lo que puede provocar complicaciones sistémicas. Por esa razón la paciente fue orientada a buscar atención médica. Sin embargo, abandonó el tratamiento y falleció 6 meses después del diagnóstico de la enfermedad. Lesiones bucales aparentemente simples pueden revelar enfermedades raras y de difícil tratamiento. El diagnóstico preciso y la supervisión médica son fundamentales para la sobrevida del paciente.Amyloidosis is an uncommon complicated disease of a difficult diagnosis occurring due to the amyloid substance depot in the extracellular medium. Being diagnosed in the oral cavity, the patient must to be supervised to assess the potential systemic complications of disease. The aim of present paper was to present a case of oral amyloidosis in a female patient ages 72 presenting with traumatic fibroma. After performance of a biopsy and the histopathological examination, the diagnosis was the presence of amyloidosis, confirmed with the help of the sample using Congo red reactant. Amyloid depots were found in the conjunctive tissue which under the polarized light showed birefringence. This finding was worrying since the amyloidosis involves different tissues leading to systemic complications. Thus, the patient was oriented to search medical care; however she abandons treatment dying 6 months after diagnosis of the disease. The apparently single oral injuries may to reveal uncommon diseases and of difficult treatment. The precise treatment and the medical supervision are essential in the patient's survival.

  13. Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Balwani Manish R

    2015-04-01

    Full Text Available Common variable immunodeficiency (CVID usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR, hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.

  14. Diagnostic performance and prognostic value of extravascular retention of I-123-labeled serum amyloid P component in systemic amyloidosis

    NARCIS (Netherlands)

    Hazenberg, Bouke P. C.; van Rijswijk, Martin H.; Lub-de Hooge, Marjolijn N.; Vellenga, Edo; Haagsma, Elizabeth B.; Posthumus, Marcel D.; Jager, Pieter L.

    Serum amyloid P component (SAP) binds to amyloid.I-123-SAP scintigraphy is used to evaluate the extent and distribution of amyloid in systemic amyloidosis and has great clinical value in the detection of systemic amyloidosis. The aim of the study was to assess during scintigraphy the diagnostic

  15. Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model

    DEFF Research Database (Denmark)

    Nikolajsen, Gitte; Jensen, Morten Skovgaard; West, Mark J.

    2011-01-01

    Modern stereological techniques have been used to show that the total length of the cholinergic fibers in the cerebral cortex of the APPswe/PS1deltaE9 mouse is reduced by almost 300 meters at 18 months of age and has a nonlinear relationship to the amount of transgenetically-induced amyloidosis. ....... These data provide rigorous quantitative morphological evidence that Alzheimer's-like amyloidosis affects the axons of the cholinergic enervation of the cerebral cortex....

  16. Leukocyte derived chemotaxin 2 (ALECT2 amyloidosis

    Directory of Open Access Journals (Sweden)

    Uday P Kulkarni

    2015-07-01

    Full Text Available We describe the first case from India of ALECT2 amyloidosis. An adult Punjabi male presented with progressive renal dysfunction and non-nephrotic range proteinuria. Serum protein electrophoresis and Immunofixation were normal, with mildly elevated serum free light chain ratio. Renal biopsy confirmed the presence of amyloid. Immunohistochemistry was negative for monoclonal light chains. Proteomic analysis confirmed the presence of ALECT2 amyloid. The present case highlights the need for confirmatory testing for typing of amyloid.

  17. Cerebral responses to exercise and the influence of heat stress in human fatigue.

    Science.gov (United States)

    Robertson, Caroline V; Marino, Frank E

    2017-01-01

    There are a number of mechanisms thought to be responsible for the onset of fatigue during exercise-induced hyperthermia. A greater understanding of the way in which fatigue develops during exercise could be gleaned from the studies which have examined the maintenance of cerebral blood flow through the process of cerebral autoregulation. Given that cerebral blood flow is a measure of the cerebral haemodynamics, and might reflect a level of brain activation, it is useful to understand the implications of this response during exercise and in the development of fatigue. It is known that cerebral blood flow is significantly altered under certain conditions such as altitude and exacerbated during exercise induced - hyperthermia. In this brief review we consider the processes of cerebral autoregulation predominantly through the measurement of cerebral blood flow and contrast these responses between exercise undertaken in normothermic versus heat stress conditions in order to draw some conclusions about the role cerebral blood flow might play in determining fatigue. Copyright © 2016. Published by Elsevier Ltd.

  18. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL) : A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

    NARCIS (Netherlands)

    Gertz, MA; Comenzo, R; Falk, RH; Fermand, JP; Hazenberg, BP; Hawkins, PN; Merlini, G; Moreau, P; Ronco, P; Sanchorawala, [No Value; Sezer, O; Solomon, A; Grateau, G

    We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of

  19. A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin

    DEFF Research Database (Denmark)

    Caubet, Cécile; Bousset, Luc; Clemmensen, Ole

    2010-01-01

    with circular dichroism measurements. This identifies HSS as a human amyloidosis related to the aggregation of natively unfolded (mut)CDSN polypeptides into amyloid fibrils.-Caubet, C., Bousset, L., Clemmensen, O., Sourigues, Y., Bygum, A., Chavanas, S., Coudane, F., Hsu, C.-Y., Betz, R. C., Melki, R., Simon, M...

  20. Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2005-01-01

    Full Text Available We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3, which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.

  1. Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

    Science.gov (United States)

    Wagner, T; Page, J; Burniston, M; Skillen, A; Ross, J C; Manwani, R; McCool, D; Hawkins, P N; Wechalekar, Ashutosh D

    2018-07-01

    18 F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18 F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. Seventeen patients with proven cardiac amyloidosis underwent 18 F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123 I-serum amyloid P component (SAP). 18 F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUV mean ) were produced. All 17 patients showed 18 F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123 I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18 F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123 I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. 18 F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18 F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool

  2. Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis.

    Science.gov (United States)

    Kanaan, M Z; Lorenzi, A R; Thampy, N; Pandit, R; Dayan, Margaret

    2017-12-01

    A 75-year-old hypertensive female with stable idiopathic intermediate uveitis presented with bilateral sequential optic neuropathy with optic disc swelling. The optic neuropathy in the first affected eye (right) was thought to be due to non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left optic disc swelling was found at routine review 2 months later, and a diagnosis of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound showed the "halo sign," but a subsequent temporal artery biopsy showed light-chain (AL) amyloidosis with no signs of giant cell arteritis. In this case, bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior ischaemic optic neuropathy was the presenting sign of systemic amyloidosis involving the temporal arteries.

  3. Effects of Biologic Agents in Patients with Rheumatoid Arthritis and Amyloidosis Treated with Hemodialysis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Kobayashi, Daisuke; Wada, Yoko; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    Objective Our objective was to examine the safety and effects of therapy with biologics on the prognosis of rheumatoid arthritis (RA) patients with reactive amyloid A (AA) amyloidosis on hemodialysis (HD). Methods Twenty-eight patients with an established diagnosis of reactive AA amyloidosis participated in the study. The survival was calculated from the date of HD initiation until the time of death, or up to end of June 2015 for the patients who were still alive. HD initiation was according to the program of HD initiation for systemic amyloidosis patients associated with RA. Results Ten patients had been treated with biologics before HD initiation for a mean of 28.2 months (biologic group), while 18 had not (non-biologic group). HD was initiated in patients with similar characteristics except for the tender joint count, swollen joint count, and disease activity score (DAS)28-C-reactive protein (CRP). History of biologics showed that etanercept was frequently used for 8 patients as the first biologic. There was no significant difference in the mortality rate according to a Kaplan-Meier analysis (p=0.939) and or associated risk of death in an age-adjusted Cox proportional hazards model (p=0.758) between both groups. Infections were significantly more frequent causes of death in the biologic group than in the non-biologic group (p=0.021). However, treatment with biologics improved the DAS28-CRP score (p=0.004). Conclusion Under the limited conditions of AA amyloidosis treated with HD, the use of biologics might affect infection and thus may not improve the prognosis. Strict infection control is necessary for the use of biologics with HD to improve the prognosis.

  4. A prospective study of nutritional status in immunoglobulin light chain amyloidosis

    DEFF Research Database (Denmark)

    Sattianayagam, PT; Lane, T; Fox, Z

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagno...

  5. Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

    Science.gov (United States)

    Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

    2018-02-01

    Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

  6. Light chain (AL amyloidosis: update on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Rosenzweig Michael

    2011-11-01

    Full Text Available Abstract Light chain (AL amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM followed by autologous hematopoietic stem cell transplantation (SCT or oral melphalan with dexamethasone (MDex. The use of novel agents (thalidomide, lenalidomide and bortezomib alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

  7. Pulmonary uptake of 198Au during liver scanning in two patients with amyloidosis

    International Nuclear Information System (INIS)

    Goebel, R.

    1976-01-01

    Lung uptake of 198 Au-colloid, injected for a liver scan, is demonstrated in two patients with systemic amyloidosis. The incidence, importance and mechanism of this phenomenon is discussed. (orig.) [de

  8. Long-Term Results of Conformal Radiotherapy for Progressive Airway Amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Truong, Minh Tam, E-mail: mitruong@bu.edu [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Grillone, Gregory A. [Department of Otolaryngology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Bohrs, Harry K.; Lee, Richard [Department of Radiation Oncology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Sakai, Osamu [Department of Radiology, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States); Berk, John L. [Department of Medicine, Amyloid Treatment and Research Program, Boston University School of Medicine, Boston Medical Center, Boston, MA (United States)

    2012-06-01

    Purpose: To evaluate the efficacy of conformal external beam radiotherapy (RT) for local control of progressive airway amyloidosis. Methods and Materials: We conducted a retrospective review of patients with biopsy-proven progressive airway amyloidosis treated with conformal RT between 2000 and 2006 at Boston Medical Center. The patients were evaluated for performance status and pulmonary function, with computed tomography and endoscopy after RT compared with the pretreatment studies. Local control was defined as the lack of progression of airway wall thickening on computed tomography imaging and stable endobronchial deposits by endoscopy. Results: A total of 10 symptomatic airway amyloidosis patients (3 laryngeal and 7 tracheobronchial) received RT to a median total dose of 20 Gy in 10 fractions within 2 weeks. At a median follow-up of 6.7 years (range, 1.5-10.3), 8 of the 10 patients had local control. The remaining 2 patients underwent repeat RT 6 and 8.4 months after initial RT, 1 for persistent bronchial obstruction and 1 for progression of subglottic amyloid disease with subsequent disease control. The Eastern Cooperative Oncology Group performance status improved at a median of 18 months after RT compared with the baseline values, from a median score of 2 to a median of 1 (p = .035). Airflow (forced expiratory volume in 1 second) measurements increased compared with the baseline values at each follow-up evaluation, reaching a 10.7% increase (p = .087) at the last testing (median duration, 64.8 months). Acute toxicity was limited to Grade 1-2 esophagitis, occurring in 40% of patients. No late toxicity was observed. Conclusions: RT prevented progressive amyloid deposition in 8 of 10 patients, resulting in a marginally increased forced expiratory volume in 1 second, and improved functional capacity, without late morbidity.

  9. Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice

    DEFF Research Database (Denmark)

    Olesen, Louise Orum; Sivasaravanaparan, Mithula; Severino, Maurizio

    2017-01-01

    Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the...... working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory....... the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APPswe/PS1dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis......Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess...

  10. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

    Directory of Open Access Journals (Sweden)

    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  11. Innovative Magnetic Resonance Imaging Markers of Hereditary Cerebral Amyloid Angiopathy at 7 Tesla.

    Science.gov (United States)

    Koemans, Emma A; van Etten, Ellis S; van Opstal, Anna M; Labadie, Gerda; Terwindt, Gisela M; Wermer, Marieke J H; Webb, Andrew G; Gurol, Edip M; Greenberg, Steven M; van Buchem, Mark A; van der Grond, Jeroen; van Rooden, Sanneke

    2018-06-01

    The aim of the present study is to explore whether using 7 Tesla magnetic resonance imaging, additional brain changes can be observed in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) patients as compared with the established magnetic resonance imaging features of sporadic cerebral amyloid angiopathy. The local institutional review board approved this prospective cohort study. In all cases, informed consent was obtained. This prospective parallel cohort study was conducted between 2012 and 2014. We performed T 2 *-weighted magnetic resonance imaging performed at 7 Tesla in presymptomatic mutation carriers (n=11, mean age 35±12 years), symptomatic HCHWA-D patients (n=15, mean age 45±14 years), and in control subjects (n=29, mean age 45±14 years). Images were analyzed for the presence of changes that have not been reported before in sporadic cerebral amyloid angiopathy and HCHWA-D. Innovative observations comprised intragyral hemorrhaging and cortical changes. The presence of these changes was systematically assessed in all participants of the study. Symptomatic HCHWA-D-patients had a higher incidence of intragyral hemorrhage (47% [7/15], controls 0% [0/29], P <0.001), and a higher incidence of specific cortical changes (40% [6/15] versus 0% [0/29], P <0.005). In presymptomatic HCHWA-D-mutation carriers, the prevalence of none of these markers was increased compared with control subjects. The presence of cortical changes and intragyral hemorrhage are imaging features of HCHWA-D that may help recognizing sporadic cerebral amyloid angiopathy in living patients. © 2018 American Heart Association, Inc.

  12. Exacerbations of asthma - A descriptive study of 425 severe exacerbations

    NARCIS (Netherlands)

    Tattersfield, AE; Postma, DS; Barnes, PJ; Svensson, K; Bauer, CA; O'Byrne, PM; Lofdahl, CG; Pauwels, RA; Ullman, A

    The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue p-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high

  13. The hormonal and radiological evaluation of adrenal glands, and the determination of the usefulness of low dose ACTH test in patients with renal amyloidosis.

    Science.gov (United States)

    Gündüz, Z; Keleştimur, F; Durak, A C; Utaş, C; Büyükberber, M; Düşünsel, R; Kurtoğlu, S; Poyrazoglu, M H

    2001-03-01

    Amyloidosis is a multisystem disease which may cause organ loss. Renal involvement is the most common clinical problem in amyloidosis, however involvement of endocrin organs is possible. In this study to assess adrenocortical function and to evaluate the usefulness of low dose ACTH test in patients with renal amyloidosis, we determined cortisol, 17-hydroxyprogesteron (17-OHP) and 11-deoxycortisol (11-DOC) responses to both 1 microg and 250 microg Synacthen. We also determined the size of adrenal glands radiologically by using computerized tomography. Twenty one patients with renal amyloidosis and 16 healthy subjects for hormonal evaluation, and 20 patients with renal amyloidosis and 22 healthy subjects for radiologic evaluation were included in the study. In four patients (19%) peak serum cortisol levels following stimulation with the low dose of Synacthen were less than 20 microg/dL (550 nmol/L). Two of them had also subnormal cortisol response to the 250 microg Synacthen stimulation test. Basal and stimulated levels of 11-DOC were lower than those of control values (p=0.000 and p<0.01 respectively). The mean 11-DOC responses to stimulation with 1 microg Synacthen were also significantly lower than the values obtained after the simulation with 250 microg Synacthen (p<0.01 and p=0.000). Cortisol responses to the stimulation with 250 microg Synacthen were also lower than the control responses (p<0.05). 17-OHP responses were similar to the control values in both tests. In the radiological evaluation the mean maximum width of right adrenal glands and the mean anterior and maximum width of left adrenal glands were significantly greater in the patient group (p<0.01). In conclusion, adrenal involvement and adrenal insufficiency is common in amyloidosis. Low 11-DOC levels in amyloidosis is a new finding and further detailed studies is required to explain its cause.

  14. Impact of exacerbations on COPD

    Directory of Open Access Journals (Sweden)

    A. Anzueto

    2010-06-01

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD determine disease-associated morbidity, mortality, resource burden and healthcare costs. Acute exacerbation care requirements range from unscheduled primary care visits to emergency room, inpatient or intensive care, generating significant costs in COPD. Even after an exacerbation resolves, respiratory, physical, social and emotional impairment may persist for prolonged time. Frequent exacerbations, mainly in patients with severe COPD, accelerate disease progression and mortality. Thus, patients with frequent exacerbations have a more rapid decline in lung function, worse quality of life and decreased exercise performance. Management of COPD directed to reduce incidence and severity of exacerbations improves long-term health status and conserves health care resources and costs.

  15. Autonomic Neuropathy and Albuminocytologic Dissociation in Cerebrospinal Fluid As the Presenting Features of Primary Amyloidosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    2017-07-01

    Full Text Available ObjectivePrimary amyloidosis is a disease with a poor prognosis and multi-organ involvement. Here, we report the clinical and pathological features of a patient with primary amyloidosis featuring autonomic neuropathy as the initial symptom and albuminocytologic dissociation in the cerebrospinal fluid (CSF.MethodsThe patient was a 60-year-old Chinese male with numbness, orthostatic hypotension, and gastrointestinal symptoms. For diagnosis, we performed an electromyogram (EMG, lumbar puncture, Bence Jones protein urine test, serum electrophoresis blood test, sural nerve and rectal membrane biopsies, transthyretin (TTR gene sequencing, and bone marrow puncture.ResultsCongo red staining of sural nerve and rectal membrane biopsies showed amyloid deposition and apple-green birefringence was visualized under polarized light microscopy. TTR gene sequencing showed no causative mutation. Following lumbar puncture, normal CSF cell counts and elevated CSF protein concentration (1,680 mg/L were detected. Bone marrow puncture showed that out of the total number of whole blood cells, 0.56% were abnormal plasma cells and that 87.4% of the total number of plasma cells were abnormal. EMG results showed mixed peripheral nerve damage predominately in the sensory nerve fibers.ConclusionObvious symptoms of neuropathy, particularly autonomic neuropathy, albuminocytologic dissociation, and organ function damage suggested a diagnosis of amyloidosis. In such patients, neurologists should use caution to differentiate between chronic inflammatory demyelinating polyneuropathy, primary amyloidosis, and familial amyloid neuropathy.

  16. Acute exacerbation of COPD.

    Science.gov (United States)

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations. © 2016 Asian Pacific Society of Respirology.

  17. Acquired A amyloidosis from injection drug use presenting with atraumatic splenic rupture in a hospitalized patient: a case report

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    Hanks Douglas K

    2011-01-01

    Full Text Available Abstract Introduction Little is known about splenic rupture in patients who develop systemic acquired A amyloidosis. This is the first report of a case of atraumatic splenic rupture in a patient with acquired A amyloidosis from chronic injection drug use. Case presentation A 58-year-old Caucasian man with a long history of injection drug use, hospitalized for infective endocarditis, experienced atraumatic splenic rupture and underwent splenectomy. Histopathological and microbiological analyses of the splenic tissue were consistent with systemic acquired A amyloidosis, most likely from injection drug use, that led to splenic rupture without any recognized trauma or evidence of bacterial embolization to the spleen. Conclusion In patients with chronic inflammatory conditions, including the use of injection drugs, who experience acute onset of left upper quadrant pain, the diagnosis of atraumatic splenic rupture must be considered.

  18. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  19. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    Directory of Open Access Journals (Sweden)

    Arahata M

    2016-08-01

    Full Text Available Masahisa Arahata,1 Shigeru Shimadoi,1 Satosi Yamatani,1 Shin-ichi Hayashi,2 Shigeharu Miwa,2 Hidesaku Asakura,3 Shinji Nakao4 1Department of Internal Medicine, Nanto Municipal Hospital, Nanto, 2Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Internal Medicine (III, 4Department of Cellular Transplantation Biology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Abstract: Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. Keywords: systemic amyloidosis, amyloid cardiomyopathy, fine-needle aspiration biopsy, subcutaneous fat tissue, hip

  20. Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

    Science.gov (United States)

    Kagawa, Miwako; Fujino, Yasuteru; Muguruma, Naoki; Murayama, Noriaki; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Kishi, Kazuhiro; Miyamoto, Hiroshi; Uehara, Hisanori; Takayama, Tetsuji

    2016-06-01

    A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years.

  1. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis.

    Science.gov (United States)

    Bever, Katherine M; Masha, Luke I; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L; Sanchorawala, Vaishali; Seldin, David C; Sloan, J Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Copyright© Ferrata Storti Foundation.

  2. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    Science.gov (United States)

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  3. Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

    Science.gov (United States)

    Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

    2015-05-01

    The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

  4. Three-dimensional Speckle Tracking Echocardiography in Light Chain Cardiac Amyloidosis: Examination of Left and Right Ventricular Myocardial Mechanics Parameters.

    Science.gov (United States)

    Urbano-Moral, Jose Angel; Gangadharamurthy, Dakshin; Comenzo, Raymond L; Pandian, Natesa G; Patel, Ayan R

    2015-08-01

    The study of myocardial mechanics has a potential role in the detection of cardiac involvement in patients with amyloidosis. This study aimed to characterize 3-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics in light chain amyloidosis and examine their relationship with brain natriuretic peptide. In patients with light chain amyloidosis, left ventricular longitudinal and circumferential strain (n=40), and right ventricular longitudinal strain and radial displacement (n=26) were obtained by 3-dimensional-speckle tracking echocardiography. Brain natriuretic peptide levels were determined. All myocardial mechanics measurements showed differences when compared by brain natriuretic peptide level tertiles. Left and right ventricular longitudinal strain were highly correlated (r=0.95, P<.001). Left ventricular longitudinal and circumferential strain were reduced in patients with cardiac involvement (-9±4 vs -16±2; P<.001, and -24±6 vs -29±4; P=.01, respectively), with the most prominent impairment at the basal segments. Right ventricular longitudinal strain and radial displacement were diminished in patients with cardiac involvement (-9±3 vs -17±3; P<.001, and 2.7±0.8 vs 3.8±0.3; P=.002). On multivariate analysis, left ventricular longitudinal strain was associated with the presence of cardiac involvement (odds ratio = 1.6; 95% confidence interval, 1.04 to 2.37; P=.03) independent of the presence of brain natriuretic peptide and troponin I criteria for cardiac amyloidosis. Three-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics are increasingly altered as brain natriuretic peptide increases in light chain amyloidosis. There appears to be a strong association between left ventricular longitudinal strain and cardiac involvement, beyond biomarkers such as brain natriuretic peptide and troponin I. Copyright © 2015 Sociedad Española de Cardiología. Published by

  5. Rheumatic polymyalgia like presentation of multiple myeloma and amyloidosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose Bernardo; Restrepo, Jose Felix; Rondon, Federico; Iglesias Gamarra, Antonio

    2005-01-01

    Polymyalgia rheumatica is a disorder with defined clinical characteristics and may be the initial expression or to be associated to other diseases. Although it is not associated to neoplastic diseases, may be their initial manifestation. We report a patient who presented the initial complaining of polymyalgia rheumatica as a manifestation of another illness, amyloidosis associated to multiple myeloma. We also discuss the clinical characteristics of these entities and revised the available literature with regard to this association

  6. Behcet's disease with cerebral vasculitis

    International Nuclear Information System (INIS)

    Scardamaglia, L.; Desmond, P.M.; Gonzales, M.F.; Bendrups, A.; Brodtmann, A.

    2001-01-01

    The case presented illustrates the diagnostic dilemma off neurological involvement in Behcet's disease and other inflammatory diseases. 'Psychiatric' symptoms were present for 2 years without abnormalities on SPECT or MRI and without CSF pleocytosis. Even at the time of fitting, no CSF abnormalities were observed. The preceding psychiatric presentations may have been due to cerebral vasculitis that was exacerbated by withdrawal of steroids. Magnetic resonance imaging is currently the most sensitive imaging modality. Lesions are usually in the brainstem, cerebellum, basal ganglia region or periventricular white matter, and the pons and the mesencephalon are commonly affected. In our patient there was no diencephalic or brainstem involvement. The inflammatory process can appear as a very large lesion, with gadolinium enhancement and significant mass effect, as in our patient. Brain magnetic resonance imaging. Postgadolinium-diethylenetriamine pentaacetic acid, axial image shows two large lesions in the right frontal lobe, with the larger, posterior lesion demonstrating vivid ring enhancement. A central nodule is isodense, with the cerebral white matter within the larger lesion. Surrounding low T 1 signal involves the hemispheric white matter without cortical extension and is consistent with vasogenic oedema. Minor mass effect is demonstrated with bowing of the anterior falx cerebri to the left. Biopsy shows prominent fibrinoid necrosis in small calibre postcapillary venules and cerebral white matter. There are surrounding acute and chronic inflammatory cells and nuclear debris, consistent with vasculitis

  7. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-01-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal...... that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care...... to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome....

  8. A case of cerebral reversible vasoconstriction syndrome triggered by repetition transcranial magnetic stimulation.

    Science.gov (United States)

    Sato, Mamiko; Yamate, Koji; Hayashi, Hiromi; Miura, Toyoaki; Kobayashi, Yasutaka

    2017-08-31

    A 75-year-old man was admitted for combined low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy. Five days after the initiation of rTMS, he developed hypotension and temporary exacerbation of the right hemiplegia with thunderclap headache. MRA showed segmental stenosis of the left middle cerebral artery, which findings were improved at 9 days after the onset of the headache. He was diagnosed as having the reversible cerebral vasoconstriction syndrome (RCVS). The rTMS was recognized as safe rehabilitation treatment. However, it is necessary to recognize that RCVS can become one of the precipitants. This is the first report of RCVS triggered by rTMS.

  9. Amyloidosis: A story of how inframammary erosions eclipsed inconspicuous periorbital ecchymoses

    Directory of Open Access Journals (Sweden)

    Andrew Kelsey, MD

    2016-03-01

    Full Text Available Systemic amyloidosis is a rare disease that can be rapidly progressive due to widespread organ involvement. There are well-described renal, cardiac, pulmonary, neurological, and dermatologic findings. Here, we outline one patient’s experience with the condition from presentation to making the diagnosis. She presented with pathognomonic dermatologic findings including pinch purpura and ecchymoses found in the skin folds.

  10. Visualization of multiple organ amyloid involvement in systemic amyloidosis using {sup 11}C-PiB PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ezawa, Naoki; Katoh, Nagaaki; Yoshinaga, Tsuneaki [Shinshu University School of Medicine, Department of Medicine (Neurology and Rheumatology), Nagano (Japan); Oguchi, Kazuhiro [Jisenkai Brain Imaging Research Center, Matsumoto (Japan); Yazaki, Masahide [Shinshu University School of Health Sciences, Department of Biomedical Laboratory Sciences, Matsumoto (Japan); Shinshu University, Institute for Biomedical Sciences, Matsumoto (Japan); Sekijima, Yoshiki [Shinshu University School of Medicine, Department of Medicine (Neurology and Rheumatology), Nagano (Japan); Jisenkai Brain Imaging Research Center, Matsumoto (Japan); Shinshu University, Institute for Biomedical Sciences, Matsumoto (Japan)

    2018-03-15

    To investigate the utility of Pittsburgh compound B (PiB) positron emission tomography (PET) imaging for evaluating whole-body amyloid involvement in patients with systemic amyloidosis. Whole-body {sup 11}C-PiB PET was performed in seven patients with systemic immunoglobulin light-chain (AL) amyloidosis, seven patients with hereditary transthyretin (ATTRm) amyloidosis, one asymptomatic TTR mutation carrier and three healthy controls. The correlations between clinical organ involvement, radiological {sup 11}C-PiB uptake and histopathological findings were analysed for each organ. Organ involvement on {sup 11}C-PiB PET imaging showed good correlations with the clinical findings for the heart and stomach. Abnormal tracer uptake was also observed in the spleen, lachrymal gland, submandibular gland, sublingual gland, lymph node, brain, scalp, extraocular muscles, nasal mucosa, pharynx, tongue and nuchal muscles, most of which were asymptomatic. Physiological tracer uptake was universally observed in the urinary tract (kidney, renal pelvis, ureter and bladder) and enterohepatic circulatory system (liver, gallbladder, bile duct and small intestine) in all participants. Most of the patients and one healthy control subject showed asymptomatic tracer uptake in the lung and parotid gland. The peripheral nervous system did not show any tracer uptake even in patients with apparent peripheral neuropathy. Histological amyloid deposition was confirmed in biopsied myocardium and gastric mucosa where abnormal {sup 11}C-PiB retention was observed. {sup 11}C-PiB PET imaging can be used clinically in the systemic evaluation of amyloid distribution in patients with AL and ATTRm amyloidosis. Quantitative analysis of {sup 11}C-PiB PET images may be useful in therapy evaluation and will reveal whether amyloid clearance is correlated with clinical response. (orig.)

  11. Systemic Amyloidosis and Testicular Interstitial Tumor in a Zebra Finch (Taeniopygia guttata: a Case Report in Iran

    Directory of Open Access Journals (Sweden)

    Mehrnoush Moeini Jazani

    2011-09-01

    Full Text Available Abstract Systemic amyloidosis and testicular interstitial tumor are rare conditions in birds and this is the first report in Iran. A male zebra finch was presented because of white diarrhea, anorexia, loss of weight and lethargy. At necropsy, the small intestine was edematous and congested. The spleen appeared pale. The liver was large, firm and brown. One testis was cystic and neoplastic and the remaining testis was atrophic. Histologically, amyloid materials were seen predominantly in the liver and spleen. Hyaline substances were deposited in the Disse space and in the media of blood vessels of the liver. In spleen, marked deposits thickened the basement membranes of blood vessels and extended into the surrounding parenchyma. In addition, there were lesser degrees of amyloidosis in other organs such as small intestine. Amyloid stained positively with Congo red. In testis, there was encapsulated unilateral interstitial cell tumor, with multiple foci of necrosis and hemorrhage. The neoplastic cells were round to polyhedral, with small round hyperchromatic nuclei and finely vacuolated cytoplasm. Signs of feminization were observed. The cause of amyloidosis in this study was not conclusively identified.

  12. Assessment and Management of the Communication Difficulties of Children with Cerebral Palsy: A UK Survey of SLT Practice

    Science.gov (United States)

    Watson, Rose Mary; Pennington, Lindsay

    2015-01-01

    Background: Communication difficulties are common in cerebral palsy (CP) and are frequently associated with motor, intellectual and sensory impairments. Speech and language therapy research comprises single-case experimental design and small group studies, limiting evidence-based intervention and possibly exacerbating variation in practice. Aims:…

  13. Programmed initiation of hemodialysis for systemic amyloidosis patients associated with rheumatoid arthritis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Sakatsume, Minoru; Nakano, Masaaki; Narita, Ichiei

    2011-09-01

    Reactive amyloidosis is a serious systemic disease in rheumatoid arthritis (RA). Amyloid protein can be deposited in kidneys, heart or gastrointestinal tract leading to organ failure. Renal involvement is a well-known complication in amyloidosis as this may culminate in end-stage renal disease (ESRD). Hemodialysis (HD) is always considered the treatment of choice for such patients; however, the prognosis is usually poor due to a large number of sudden deaths immediately following HD therapy. To circumvent the problem of HD initiation while instituting HD safety, we devised a plan to start HD and compare patient's survival with our previous data. Sixty-three patients were treated with HD. They were categorized according to the initiation of first dialysis. All patients were divided into planned, unplanned and programmed initiation groups. First dialysis that had been initiated as not urgent was considered 'planned' (20 patients). First dialysis that had been performed urgently for life-threatening renal insufficiency was considered 'unplanned' (31 patients). First dialysis that had been initiated as not urgent and according to our dialysis program was considered 'programmed' (12 patients). Survival of these 63 patients from the initiation of HD at 38 days was 75%, at 321 days was 50% and at 1,784 days was 25%. Patients with unplanned initiation of HD showed a significant poor survival compared with those of both planned and programmed initiation. Additionally, patients with planned and programmed initiation of HD showed no significant difference for the patients' survival. Our study demonstrates that patients with amyloidosis have a higher mortality rate. Nevertheless, programmed initiation of HD will improve the prognosis of patients with ESRD. Such possibility needs to be considered in more detail in the future.

  14. Prevention of COPD exacerbations

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Lange, Peter

    2015-01-01

    Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is eviden...

  15. Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging.

    Science.gov (United States)

    Tarantini, Stefano; Tucsek, Zsuzsanna; Valcarcel-Ares, M Noa; Toth, Peter; Gautam, Tripti; Giles, Cory B; Ballabh, Praveen; Wei, Jeanne Y; Wren, Jonathan D; Ashpole, Nicole M; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular regression in the hippocampus. To achieve that goal, we induced hypertension in control and IGF-1 deficient mice (Igf1 f/f  + TBG-Cre-AAV8) by chronic infusion of angiotensin II. We found that circulating IGF-1 deficiency is associated with decreased microvascular density and exacerbates hypertension-induced microvascular rarefaction both in the hippocampus and the neocortex. The anti-angiogenic hippocampal gene expression signature observed in hypertensive IGF-1 deficient mice in the present study provides important clues for subsequent studies to elucidate mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of VCI. In conclusion, adult-onset, isolated endocrine IGF-1 deficiency exerts deleterious effects on the cerebral microcirculation, leading to a significant decline in cortical and hippocampal capillarity and exacerbating hypertension-induced cerebromicrovascular rarefaction. The morphological impairment of the cerebral microvasculature induced by IGF-1 deficiency and hypertension reported here, in combination with neurovascular uncoupling, increased

  16. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

    2013-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

  17. Comparison of Different Stem Cell Mobilization Regimens in AL Amyloidosis Patients.

    Science.gov (United States)

    Lisenko, Katharina; Wuchter, Patrick; Hansberg, Marion; Mangatter, Anja; Benner, Axel; Ho, Anthony D; Goldschmidt, Hartmut; Hegenbart, Ute; Schönland, Stefan

    2017-11-01

    High-dose melphalan (HDM) and autologous blood stem cell transplantation (ABSCT) is an effective treatment for transplantation-eligible patients with systemic light chain (AL) amyloidosis. Whereas most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells (PBSC), the application of mobilization chemotherapy might offer specific advantages. We retrospectively analyzed 110 patients with AL amyloidosis who underwent PBSC collection. Major eligibility criteria included age CSF (n = 78, 71%); ifosfamide/G-CSF (n = 14, 13%); or other regimens (n = 8, 7%). AL amyloidosis patients with predominant heart involvement and/or status post heart transplantation were mobilized with G-CSF only (n = 10, 9%). PBSC collection was successful in 101 patients (92%) at first attempt. The median number of CD34 + cells was 8.7 (range, 2.1 to 45.5) × 10 6 CD34 + /kg collected in a median of 1 leukapheresis (LP) session. Compared with G-CSF-only mobilization, a chemo-mobilization with CAD/G-CSF or ifosfamide/G-CSF had a positive impact on the number of collected CD34 + cell number/kg per LP (P CSF mobilization (median CTC: grade 3; range, 1 to 4). Toxicity in patients undergoing ifosfamide/G-CSF mobilization was higher than in with those who received G-CSF-only mobilization. HDM and ABSCT were performed in 100 patients. Compared with >6.5 × 10 6 transplanted CD34 + cells/kg, an ABSCT with 1 × 10 9 /L and a reduced platelet count CSF mobilization alone is also safe and effective. Considering the hematopoietic reconstitution and long-term stem cell function, our results provide a rationale to collect and transplant as many as >6.5 × 10 6 CD34 + cells/kg, if feasible with reasonable effort. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes

    NARCIS (Netherlands)

    Rensink, Annemieke A M; Otte-Höller, Irene; de Boer, Roelie; Bosch, Remko R; ten Donkelaar, Hans J; de Waal, Robert M W; Verbeek, Marcel M; Kremer, Berry

    Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of

  19. Unsuitable value of abdominal fat tissue aspirate examination for the diagnosis of amyloidosis in long-term hemodialysis patients.

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    Orfila, C; Goffinet, F; Goudable, C; Eche, J P; Ton That, H; Manuel, Y; Suc, J M

    1988-01-01

    Abdominal fat tissue aspiration was used in 22 long-term hemodialysis patients (5-17 years). Fourteen of these patients had carpal tunnel syndrome and amyloid deposits of beta 2-microglobulin in the synovium. One patient had a spontaneous rupture of the spleen with amyloid deposits in spleen vessels. Seven other patients presented carpal tunnel syndrome and/or articular pains, and radiological lytic lesions in bone, strongly suggesting an amyloid origin. As a control group, in 22 patients with biopsy-proven amyloidosis, abdominal fat tissue aspirates were performed and were studied under the same conditions: by light microscopy these tissues were stained with Congo red and examined with a polarizing microscope; these specimens were also studied by electron microscopy. In all hemodialyzed patients, no amyloid deposit was present in fat tissue with Congo red staining and by electron microscopy. On the contrary, amyloid was observed in 17 of 22 cases in other types of amyloidosis. It seems that this method which has been proved to be simple and sensitive for the diagnosis of systemic amyloidosis is not a good marker for the presence of amyloid in long-term hemodialysis patients.

  20. Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement.

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    Girnius, S; Seldin, D C; Meier-Ewert, H K; Sloan, J M; Quillen, K; Ruberg, F L; Berk, J L; Doros, G; Sanchorawala, V

    2014-03-01

    In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

  1. Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a Novel Mutation in the Gelsolin Gene.

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    Oregel, Karlos Z; Shouse, Geoffrey P; Oster, Cyrus; Martinez, Freddy; Wang, Jun; Rosenzweig, Michael; Deisch, Jeremy K; Chen, Chien-Shing; Nagaraj, Gayathri

    2018-03-30

    BACKGROUND Gelsolin amyloidosis is a very rare systemic disease presenting with a pathognomonic triad of corneal lattice dystrophy, cutis laxa, and polyneuropathy. The disease is mostly restricted to a Finnish population with known mutations (G654A, G654T) in exon 4 of the gelsolin gene. The mutations lead to errors in protein processing and folding, and ultimately leads to deposition of an amyloidogenic fragment in the extracellular space, causing the symptoms of disease. CASE REPORT We present a case of gelsolin amyloidosis in a male of African descent with an atypical clinical presentation including fevers, skin rash, polyneuropathy, and anemia. Gelsolin amyloidosis was diagnosed based on mass spectrometry of tissue samples. Importantly, a novel mutation in the gelsolin gene (C1375G) in exon 10 was found in this patient. His atypical presentation can possibly be attributed to the presence of a novel mutation in the gelsolin gene as the likely underlying cause of the syndrome. PCR primers were used to amplify the gelsolin gene from genomic DNA. Purified PCR products were then shipped to Eton Biosciences (San Diego, CA) for sequencing. CONCLUSIONS This study carries several important lessons relevant to the practice of medicine. First, the differential diagnosis for multisystem disease presentations should always include amyloidosis. Second, despite what has been uncovered about the molecular biology of disease, there is always more that can be discovered. Finally, further work to verify the link between this mutation and the clinical syndrome is still needed, as are effective treatments for this disease.

  2. Adoptive regulatory T-cell therapy preserves systemic immune homeostasis after cerebral ischemia.

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    Li, Peiying; Mao, Leilei; Zhou, Guoqing; Leak, Rehana K; Sun, Bao-Liang; Chen, Jun; Hu, Xiaoming

    2013-12-01

    Cerebral ischemia has been shown to result in peripheral inflammatory responses followed by long-lasting immunosuppression. Our recent study demonstrated that intravenous delivery of regulatory T cells (Tregs) markedly protected against transient cerebral ischemia by suppressing neutrophil-derived matrix metallopeptidase 9 production in the periphery. However, the effect of Tregs on systemic inflammatory responses and immune status has not been fully characterized. Cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were isolated from donor animals by CD4 and CD25 double selection and transferred intravenously to ischemic recipients at 2 hours after middle cerebral artery occlusion. Animals were euthanized on different days after reperfusion. The effects of Tregs on systemic inflammation and immune status were evaluated using flow cytometry, ELISAs, and immunohistochemistry. Systemic administration of purified Tregs raises functional Tregs in the blood and peripheral organs, including spleen and lymph nodes. These exogenous Tregs remain in the blood and peripheral organs for ≥12 days. Functionally, Treg adoptive transfer markedly inhibits middle cerebral artery occlusion-induced elevation of inflammatory cytokines (interleukin-6 and tumor necrosis factor α) in the blood. Furthermore, Treg treatment corrects long-term lymphopenia and improves cellular immune functions after ischemic brain injury. As a result, Treg-treated animals exhibit decreased bacterial loads in the blood during recovery from cerebral ischemic attack. Treg treatment did not exacerbate poststroke immunosuppression. On the contrary, Treg-treated animals displayed improved immune status after focal cerebral ischemia.

  3. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

    Science.gov (United States)

    Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

    2014-08-01

    Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

  4. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

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    Lia Millucci

    2014-01-01

    Full Text Available Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.

  5. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

    Science.gov (United States)

    Ghezzi, Lorenzo; Giorgetti, Giovanna; Viti, Cecilia; Geminiani, Michela; Soldani, Patrizia; Lupetti, Pietro; Benvenuti, Chiara; Perfetto, Federico; Spreafico, Adriano; Santucci, Annalisa

    2014-01-01

    Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart. PMID:24876668

  6. Diagnostic performance of I-123-labeled serum amyloid P component scintigraphy in patients with amyloidosis

    NARCIS (Netherlands)

    Hazenberg, BPC; van Rijswijk, MH; Piers, DA; Lub-de Hooge, MN; Vellenga, E; Haagsma, EB; Hawkins, PN; Jager, PL

    Purpose: To assess the diagnostic accuracy and additional information provided by I-123-labeled serum amyloid P component ( SAP) scintigraphy in patients with systemic and localized amyloidosis. Subjects and Methods: I-123-labeled human SAP was injected intravenously into 20 controls and 189

  7. Pathology of AA amyloidosis in domestic sheep and goats.

    Science.gov (United States)

    Ménsua, C; Carrasco, L; Bautista, M J; Biescas, E; Fernández, A; Murphy, C L; Weiss, D T; Solomon, A; Luján, L

    2003-01-01

    We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.

  8. [The prognostic value of baseline serum free light chain in cardiac amyloidosis].

    Science.gov (United States)

    Zhao, Lei; Tian, Zhuang; Fang, Quan

    2016-03-01

    To analyze the prognostic value of baseline serum free light chain (sFLC) in light-chain (AL) cardiac amyloidosis. Twenty-seven patients with AL cardiac amyloidosis were retrospectively reviewed from January 2014 to January 2015. sFLC was measured by immuoturbidimetric assay. Baseline characteristics, echocardiographic parameters and electrocardiogram data were analyzed. According to the median baseline dFLC (involved sFLC minus uninvolved sFLC), patients were categorized into either the low dFLC(≤ 307 mg/L) or the high dFLC group (>307 mg/L). More subjects in the high dFLC group with early/late diastolic mitral velocity ratio (E/A ratio) over 2 (71.4% vs 30.8%, P=0.035), and subjects in this group had a shorter median survival time than those in the low dFLC group (3 months vs 17 months, P=0.004). A similar phenomenon for median survival time was observed when the subjects were redivided either by a new cut-off value of 180 mg/L for dFLC (low dFLC group: 17 months; high dFLC group: 4 months, P=0.014) or a κ/λ ratio, in which subjects with κ type sFLC-ratio ≤ 19.6 and λ type sFLC-ratio>0.065 were in the low sFLC-ratio group (17 months) and those with κ type sFLC-ratio > 19.6 and λ type sFLC-ratio ≤ 0.065 were in the high sFLC-ratio group (4 months, P=0.023). In multivariate analysis, dFLC and New York Heart Association (NYHA)classification of cardiac function were two risk factors associated with all-cause mortality in patients, among which the hazard ratio for higher dFLC was 4.28 (95%CI 1.55-11.8, P=0.005). The level of sFLC could be a marker for the prognosis of AL cardiac amyloidosis.

  9. Optimizing antibiotic selection in treating COPD exacerbations

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    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  10. Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase

    Science.gov (United States)

    Huang, Zhihong; Huang, Paul L.; Panahian, Nariman; Dalkara, Turgay; Fishman, Mark C.; Moskowitz, Michael A.

    1994-09-01

    The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.

  11. [Predictive factors associated with severity of asthma exacerbations].

    Science.gov (United States)

    Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

    2008-01-01

    Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

  12. 2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †.

    Science.gov (United States)

    Renz, Mark; Torres, Ronald; Dolan, Philip J; Tam, Stephen J; Tapia, Jose R; Li, Lauri; Salmans, Joshua R; Barbour, Robin M; Shughrue, Paul J; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G; Zago, Wagner

    2016-09-01

    Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency-approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T-positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis.

  13. 2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †

    Science.gov (United States)

    Renz, Mark; Torres, Ronald; Dolan, Philip J.; Tam, Stephen J.; Tapia, Jose R.; Li, Lauri; Salmans, Joshua R.; Barbour, Robin M.; Shughrue, Paul J.; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G.; Zago, Wagner

    2016-01-01

    Abstract Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency–approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T–positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis. PMID:27494229

  14. Renal and suprarenal insufficiency secondary to familial Mediterranean fever associated with amyloidosis: a case report

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    Sari Nagehan

    2011-08-01

    Full Text Available Abstract Introduction Familial Mediterranean fever is an autosomal recessive disease that predominantly affects people of the Mediterranean coast. One of the most frequent complications of the disease is amyloidosis. This clinical entity is known as secondary (also called AA amyloidosis. Case presentation In this report, we describe the case of a 33-year-old Turkish man with familial Mediterranean fever and chronic renal insufficiency. He was admitted to our clinic with symptoms of suprarenal insufficiency. The patient died three months later as a result of cardiac arrest. Conclusion Our aim is to make a contribution to the literature by reporting a case of combined insufficiency due to the accumulation of renal and adrenal amyloid in a patient with familial Mediterranean fever, which has very rarely been described in the literature. We hope that adrenal insufficiency, which becomes fatal if not diagnosed and treated rapidly, will come to mind as easily as chronic renal failure in clinical practice.

  15. Relationship Between Short Term Variability (STV and Onset of Cerebral Hemorrhage at Ischemia–Reperfusion Load in Fetal Growth Restricted (FGR Mice

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    Takahiro Minato

    2018-05-01

    Full Text Available Fetal growth restriction (FGR is a risk factor exacerbating a poor neurological prognosis at birth. A disease exacerbating a poor neurological prognosis is cerebral palsy. One of the cause of this disease is cerebral hemorrhage including intraventricular hemorrhage. It is believed to be caused by an inability to autoregulate cerebral blood flow as well as immaturity of cerebral vessels. Therefore, if we can evaluate the function of autonomic nerve, cerebral hemorrhage risk can be predicted beforehand and appropriate delivery management may be possible. Here dysfunction of autonomic nerve in mouse FGR fetuses was evaluated and the relationship with cerebral hemorrhage incidence when applying hypoxic load to resemble the brain condition at the time of delivery was examined. Furthermore, FGR incidence on cerebral nerve development and differentiation was examined at the gene expression level. FGR model fetuses were prepared by ligating uterine arteries to reduce placental blood flow. To compare autonomic nerve function in FGR mice with that in control mice, fetal short term variability (STV was measured from electrocardiograms. In the FGR group, a significant decrease in the STV was observed and dysfunction of cardiac autonomic control was confirmed. Among genes related to nerve development and differentiation, Ntrk and Neuregulin 1, which are necessary for neural differentiation and plasticity, were expressed at reduced levels in FGR fetuses. Under normal conditions, Neurogenin 1 and Neurogenin 2 are expressed mid-embryogenesis and are related to neural differentiation, but they are not expressed during late embryonic development. The expression of these two genes increased in FGR fetuses, suggesting that neural differentiation is delayed with FGR. Uterine and ovarian arteries were clipped and periodically opened to give a hypoxic load mimicking the time of labor, and the bleeding rate significantly increased in the FGR group. This suggests that

  16. The pathogenesis of amyloidosis in periodic disease: Some aspects

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    Z. T. Djndoyan

    2014-07-01

    Full Text Available Sufficient information indicating the implication of dysfunction of interleukins (IL-6 and IL-1 in particular in the pathogenesis of amyloidosis in a number of autoinflammatory, rheumatic, and autoimmune diseases, including those in periodic disease (PD, has been recently accumulated. Its genetic defect – pirin mutation – gives rise to an alternative innate immune response (phagocytic cell activation to secrete IL-1 by macrophages and to activate T-helper cells. This causes imbalance in the synthesis of proinflammatory (IL-6, IL-8, and TNF-α and anti-inflammatory (IL-4, IL-10, and IL-1 receptor antagonist cytokines. Moreover, the uncontrolled macrophage (monocyte secretion of a great deal of IL-6 that together with IL-1 is a mediator of the synthesis of the serum amyloid fibril protein precursor SAA by hepatocytes, neutrophils, and fibroblasts plays one of the key roles in the pathogenesis of PD through amyloidosis. With this, IL-6 stimulates the inflammatory process, by enhancing the release of lysosomal enzymes, reactive oxygen species, and eicosanoids (prostaglandins, leukotrienes, thromboxane from the polymorphic nuclear leukocytes, macrophages, endotheliocytes, and fibroblasts and by augmenting the chemotaxis of macrophages and neutrophils, and the degranulation of the latter, i.e. through its action on the effector cells of inflammation, and prepares the tissue basis for amyloid deposits in this fashion. Thus, the analysis of literary and own materials gives grounds to suggest that pirin mutation is a trigger of the synthesis of IL-1 and IL-6 in PD and their hypersecretion is an initial link of the synthesis of SAA.

  17. Primary extranodal marginal zone B-cell lymphoma with AL amyloidosis in cerebral parenchyma in an immunocompetent patient

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    Tadashi Terada, M.D., Ph.D.

    2015-09-01

    Full Text Available Herein reported is an extremely rare case of primary MALT lymphoma of cerebral parenchyma. A 79-year-old man presented with paresis. Imaging modalities identified a tumor measuring 3 cm in diameter in right cerebral parenchyma. An operation completely resected the tumor. Macroscopically, the tumor was well defined, but showed mild infiltrative features. Histologically, the tumor showed proliferation of small atypical lymphocytes separated by fibrous septae with AL amyloid depositions. No apparent plasma cell differentiation was seen. The tumor cells showed monotonous appearances with hyperchromatic nuclei but without nucleoli and nuclear indentations. Immunoblastic cells were scattered. Immunohistochemically, tumor cells were positive for vimentin, CD45, CD20, CD79α, bcl-2, CD3 (focal, CD45RO (focal, CD5 (focal, CD10, CD23, bcl-6, CD138, p53, and Ki-67 (labeling = 27%. The immunoblastic cells were positive for CD30. The lymphoid cells were negative for Epstein–Barr virus (EBV-related molecules of EBV latent membrane protein-1 (LMP-1 and EBV early RNAs (EBER. They were also negative for cytokeratins AE 1/3 and CAM5.2, cyclin D1, CD34, GFAP, α-smooth muscle actin, and S100 protein. Because of the heterogeneity of tumor cells and positive AL amyloid deposition, the author diagnosed it as primary MALT lymphoma. The patient is now free from tumors. Differential diagnosis was discussed.

  18. Asthma Exacerbation in Children: A Practical Review

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    Lin-Shien Fu

    2014-04-01

    Full Text Available Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important.

  19. Detection of AA76, a Common Form of Amyloid A Protein, as a Way of Diagnosing AA Amyloidosis.

    Science.gov (United States)

    Sato, Junji; Okuda, Yasuaki; Kuroda, Takeshi; Yamada, Toshiyuki

    2016-01-01

    Reactive amyloid deposits consist of amyloid A (AA) proteins, the degradation products of serum amyloid A (SAA). Since the most common species of AA is the amino terminal portion produced by cleavage between residues 76 and 77 of SAA (AA76), the presence of AA76 in tissues could be a consequence of AA amyloid deposition. This study assessed the diagnostic significance of the detection of AA76 for AA amyloidosis using two different approaches. Biopsy specimens (n=130 from 54 subjects) from gastroduodenal mucosa or abdominal fat (n=9 from 9 subjects) of patients who had already been diagnosed with or were suspected of having AA amyloidosis were used. Fixed mucosal sections were subjected to immunohistochemistry using a newly developed antibody recognizing the carboxyl terminal end of AA76 (anti-AA76). The non-fixed materials from gastroduodenal mucosa or abdominal fat were subjected to immunoblotting for detection of the size of AA76. Among the gastroduodenal specimens (n=115) from already diagnosed patients, the positive rates of Congo red staining, immunohistochemistry using anti-AA76, and immunoblotting were 68.4%, 73.0%, and 92.2%, respectively. The anti-AA76 did not stain the supposed SAA in the blood or leakage, which was stained by anti-SAA antibody. AA76 was not detected either by immunohistochemistry or by immunoblot in the materials from patients in whom AA amyloidosis had been ruled out. In the abdominal fat, the immunoblot detected AA76 in 8 materials from 8 already diagnosed patients and did not in 1 patient whose gastroduodenal mucosa was negative. In conclusion, the detection of AA76 may alter the ability to diagnose AA amyloidosis. In immunohistochemistry for fixed specimens, the new anti-AA76 antibody can improve the specificity. Immunoblot for non-fixed materials, which can considerably improve the sensitivity, should be beneficial for small materials like abdominal fat. © 2016 by the Association of Clinical Scientists, Inc.

  20. RE: Imaging Features of Hepato-Splenic Amyloidosis at PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Mainenti, Pier Paolo [IBB CNR, Napoli (Italy)

    2012-06-15

    Regarding the imaging of hepatic amyloidosis with PET/CT, we read with interest the case report by Son and colleagues (1) in the Sep-Oct 2011 issue of the Korean Journal of Radiology. A few points need to be discussed with more detail. First, although the enhanced CT scan of the spleen exhibited a decreased and diffuse parenchymal attenuation, this observation was not sufficiently emphasized within the manuscript. The radiological finding of splenic hypoperfusion has been well described in the literature as a marker of systemic amyloidosis, which presents a useful clue when clinical findings fail to determine the proper diagnosis (2). In the case reported by Son and colleagues, if the radiologist had immediately suggested the correct diagnostic hypothesis, the patient would have been directed to have the the appropriate laboratory examinations conducted. Specifically, the abdominal fat aspirate test which would have eliminated the need for the PET/CT scan and a risky invasive procedure such as a liver biopsy. The PET/CT images revealed a marked and diffuse increase in the 18F-FDG uptake in the enlarged liver. How do the Authors explain this finding considering the diagnosis of the disease which is characterized by the deposition and storage of an amorphous substance including amyloid? Did the compressed hepatic cells and the encased bile duct epithelium increase the glucose metabolism or was the amyloid deposition accompanied by the inflammation due to the infiltration of cells? The authors might offer us an hypothesis about the physio-pathological mechanism causing the 18F-FDG uptake in the amyloidotic liver.

  1. Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction.

    Science.gov (United States)

    Mesquita, Evandro Tinoco; Jorge, Antonio José Lagoeiro; Souza, Celso Vale; Andrade, Thais Ribeiro de

    2017-07-01

    Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiologists to investigate this etiology in suspect cases. The clinical suspicion of amyloidosis should be increased in cases of HFPS where the cardio imaging methods are compatible with infiltrative cardiomyopathy. Advances in cardio imaging methods combined with the possibility of performing genetic tests and identification of the type of amyloid material allow the diagnosis to be made. The management of the diagnosed patients can be done in partnership with centers specialized in the study of amyloidosis, which, together with the new technologies, investigate the possibility of organ or bone marrow transplantation and also the involvement of patients in clinical studies that evaluate the action of the new emerging drugs. Resumo A insuficiência cardíaca com fração de ejeção preservada (ICFEP) é hoje uma epidemia cardiovascular emergente, sendo identificada como o principal fenótipo observado na prática clínica. Está mais associado ao sexo feminino, idade avançada e a comorbidades como hipertensão arterial, diabetes, obesidade e doença renal crônica. A amiloidose é uma desordem clínica caracterizada pelo depósito de agregados de fibrilas insolúveis originadas de proteínas que apresentam dobramento anômalo. Recentemente, têm sido descritos quadros de amiloidose senil em pacientes com ICFEP, demonstrando a necessidade de os cardiologistas clínicos investigarem

  2. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

    Science.gov (United States)

    Buss, Sebastian J; Emami, Mostafa; Mereles, Derliz; Korosoglou, Grigorios; Kristen, Arnt V; Voss, Andreas; Schellberg, Dieter; Zugck, Christian; Galuschky, Christian; Giannitsis, Evangelos; Hegenbart, Ute; Ho, Anthony D; Katus, Hugo A; Schonland, Stefan O; Hardt, Stefan E

    2012-09-18

    The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p < 0.0001), diastolic dysfunction (p < 0.01), the pathologic free light chains (p < 0.05), cardiac troponin-T (cTnT) (p < 0.01), and the Karnofsky index (p < 0.001) remained as independent predictors. 2D-GLS delineated a superior prognostic value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and

  3. Prevention of exacerbations of COPD with pharmacotherapy

    Directory of Open Access Journals (Sweden)

    M. Miravitlles

    2010-06-01

    Full Text Available Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations. Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results. Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.

  4. Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide.

    Science.gov (United States)

    Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

    2018-01-01

    The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Systemic AL amyloidosis with unusual cutaneous presentation unmasked by carotenoderma

    Czech Academy of Sciences Publication Activity Database

    Hůlková, H.; Vlášková, H.; Elleder, M.; Svojanovský, J.; Ševela, K.; Krusová, D.; Hanuš, J.; Souček, M.; Vězda, P.; Márová, I.; Feit, J.; Zambo, I.; Kovačevicova, M.; Kostrouchová, V.; Kostrouch, Z.; Novák, Petr

    2014-01-01

    Roč. 21, č. 5 (2014), s. 57-61 ISSN 1350-6129 R&D Projects: GA MŠk ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.20.0055; GA MŠk LO1211; GA MŠk EE2.3.30.0003 Grant - others:Masaryk University, Brno(CZ) MUNI/A/1012/2009; GA MŠk(CZ) Prvouk-P27/LF1/1; Karlova Universita(CZ) UNCE 20422; Universita Karlova(CZ) UNCE 204011; Universita Karlova(CZ) PRVOUK-P24/LF1/3 Institutional support: RVO:61388971 Keywords : alzheimer * gene * amyloidosis Subject RIV: EC - Immunology Impact factor: 2.010, year: 2014

  6. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor

    Directory of Open Access Journals (Sweden)

    Elif Tanrıverdi

    2016-01-01

    Full Text Available Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC, and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important.

  7. Histological regression of amyloid in AL amyloidosis is exclusively seen after normalization of serum free light chain

    NARCIS (Netherlands)

    van Gameren, Ingrid I.; van Rijswijk, Martin H.; Bijzet, Johan; Vellenga, Edo; Hazenberg, Bouke P.

    Background Histological regression of amyloid has not been studied systematically but is assessed by clinical parameters. We analyzed the change of amyloid deposition in fat tissue in patients with AL amyloidosis following chemotherapy and studied the relation with type of hematologic response.

  8. Virus-induced exacerbations in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Daisuke eKurai

    2013-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses.COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage.In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.

  9. Primary tracheobronchial amyloidosis: Two case reports Amiloidose traqueobrônquica primária: A propósito de dois casos clínicos

    Directory of Open Access Journals (Sweden)

    Sandra Saleiro

    2008-07-01

    Full Text Available Primary tracheobronchial amyloidosis is a form of respiratory amyloidosis, characterised by insoluble amyloid fibril proteins deposits along the airways wall. It is an uncommon disease, requiring a tissue sample to establish the definite diagnosis based on specific pathological features. The authors report two cases of tracheobronchial amyloidosis, describing their symptoms and the diagnostic and therapeutic procedures that were performed.A amiloidose traqueobrônquica primária é uma forma de amiloidose respiratória, caracterizada pela presença de depósitos insolúveis de proteína fibrilar amilóide, ao longo da parede das vias aéreas. É uma doença pouco frequente, sendo necessário uma amostra de tecido para estabelecer o diagnóstico definitivo, com base em características histológicas específicas. Os autores relatam dois casos clínicos de amiloidose traqueobrônquica, descrevendo os seus sintomas e os procedimentos diagnósticos e terapêuticos que foram efectuados.

  10. Outcome of patients with reactive amyloidosis associated with rheumatoid arthritis in dialysis treatment.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Sato, Hiroe; Ajiro, Jyunya; Wada, Yoko; Murakami, Syuichi; Hasegawa, Hisashi; Sakatsume, Minoru; Nakano, Masaaki; Gejyo, Fumitake

    2006-10-01

    The aim was to analyze the clinical outcome of a group of 51 patients diagnosed with systemic amyloidosis associated with rheumatoid arthritis who received hemodialysis (HD) as renal replacement therapy. We monitored the clinical course of the disease and factors that could influence survival. Determination of the onset of the underlying disorder was made retrospectively by reviewing the patient's chart when a diagnosis of amyloid was confirmed. During a 96.9 person-year follow-up, 42 patients died. Survival of these 51 patients from the initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was mainly due to a large number of sudden deaths immediately following HD therapy. Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation was significantly associated with poor survival. Seventy-five percentile of creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who initiated HD had highly impaired renal functional states. These data indicated that amyloidotic patients with HD showed a high mortality rate; therefore, planned initiation of HD was highly recommended to improve the patient's survival. Particular attention was given to the Ccr levels, because the levels of serum creatinine may not be a useful marker for some patients with amyloidosis.

  11. Nonfluent/Agrammatic PPA with In-Vivo Cortical Amyloidosis and Pick’s Disease Pathology

    Directory of Open Access Journals (Sweden)

    Francesca Caso

    2013-01-01

    Full Text Available The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA. She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom, post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer’s disease (AD (CERAD frequent/Braak Stage V was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.

  12. Fatal acute pancreatitis associated with reactive AA amyloidosis in rheumatoid arthritis with end-stage renal disease: a report of three cases.

    Science.gov (United States)

    Kuroda, Takeshi; Sato, Hiroe; Hasegawa, Hisashi; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    2011-01-01

    We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.

  13. Bone marrow amyloid spherulites in a case of AL amyloidosis.

    Science.gov (United States)

    Bommannan B K, Karthik; Sonai, Mukinkumar; Sachdeva, Man Updesh Singh

    2016-05-01

    Parallel arrangement of β-pleated sheets by amyloidogenic proteins is a well known phenomenon. Rarely, amyloid fibrils undergo radial orientation to form globular structures called spherulites. These amyloid spherulites show Maltese cross pattern under polarized microscopy. The clinical significance of amyloid spherulites is undetermined. Amyloidogenic proteins like insulin and β-lactoglobulin form spherulites in vitro. The senile plaques of Alzheimer's disease rarely form in vivo spherulites. Amyloid spherulites have been described in the liver and small intestine. For the first time, we document amyloid spherulite formation in the bone marrow biopsy of an AL amyloidosis patient. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. CRYPTOCOCCUS NEOFORMANS VAR. GRUBII-ASSOCIATED RENAL AMYLOIDOSIS CAUSING PROTEIN-LOSING NEPHROPATHY IN A RED KANGAROO (MACROPUS RUFUS).

    Science.gov (United States)

    Thurber, Mary Irene; Gjeltema, Jenessa; Sheley, Matthew; Wack, Ray F

    2017-09-01

    A 10-year-old male castrated red kangaroo (Macropus rufus) presented with mandibular swelling. Examination findings included pitting edema with no dental disease evident on examination or radiographs. The results of blood work were moderate azotemia, hypoalbuminemia, and severely elevated urine protein:creatinine ratio (9.9). Radiographs showed an interstitial pattern of the caudal right lung, and an abdominal ultrasound demonstrated scant effusion. Symptomatic and empirical therapy with antibiotics, anti-inflammatory drugs, and an angiotensin-converting enzyme (ACE) inhibitor did not resolve clinical signs. Due to poor prognosis and declining quality of life, euthanasia was elected. Necropsy revealed chronic granulomatous pneumonia of the caudal right lung lobe with intralesional Cryptococcus, identified as C. neoformans var. grubii by DNA sequencing. Severe bilateral glomerular and tubulointerstitial amyloidosis induced protein-losing nephropathy, leading to tri-cavitary effusion, subcutaneous edema, and cachexia. The authors speculate that renal amyloidosis was associated with chronic cryptococcal pneumonia in this red kangaroo.

  15. [The effect of fenspiride on the number of exacerbations and the time of first exacerbation in patients with chronic bronchitis].

    Science.gov (United States)

    Pirozyński, Michał; Skucha, Wojciech; Słomiński, Marek; Chyczewska, Elzbieta; Malinowski, Janusz; Nowak, Dariusz; Bartmińiski, Wojciech; Pachocki, Robert

    2005-08-01

    The aim of the work was evaluation of efficacy of fenspiride b.i.d. on the number of exacerbations and the time to the first exacerbation in patients with chronic bronchitis. Randomized, multicentre study controlled versus placebo was carried out in 12 centers in Poland. All patients, 89 females and 68 males aged between 20 and 74, were treated with fenspiride at the dose of 160 mg/day for a period of 6 months. The following symptoms were recorded every month in order to evaluate the therapeutic efficacy: sputum quality and quantity, cough intensity, dyspnea and bronchospasm. Based on these symptoms diagnosis of exacerbation was performed according to American Thoracic Society criteria. Quality and quantity of sputum and cough significantly improved in the fenspiride group (comparing to the placebo group p= 0.027 and p = 0.049 adequately for sputum and cough). A significant difference between groups was observed in the number of exacerbation episodes and their duration. In the fenspiride group there were 0.53 episodes of exacerbation compared with 1.12 episodes in the placebo group (p = 0.038). Mean duration of exacerbation was 3.3 days in the fenspiride group and 7.3 days in the placebo treated patients (p = 0.034). Time to the first exacerbation differed between groups, but this difference was not statistically significant. Number of side effects observed did not differ between groups. Fenspiride treatment was assessed as relatively effective in terms of influence on exacerbations, and well tolerated during six month therapy.

  16. Pretargeting immunotherapy: a novel treatment approach for systemic amyloidosis.

    Science.gov (United States)

    Wall, Jonathan S; Foster, James S; Martin, Emily B; Kennel, Stephen J

    2017-09-01

    The amyloidoses are a complex group of disorders characterized by the deposition of proteinaceous amyloid fibrils in vital organs. The deposits are nonimmunogenic and may be composed of one of more than 35 proteins. We have developed a two-stage immunotherapeutic approach using peptides that recognize most, if not all, amyloid deposits to facilitate amyloid clearance. In the first embodiment, we have developed a bifunctional peptope to enhance and expand the utility of currently available antibodies. In the second, we have generated peptide-reactive antibodies that can be targeted to the amyloid deposits by peptides thereby providing alternative reagents for immunotherapy of amyloidosis. These technologies provide tools for treating the many forms of amyloid disease, restoring organ function and enhancing patient survival.

  17. Utility of abdominal skin plus subcutaneous fat and rectal mucosal biopsy in the diagnosis of AL amyloidosis with renal involvement.

    Directory of Open Access Journals (Sweden)

    Ting Li

    Full Text Available Skin fat biopsy of the abdominal wall is a simple and safe method for detecting amyloidosis, and rectal mucosal biopsy is also frequently used for screening for the disease; however, the sensitivity of these approaches has not been fully studied. The aim of this study was to evaluate the efficacy of skin fat biopsy combined with rectal mucosal biopsy as a screening procedure for the diagnosis of systemic immunoglobulin light-chain (AL amyloidosis.We retrospectively analyzed 224 AL amyloidosis patients confirmed by renal biopsy, including a test group of 165 patients and validation group of 59 patients. Surgical skin fat biopsy from the abdominal wall and rectal mucosal biopsy under endoscopy was performed to obtain specimens. Congo red staining and immunofluorescence staining with antibodies against light chains were performed to type the disease. Pathology reports were reviewed to assess the diagnostic sensitivity of skin fat biopsy and rectal mucosal biopsy. Diagnostic specificity was not examined in the present study, because no healthy volunteers and only few patients with other diseases had performed immunofluorescence staining on skin fat and rectal specimens.Of the 165 patients in the test group, Congo red staining of skin fat and rectal mucosal specimens was associated with a sensitivity of 89.3% and 94.8%, respectively. The sensitivity increased to 98.9% by combining both biopsy methods. Immunofluorescence stains were positive in 81.1% of patients undergoing skin fat biopsy and 84.7% of patients undergoing rectal mucosal biopsy. Immunofluorescence stains yielded positive results in 86.7% of cases combining skin fat biopsy with rectal mucosal biopsy. The diagnostic results also performed well in the validation group.Surgical skin biopsy including the subcutaneous fat pad can be performed safely at the bedside and is useful for diagnosing AL amyloidosis. Combining skin fat biopsy with rectal mucosal biopsy may identify amyloid deposits in

  18. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

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    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  19. Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise Initiation Timing

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    Fengwu Li

    2017-10-01

    Full Text Available Accumulating evidence has demonstrated that post-stroke physical rehabilitation may reduce morbidity. The effectiveness of post-stroke exercise, however, appears to be contingent upon exercise initiation. This study assessed the hypothesis that very early exercise exacerbates brain injury, induces reactive oxygen species (ROS generation, and promotes energy failure. A total of 230 adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA occlusion for 2 h, and randomized into eight groups, including two sham injury control groups, three non-exercise and three exercise groups. Exercise was initiated after 6 h, 24 h and 3 days of reperfusion. Twenty-four hours after completion of exercise (and at corresponding time points in non-exercise controls, infarct volumes and apoptotic cell death were examined. Early brain oxidative metabolism was quantified by examining ROS, ATP and NADH levels 0.5 h after completion of exercise. Furthermore, protein expressions of angiogenic growth factors were measured in order to determine whether post-stroke angiogenesis played a role in rehabilitation. As expected, ischemic stroke resulted in brain infarction, apoptotic cell death and ROS generation, and diminished NADH and ATP production. Infarct volumes and apoptotic cell death were enhanced (p < 0.05 by exercise that was initiated after 6 h of reperfusion, but decreased by late exercise (24 h, 3 days. This exacerbated brain injury at 6 h was associated with increased ROS levels (p < 0.05, and decreased (p < 0.05 NADH and ATP levels. In conclusion, very early exercise aggravated brain damage, and early exercise-induced energy failure with ROS generation may underlie the exacerbation of brain injury. These results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.

  20. Severe exacerbations and decline in lung function in asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Søren; Lamm, Carl Johan

    2009-01-01

    RATIONALE: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. OBJECTIVES: To determine whether severe asthma exacerbations...... with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable...... of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). CONCLUSIONS: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses...

  1. Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  2. Antibiotics usefulness and choice in BPCO acute exacerbation

    Directory of Open Access Journals (Sweden)

    Bruno Tartaglino

    2005-10-01

    Full Text Available Although the debate on the role of bacterial infections and antibiotic treatment in AE-COPD remains open, there is evidence that the persistence of bacteria after acute exacerbation (residual bacterial colony influences the frequency and severity of subsequent acute exacerbation and that antibiotic treatment that induces faster and more complete eradication produces better clinical outcomes. New aspects must now be considered, given that COPD is a chronic illness subject to acute exacerbations of varying frequencies and that acute exacerbations correspond to functional respiratory deterioration. One of the parameters that is currently acquiring clinical relevance is the interval free of infection (IFI, the period that elapses between one acute exacerbation and the next, caused by bacterial infection. Another guiding concept in the choice of antibiotic treatment is that not all patients benefit in the same way; those requiring more aggressive treatment are most likely to be those with FEV1 < 50%, frequent exacerbations (> 3/year treated with antibiotics, relevant co-morbidity, under chronic steroid treatment, etc., for these patients it is recommended to administer antibiotics active on the three most common pathogens (in particular H. influenzae, considering the resistance acquired in recent years, and on Pseudomomias aeruginosa.

  3. Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

    Science.gov (United States)

    Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

    2015-10-22

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

    Directory of Open Access Journals (Sweden)

    Vogelmeier CF

    2018-04-01

    Full Text Available Claus F Vogelmeier,1 Kenneth R Chapman,2 Marc Miravitlles,3 Nicolas Roche,4 Jørgen Vestbo,5 Chau Thach,6 Donald Banerji,6 Robert Fogel,6 Francesco Patalano,7 Petter Olsson,8 Konstantinos Kostikas,7 Jadwiga A Wedzicha9 1Member of the German Center for Lung Research (DZL, Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 2Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, ON, Canada; 3Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Service de Pneumologie AP-HP, Cochin Hospital, University Paris Descartes (EA2511, Paris, France; 5Institute of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Novartis Sverige AB, Täby, Sweden; 9National Heart and Lung Institute, Imperial College London, London, UK Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY 110/50 µg with twice-daily salmeterol/fluticasone (SFC 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1 moderate/severe exacerbations according to prior exacerbation history and treatment, and 2 types of exacerbations according to health care resource utilization (HCRU during 1-year follow-up. Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75–0.93, ≥2 exacerbations (RR: 0.85, 95% CI: 0.70–1.03 and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74

  5. Characterisation and prevention of exacerbations in frequently exacerbating patienst with COPD

    NARCIS (Netherlands)

    S. Uzun (Sevim)

    2014-01-01

    markdownabstract__Abstract__ Chronic obstructive pulmonary disease (COPD) is a disease which is characterised by airway inflammation and progressive airflow limitation with poor reversibility. Periods of acute deterioration lie in the natural course of the disease and are called exacerbations.

  6. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.

    Science.gov (United States)

    Muchtar, Eli; Gertz, Morie A; Kumar, Shaji K; Lacy, Martha Q; Dingli, David; Buadi, Francis K; Grogan, Martha; Hayman, Suzanne R; Kapoor, Prashant; Leung, Nelson; Fonder, Amie; Hobbs, Miriam; Hwa, Yi Lisa; Gonsalves, Wilson; Warsame, Rahma; Kourelis, Taxiarchis V; Russell, Stephen; Lust, John A; Lin, Yi; Go, Ronald S; Zeldenrust, Steven; Kyle, Robert A; Rajkumar, S Vincent; Dispenzieri, Angela

    2017-04-13

    In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone, and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of better than very good partial response (VGPR) was higher in more recent periods (66% vs 58% vs 51%; P = .001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS, 91% compared with 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS, 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the 2 later periods (24% vs 25% vs 37%; P < .001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality, and improved OS. © 2017 by The American Society of Hematology.

  7. Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

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    Sora Yasri

    2017-01-01

    Full Text Available An important problem in management of the case with myasthenia gravis (MG is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

  8. Determinants of low risk of asthma exacerbation during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Nilas, L; Ulrik, C S

    2018-01-01

    of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FENO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low......: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.......BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management...

  9. Detection of rhinovirus-associated asthma exacerbations using ...

    African Journals Online (AJOL)

    Ehab

    between common viral respiratory infections and asthma exacerbations. Respiratory viruses have ... positive Rhinovirus RT-PCR test and 4 (50%) of the HRV positive patients were of the ... reaction volume was 50 µl, and the reaction mixture contained 0.9 ..... significance in asthma exacerbation and airway remodeling.

  10. Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis.

    Science.gov (United States)

    Guirl, Michael J; Högenauer, Christoph; Santa Ana, Carol A; Porter, Jack L; Little, Katherine H; Stone, Marvin J; Fordtran, John S

    2003-10-01

    The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

  11. Incidence and risk factors for exacerbations of asthma during pregnancy

    Directory of Open Access Journals (Sweden)

    Ali Z

    2013-05-01

    Full Text Available Zarqa Ali, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.Methods: A narrative literature review was carried out using the PubMed database.Results: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.Discussion: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma – better described as difficult-to-control asthma – nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.Keywords: acute exacerbations

  12. Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.

    2015-01-01

    Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... and exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

  13. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  14. COPD exacerbations by disease severity in England

    Directory of Open Access Journals (Sweden)

    Merinopoulou E

    2016-04-01

    Full Text Available Evie Merinopoulou,1 Mireia Raluy-Callado,1 Sreeram Ramagopalan,1 Sharon MacLachlan,1 Javaria Mona Khalid2 1Real-World Evidence, Evidera, 2Takeda Development Centre Europe Ltd, London, UK Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2013.Methods: Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013 were exacerbation rates and resource utilization (general practitioner visits, hospital admissions.Results: From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85 for GOLD A to 2.51 (95% CI: 2.47–2.55 for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93 for GOLD A to 7.44 (95% CI: 7.31–7.61 for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39 to more symptoms (GOLD B: 0.52, GOLD D: 0.84.Conclusion: Patients in the most severe category (GOLD D experienced nearly three times the number of exacerbations and COPD

  15. Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter

    2016-01-01

    RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhagen...... General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment of systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk...... in a subgroup of 203 COPD individuals with clinical COPD, defined as participants with ≥ 10 pack-years, FEV1

  16. Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

    Science.gov (United States)

    Ochs, Marco M; Fritz, Thomas; Arenja, Nisha; Riffel, Johannes; Andre, Florian; Mereles, Derliz; Siepen, Fabian Aus dem; Hegenbart, Ute; Schönland, Stefan; Katus, Hugo A; Friedrich, Matthias G W; Buss, Sebastian J

    2017-11-09

    To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSE anterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ 2  = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ 2  = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ 2  = 6.2, p = 0.01). In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

  17. Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis.

    Science.gov (United States)

    Chandan, Vishal S; Shah, Sejal S; Lam-Himlin, Dora M; Petris, Giovanni De; Mereuta, Oana M; Dogan, Ahmet; Torbenson, Michael S; Wu, Tsung-Teh

    2015-04-01

    Globular hepatic amyloid (GHA) is rare, and its clinical significance remains unclear. Recently, leukocyte chemotactic factor-associated amyloidosis (ALECT2) has been reported to involve the liver, showing a globular pattern. We reviewed 70 consecutive cases of hepatic amyloidosis to determine the prevalence and morphology of hepatic amyloid subtypes, especially ALECT2 and its association with GHA. Each case was reviewed for amyloid subtype (immunohistochemistry and/or mass spectrometry), its pattern (linear or globular), and distribution (vascular, perisinusoidal, or stromal). In addition, 24 cases of confirmed hepatic ALECT2 on mass spectrometry from our consultation files were also reviewed. LECT2 immunostaining was performed in 49 cases. Of the 70 cases, immunoglobulin light chain (AL) type was most common with 41 cases (59%), followed by transthyretin (ATTR) 15 cases (22%), 3 cases each of fibrinogen A (AFib) (4%), serum amyloid A (AA) (4%), and ALECT2 (4%), 2 cases of apolipoproteins (AApoA1) (3%), and 3 cases (4%) were unclassified. Three of our 70 cases (4%), with ALECT2, and all 24 cases (100%) of mass spectrometry-confirmed hepatic ALECT2 showed only GHA deposits in the hepatic sinusoids and portal tracts. Three (4%) other cases of AL type showed a focal globular pattern admixed with prominent linear amyloid. None of the other amyloid subtypes showed GHA. LECT2 immunostain was positive in all 27 cases (100%) of ALECT2 and negative in the other 22 non-ALECT2 cases (100%) (14 AL, 5 ATTR, 1 AA, 1 AFib, 1 AApoA1). Pure GHA is uncommon (4%) but is highly specific for ALECT2, and LECT2 immunostain is helpful in confirming this amyloid type.

  18. Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.

    Science.gov (United States)

    Grolimund, Eva; Kutz, Alexander; Marlowe, Robert J; Vögeli, Alaadin; Alan, Murat; Christ-Crain, Mirjam; Thomann, Robert; Falconnier, Claudine; Hoess, Claus; Henzen, Christoph; Zimmerli, Werner; Mueller, Beat; Schuetz, Philipp

    2015-06-01

    Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

  19. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio

    2010-01-01

    BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype...... of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3...... of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider...

  20. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2012-07-01

    The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.

  1. Prognosis of Light Chain Amyloidosis With Preserved LVEF: Added Value of 2D Speckle-Tracking Echocardiography to the Current Prognostic Staging System.

    Science.gov (United States)

    Barros-Gomes, Sergio; Williams, Brittney; Nhola, Lara F; Grogan, Martha; Maalouf, Joseph F; Dispenzieri, Angela; Pellikka, Patricia A; Villarraga, Hector R

    2017-04-01

    This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction. Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff). Consecutive patients with biopsy-proven AL amyloidosis and left ventricular ejection fraction ≥55% were divided into group 1 with CA (n = 63) and group 2 without CA (n = 87). Global longitudinal strain (GLS) by 2D-STE was performed with Vivid E9 (GE Healthcare Co., Milwaukee, Wisconsin) and syngo Velocity Vector Imaging (VVI) software (Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania) (GLS GE and GLS VVI , respectively). Thirty-two deaths (51%) occurred in group 1 and 13 (15%) in group 2 (p ≤ 0.001). Group 1 had thicker walls, lower early diastolic tissue Doppler velocity at septal mitral annulus, and greater left ventricular mass, left atrial volume, glomerular filtration rate, FLC-diff, cTnT, and NT-proBNP (p value over cTnT, NT-proBNP, and FLC-diff. For survival analysis limited to group 2 (non-CA), GLS GE and GLS VVI both predicted all-cause mortality (GLS GE HR: 1.23; 95% CI: 1.03 to 1.47 [p = 0.02]; GLS VVI HR: 1.22; 95% CI: 1.01 to 1.49 [p = 0.04], respectively). 2D-STE predicted outcome and provided incremental prognostic information over the current prognostic staging system, especially in the group without CA. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders: Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    Dudok-de Wit, A. C.; Tibben, A.; Duivenvoorden, H. J.; Niermeijer, M. F.; Passchier, J.; Trijsburg, R. W.; Lindhout, D.; Meijers-Heijboer, E. J.; Frets, P. G.; Lodder, L. N.; Zoetewij, M. W.; Klijn, J. G. M.; Brocker-Vriends, A.; van Haeringen, A.; Helderman, A. T. J. M.; Hilhorst-Hofstee, Y.; Kant, S.; Maat-Kievit, J. A.; Oosterwijk, J. C.; van der Smagt, J. J.; Vegter-van der Vlis, M.; Vries-van der Weerd, M. A. C. S.; Zoeteweij, M. W.; Bakker, E.; Devilee, P.; Losekoot, M.; Tops, C.; Cornelisse, C. J.; Vasen, H. F. A.

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression

  3. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders : Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    DudokdeWit, AC; Tibben, A; Duivenvoorden, HJ; Niermeijer, MF; Passchier, J; Trijsburg, RW; Lindhout, D; Meijers-Heijboer, EJ; Frets, PG; Frets, PG; Lodder, LN; Zoetewij, MW; Klijn, JGM; Brocker-Vriends, A; van Haeringen, A; Helderman, ATJM; Hilhorst-Hofstee, Y; Kant, S; Maat-Kievit, JA; Oosterwijk, JC; van der Smagt, JJ; Vegter-van der Vlis, M; Vries-van der Weerd, MACS; Zoeteweij, MW; Bakker, E; Devilee, P; Losekoot, M; Tops, C; Cornelisse, CJ; Vasen, HFA

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression

  4. Predicting Acute Exacerbations in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Samp, Jennifer C; Joo, Min J; Schumock, Glen T; Calip, Gregory S; Pickard, A Simon; Lee, Todd A

    2018-03-01

    With increasing health care costs that have outpaced those of other industries, payers of health care are moving from a fee-for-service payment model to one in which reimbursement is tied to outcomes. Chronic obstructive pulmonary disease (COPD) is a disease where this payment model has been implemented by some payers, and COPD exacerbations are a quality metric that is used. Under an outcomes-based payment model, it is important for health systems to be able to identify patients at risk for poor outcomes so that they can target interventions to improve outcomes. To develop and evaluate predictive models that could be used to identify patients at high risk for COPD exacerbations. This study was retrospective and observational and included COPD patients treated with a bronchodilator-based combination therapy. We used health insurance claims data to obtain demographics, enrollment information, comorbidities, medication use, and health care resource utilization for each patient over a 6-month baseline period. Exacerbations were examined over a 6-month outcome period and included inpatient (primary discharge diagnosis for COPD), outpatient, and emergency department (outpatient/emergency department visits with a COPD diagnosis plus an acute prescription for an antibiotic or corticosteroid within 5 days) exacerbations. The cohort was split into training (75%) and validation (25%) sets. Within the training cohort, stepwise logistic regression models were created to evaluate risk of exacerbations based on factors measured during the baseline period. Models were evaluated using sensitivity, specificity, and positive and negative predictive values. The base model included all confounding or effect modifier covariates. Several other models were explored using different sets of observations and variables to determine the best predictive model. There were 478,772 patients included in the analytic sample, of which 40.5% had exacerbations during the outcome period. Patients with

  5. Dialysis-related amyloidosis of the hip joints in long-term hemodialysis patients. MRI findings of hip joints in twelve female hemodialysis patients

    International Nuclear Information System (INIS)

    Suzuki, Hitoe; Shibuya, Asuka; Ando, Minoru; Akiba, Takashi; Nitta, Kosaku

    2007-01-01

    We report a female with amyloid arthropathy of the hip joints. She was a 67-year-old woman who had been treated by hemodialysis for 22 years. She had demonstrated a 5-month history of continuous low-grade fever and pain in her left hip and she was finally unable to walk by herself. Findings on X-ray films and MRI of the hip joints suggested avascular necrosis in both femur heads. To palliate symptoms, bipolar surgery on the left hip joint was performed. Pathological examination of bone tissue specimen demonstrated that there was some , β 2 -microglobulin (β 2 -MG)-related amyloid accumulation in the femur head. Based on this clinical experience, we performed MRI screening for amyloid lesions of the hip joints in another 11 asymptomatic female patients undergoing hemodialysis for 20 years or more. Cystic lesions of the hip joints were observed in 8 patients, amyloid arthropathy in 2 patients, and fluid trapped in the joint in 1 patient. Patients with amyloidosis had significantly lower serum β 2 -MG levels than patients without amyloidosis (28.6 mg/L versus 41.4 mg/L; p=0.0339). Our findings show that dialysis-related amyloidosis of the hip joints is one of the potential and significant problems in female patients on long-term hemodialysis therapy. It may be important to screen for this pathological condition in long-term hemodialysis patients. (author)

  6. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

    Science.gov (United States)

    Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

    2018-03-08

    Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

  7. Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value

    NARCIS (Netherlands)

    Jager, PL; Hazenberg, BPC; Franssen, EJF; Limburg, PC; van Rijswijk, MH; Piers, DA

    In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP)

  8. Cerebral microangiopathies

    International Nuclear Information System (INIS)

    Linn, Jennifer

    2011-01-01

    Cerebral microangiopathies are a very heterogenous group of diseases characterized by pathological changes of the small cerebral vessels. They account for 20 - 30 % of all ischemic strokes. Degenerative microangiopathy and sporadic cerebral amyloid angiography represent the typical acquired cerebral microangiopathies, which are found in over 90 % of cases. Besides, a wide variety of rare, hereditary microangiopathy exists, as e.g. CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), Fabrys disease and MELAS syndrome (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes). (orig.)

  9. Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Pun, Shawn C; Landau, Heather J; Riedel, Elyn R; Jordan, Jonathan; Yu, Anthony F; Hassoun, Hani; Chen, Carol L; Steingart, Richard M; Liu, Jennifer E

    2018-01-01

    Autologous hematopoietic cell transplantation (HCT) is a first-line therapy for prolonging survival in patients with light-chain (AL) amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT because of high risk for transplantation-related mortality and poor overall survival. Whether baseline left ventricular global longitudinal strain (GLS) can provide additional risk stratification and predict survival after HCT in this high-risk population remains unclear. The aim of this study was to evaluate the prognostic implication of baseline GLS and the added value of GLS beyond circulating cardiac biomarkers for risk stratification in patients with AL amyloidosis undergoing HCT. Eighty-two patients with newly diagnosed AL amyloidosis who underwent upfront HCT between January 2007 and April 2014 were included in the study. Clinical, echocardiographic, and serum cardiac biomarker data were collected at baseline and 12 months following HCT. GLS measurements were performed using a vendor-independent offline system. The median follow-up time for survivors was 58 months. Sixty-four percent of patients were in biomarker-based Mayo stage II or III. GLS, brain natriuretic peptide, troponin, and mitral E/A ratio were identified as the strongest predictors of survival (P value that best discriminated survivors from nonsurvivors, and the application of this cutoff value provided further mortality risk stratification within each Mayo stage. GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  10. Effects of Milrinone continuous intravenous infusion on global cerebral oxygenation and cerebral vasospasm after cerebral aneurysm surgical clipping

    Directory of Open Access Journals (Sweden)

    Mohamed A. Ghanem

    2014-01-01

    Conclusions: Milrinone improved significantly the global cerebral oxygenation and reduced the incidence of cerebral vasospasm during the dangerous period of cerebral spasm after cerebral aneurysm clipping.

  11. Low serum levels of prohepcidin, but not hepcidin-25, are related to anemia in familial amyloidosis TTR V30M.

    NARCIS (Netherlands)

    Beirao, I.; Almeida, S.; Swinkels, D.W.; Costa, P.M.; Moreira, L.; Fonseca, I.; Freitas, C.; Cabrita, A.; Porto, G.

    2008-01-01

    Familial amyloidosis TTR V30M (FAP-I) usually presents as a sensorimotor and autonomic neuropathy. Anemia was first described in this disease more than 20 years ago and classified as an anemia of chronic disease. However, so far no studies have addressed the role of inflammatory proteins in this

  12. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    Science.gov (United States)

    McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

    2018-03-08

    Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology

  13. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    Directory of Open Access Journals (Sweden)

    Søgaard M

    2016-03-01

    Full Text Available Mette Søgaard,1 Morten Madsen,1 Anders Løkke,2 Ole Hilberg,2 Henrik Toft Sørensen,1 Reimar W Thomsen1 1Department of Clinical Epidemiology, 2Department of Respiratory Medicine, Aarhus University Hospital, Aarhus C, Denmark Background: Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD exacerbation and influence their outcomes.Methods: We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012.Results: We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%. Pneumonia was frequent in first-time exacerbations (36.1%, but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days, intensive care unit admission (7.7% vs 12.5%, and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24. Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18, and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13. In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations.Conclusions: Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care

  14. Nebulized corticosteroids in the management of acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Gaude G

    2010-01-01

    Full Text Available Acute exacerbations in chronic onstructive pulmonary disease (COPD are common and systemic steroids play an important role in the management of these cases along with the bronchodilators. Nebulized budesonide is being used in the acute attacks of bronchial asthma either in children or in adults. But the role of nebulized steroids in acute exacerbation of COPD is not much studied in the literature. In this clinical review we have evaluated the role of nebulized corticosteroids in the management of acute exacerbation of COPD (AECOPD. Through Medline, Pubmed and Embase we analyzed the various studies that has been done to study the role of nebulized corticosteroids in the management of acute exacerbation of COPD. The key words used for the search criteria were: acute exacerbation, COPD, nebulized corticosteroids, budesonide, fluticasone. Only eight studies were found which had evaluated the role of nebulized corticosteroids in acute exacerbations of COPD. All these studies had used nebulized budesonide in AECOPD in different dosages, and had been compared with both either parental or oral steroids, and standard bronchodilator therapy. All the studies had found the clinical efficacy of nebulized budesonide to be of similar extent to that of either parental or oral steroids in AECOPD. Side effects profile of nebulized budesonide was minimal and acceptable as compared to systemic steroids. Nebulized budesonide may be an alternative to parental/oral prednisolone in the treatment of acute exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.

  15. Stability of the frequent COPD exacerbator in the general population

    DEFF Research Database (Denmark)

    Reilev, Mette; Lykkegaard, Jesper; Halling, Anders

    2017-01-01

    Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time is c...... considerably over time. This could hold implications for COPD treatment and challenge assumptions made about disease progression....... is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one...... obstructive pulmonary disease treatment guidelines and their practical application. CHRONIC OBSTRUCTIVE LUNG DISEASE: VARIATIONS IN DISEASE PROGRESSION: Patients with chronic obstructive pulmonary disease (COPD) who suffer from frequent exacerbations do not necessarily persist with such severity over time...

  16. Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

    Science.gov (United States)

    Tumkaya, Munir; Atis, Sibel; Ozge, Cengiz; Delialioglu, Nuran; Polat, Gurbuz; Kanik, Arzu

    2007-04-01

    To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

  17. Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

    Science.gov (United States)

    Wells, J. Michael; Farris, Roopan F.; Gosdin, Taylor A.; Dransfield, Mark T.; Wood, Michelle E.; Bell, Scott C.; Rowe, Steven M.

    2017-01-01

    Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:Apulmonary exacerbation risk in two well-characterized cohorts. PA:A may be a predictive marker in CF. PMID:27298019

  18. Patterns and characterization of COPD exacerbations using real-time data collection

    Directory of Open Access Journals (Sweden)

    Ejiofor SI

    2017-01-01

    Full Text Available Stanley I Ejiofor,1,2 Jan Stolk,3 Pablo Fernandez,4 Robert A Stockley1,2 1Centre for Translational Inflammation Research, University of Birmingham, 2ADAPT Project, University Hospital Birmingham, Birmingham, UK; 3Leiden University Medical Centre, Leiden, the Netherlands; 4Independent consultant, Penn, UK Introduction: Patients with chronic obstructive pulmonary disease often experience exacerbations. These events are important as they are a major cause of morbidity and mortality. Recently, it has been increasingly recognized that patients may experience symptoms suggestive of an exacerbation but do not seek treatment, which are referred to as unreported or untreated exacerbations. Symptom diaries used in clinical trials have the benefit of identifying both treated and untreated exacerbation events. Methods: The Kamada study was a multicenter, double-blind randomized controlled trial of inhaled augmentation therapy in alpha-1 antitrypsin deficiency (AATD. A retrospective review of daily electronic symptom diary cards was undertaken from the two leading centers to identify symptomatic episodes consistent with a definition of an exacerbation. The aims were to explore the relationship between exacerbation events and classical “Anthonisen” symptoms and to characterize treated and untreated episodes. Results: Forty-six AATD patients with airflow obstruction and history of exacerbations were included in the analysis. Two hundred thirty-three exacerbation episodes were identified: 103 untreated and 130 treated. Untreated episodes were significantly shorter (median 6 days; interquartile range [IQR] 3–10 days than the treated episodes (median 10 days; IQR 5–18.25 days: P<0.001. Using logistic regression analysis, Anthonisen type and length of dyspnea were significant predictors of the treatment of an exacerbation event. Conclusion: Real-time electronic diary cards provide valuable information about the characterization of exacerbations

  19. Factors influencing exacerbation-related self-management in patients with COPD: a qualitative study.

    Science.gov (United States)

    Korpershoek, Yjg; Vervoort, Scjm; Nijssen, Lit; Trappenburg, Jca; Schuurmans, M J

    2016-01-01

    In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related self-management. Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior. A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated. Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015. Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed. Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management. Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions. This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients. The conceptual model can be used as a framework for health care professionals providing self-management support. In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.

  20. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, A.S.; Tozzi, C.A.; Knorr, B.

    2008-01-01

    BACKGROUND: Asthma exacerbations in young children are prevalent. Identification of symptoms or other factors that are precursors of asthma exacerbations would be useful for early treatment and prevention. OBJECTIVES: To determine whether diary symptoms and beta2-agonist use before an exacerbation...... could predict an asthma exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were conducted on data collected in a study of 689 patients 2 to 5 years of age with asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12 weeks. During the study, 196 patients had...... of an exacerbation. These methods predicted 149 (66.8%) of the exacerbations with a very low false-positive rate of 14.2%. CONCLUSIONS: No individual symptom was predictive of an imminent asthma exacerbation, but a combination of increased daytime cough, daytime wheeze, and nighttime beta2-agonist use 1 day before...

  1. Dark chocolate exacerbates acne.

    Science.gov (United States)

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. © 2015 The International Society of Dermatology.

  2. Early Impairment of Cardiac Function and Asynchronization of Systemic Amyloidosis with Preserved Ejection Fraction Using Two-Dimensional Speckle Tracking Echocardiography.

    Science.gov (United States)

    Huang, He; Jing, Xian-chao; Hu, Zhang-xue; Chen, Xi; Liu, Xiao-qin

    2015-12-01

    To observe the ventricular global and regional function of the patients with systemic amyloidosis using two-dimensional speckle tracking echocardiography. The study enrolled 31 consecutive biopsy-proved patients with systemic amyloidosis who underwent echocardiographic examination and EF ≥ 55% and 37 age- and gender-matched healthy controls. We compared systolic strain and strain rate, diastolic strain rate, time to peak strain, peak delay time in longitudinal, radial, circumferential directions in 16 left ventricular segments. The global peak systolic longitudinal and radial strain of left ventricle, peak systolic longitudinal strain and strain rate, diastolic strain rate of right ventricular free wall were also compared. (1) Global peak systolic longitudinal strain (GPSLS), peak systolic longitudinal strain (PSLS) and strain rate (PSLSR), peak early diastolic longitudinal strain rate (PELSR) in 16 segments were decreased in case (P < 0.05). (2) Peak systolic radial strain and strain rate of inferoseptum and inferolateral at the level of papillary muscle were lower (P < 0.05), and peak early diastolic radial strain rate (PERSR) was reduced (P < 0.05). (3) Peak early diastolic circumferential strain rate was lower (P < 0.05). (4) Time to peak systolic longitudinal, radial, circumferential strain was longer, and peak delay time at the same level retarded (P < 0.05). (5) Into right ventricular wall, PSLS and PSLSR at mid-segment, and PSLSR, PELSR, peak atrial systolic longitudinal strain rate (PALSR) at basal were reduced (P < 0.05). (6) Inverse correlation between interventricular septum (IVS) thickness and GPSLS and GPSRS was found (P < 0.05). Systolic and diastolic dysfunction existed in systemic amyloidosis with preserved EF. Mechanical contraction disorder may be one reason for systolic dysfunction. GPLSR and GPRSR were negatively related to IVS thickness. © 2015, Wiley Periodicals, Inc.

  3. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Ingebrigtsen, Truls Sylvan; Marott, Jacob Louis

    2013-01-01

    Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients.......Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients....

  4. Anestesia e paralisia cerebral Anestesia y parálisis cerebral Anesthesia and cerebral palsy

    Directory of Open Access Journals (Sweden)

    Március Vinícius M Maranhão

    2005-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A paralisia cerebral (PC é uma doença não progressiva decorrente de lesão no sistema nervoso central, levando a um comprometimento motor do paciente. O portador de PC freqüentemente é submetido a procedimentos cirúrgicos devido a doenças usuais e situações particulares decorrentes da paralisia cerebral. Foi objetivo deste artigo revisar aspectos da paralisia cerebral de interesse para o anestesiologista, permitindo um adequado manuseio pré, intra e pós-operatório neste tipo de paciente. CONTEÚDO: O artigo aborda aspectos da paralisia cerebral como etiologia, classificação, fatores de risco, fisiopatologia, quadro clínico, diagnóstico, terapêuticas utilizadas bem como avaliação pré-operatória, medicação pré-anestésica, manuseio intra e pós-operatório, analgesia pós-operatória e dor crônica. CONCLUSÕES: O anestesiologista desempenha um papel importante na diminuição da morbidade e mortalidade anestésico-cirúrgica em pacientes portadores de paralisia cerebral. O conhecimento da fisiopatologia dos diferentes tipos de paralisia cerebral bem como das doenças associadas e suas terapêuticas é imprescindível, pois permite ao anestesiologista antecipar e prevenir complicações intra e pós-operatórias neste tipo de paciente.JUSTIFICATIVA Y OBJETIVOS: La parálisis cerebral (PC es una enfermedad no progresiva consecuente de una lesión en el sistema nervioso central, llevando a un comprometimiento motor del paciente. El portador de PC, frecuentemente es sometido a procedimientos quirúrgicos debido a enfermedades usuales y situaciones particulares consecuentes de la parálisis cerebral. El objetivo de este artículo, fue revisar aspectos de la parálisis cerebral de interés para el anestesista, permitiendo un adecuado manoseo pre, intra y posoperatorio en este tipo de paciente. CONTENIDO: El artículo aborda aspectos de la parálisis cerebral como etiología, clasificación, factores de

  5. Cerebral atrophic and degenerative changes following various cerebral diseases, (1)

    International Nuclear Information System (INIS)

    Kino, Masao; Anno, Izumi; Yano, Yuhiko; Anno, Yasuro.

    1980-01-01

    Patients having cerebral atrophic and degenerative changes following hypoglycemia, cerebral contusion, or cerebral hypoxia including cerebrovascular disorders were reported. Description was made as to cerebral changes visualized on CT images and clinical courses of a patient who revived 10 minutes after heart stoppage during neurosurgery, a newborn with asphyxia, a patient with hypoglycemia, a patient who suffered from asphyxia by an accident 10 years before, a patient with carbon monoxide poisoning at an acute stage, a patient who had carbon monoxide poisoning 10 years before, a patient with diffuse cerebral ischemic changes, a patient with cerebral edema around metastatic tumor, a patient with respiration brain, a patient with neurological sequelae after cerebral contusion, a patient who had an operation to excise right parietal lobe artery malformation, and a patient who was shooted by a machine gun and had a lead in the brain for 34 years. (Tsunoda, M.)

  6. Factors associated with change in exacerbation frequency in COPD

    DEFF Research Database (Denmark)

    Donaldson, Gavin C; Müllerova, Hanna; Locantore, Nicholas

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to y...

  7. Medically treated exacerbations in COPD by GOLD 1-4

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Marott, Jacob L; Lange, Peter

    2015-01-01

    AIM: We hypothesized that medically treated exacerbations in COPD defined as treatments with oral corticosteroids alone or in combination with antibiotics by register linkage with a nationwide prescription registry is a valid, robust and low-biased measure of exacerbations. METHODS: A total of 13...

  8. The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada

    Directory of Open Access Journals (Sweden)

    Tam Dang-Tan

    2017-01-01

    Full Text Available Background. Chronic obstructive pulmonary disease (COPD prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe. Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations. Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01 for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001. Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

  9. COPD exacerbation: anthropometric characteristics of patients and the frequency of hospital admissions

    Directory of Open Access Journals (Sweden)

    Gashynova K.Y.

    2014-11-01

    Full Text Available Exceptional importance of exacerbations for COPD course prognosing was reflected in the GOLD, 2011, where the number of exacerbations during the past year has been recognized as one of the main criteria of the future risks for patients. The aim of study was to determine the anthropometric indicators that increase the risk of re-hospitalization due to acute exacerbation of COPD. A retrospective analysis of medical records of inpatients who were hospitalized with COPD exacerbation to therapeutic department of CI "Dnipropetrovs’k sixth municipal clinical hospital" of Dnipropetrovsk regional council" during three years was done. It was established that neither sex, nor height, nor weight affect the rate of hospitalization due to COPD exacerbations. Older age is not a factor that increases the risk of hospitalization due to COPD exacerbation (despite the fact that the majority of hospitalized patients were elderly patients, 37% of them were persons of potentially working age. Severe exacerbation of COPD may occur in any patients with, even one year, experience of the disease. Among anthropometric indices, the most important predictor of re-hospitalization due to exacerbation of COPD is BMI<18.5, so its calculation is advisable in long-term observation of patients.

  10. Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

    Science.gov (United States)

    Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

    2013-11-01

    Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

  11. Hereditär hjärnblödning. Demens vid cystatin C amyloidos

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1990-01-01

    Nineteen cases of hereditary cystatin C amyloidosis with cerebral haemorrhage are described. The first haemorrhage occurred between the ages of 20 and 41 years and the period of survival varied from 10 days to 23 years after the first insult. Progressive dementia was a striking clinical symptom...... in 17 of the patients and in two cases dementia was the first sign. At the last examination severe dementia and pronounced pathological EEG were established in the majority of the patients. Infiltration of amyloid substance positive for anti-cystatin C was found in the proximity of the blood vessels...... the name Hereditary Cystatin C Amyloidosis (HCCA)....

  12. Glucose tolerance during pulmonary exacerbations in children with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    John Widger

    Full Text Available BACKGROUND: Patients with Cystic Fibrosis (CF are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77. At the follow up OGTT, 8 of 9 (89% remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

  13. Amiloidose pulmonar: relato de caso de achado radiológico da apresentação nodular em grande fumante Pulmonary amyloidosis: radiographic finding of nodular opacities in a heavy smoker

    Directory of Open Access Journals (Sweden)

    Jorge Montessi

    2007-06-01

    Full Text Available A amiloidose pulmonar é uma doença rara, caracterizada pelo depósito extracelular de proteínas fibrilares no pulmão. Amiloidose é um termo genérico para grupos heterogêneos de doenças, incluindo doença de Alzheimer e diabetes mellitus tipo II. Apresenta-se no aparelho respiratório sob as formas traqueobrônquica, nodular pulmonar e septal alveolar (parenquimatosa difusa. Relata-se o caso de uma mulher, tabagista (20 anos/maço, portadora de amiloidose nodular pulmonar, diagnosticada através de exames pré-operatórios à realização de colecistectomia videolaparoscópica.Pulmonary amyloidosis is a rare disease, characterized by extracellular deposition of fibrillary protein in the lungs. Amyloidosis is a generic term for a heterogeneous group of diseases, including Alzheimer's disease and type 2 diabetes mellitus. In the respiratory system, it appears in various forms: tracheobronchial; nodular pulmonary; and alveolar septal (diffuse parenchymal. We present the case of a woman who was a 20 pack-year smoker and had nodular pulmonary amyloidosis, as diagnosed through tests performed prior to laparoscopic cholecystectomy.

  14. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  15. Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

    Science.gov (United States)

    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

    2015-08-01

    Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and

  16. The reliability and validity of patient-reported chronic obstructive pulmonary disease exacerbations.

    Science.gov (United States)

    Mohan, Arjun; Sethi, Sanjay

    2014-03-01

    Despite the increasing awareness of their pathogenesis and clinical consequences, research on and clinical management of acute exacerbations of chronic obstructive lung disease (AECOPDs) have been hindered by the lack of a consistent and reliable definition. Symptom-based definitions of exacerbations are sensitive to events and account for unreported exacerbations. Event (healthcare utilization)-based definitions are somewhat more definitive but miss unreported events. Objective quantification of symptoms in AECOPD is now possible with the development of the Exacerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT-PRO), a patient-reported outcome (PRO) measure. Several studies have revealed that unreported AECOPDs are more frequent than reported events and are associated with long-term adverse consequences. New antibiotic development for AECOPD has been hampered by the lack of validated measures for resolution of exacerbations. As a result of these observations, a unique collaborative effort between academia, industry and regulatory agencies resulted in the development of the EXACT-PRO. It consists of 14 questions that generate a score between 0 and 100, and it has been shown to have excellent reliability and validity. In the absence of a reliable biomarker, the definition and measurement of exacerbations has been subjective and imprecise. PRO measures such as EXACT can provide much needed objectivity in assessing symptom-defined exacerbations, which may translate into a uniform outcome measure in clinical trials. With further development and validation, it may have a role in clinical practice in the earlier detection of exacerbations, stratification of an exacerbation severity and the assessment of clinical response to treatment.

  17. Impact and prevention of severe exacerbations of COPD: a review of the evidence

    Science.gov (United States)

    Halpin, David MG; Miravitlles, Marc; Metzdorf, Norbert; Celli, Bartolomé

    2017-01-01

    Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. PMID:29062228

  18. High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

    Science.gov (United States)

    Seldin, D. C.; Andrea, N.; Berenbaum, I.; Berk, J. L.; Connors, L.; Dember, L. M.; Doros, G.; Fennessey, S.; Finn, K.; Girnius, S.; Lerner, A.; Libbey, C.; Meier-Ewert, H. K.; O’Connell, R.; O’Hara, C.; Quillen, K.; Ruberg, F. L.; Sam, F.; Segal, A.; Shelton, A.; Skinner, M.; Sloan, J. M.; Wiesman, J. F.; Sanchorawala, V.

    2017-01-01

    Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years. PMID:21838459

  19. Experimental induction of chicken amyloid A amyloidosis in white layer chickens by inoculation with inactivated vaccines.

    Science.gov (United States)

    Habibi, Wazir Ahmad; Hirai, Takuya; Niazmand, Mohammad Hakim; Okumura, Naoko; Yamaguchi, Ryoji

    2017-10-01

    We investigated the amyloidogenic potential of inactivated vaccines and the localized production of serum amyloid A (SAA) at the injection site in white layer chickens. Hens in the treated group were injected intramuscularly three times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week intervals. Chickens in the control group did not receive any inoculum. In the treated group, emaciation and granulomas were present, while several chickens died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at necropsy, and the liver parenchyma showed inconsistent discolouration with patchy green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage. Amyloid deposition in the liver, spleen, duodenum, and at injection sites was demonstrated using haematoxylin and eosin staining, Congo red, and immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47% (28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA mRNA was detected by in situ hybridization in fibroblasts at the injection sites, and also in hepatocytes. We believe that this is the first report of the experimental induction of systemic AA amyloidosis in white layer chickens following repeated inoculation with inactivated vaccines without the administration of amyloid fibrils or other amyloid-enhancing factors.

  20. Scintigraphic imaging and turnover studies with iodine-131 labelled serum amyloid P component in systemic amyloidosis

    International Nuclear Information System (INIS)

    Hawkins, P.N.; Pepys, M.B.; Aprile, C.; Capri, G.; Vigano, L.; Munzone, E.; Gianni, L.; Merlini, G.

    1998-01-01

    Radiolabelled serum amyloid P component (SAP) is a specific tracer for amyloid. Iodine-123 has ideal physical characteristics for scintigraphy but is expensive and not widely available. Here we report serial imaging and turnover studies in which we labelled SAP with iodine-131, a cheap alternative isotope which would be expected to yield poorer images but permit more prolonged turnover measurements. Imaging and plasma clearance and whole body retention (WBR) of tracer were studied for up to 7 days in ten patients with proven systemic AL amyloidosis and two patients in whom the diagnosis was suspected, after i.v. administration of about 37 MBq of 131 I-SAP. Normal blood pool images were obtained in the latter two subjects and amyloidosis was subsequently refuted histologically. WBR at 48 h was 65% of the injected dose (i.d.). Among the other ten patients, amyloid deposits were identified in the spleen in eight cases, liver in five and kidneys in four; other sites that gave positive results included bone, joints and soft tissues, and the myocardium in one case. Up to 95% of the tracer localised into amyloid within 6-h, and the values for WBR became progressively more discriminating during the study period, exceeding the normal reference value ( 131 I-SAP produced diagnostic scans in every patient in this series and, coupled with the detailed turnover information, is adequate for monitoring disease progress. (orig.)

  1. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years...... of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association...... between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression...

  2. Differential Features of Cerebral Perfusion in Dementia with Lewy Bodies Compared to Alzheimer's Dementia using SPM Analysis

    International Nuclear Information System (INIS)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

    2003-01-01

    Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB) are most common cause of dementia in elderly people. Clinical distinction in some cases of DLB from AD may be difficult as symptom profiles overlap. Some neuropathologic overlap is also seen as beta-amyloidosis and senile plaques can be found in both disease. Both disease also share severe acetylcholine depletion. We evaluated the differences of brain perfusion between DLB and AD using statistical parametric mapping analysis. Twelve DLB (mean age ; 68.8±8.3 years, K-MMSE ; 17.3±6.1) and 51 AD patients (mean age ; 71.4±7.2 years, K-MMSE ; 16.7±4.5), which were matched for age and severity of dementia, participated in this study. Tc-99m HMPAO SPECT was performed for measuring regional cerebral blood flow. Statistical parametric mapping (SPM99) software was used for automatic and objective approach to analyze SPECT image data. The SPECT data of the patients with DLB were compared to patients with AD. Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both occipital (both middle occipital gyrus, Rt B no. 18 and Lt cuneus), both parietal (Lt parietal precuneus, Lt B no. 39, Lt inferior parietal lobule and Rt supramarginal gyrus) lobes in DLB compared with AD. Significant hyperperfusion was noted in Rt frontal (sup. frontal gyrus, B no.10, middle frontal gyrus, B no. 9, B no. 11, inf. frontal gyrus), Rt putamen, Lt ant. cingulate gyrus (B no. 24), both cerebellar post. lobe (Lt tuber, Lt declive, Lt tonsil, Rt declive) in DLB compared with AD. We found a significant differences in the cerebral perfusion pattern between DLB and AD. Differential feature of cerebral perfusion in DLB was both occipital hypoperfusion and preserved Rt frontal perfusion compared to AD. Therefore in difficult case of clinical an neuro pathologic diagnosis, brain perfusion SPECT with SPM analysis may be helpful to differentiate DLB from AD

  3. PirB Overexpression Exacerbates Neuronal Apoptosis by Inhibiting TrkB and mTOR Phosphorylation After Oxygen and Glucose Deprivation Injury.

    Science.gov (United States)

    Zhao, Zhao-Hua; Deng, Bin; Xu, Hao; Zhang, Jun-Feng; Mi, Ya-Jing; Meng, Xiang-Zhong; Gou, Xing-Chun; Xu, Li-Xian

    2017-05-01

    Previous studies have proven that paired immunoglobulin-like receptor B (PirB) plays a crucial suppressant role in neurite outgrowth and neuronal plasticity after central nervous system injury. However, the role of PirB in neuronal survival after cerebral ischemic injury and its mechanisms remains unclear. In the present study, the role of PirB is investigated in the survival and apoptosis of cerebral cortical neurons in cultured primary after oxygen and glucose deprivation (OGD)-induced injury. The results have shown that rebarbative PirB exacerbates early neuron apoptosis and survival. PirB gene silencing remarkably decreases early apoptosis and promotes neuronal survival after OGD. The expression of bcl-2 markedly increased and the expression of bax significantly decreased in PirB RNAi-treated neurons, as compared with the control- and control RNAi-treated ones. Further, phosphorylated TrkB and mTOR levels are significantly downregulated in the damaged neurons. However, the PirB silencing markedly upregulates phosphorylated TrkB and mTOR levels in the neurons after the OGD. Taken together, the overexpression of PirB inhibits the neuronal survival through increased neuron apoptosis. Importantly, the inhibition of the phosphorylation of TrkB and mTOR may be one of its mechanisms.

  4. Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9 transgenic mice: Effect of long-term treatment with paroxetine.

    Science.gov (United States)

    Olesen, Louise Ørum; Sivasaravanaparan, Mithula; Severino, Maurizio; Babcock, Alicia A; Bouzinova, Elena V; West, Mark J; Wiborg, Ove; Finsen, Bente

    2017-08-01

    Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP swe /PS1 dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. United Cerebral Palsy

    Science.gov (United States)

    ... your local affiliate Find your local affiliate United Cerebral Palsy United Cerebral Palsy (UCP) is a trusted resource for individuals with Cerebral Palsy and other disabilities and their networks. Individuals with ...

  6. Antibiotics usefulness and choice in BPCO acute exacerbation

    OpenAIRE

    Bruno Tartaglino

    2005-01-01

    Although the debate on the role of bacterial infections and antibiotic treatment in AE-COPD remains open, there is evidence that the persistence of bacteria after acute exacerbation (residual bacterial colony) influences the frequency and severity of subsequent acute exacerbation and that antibiotic treatment that induces faster and more complete eradication produces better clinical outcomes. New aspects must now be considered, given that COPD is a chronic illness subject to acute exacerbatio...

  7. Bringing stability to the COPD patient: clinical and pharmacological considerations for frequent exacerbators

    Science.gov (United States)

    Gulati, Swati

    2017-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A “frequent exacerbator” is a sub-phenotype of COPD that is defined as an individual who experiences ≥2 moderate to severe exacerbations per year. This distinct subgroup has higher mortality and account for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for utilizing combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: 1) maximizing bronchodilation, 2) reducing inflammation, and 3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies include combination long acting muscarinic agents (LAMA) plus long acting beta agonists (LABA) show promising results compared to monotherapy or LABA inhaled corticosteroid (ICS) combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase (PDE4) inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on identification of various subtypes or “endotypes” and targeting therapies based on their pathophysiology. This review aims to describe the impact of AECOPD, challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these

  8. A score to predict short-term risk of COPD exacerbations (SCOPEX

    Directory of Open Access Journals (Sweden)

    Make BJ

    2015-01-01

    Full Text Available Barry J Make,1 Göran Eriksson,2 Peter M Calverley,3 Christine R Jenkins,4 Dirkje S Postma,5 Stefan Peterson,6 Ollie Östlund,7 Antonio Anzueto8 1Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Health, University of Colorado Denver School of Medicine, Denver, CO, USA; 2Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 3Pulmonary and Rehabilitation Research Group, University Hospital Aintree, Liverpool, UK; 4George Institute for Global Health, The University of Sydney and Concord Clinical School, Woolcock Institute of Medical Research, Sydney, NSW, Australia; 5Department of Pulmonology, University of Groningen and GRIAC Research Institute, University Medical Center Groningen, Groningen, The Netherlands; 6StatMind AB, Lund, Sweden; 7Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; 8Department of Pulmonary/Critical Care, University of Texas Health Sciences Center and South Texas Veterans Healthcare System, San Antonio, TX, USA Background: There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Methods: Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC curves and the corresponding C-index were used to investigate the discriminatory

  9. Treatment of exacerbations as a predictor of subsequent outcomes in patients with COPD

    Directory of Open Access Journals (Sweden)

    Calverley PMA

    2018-04-01

    Full Text Available Peter MA Calverley,1 Antonio R Anzueto,2 Daniel Dusser,3 Achim Mueller,4 Norbert Metzdorf,5 Robert A Wise6 1Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK; 2Pulmonary/Critical Care, University of Texas and South Texas Veterans Health Care System, San Antonio, TX, USA; 3Department of Pneumology, Hôpital Cochin, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 4Biostatistics and Data Sciences Europe, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany; 5Respiratory Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Rationale: Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown. Objective: We examined whether the treatment given for exacerbations predicted subsequent outcomes. Methods: This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®. Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan–Meier plots. Results: Of 8,061 patients with moderate to severe exacerbation(s, demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization. Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively, and a greater risk of having a hospitalized (severe exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively compared with exacerbations treated

  10. Increased neutrophil expression of pattern recognition receptors during COPD exacerbations

    NARCIS (Netherlands)

    Pouwels, Simon D.; Van Geffen, Wouter H.; Jonker, Marnix R.; Kerstjens, Huib A. M.; Nawijn, Martijn C.; Heijink, Irene H.

    Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of

  11. Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: Role of electron microscopy and Congo red stained cell block sections

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    Sumana Devata

    2011-01-01

    Full Text Available Background: Fine-needle aspiration biopsy (FNA of the abdominal fat pad is a minimally invasive procedure to demonstrate tissue deposits of amyloid. However, protocols to evaluate amyloid in fat pad aspirates are not standardized, especially for detecting scant amyloid in early disease. Materials and Methods: We studied abdominal fat pad aspirates from 33 randomly selected patients in whom subsequent tissue biopsy, autopsy, and/or medical history for confirmation of amyloidosis (AL were also available. All these cases were suspected to have early AL, but had negative results on abdominal fat pad aspirates evaluated by polarizing microscopy of Congo Red stained sections (CRPM. The results with CRPM between four reviewers were compared in 12 cases for studying inter observer reproducibility. 24 cases were also evaluated by ultrastructural study with electron microscopy (EM. Results: Nine of thirty-three (27% cases reported negative by polarizing microscopy had amyloidosis. Reanalysis of 12 mixed positive-negative cases, showed considerable inter-observer variability with frequent lack of agreement between four observers by CRPM alone (Cohen′s Kappa index of 0.1, 95% CI -0.1 to 0.36. EM showed amyloid in the walls of small blood vessels in fibroadipose tissue in four out of nine cases (44% with amyloidosis. Conclusion: In addition to poor inter-observer reproducibility, CRPM alone in cases with scant amyloid led to frequent false negative results (9 out of 9, 100%. For improved detection of AL, routine ultrastructural evaluation with EM of fat pad aspirates by evaluating at least 15 small blood vessels in the aspirated fibroadipose tissue is recommended. Given the high false negative rate for CRPM alone in early disease, routine reflex evaluation with EM is highly recommended to avert the invasive option of biopsying various organs in cases with high clinical suspicion for AL.

  12. Asthma Exacerbations and Unconventional Natural Gas Development in the Marcellus Shale

    Science.gov (United States)

    Rasmussen, Sara G.; Ogburn, Elizabeth L.; McCormack, Meredith; Casey, Joan A.; Bandeen-Roche, Karen; Mercer, Dione G.; Schwartz, Brian S.

    2017-01-01

    Importance Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, development began in 2005 and by 2012, 6,253 wells were drilled. There are no prior studies of UNGD and objective respiratory outcomes. Objective To evaluate associations between UNGD and asthma exacerbations. Design A nested case-control study comparing asthma patients with exacerbations to asthma patients without exacerbations from 2005–12. Setting The Geisinger Clinic, which provides primary care services to over 400,000 patients in Pennsylvania. Participants Asthma patients aged 5–90 years (n = 35,508) were identified in electronic health records; those with exacerbations were frequency-matched on age, sex, and year of event to those without. Exposure(s) On the day before each patient’s index date (cases: date of event or medication order; controls: contact date), we estimated UNGD activity metrics for four phases (pad preparation, drilling, stimulation [“fracking”], and production) using distance from the patient’s home to the well, well characteristics, and the dates and durations of phases. Main Outcome(s) and Measure(s) We identified mild, moderate, and severe asthma exacerbations (new oral corticosteroid medication order, emergency department encounter, and hospitalization, respectively). Results We identified 20,749 mild, 1,870 moderate, and 4,782 severe asthma exacerbations, and frequency-matched these to 18,693, 9,350, and 14,104 control index dates, respectively. In three-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared to the lowest group for 11 out of 12 UNGD-outcome pairs (odds ratios [95% CI] ranged from 1.5 [1.2–1.7] for the association of the pad metric with severe exacerbations to 4.4 [3.8–5.2] for the association of the production metric with mild exacerbations). Six of

  13. The profile of psychiatric symptoms exacerbated by methamphetamine use.

    Science.gov (United States)

    McKetin, Rebecca; Dawe, Sharon; Burns, Richard A; Hides, Leanne; Kavanagh, David J; Teesson, Maree; McD Young, Ross; Voce, Alexandra; Saunders, John B

    2016-04-01

    Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056). Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Malaria cerebral Cerebral malaria

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    Carlos Hugo Zapata Zapata

    2003-03-01

    Full Text Available La malaria Cerebral (MC es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1 citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2 formación de rosetas y aglutinación de glóbulos rojos parasitados; 3 producción de citoquinas y activación de segundos mensajeros y, 4 apertura de la barrera hematoencefálica. Sin embargo, queda un interrogante sin resolver aún: ¿qué proceso se lleva a cabo para que el parásito, desde el espacio microvascular, pueda interferir transitoriamente con la función cerebral? Recientemente se ha utilizado el precursor de la proteína b-Amiloide como un marcador de daño neuronal en MC; este precursor será de gran ayuda en futuras investigaciones realizadas en nuestro medio que aporten información para comprender la patogénesis de la MC. Is the most common complication of P. falciparum malaria; nearly 90% of people who have suffered CM can recover without neurological problems. Currently there are four hypotheses that explain pathogenesis of CM: cytoadherence and sequestering of parasitized red blood cells to cerebral capillaries; rosette formation and parasitized red blood cells agglutination; production of cytokines and activation of second messengers and opening of the blood-brain barrier. However the main question remains to be answered; how the host-parasite interaction in the vascular space interferes transiently with cerebral function? Recently, the beta amyloid precursor peptide has been employed as marker of neural injury in CM. It is expected that the beta amyloid precursor peptide will help to understand the pathogenesis of CM in complicated patients of endemic areas of Colombia.

  15. Regional cerebral blood flow in Parkinson's disease by [sup 123]I-IMP SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Yoshihiro [Okayama Univ. (Japan). School of Medicine

    1994-06-01

    Regional cerebral blood flow (rCBF) was evaluated in 63 patients with Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) using N-isopropyl-p-[sup 123]I-iodoamphetamine ([sup 123]I-IMP) as a tracer. Evaluation of the SPECT images was performed in accordance with the rCBF quantification method using a microsphere model. Patients in stage IV demonstrated significantly lower rCBF than those in stage II at the frontal, temporal, parietal, occipital regions and in the thalamus and cerebellum. Subjects with mental symptoms demonstrated decreased rCBF in every region in the brain. The present study indicates that clinical exacerbation and manifestation of dementia and other psychiatric symptoms in Parkinson's disease are associated with decreased blood flow in various brain regions. (author).

  16. Accelerated extracellular matrix turnover during exacerbations of COPD

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Knox, Alan J; Lange, Peter

    2015-01-01

    progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. METHODS: 69 patients with COPD hospitalised...... of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression....

  17. Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

    Science.gov (United States)

    Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

    2017-11-01

    Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

  18. Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

    Directory of Open Access Journals (Sweden)

    Yong Hwan Ahn

    2018-05-01

    Full Text Available Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

  19. [The Chinese experts' consensus on the evaluation and management of asthma exacerbation].

    Science.gov (United States)

    2018-01-01

    Asthma exacerbations can do a lot of harm to the patients and consume large amounts of medical resources. This consensus is based on the domestic and foreign guidelines and literatures to standardize the evaluation and management of asthma exacerbations in China. Asthma exacerbations are characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing or chest tightness and progressive decrease in lung function, and usually require modification of treatment. Recognizing risk factors and triggering factors of asthma exacerbations is helpful for the prevention and long-term management. Evaluation of asthma exacerbations is based on symptoms, lung function, and arterial blood gas. Management is stratified according to the severity of disease. Different regimens to treat asthma exacerbations are discussed in this consensus. Glucocorticoids should be used properly. Overuse of antibiotics should be avoided. Management of life-threatening asthma is discussed separately. Special attention should be paid in some special respects, such as asthma during peri-operation period, gestation period, and childhood. Diagnosis and management of complications are also of great significance and are discussed in details.

  20. Cerebral Palsy (For Teens)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Teens / Cerebral Palsy What's in this ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

  1. Home-Based Telehealth Hospitalization for Exacerbation of Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Jakobsen, Anna Svarre; Laursen, Lars C; Rydahl-Hansen, Susan

    2015-01-01

    Background: Telehealth interventions for patients with chronic obstructive pulmonary disease (COPD) have focused primarily on stable outpatients. Telehealth designed to handle the acute exacerbation that normally requires hospitalization could also be of interest. The aim of this study...... was to compare the effect of home-based telehealth hospitalization with conventional hospitalization for exacerbation in severe COPD. Materials and Methods: A two-center, noninferiority, randomized, controlled effectiveness trial was conducted between June 2010 and December 2011. Patients with severe COPD...... admitted because of exacerbation were randomized 1:1 either to home-based telehealth hospitalization or to continue standard treatment and care at the hospital. The primary outcome was treatment failure defined as re-admission due to exacerbation in COPD within 30 days after initial discharge...

  2. Postpartum airway responsiveness and exacerbation of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Nilas, Lisbeth; Ulrik, Charlotte Suppli

    2017-01-01

    , diffusing capacity for carbon monoxide, bronchial responsiveness to inhaled mannitol, and inflammatory characteristics in induced sputum. Obtained data were analyzed in relation to exacerbation status during pregnancy. The PD15 is defined as the cumulative administered dose causing a 15% decline in forced......BACKGROUND: Airway responsiveness and inflammation are associated with the clinical manifestations of asthma and the response to pharmacological therapy. OBJECTIVE: To investigate if airway responsiveness and inflammatory characteristics are related to asthma exacerbations during pregnancy....... MATERIALS AND METHODS: In women with asthma who were prescribed controller medication and monitored closely during pregnancy, the risk of exacerbations was analyzed in relation to postpartum measures of fractional exhaled nitric oxide (FENO), skin prick test reactivity, static and dynamic lung volumes...

  3. Inflammatory bowel disease exacerbation associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Dimitroulia, Evangelia; Pitiriga, Vassiliki C; Piperaki, Evangelia-Theophano; Spanakis, Nicholas E; Tsakris, Athanassios

    2013-03-01

    Epstein-Barr virus infection is associated with inflammatory bowel disease, but its role as a pathogenetic or exacerbating factor remains unclear. The aim of this study was to evaluate the association between Epstein-Barr virus infection and inflammatory bowel disease, particularly in regard to exacerbation of disease activity. This was a nonrandomized crosssectional study in subgroups of patients with inflammatory bowel disease compared with a control group with noninflammatory disease. Participants were patients treated for ulcerative colitis or Crohn's disease and individuals undergoing evaluation for noninflammatory disease recruited from 2 urban adult gastrointestinal referral centers in Greece. Diagnosis of inflammatory bowel disease was based on standard clinical and endoscopic criteria. Demographic and clinical characteristics of all participants were recorded. Whole blood samples and fresh tissue samples from biopsy of intestinal sites were obtained from each participant. The presence of Epstein-Barr virus was determined by amplifying the LMP1 gene of the virus in blood and intestinal tissue samples. The study comprised 94 patients with inflammatory bowel disease (63 with ulcerative colitis and 31 with Crohn's disease) and 45 controls with noninflammatory disease. Of the 94 patients, 67 (71.3%) had disease exacerbation and 27 (28.7%) were in remission. The prevalence of Epstein-Barr virus genome was significantly higher in patients than in controls for intestinal tissue (44 patients, 46.8% vs 6 controls, 13.3%; p = 0.001), but not for whole blood (24 patients, 25.5% vs 9 controls, 20%; p = 0.3). The viral genome was found significantly more frequently in intestinal samples from patients with disease exacerbation compared with patients in remission (38 patients with exacerbation, 56.7% vs 6 patients in remission, 22.2%; p = 0.001), but no significant difference was found for whole blood (18 patients with exacerbation, 26.8% vs 6 patients in remission, 22

  4. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis.

    Science.gov (United States)

    Landau, H; Smith, M; Landry, C; Chou, J F; Devlin, S M; Hassoun, H; Bello, C; Giralt, S; Comenzo, R L

    2017-01-01

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m 2 . The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41-5.01 years); median OS was 10.4 years (95% CI: 7.3-not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.

  5. Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

    Directory of Open Access Journals (Sweden)

    Donald P Tashkin

    2010-02-01

    Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

  6. Impact and prevention of severe exacerbations of COPD: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Halpin DMG

    2017-10-01

    Full Text Available David MG Halpin,1 Marc Miravitlles,2 Norbert Metzdorf,3 Bartolomé Celli4 1Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 2Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 3Respiratory Medicine, Boehringer Ingelheim Pharma GmBH & Co KG, Ingelheim am Rhein, Germany; 4Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. Keywords

  7. Caffeine consumption and exacerbations of chronic obstructive pulmonary disease: Retrospective study

    Directory of Open Access Journals (Sweden)

    P.O. Lopes

    2015-09-01

    Full Text Available Background: The modulation of adenosine receptors has been proposed as new therapeutic target for chronic obstructive pulmonary disease, but studies in humans were negative. Caffeine is widely consumed and acts by non-selective modulation of these receptors, allowing for a non-interventional evaluation of the purinergic effects on COPD. We evaluated the effects of chronic caffeine consumption on the risk for COPD exacerbations. Methods: Retrospective study including patients with COPD. The total number of exacerbations during a three-year period and the mean daily caffeine consumption in the last twenty years were evaluated. A univariate and multiple regression analysis were performed for evaluation of the significant predictors of exacerbations. Results: A total of 90 patients were included. Most were males (82.2% and had a mean forced expiratory volume in the first second (FEV1 of 57.0 ± 17.1% predicted. The mean daily caffeine consumption was 149.7 ± 140.9 mg. There was no correlation between the mean caffeine consumption and exacerbations (p > 0.05. Discussion: Our results suggest that caffeine has no significant effect on the frequency of COPD exacerbations. These conclusions are limited by the sample size and the retrospective nature of the study. Keywords: COPD, Caffeine, Disease exacerbation, Purines, Pharmacology, Coffee, Respiratory Tract Diseases

  8. Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

    Directory of Open Access Journals (Sweden)

    Bohacek Ivan

    2012-08-01

    Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

  9. COPD exacerbations in general practice: variability in oral prednisolone courses

    Directory of Open Access Journals (Sweden)

    de Vries Marianne

    2012-01-01

    Full Text Available Abstract Background The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs who adjust their treatment according to the presence of diabetic co-morbidity. Methods Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands. Results The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity. Conclusion Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.

  10. Cerebral Angiographic Findings of Cosmetic Facial Filler-related Ophthalmic and Retinal Artery Occlusion.

    Science.gov (United States)

    Kim, Yong-Kyu; Jung, Cheolkyu; Woo, Se Joon; Park, Kyu Hyung

    2015-12-01

    Cosmetic facial filler-related ophthalmic artery occlusion is rare but is a devastating complication, while the exact pathophysiology is still elusive. Cerebral angiography provides more detailed information on blood flow of ophthalmic artery as well as surrounding orbital area which cannot be covered by fundus fluorescein angiography. This study aimed to evaluate cerebral angiographic features of cosmetic facial filler-related ophthalmic artery occlusion patients. We retrospectively reviewed cerebral angiography of 7 patients (4 hyaluronic acid [HA] and 3 autologous fat-injected cases) showing ophthalmic artery and its branches occlusion after cosmetic facial filler injections, and underwent intra-arterial thrombolysis. On selective ophthalmic artery angiograms, all fat-injected patients showed a large filling defect on the proximal ophthalmic artery, whereas the HA-injected patients showed occlusion of the distal branches of the ophthalmic artery. Three HA-injected patients revealed diminished distal runoff of the internal maxillary and facial arteries, which clinically corresponded with skin necrosis. However, all fat-injected patients and one HA-injected patient who were immediately treated with subcutaneous hyaluronidase injection showed preserved distal runoff of the internal maxillary and facial arteries and mild skin problems. The size difference between injected materials seems to be associated with different angiographic findings. Autologous fat is more prone to obstruct proximal part of ophthalmic artery, whereas HA obstructs distal branches. In addition, hydrophilic and volume-expansion property of HA might exacerbate blood flow on injected area, which is also related to skin necrosis. Intra-arterial thrombolysis has a limited role in reconstituting blood flow or regaining vision in cosmetic facial filler-associated ophthalmic artery occlusions.

  11. Job strain and the risk of severe asthma exacerbations

    DEFF Research Database (Denmark)

    Heikkilä, K; Madsen, I E H; Nyberg, S T

    2014-01-01

    BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations...... in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe...... asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years...

  12. Differential Features of Cerebral Perfusion in Dementia with Lewy Bodies Compared to Alzheimer's Dementia using SPM Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB) are most common cause of dementia in elderly people. Clinical distinction in some cases of DLB from AD may be difficult as symptom profiles overlap. Some neuropathologic overlap is also seen as beta-amyloidosis and senile plaques can be found in both disease. Both disease also share severe acetylcholine depletion. We evaluated the differences of brain perfusion between DLB and AD using statistical parametric mapping analysis. Twelve DLB (mean age ; 68.8{+-}8.3 years, K-MMSE ; 17.3{+-}6.1) and 51 AD patients (mean age ; 71.4{+-}7.2 years, K-MMSE ; 16.7{+-}4.5), which were matched for age and severity of dementia, participated in this study. Tc-99m HMPAO SPECT was performed for measuring regional cerebral blood flow. Statistical parametric mapping (SPM99) software was used for automatic and objective approach to analyze SPECT image data. The SPECT data of the patients with DLB were compared to patients with AD. Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both occipital (both middle occipital gyrus, Rt B no. 18 and Lt cuneus), both parietal (Lt parietal precuneus, Lt B no. 39, Lt inferior parietal lobule and Rt supramarginal gyrus) lobes in DLB compared with AD. Significant hyperperfusion was noted in Rt frontal (sup. frontal gyrus, B no.10, middle frontal gyrus, B no. 9, B no. 11, inf. frontal gyrus), Rt putamen, Lt ant. cingulate gyrus (B no. 24), both cerebellar post. lobe (Lt tuber, Lt declive, Lt tonsil, Rt declive) in DLB compared with AD. We found a significant differences in the cerebral perfusion pattern between DLB and AD. Differential feature of cerebral perfusion in DLB was both occipital hypoperfusion and preserved Rt frontal perfusion compared to AD. Therefore in difficult case of clinical an neuro pathologic diagnosis, brain perfusion SPECT with SPM analysis may be helpful to differentiate DLB from AD.

  13. Mannose-binding lectin deficiency and acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Woodruff PG

    2012-11-01

    Full Text Available Richard K Albert,1 John Connett,2 Jeffrey L Curtis,3,4 Fernando J Martinez,3 MeiLan K Han,3 Stephen C Lazarus,5 Prescott G Woodruff51Medicine Service, Denver Health and Department of Medicine, University of Colorado Denver, Denver, CO, 2Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, 3Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, 4Pulmonary and Critical Care Medicine, VA Medical Center, Ann Arbor, MI, 5Pulmonary and Critical Care Medicine, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USABackground: Mannose-binding lectin is a collectin involved in host defense against infection. Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated.Methods: Participants in a study designed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment.Results: Samples were obtained from 1037 subjects (91% in the trial. The prevalence of mannose-binding lectin deficiency ranged from 0.5% to 52.2%, depending on how deficiency was defined. No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed, and no differences were observed in time to first exacerbation, rate of exacerbations, or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without, regardless of how deficiency was defined.Conclusion: In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease, only 1.9% had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin

  14. Unilateral cerebral polymicrogyria with ipsilateral cerebral hemiatrophy

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Katsumi [Department of Radiology, Kyoto City Hospital, 1-2 Higashi-Takada-cho, Mibu, Nakagyo-ku, 604-8845 Kyoto (Japan); Kanda, Toyoko; Yamori, Yuriko [Department of Pediatric Neurology, St. Joseph Hospital for Handicapped Children, 603-8323 Kyoto (Japan)

    2002-10-01

    We evaluated six children in whom MR imaging showed unilateral cerebral polymicrogyria associated with ipsilateral cerebral atrophy and ipsilateral brain stem atrophy. The aim of this study was to clarify whether this disorder based on neuroimaging constitutes a new homogeneous clinical entity. The subjects were six children whose ages at the time of MR imaging ranged from 8 months to 11 years. Their clinical and MR features were analyzed. All of the children were born between 38 and 42 weeks gestation, without any significant perinatal events. Spastic hemiplegia and epilepsy were observed in all of the patients, and mental retardation was observed in four. The MR findings included unilateral cerebral polymicrogyria associated with ipsilateral cerebral hemiatrophy and ipsilateral brain stem atrophy in all patients. The ipsilateral sylvian fissure was hypoplastic in four patients. These patients showed relatively homogeneous clinical and neuroimaging features. Although the additional clinical features varied according to the site and the extent affected by the polymicrogyria, this disorder could constitute a new relatively homogeneous clinical entity. (orig.)

  15. Unilateral cerebral polymicrogyria with ipsilateral cerebral hemiatrophy

    International Nuclear Information System (INIS)

    Hayakawa, Katsumi; Kanda, Toyoko; Yamori, Yuriko

    2002-01-01

    We evaluated six children in whom MR imaging showed unilateral cerebral polymicrogyria associated with ipsilateral cerebral atrophy and ipsilateral brain stem atrophy. The aim of this study was to clarify whether this disorder based on neuroimaging constitutes a new homogeneous clinical entity. The subjects were six children whose ages at the time of MR imaging ranged from 8 months to 11 years. Their clinical and MR features were analyzed. All of the children were born between 38 and 42 weeks gestation, without any significant perinatal events. Spastic hemiplegia and epilepsy were observed in all of the patients, and mental retardation was observed in four. The MR findings included unilateral cerebral polymicrogyria associated with ipsilateral cerebral hemiatrophy and ipsilateral brain stem atrophy in all patients. The ipsilateral sylvian fissure was hypoplastic in four patients. These patients showed relatively homogeneous clinical and neuroimaging features. Although the additional clinical features varied according to the site and the extent affected by the polymicrogyria, this disorder could constitute a new relatively homogeneous clinical entity. (orig.)

  16. Statistical analysis of exacerbation rates in COPD: TRISTAN and ISOLDE revisited

    DEFF Research Database (Denmark)

    Keene, O N; Calverley, P M A; Jones, P W

    2008-01-01

    different analysis methods, we have reanalysed data from two large studies which, among other objectives, investigated the effectiveness of inhaled corticosteroids in reducing COPD exacerbation rates. Using the negative binomial model to reanalyse data from the TRISTAN and ISOLDE studies, the overall...... estimates of exacerbation rates on each treatment arm are higher and the confidence intervals for comparisons between treatments are wider, but the overall conclusions of TRISTAN and ISOLDE regarding reduction of exacerbations remain unchanged. The negative binomial approach appears to provide a better fit...

  17. Exacerbations of COPD and symptoms of gastroesophageal reflux: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Thiago Mamoru Sakae

    2013-06-01

    Full Text Available OBJECTIVE: To examine the relationship between gastroesophageal reflux (GER and COPD exacerbations. METHODS: We conducted a systematic search of various electronic databases for articles published up through December of 2012. Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls; and describing relative risks (RRs and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations for the association between GER and COPD-as well as exacerbation rates. Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use; GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms; annual frequency of exacerbations; GER treatment; and severity of airflow obstruction. RESULTS: Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94, with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36. The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001. CONCLUSIONS: GER is a risk factor for COPD exacerbations. The role of GER in COPD management should be studied in greater detail.

  18. Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs.

    Directory of Open Access Journals (Sweden)

    Kristina S Sobotka

    Full Text Available A sustained inflation (SI rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF and cerebral vascular integrity in asphyxiated near-term lambs.Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6, a single 30 s SI (single SI; n = 6 or conventional ventilation (no SI; n = 6. Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage.CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01, which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01. Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001 in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs.Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation.

  19. Genetic alterations of the BR12 Gene: familial British and Danish dementias

    DEFF Research Database (Denmark)

    Ghiso, J.; Rostagno, A.; Tomidokoro, Y.

    2006-01-01

    Classic arguments sustaining the importance of amyloid in the pathogenesis of dementia are usually centered on amyloid β (Aβ) and its role in neuronal loss characteristic of Alzheimer disease, the most common form of human cerebral amyloidosis. Two non-Aβ cerebral amyloidoses, familial British...... and their relation to cognitive impairment remain to be clarified, new evidence indicates that, independent of the differences in their primary structures, Aβ, ABri, and ADan subunits are able to form morphologically compatible ion-channel-like structures and elicit single ion-channel currents in reconstituted lipid...

  20. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

    Science.gov (United States)

    Han, MeiLan K; Quibrera, Pedro M; Carretta, Elizabeth E; Barr, R Graham; Bleecker, Eugene R; Bowler, Russell P; Cooper, Christopher B; Comellas, Alejandro; Couper, David J; Curtis, Jeffrey L; Criner, Gerard; Dransfield, Mark T; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Krishnan, Jerry A; Martinez, Carlos H; Pirozzi, Cheryl B; O'Neal, Wanda K; Rennard, Stephen; Tashkin, Donald P; Wedzicha, Jadwiga A; Woodruff, Prescott; Paine, Robert; Martinez, Fernando J

    2017-08-01

    Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV 1 . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas

  1. Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog.

    Science.gov (United States)

    Besancon, M Faulkner; Stacy, Brian A; Kyles, Andrew E; Moore, Peter F; Vernau, William; Smarick, Sean D; Rasor, Liberty A

    2004-04-15

    A 7-year-old castrated male Miniature Schnauzer was examined because of labored breathing and episodes of respiratory distress that progressed to collapse. On cervical radiographs, a focal soft tissue mass in the caudal cervical portion of the trachea was observed, and during tracheoscopy, a 1 x 1 cm, pedunculated, multinodular, pink, intraluminal mass extending from the dorsal tracheal membrane and obstructing approximately 80% of the tracheal lumen was seen. Tracheal resection and anastomosis was performed to remove the mass, and the dog recovered without complications. On histologic examination, the mass consisted of a large accumulation of homogeneous, faintly fibrillar eosinophilic material admixed with a predominantly plasma cell infiltrate; examination of sections stained with thioflavin T and Congo red stain confirmed that the eosinophilic material was amyloid. A diagnosis of nodular, immunocyte-derived (AL) amyloidosis was made. Seventeen months after surgery, the dog had a relapse of respiratory distress because of an extramedullary plasmacytoma involving the trachea.

  2. A search for covert precipitating clinical parameters in frequent exacerbators of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ankit Bhatia

    2016-01-01

    Full Text Available Introduction: Acute exacerbations are a significant source of morbidity and mortality associated with chronic obstructive pulmonary disease (COPD. Some patients suffer an inordinate number of exacerbations while others remain relatively protected. The aim of this study was to evaluate the potentially modifiable precipitating parameters of frequent severe exacerbations requiring hospital admission in COPD. Materials and Methods: Consecutive patients admitted with acute exacerbation of COPD for a period of one year in a tertiary care hospital were evaluated prospectively. Data regarding the number of exacerbations in the previous year, current comorbidities, medications, and clinical and functional status of COPD patients were evaluated. Results: We included 98 COPD patients (81.63% men admitted consecutively with exacerbations in our department. The mean number of severe exacerbations was (2.42 per patient/per year, and 65% of the patients had frequent severe exacerbations. Multivariate analysis indicated that serum uric acid, serum total IgE, depression and anxiety, gastroesophageal reflux disease symptoms, air pollution, poor adherence to inhaled therapy, and irregular outpatient followup visits were independent predictors of frequent severe exacerbations. Conclusion: COPD patients with frequent exacerbations should be carefully assessed for modifiable confounding risk factors regardless of poor lung function to decrease exacerbation frequency and related poor prognosis. Raised serum total IgE levels may point towards atopy as an additional comorbidity in COPD while uric acid can have a clinically useful role in risk stratification in a primary care setting.

  3. Reduced COPD Exacerbation Risk Correlates With Improved FEV1: A Meta-Regression Analysis.

    Science.gov (United States)

    Zider, Alexander D; Wang, Xiaoyan; Buhr, Russell G; Sirichana, Worawan; Barjaktarevic, Igor Z; Cooper, Christopher B

    2017-09-01

    The mechanism by which various classes of medication reduce COPD exacerbation risk remains unknown. We hypothesized a correlation between reduced exacerbation risk and improvement in airway patency as measured according to FEV 1 . By systematic review, COPD trials were identified that reported therapeutic changes in predose FEV 1 (dFEV 1 ) and occurrence of moderate to severe exacerbations. Using meta-regression analysis, a model was generated with dFEV 1 as the moderator variable and the absolute difference in exacerbation rate (RD), ratio of exacerbation rates (RRs), or hazard ratio (HR) as dependent variables. The analysis of RD and RR included 119,227 patients, and the HR analysis included 73,475 patients. For every 100-mL change in predose FEV 1 , the HR decreased by 21% (95% CI, 17-26; P < .001; R 2  = 0.85) and the absolute exacerbation rate decreased by 0.06 per patient per year (95% CI, 0.02-0.11; P = .009; R 2  = 0.05), which corresponded to an RR of 0.86 (95% CI, 0.81-0.91; P < .001; R 2  = 0.20). The relationship with exacerbation risk remained statistically significant across multiple subgroup analyses. A significant correlation between increased FEV 1 and lower COPD exacerbation risk suggests that airway patency is an important mechanism responsible for this effect. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Cerebral palsy and congenital malformations

    DEFF Research Database (Denmark)

    Garne, Ester; Dolk, Helen; Krägeloh-Mann, Inge

    2007-01-01

    AIM: To determine the proportion of children with cerebral palsy (CP) who have cerebral and non-cerebral congenital malformations. METHODS: Data from 11 CP registries contributing to the European Cerebral Palsy Database (SCPE), for children born in the period 1976-1996. The malformations were...... classified as recognized syndromes, chromosomal anomalies, cerebral malformations or non-cerebral malformations. Prevalence of malformations was compared to published data on livebirths from a European database of congenital malformations (EUROCAT). RESULTS: Overall 547 out of 4584 children (11.9%) with CP...... were reported to have a congenital malformation. The majority (8.6% of all children) were diagnosed with a cerebral malformation. The most frequent types of cerebral malformations were microcephaly and hydrocephaly. Non-cerebral malformations were present in 97 CP children and in further 14 CP children...

  5. Cerebral Palsy

    Science.gov (United States)

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  6. Serum eosinophil cationic protein levels can be useful for predicting acute exacerbation of asthma

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Kamimura

    1998-01-01

    Full Text Available We report on a case in which five consecutive exacerbations of asthma were monitored by following serum eosinophil cationic protein (ECP levels. The serum ECP level correlated well with each exacerbation and tended to increase even before the exacerbations of asthma became apparent. This case shows that serum levels of ECP can be useful markers of disease activity and may also be predictive markers for acute exacerbation.

  7. Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

    Science.gov (United States)

    Vijay, Anantha; Santhanam, R; Katusic, Zvonimir S

    2006-10-01

    Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

  8. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review

    Directory of Open Access Journals (Sweden)

    Steurer Johann

    2007-04-01

    Full Text Available Abstract Background For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD. The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations. Methods We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment. Results We included 13 trials (1557 patients of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I2 = 82%. Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.016: Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.09, 95% CI 0.75–1.59, I2 = 18%. Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16–0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3–5 and on mortality (pooled odds ratio of 0.20, 95% CI 0.06–0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12–30. Conclusion Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients.

  9. Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis

    Directory of Open Access Journals (Sweden)

    Hund E

    2012-06-01

    removing the main source of mutant TTR. Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.Keywords: FAP, transthyretin, amyloidosis, treatment, therapy

  10. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  11. Cerebral and non-cerebral coenurosis: on the genotypic and phenotypic diversity of Taenia multiceps.

    Science.gov (United States)

    Christodoulopoulos, Georgios; Dinkel, Anke; Romig, Thomas; Ebi, Dennis; Mackenstedt, Ute; Loos-Frank, Brigitte

    2016-12-01

    We characterised the causative agents of cerebral and non-cerebral coenurosis in livestock by determining the mitochondrial genotypes and morphological phenotypes of 52 Taenia multiceps isolates from a wide geographical range in Europe, Africa, and western Asia. Three studies were conducted: (1) a morphological comparison of the rostellar hooks of cerebral and non-cerebral cysts of sheep and goats, (2) a morphological comparison of adult worms experimentally produced in dogs, and (3) a molecular analysis of three partial mitochondrial genes (nad1, cox1, and 12S rRNA) of the same isolates. No significant morphological or genetic differences were associated with the species of the intermediate host. Adult parasites originating from cerebral and non-cerebral cysts differed morphologically, e.g. the shape of the small hooks and the distribution of the testes in the mature proglottids. The phylogenetic analysis of the mitochondrial haplotypes produced three distinct clusters: one cluster including both cerebral isolates from Greece and non-cerebral isolates from tropical and subtropical countries, and two clusters including cerebral isolates from Greece. The majority of the non-cerebral specimens clustered together but did not form a monophyletic group. No monophyletic groups were observed based on geography, although specimens from the same region tended to cluster. The clustering indicates high intraspecific diversity. The phylogenetic analysis suggests that all variants of T. multiceps can cause cerebral coenurosis in sheep (which may be the ancestral phenotype), and some variants, predominantly from one genetic cluster, acquired the additional capacity to produce non-cerebral forms in goats and more rarely in sheep.

  12. Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide

    NARCIS (Netherlands)

    Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

    2018-01-01

    The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center

  13. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen; Nordestgaard, Børge G; Hallas, Jesper; Lange, Peter

    2015-01-01

    We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3-5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6-2.7, P = 0.63). Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly. © 2014 Asian Pacific Society of Respirology.

  14. Cerebral Palsy. Fact Sheet = La Paralisis Cerebral. Hojas Informativas Sobre Discapacidades.

    Science.gov (United States)

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This fact sheet on cerebral palsy is written in both English and Spanish. First, it provides a definition of cerebral palsy and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy:…

  15. Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma

    NARCIS (Netherlands)

    Westerhof, Guus A.; de Groot, Jantina C.; Amelink, Marijke; de Nijs, Selma B.; ten Brinke, Anneke; Weersink, Els J.; Bel, Elisabeth H.

    2016-01-01

    Persistent eosinophilic airway inflammation is an important driver for asthma exacerbations in non-smokers with asthma. Whether eosinophilic inflammation is also a predictor of asthma exacerbations in (ex)smokers is not known. The aim was to investigate factors associated with frequent exacerbations

  16. Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

    Science.gov (United States)

    Yii, A C A; Tan, J H Y; Lapperre, T S; Chan, A K W; Low, S Y; Ong, T H; Tan, K L; Chotirmall, S H; Sterk, P J; Koh, M S

    2017-09-01

    Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m 2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently

  17. Microembolism after cerebral angiography

    International Nuclear Information System (INIS)

    Manaka, Hiroshi; Sakai, Hideki; Nagata, Izumi

    2000-01-01

    Acute microemboli are detected more precisely with the recently developed diffusion-weighted MR imaging (DWI). We happened to obtain 24 DWIs after 350 diagnostic cerebral angiographies in 1999. DWIs after cerebral angiographies showed bright lesions in 7 patients (28%), of whom 6 had no neurological symptoms after cerebral angiography. Seven of the 24 patients had risk factors for arteriosclerosis. Only one patient had embolic events due to angiography. Microemboli related to cerebral angiographies are inevitable in some patients. Most are silent, however, we should investigate the cause of microemboli and should make cerebral angiography safer. (author)

  18. Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography

    Directory of Open Access Journals (Sweden)

    Truran Seth

    2008-08-01

    Full Text Available Abstract Background Light chain amyloidosis (AL is a rare but often fatal disease due to intractable heart failure. Amyloid deposition leads to diastolic dysfunction and often preserved ejection fraction. We hypothesize that AL is associated with regional systolic dyssynchrony. The aim is to compare left ventricular (LV regional synchrony in AL subjects versus healthy controls using 16-segment dyssynchrony index measured from 3-dimension-al (3D echocardiography. Methods Cardiac 3D echocardiography full volumes were acquired in 10 biopsy-proven AL subjects (60 ± 3 years, 5 females and 10 healthy controls (52 ± 1 years, 5 females. The LV was subdivided into 16 segments and the time from end-diastole to the minimal systolic volume for each of the 16 segments was expressed as a percent of the cycle length. The standard deviations of these times provided a 16-segment dyssynchrony index (16-SD%. 16-SD% was compared between healthy and AL subjects. Results Left ventricular ejection fraction was comparable (control vs. AL: 62.4 ± 0.6 vs. 58.6 ± 2.8%, p = NS. 16-SD% was significantly higher in AL versus healthy subjects (5.93 ± 4.4 vs. 1.67 ± 0.87%, p = 0.003. 16-SD% correlated with left ventricular mass index (R 0.45, p = 0.04 but not to left ventricular ejection fraction. Conclusion Light chain amyloidosis is associated with left ventricular regional systolic dyssynchrony. Regional dyssynchrony may be an unrecognized mechanism of heart failure in AL subjects.

  19. Significant association between renal function and amyloid-positive area in renal biopsy specimens in AL amyloidosis

    Directory of Open Access Journals (Sweden)

    Kuroda Takeshi

    2012-09-01

    Full Text Available Abstract Background The kidney is a major target organ for systemic amyloidosis that often affects the kidney including proteinura, and elevated serum creatinine (Cr. The correlation between amount of amyloid deposits and clinical parameters is not known. The aim of this study was to clarify correlation the amyloid area in all renal biopsy specimen and clinical parameters. Methods Fifty-eight patients with an established diagnosis of AL amyloidosis participated in the study. All patients showed amyloid deposits in renal biopsies. We retrospectively investigated the correlation between clinical data and amyloid occupied area in whole renal biopsy specimens. Results The area occupied by amyloid was less than 10% in 57 of the 58 patients, and was under 2% in 40. For statistical analyses, %amyloid-positive areas were transformed to common logarithmic values (Log10%amyloid. Cr showed significant correlation with Log10%amyloid and estimated glomerular filtration rate (eGFR showed the significant negative correlation. Patient age, cleatinine clearance (Ccr, blood urea nitorogen, and urinary protein was not significantly correlated with Log10%amyloid. The correlation with other clinical factors such as sex, and serum concentrations of total protein, albumin, immunoglobulins, compliments was evaluated. None of these factors significantly correlated with Log10%amyloid. According to sex- and age- adjusted multiple linear regression analysis, Log10%amyloid had significant positive association with Cr and significant negative association with eGFR. Conclusion There is significant association between amyloid-positive area in renal tissue and renal function, especially Cr and eGFR. The level of Cr and eGFR may be a marker of amount of amyloid in renal tissue.

  20. Chronic Obstructive Pulmonary Disease Exacerbations Are Influenced by Gastroesophageal Reflux Disease.

    Science.gov (United States)

    Bigatao, Amilcar M; Herbella, Fernando A M; Del Grande, Leonardo M; Nascimento, Oliver A; Jardim, Jose R; Patti, Marco G

    2018-01-01

    Gastroesophageal reflux disease (GERD) is associated with different pulmonary diseases, including chronic obstructive pulmonary disease (COPD). Whether GERD is contributory to COPD severity remains unclear. This study aims to evaluate the contribution of GERD to the clinical manifestation of COPD based on ventilatory parameters and yearly clinical exacerbations. We studied 48 patients (56% females, age 66 years) with COPD. All patients underwent high-resolution manometry and esophageal pH monitoring. The patients were separated into two groups according to the presence of GERD. GERD was present in 21 (44%) patients. GERD + and GERD - groups did not differ in regard to gender, age, and body mass index. Pulmonary parameters were not different in the absence or presence of GERD. The number of yearly exacerbations was higher in patients GERD+. The severity of GERD (as measured by DeMeester score) correlated with the number of exacerbations. Our results show the following: 1) GERD does not influence pulmonary parameters and 2) GERD is associated with a higher number of annual clinical exacerbations. We believe GERD must be objectively tested in patients with COPD because the prevalence of GERD in these patients is underestimated when only symptoms are considered. GERD treatment might decrease the frequency of episodes of exacerbation.

  1. Clinical characteristics of eosinophilic asthma exacerbations

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Backer, Vibeke

    2017-01-01

    blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction...... at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P...... = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P

  2. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

  3. Birth Defects: Cerebral Palsy

    Science.gov (United States)

    ... Loss > Birth defects & other health conditions > Cerebral palsy Cerebral palsy E-mail to a friend Please fill in ... this page It's been added to your dashboard . Cerebral palsy (also called CP) is a group of conditions ...

  4. Employees with Cerebral Palsy

    Science.gov (United States)

    ... Resources Home | Accommodation and Compliance Series: Employees with Cerebral Palsy (CP) By Eddie Whidden, MA Preface Introduction Information ... SOAR) at http://AskJAN.org/soar. Information about Cerebral Palsy (CP) What is CP? Cerebral palsy is a ...

  5. Exacerbation of pneumomediastinum after air travel in a patient with dermatomyositis.

    Science.gov (United States)

    Ye, Qiuyue; Zhang, Lu; Tian, Xinlun; Shi, Juhong

    2011-07-01

    Although the presence of pneumothorax is generally considered an absolute contraindication to air travel, reports on pneumomediastinum after air travel are extremely rare. Moreover, to the best of our knowledge, exacerbation of existing pneumomediastinum after commercial air travel has never been reported. We report on a case of a patient (the first case that we are aware of) who suffered exacerbation of pneumomediastinum after commercial air travel. This patient, with confirmed pneumomediastinum before air travel, flew to our city for medical care without being warned about exacerbation by the local hospital or airlines. Obvious exacerbation of pneumomediastinum and subcutaneous emphysema was noticed after the travel. Subsequently, a diagnosis of amyopathic dermatomyositis with interstitial lung disease and pneumomediastinum was made. The patient died despite treatment with corticosteroid, cyclophosphamide and intravenous immunoglobulin. This report discusses this rare condition and offers suggestions regarding air travel for patients with presence of pneumomediastinum at the time of flight.

  6. Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization

    Science.gov (United States)

    Dilektasli, Asli Gorek; Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Budak, Ferah; Coskun, Funda; Ursavas, Ahmet; Ercan, Ilker; Ege, Ercument

    2017-01-01

    Introduction Chemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, PCOPD (168 vs 196 ng/mL) subgroups did not achieve statistical significance (P=0.09). Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92). Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, PCOPD, as it is associated with frequency of exacerbations, particularly with severe COPD exacerbations requiring hospitalization, as well as with functional parameters and symptom scores. PMID:28115842

  7. Antibiotics for exacerbations of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Vollenweider, Daniela J; Jarrett, Harish; Steurer-Stey, Claudia A; Garcia-Aymerich, Judith; Puhan, Milo A

    2012-12-12

    Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment

  8. Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers.

    Science.gov (United States)

    Murray, Clare S; Foden, Philip; Sumner, Helen; Shepley, Elizabeth; Custovic, Adnan; Simpson, Angela

    2017-07-15

    Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. To evaluate the use of house dust mite-impermeable bedding and its impact on severe asthma exacerbations in children. We randomized mite-sensitized children with asthma (ages 3-17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36-0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26-0.56] vs. placebo, 0.52 [0.35-0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58-1.17; P = 0.28). Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).

  9. Clinical assessment, staging, and epidemiology of chronic obstructive pulmonary disease exacerbations

    DEFF Research Database (Denmark)

    Vestbo, Jørgen

    2006-01-01

    Patients presenting with an exacerbation of chronic obstructive pulmonary disease (COPD) are initially assessed to ensure that a proper diagnosis has been made and that relevant differential diagnoses are excluded. Although guidelines provide indicators for use, very little systematic research has...... been done in initial assessment of COPD exacerbations. Next, the assessment should aim at stratifying patients for risk of poor outcome. For this, predictors of poor prognosis as well as knowledge of favorable treatments can be used. However, no formal and validated staging system exists today. Given...... the frequency and impact of COPD exacerbations, there seems to be a need for systematic research in this area....

  10. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs

    International Nuclear Information System (INIS)

    Busija, D.W.; Leffler, C.W.

    1987-01-01

    The authors examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-μm radioactive microspheres. Regional CBF ranged from 44 to 66 ml·min -1 ·100 g -1 , and cerebral metabolic rate was 1.94 ± 0.23 ml O 2 ·100 g -1 ·min -1 during normothermia (39 degree C). Reduction of rectal temperature to 34-35 degree C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, they examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilation during the second episode. They conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced

  11. Hypercapnic cerebral edema presenting in a woman with asthma: a case report

    Directory of Open Access Journals (Sweden)

    McGee William T

    2011-05-01

    Full Text Available Abstract Introduction Common causes of non-traumatic acute cerebral edema include malignant hypertension, hyponatremia, anoxia, and cerebral vascular accident. The computed tomographic images and data obtained during care of the patient described in this case report provide evidence that hypercarbia can cause increased intracranial pressure and coma without permanent brain injury. Partial pressure of carbon dioxide evaluation for coma is essential to provide faster diagnosis and therapeutic correction in certain common critical disease states. We present the case of a patient in a coma associated with cerebral edema during a typical asthma exacerbation with hypercapnic respiratory failure. Case presentation An obese 63-year-old African American woman with asthma presented to our hospital with facial swelling and shortness of breath. Immediately following intubation for hypercapnic respiratory failure, she was noted to have a dilated, unresponsive right pupil. An emergent computed tomographic head scan revealed that she had increased intracranial pressure. A neurosurgeon agreed with the computed tomography interpretation and recommended no surgical intervention. The patient's respiratory acidosis was corrected with ventilatory management over several hours in the intensive care unit. Nine and one-half hours later a follow-up head computed tomographic scan was read as normal without cerebral edema. At 12 hours, the patient's right pupil was 5 mm in diameter and reactive. By 24 hours, her pupils were symmetrically equal and reactive. Her symptoms had improved, and she was extubated. A brain magnetic resonance imaging scan revealed no abnormalities. Conclusion Alteration of consciousness related to hypercapnia during respiratory failure is not generally thought to be related to cerebral edema. Respiratory acidosis resulting from hypercarbia is known to produce carbon dioxide narcosis and coma, but no current treatment algorithm suggests that rapid

  12. Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115.

    Science.gov (United States)

    Sanchorawala, V; Hoering, A; Seldin, D C; Finn, K T; Fennessey, S A; Sexton, R; Mattar, B; Safah, H F; Holmberg, L A; Dean, R M; Orlowski, R Z; Barlogie, B

    2013-11-01

    We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m(2) and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity.

  13. Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

    Directory of Open Access Journals (Sweden)

    William D-C. Man

    2015-10-01

    Full Text Available Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact.

  14. Tiotropium and Salmeterol in COPD Patients at Risk of Exacerbations: A Post Hoc Analysis from POET-COPD(®).

    Science.gov (United States)

    Vogelmeier, Claus F; Asijee, Guus M; Kupas, Katrin; Beeh, Kai M

    2015-06-01

    Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.

  15. Inverse relationship between nonadherence to original GOLD treatment guidelines and exacerbations of COPD.

    Science.gov (United States)

    Foda, Hussein D; Brehm, Anthony; Goldsteen, Karen; Edelman, Norman H

    2017-01-01

    Prescriber disagreement is among the reasons for poor adherence to COPD treatment guidelines; it is yet not clear whether this leads to adverse outcomes. We tested whether undertreatment according to the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines led to increased exacerbations. Records of 878 patients with spirometrically confirmed COPD who were followed from 2005 to 2010 at one Veterans Administration (VA) Medical Center were analyzed. Analysis of variance was performed to assess differences in exacerbation rates between severity groups. Logistic regression analysis was performed to assess the relationship between noncompliance with guidelines and exacerbation rates. About 19% were appropriately treated by guidelines; 14% overtreated, 44% under-treated, and in 23% treatment did not follow any guideline. Logistic regression revealed a strong inverse relationship between undertreatment and exacerbation rate when severity of obstruction was held constant. Exacerbations per year by GOLD stage were significantly different from each other: mild 0.15, moderate 0.27, severe 0.38, very severe 0.72, and substantially fewer than previously reported. The guidelines were largely not followed. Undertreatment predominated but, contrary to expectations, was associated with fewer exacerbations. Thus, clinicians were likely advancing therapy primarily based upon exacerbation rates as was subsequently recommended in revised GOLD and other more recent guidelines. In retrospect, a substantial lack of prescriber adherence to treatment guidelines may have been a signal that they required re-evaluation. This is likely to be a general principle regarding therapeutic guidelines. The identification of fewer exacerbations in this cohort than has been generally reported probably reflects the comprehensive nature of the VA system, which is more likely to identify relatively asymptomatic (ie, nonexacerbating) COPD patients. Accordingly, these rates may

  16. Hyperventilation, cerebral perfusion, and syncope

    DEFF Research Database (Denmark)

    Immink, R V; Pott, F C; Secher, N H

    2014-01-01

    dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2...... the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced...... cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established....

  17. Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

    Science.gov (United States)

    Falagas, Matthew E; Georgiou, Maria

    2017-03-01

    Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

  18. Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Bradley S Quon

    Full Text Available BACKGROUND: One in four cystic fibrosis (CF patients diagnosed with a pulmonary exacerbation will not recover their baseline lung function despite standard treatment. This highlights the importance of preventing such events. Clinical decision-making can be improved through a simple blood test that predicts individuals at elevated short-term risk of an exacerbation. METHODS: We obtained plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF Clinic (Vancouver, Canada. For 15 patients, an additional plasma sample was obtained during an exacerbation. Soluble CD14 (sCD14 and C-reactive protein (CRP were quantified using ELISA kits. Myeloperoxidase (MPO, interleukin(IL-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1, vascular endothelial growth factor (VEGF, and granulocyte colony-stimulating factor (G-CSF were quantified using Luminex™ immunoassays. Stable state biomarker levels were examined in their ability to predict individuals that would experience a pulmonary exacerbation requiring intravenous (IV antibiotics within 4 months. Paired stable and exacerbation plasma biomarker levels were also compared. RESULTS: sCD14 levels were significantly higher in patients that experienced a pulmonary exacerbation requiring IV antibiotics within 4 months (p = 0.001. sCD14 cut-off value of 1450 ng/mL was associated with an area under the curve of 0.91 (95% CI 0.83-0.99 for predicting an exacerbation within 4 months of a stable visit, with a sensitivity of 100% and specificity of 82%. Plasma sCD14 levels were significantly higher during exacerbations than during periods of clinical stability (p = 0.03. CONCLUSIONS: Plasma sCD14 is a promising biomarker for identifying CF patients who will exacerbate within 4 months of a stable visit but requires further study in larger, independent cohorts.

  19. Proximity to Industrial Food Animal Production and Asthma Exacerbations in Pennsylvania, 2005-2012.

    Science.gov (United States)

    Rasmussen, Sara G; Casey, Joan A; Bandeen-Roche, Karen; Schwartz, Brian S

    2017-03-31

    The research on industrial food animal production (IFAP) and asthma exacerbations in the United States has relied on small sample sizes and/or self-reported outcomes. We assessed associations of proximity to large-scale and densely stocked swine and dairy/veal IFAP with three types of asthma exacerbations: hospitalizations, emergency encounters, and oral corticosteroid (OCS) medication orders from Geisinger Clinic in Pennsylvania. We used a diagnosis code ( International Classification of Diseases, 9th Revision, Clinical Modification code 493.x) and medication orders from electronic health records to identify these exacerbations among asthma patients ( n = 35,269) from 2005-2012. We compared residential proximity to swine or dairy/veal IFAP (dichotomized as <3 miles (4.8 km) or ≥3 miles) among asthma patients with and without exacerbations and estimated odds ratios using multilevel logistic regression. In adjusted models, proximity to IFAP was associated (odds ratio (95% confidence interval)) with OCS orders (1.11 (1.04-1.19)) and hospitalizations (1.29 (1.15-1.46)), but not emergency encounters (1.12 (0.91-1.37)). This study contributes to growing evidence that IFAP may impact health, in this case clinically-documented asthma exacerbations. No prior study has evaluated the association of IFAP and clinically-documented asthma exacerbations in the United States.

  20. Subtypes of Patients Experiencing Exacerbations of COPD and Associations with Outcomes

    Science.gov (United States)

    Arostegui, Inmaculada; Esteban, Cristobal; García-Gutierrez, Susana; Bare, Marisa; Fernández-de-Larrea, Nerea; Briones, Eduardo; Quintana, José M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify

  1. Predictive factors for moderate or severe exacerbations in asthma patients receiving outpatient care

    OpenAIRE

    Guti?rrez, Francisco Javier ?lvarez; Galv?n, Marta Ferrer; Gallardo, Juan Francisco Medina; Mancera, Marta Barrera; Romero, Beatriz Romero; Falc?n, Auxiliadora Romero

    2017-01-01

    Background Asthma exacerbations are important events that affect disease control, but predictive factors for severe or moderate exacerbations are not known. The objective was to study the predictive factors for moderate (ME) and severe (SE) exacerbations in asthma patients receiving outpatient care. Methods Patients aged?>?12?years with asthma were included in the study and followed-up at 4-monthly intervals over a 12-month period. Clinical (severity, level of control, asthma control test [AC...

  2. Analysis of Surgical Success in Preventing Recurrent Acute Exacerbations in Chronic Pancreatitis

    Science.gov (United States)

    Nealon, William H.; Matin, Sina

    2001-01-01

    Objective To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). Summary Background Data The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. Methods From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Results Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3

  3. Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van den Berge Maarten

    2012-06-01

    Full Text Available Abstract Background Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD. We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. Methods In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF, and salbutamol use and assessed their course during exacerbations. Results There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively, whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. Conclusions Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.

  4. Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis.

    Science.gov (United States)

    Granzow, Martin; Hegenbart, Ute; Hinderhofer, Katrin; Hose, Dirk; Seckinger, Anja; Bochtler, Tilmann; Hemminki, Kari; Goldschmidt, Hartmut; Schönland, Stefan O; Jauch, Anna

    2017-07-01

    Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered. Copyright© 2017 Ferrata Storti Foundation.

  5. Amiloidose renal em cão Shar-Pei: Relato de Caso Renal amyloidosis in a Shar-Pei dog: A case report

    Directory of Open Access Journals (Sweden)

    J.L. Reis Jr.

    2001-08-01

    Full Text Available O presente relato descreve os achados clínicos e anatomopatológicos de um caso de amiloidose renal em um cão macho de nove anos da raça Shar-Pei. O animal apresentava quadro clínico de esporotricose e de insuficiência renal e exames positivos para erlichiose e leishmaniose. No dia anterior ao óbito, o cão apresentou apatia, desidratação e anúria. À necropsia foram observados inúmeros pontos milimétricos esbranquiçados localizados no córtex renal e hepatização do lobo diafragmático esquerdo. O achado histológico mais importante foi deposição de material eosinofílico, amorfo e acelular localizado nos tufos glomerulares que se corou positivamente pelo vermelho congo (amilóide. Observaram-se nefrite supurada multifocal, espessamento da cápsula de Bowman e broncopneumonia supurada crônica, com fibrose intensa. A origem da amiloidose, no presente caso, poderia ser hereditária, assemelhando-se à amiloidose familiar descrita em cães da raça Shar-Pei, ou ser devida à inflamação supurada crônica e/ou leishmaniose.The clinical and pathological findings of a case of renal amyloidosis in a nine-year-old male Shar-Pei dog were described. Clinically, there were signs of sporotrichosis and renal insufficiency, besides being positive to leishmaniasis and ehrlichiosis. On the day before death, the animal became apathetic, dehydrated and anuric. On gross examination, there were several whitish millimetric spots seen widespread in both renal cortices and consolidation of the left diaphragmatic pulmonary lobe. The most important microscopic finding was a deposition of amorphous acellular material on the glomerular tufts which stained positively by congo red stain. Other changes were multifocal suppurative nephritis, thickening of the Bowman capsule and chronic suppurative bronchopneumonia. The origin of the amyloidosis in this case could be hereditary, being similar to familiar amyloidosis described in Shar-Pei breed, or due to

  6. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...

  7. Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.

    Directory of Open Access Journals (Sweden)

    Dave Singh

    Full Text Available Patients with chronic obstructive pulmonary disease (COPD who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01 between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations.

  8. Cerebral vasculitis

    International Nuclear Information System (INIS)

    Greenan, T.J.; Grossman, R.I.

    1990-01-01

    This paper reviews retrospectively MR, CT, and angiographic findings in patients with cerebral vasculitis in order to understand the strengths and weaknesses of the various imaging modalities, as well as the spectrum of imaging abnormalities in this disease entity. Studies were retrospectively reviewed in 12 patients with cerebral vasculitis proved by means of angiography and/or brain biopsy

  9. Particularities of COPD exacerbations in different phenotypes of the disease in Tunisia.

    Science.gov (United States)

    Zendah, Ines; Ayed, Khadija; Kwas, Hamida; Khattab, Amel; Ghédira, Habib

    2016-03-01

    Chronic Obstructive Pulmonary Disease is defined by a limitation of airflow. This disease is characterized by exacerbations that threaten the patient's life and worsens his prognosis. Moreover, COPD patients are different according to many parameters that define different phenotypes. Characteristics of exacerbations may depend on these phenotypes according to few recent studies. To determine the characteristics and the prognosis of the exacerbations in each phenotype of COPD patients phenotype in Tunisia. Retrospective study including 153 male patients hospitalized for COPD exacerbation from January 2009 to June 2012. Patients were classified into 4 phenotypes according to Burgel's classification. Patients were divided into four phenotypes: phenotype (PH)1: (n=68), PH2: (n=33), PH3: (n=25) and PH4: (n=27). Mean age for PH1, 2, 3 and 4 was: 61, 74, 56 and 72 years. The number of exacerbations per year was higher in PH1. Dyspnea was more important in PH1 and 4. Hypercapnia on admission was higher in PH4. Non invasive ventilation and transfer to resuscitation unit were more frequently mandatory in PH3 and 4.   Death occurred 2% of PH1 and 5% of PH4. Hospitalization duration was more important in PH4. COPD patients are heterogenous and belong to different phenotypes. The characteristics of the exacerbations and their prognosis widely differ according to these different groups. In Tunisia, it seems that patients who had moderate respiratory functional tests impairment are the lowest responders to treatment with a higher frequency of resuscitation unit transfer.

  10. The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

    Science.gov (United States)

    Suruki, Robert Y; Daugherty, Jonas B; Boudiaf, Nada; Albers, Frank C

    2017-04-27

    Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

  11. Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure

    Directory of Open Access Journals (Sweden)

    Toru Kadowaki

    2016-01-01

    Conclusions: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

  12. Definitions of Exacerbations Does It Really Matter in Clinical Trials on COPD?

    NARCIS (Netherlands)

    Effing, Tanja W.; Kerstjens, Huib A. M.; Monninkhof, Evelyn M.; van der Valk, Paul D. L. P. M.; Wouters, Emiel F. M.; Postma, Dirkje S.; Zielhuis, Gerhard A.; van der Palen, Job

    Many definitions of COPD exacerbations are reported. The choice for a definition determines the number of exacerbations observed. However, the effect of different definitions on the effect sizes of randomized controlled trials is unclear. This article provides an overview of the large variation of

  13. Definitions of exacerbations: does it really matter in clinical trials on COPD?

    NARCIS (Netherlands)

    Effing-Tijdhof, T.W.; Kerstjens, H.A.; Monninkhof, E.M.; Valk, P.D.L.P.M. van der; Wouters, E.F.; Postma, D.S.; Zielhuis, G.A.; Palen, J.A.M. van der

    2009-01-01

    Many definitions of COPD exacerbations are reported. The choice for a definition determines the number of exacerbations observed. However, the effect of different definitions on the effect sizes of randomized controlled trials is unclear. This article provides an overview of the large variation of

  14. Scutellarin Attenuates Microglia-Mediated Neuroinflammation and Promotes Astrogliosis in Cerebral Ischemia - A Therapeutic Consideration.

    Science.gov (United States)

    Wu, Chun-Yun; Fang, Ming; Karthikeyan, Aparna; Yuan, Yun; Ling, Eng-Ang

    2017-01-01

    Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia, which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions. Here, we review the roles of activated microglia and reactive astrocytes in brain diseases with special reference to cerebral ischemia, and the effects of scutellarin, a Chinese herbal extract on both glial cells. We first reviewed the close spatial relation between activated microglia and reactive astrocytes as it suggests that both glial cells work in concert for tissue reconstruction and repair. Secondly, we have identified scutellarin as a putative therapeutic agent as it has been found to not only suppress microglial activation thus ameliorating neuroinflammation, but also enhance astrocytic reaction. In the latter, scutellarin amplified the astrocytic reaction by upregulating the expression of neurotrophic factors among others thus indicating its neuroprotective role. Remarkably, the effects of scutellarin on reactive astrocytes were mediated by activated microglia supporting a functional "cross-talk" between the two glial types. This review highlights some of our recent findings taking into consideration of others demonstrating the beneficial effects of scutellarin on both glial cell types in cerebral ischemia as manifested by improvement of neurological functions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. [Cerebral protection].

    Science.gov (United States)

    Cattaneo, A D

    1993-09-01

    Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

  16. Dynamic digitized cerebral parenchymography

    International Nuclear Information System (INIS)

    Theron, J.; Alachkar, F.; Nelson, M.; Mazia, D.

    1992-01-01

    Aortic arch injections centred on the head have been performed routinely in patients with cerebral ischaemia. Digital angiograms with modified windowing (low and narrow) have been used. This 'cerebral' arch injection allows much improved analysis of the cerebral parenchymal vascularization, giving better understanding of hemispheric ischaemia and making the decision about revascularization more rational. (orig.)

  17. What is cerebral small vessel disease?

    International Nuclear Information System (INIS)

    Onodera, Osamu

    2011-01-01

    An accumulating amount of evidence suggests that the white matter hyperintensities on T 2 weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease. (author)

  18. High salt intake does not exacerbate murine autoimmune thyroiditis

    Science.gov (United States)

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  19. Defining moderate asthma exacerbations in clinical trials based on ATS/ERS joint statement

    DEFF Research Database (Denmark)

    Virchow, J Christian; Backer, Vibeke; de Blay, Frédéric

    2015-01-01

    from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline and/or d) visit to the emergency room/trial site for asthma treatment not requiring systemic corticosteroids. CONCLUSION: A clinically and patient-relevant, operational definition of moderate exacerbations......BACKGROUND: Exacerbations are a key outcome in clinical research, providing patient-relevant information about symptomatic control, health state and disease progression. Generally considered as an episode of (sub)acute deterioration of respiratory symptoms, a precise, clinically useful definition...... is needed for use in clinical trials. AIM AND METHODS: Focussing on moderate exacerbations, this opinion piece reviews landmark trials and current guidelines to provide a practical definition of a moderate exacerbation. Specifically, we adapt the ATS/ERS consensus statement of terminology Reddel et al...

  20. Cerebral malaria: susceptibility weighted MRI

    Directory of Open Access Journals (Sweden)

    Vinit Baliyan

    2015-03-01

    Full Text Available Cerebral malaria is one of the fatal complications of Plasmodium falciparum infection. Pathogenesis involves cerebral microangiopathy related to microvascular plugging by infected red blood cells. Conventional imaging with MRI and CT do not reveal anything specific in case of cerebral malaria. Susceptibility weighted imaging, a recent advance in the MRI, is very sensitive to microbleeds related to microangiopathy. Histopathological studies in cerebral malaria have revealed microbleeds in brain parenchyma secondary to microangiopathy. Susceptibility weighted imaging, being exquisitely sensitive to microbleeds may provide additional information and improve the diagnostic accuracy of MRI in cerebral malaria.

  1. Case-fatality of COPD exacerbations: a meta-analysis and statistical modeling approach

    DEFF Research Database (Denmark)

    Hoogendoorn, M; Hoogenveen, R T; Rutten-van Mölken, M P

    2010-01-01

    's survival curve was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case-fatality was defined as the excess mortality that results from an exacerbation...

  2. Cerebral Oximetry in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    A. N. Shepelyuk

    2012-01-01

    Full Text Available Based on the data of numerous current references, the review describes different neuromonitoring methods during cardiac surgery under extracorporeal circulation. It shows that it is important and necessary to make neuromonitoring for the early diagnosis and prevention of neurological complications after cardiac surgery. Particular attention is given to cerebral oximetry; the possibilities and advantages of this technique are described. Correction of cerebral oximetric values is shown to improve survival rates and to reduce the incidence of postoperative complications. Lack of cerebral oximetry monitoring denudes a clinician of important information and possibilities to optimize patient status and to prevent potentially menacing complications, which allows one to conclude that it is necessary to use cerebral oximetry procedures within neu-romonitoring in cardiac surgery. Key words: extracorporeal circulation, cerebral oximetry, neurological dysfunction, cerebral oxygenation.

  3. Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: The 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study.

    Science.gov (United States)

    Ferguson, Gary T; Tashkin, Donald P; Skärby, Tor; Jorup, Carin; Sandin, Kristina; Greenwood, Michael; Pemberton, Kristine; Trudo, Frank

    2017-11-01

    Prevention of exacerbations is a primary goal for chronic obstructive pulmonary disease (COPD) therapy. This randomized, double-blind, double-dummy, parallel-group, multicenter study evaluated the effect of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus formoterol dry powder inhaler (DPI) on reducing COPD exacerbations. 1219 patients aged ≥40 years with moderate-to-very-severe COPD (per lung function) and a history of ≥1 COPD exacerbation received budesonide/formoterol pMDI 320/9 μg twice daily (BID) during a 4-week run-in. Patients were then randomized 1:1 to receive budesonide/formoterol pMDI 320/9 μg BID (n = 606) or formoterol DPI 9 μg BID (n = 613) for 26 weeks. Exacerbations were identified using predefined criteria for symptom worsening and treatment with systemic corticosteroids and/or antibiotics and/or hospitalization. The primary endpoint was annual rate of exacerbations. Budesonide/formoterol pMDI resulted in a 24% reduction in annual rate of exacerbations (0.85 vs 1.12; rate ratio: 0.76 [95% CI: 0.62, 0.92]; P = 0.006), and a significant risk reduction for time to first exacerbation (hazard ratio: 0.78 [95% CI: 0.64, 0.96]; P = 0.016) versus formoterol DPI. The most commonly reported adverse events (AEs; ≥3%) in budesonide/formoterol and formoterol groups were COPD (4.5% vs 8.6%) and nasopharyngitis (5.0% vs 5.2%). Pneumonia AEs were reported in 0.5% and 1.0% of budesonide/formoterol-treated and formoterol-treated patients, respectively. Budesonide/formoterol pMDI is an effective treatment option for reducing exacerbation rates in COPD patients with moderate-to-very-severe airflow limitation and history of exacerbations. No increase in pneumonia was observed with budesonide/formoterol; safety data were consistent with its established profile. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Cerebral venous angioma

    International Nuclear Information System (INIS)

    Inagawa, Tetsuji; Taguchi, Haruyoshi; Kamiya, Kazuko; Yano, Takashi; Nakajima, Reiko

    1984-01-01

    This report presents a 27-year-old male patient who was diagnosed as having cerebral venous angioma in the postero-temporal area by CT scan and cerebral angiography. The patient improved by removing angioma with electrocoagulation of medullary veins. (Namekawa, K.)

  5. MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

    Science.gov (United States)

    The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

  6. Nanomedicine in cerebral palsy

    Science.gov (United States)

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. PMID:24204146

  7. Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

    Science.gov (United States)

    Meltzer, Eli O; Busse, William W; Wenzel, Sally E; Belozeroff, Vasily; Weng, Haoling H; Feng, JingYuan; Chon, Yun; Chiou, Chiun-Fang; Globe, Denise; Lin, Shao-Lee

    2011-01-01

    Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  8. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen

    2015-01-01

    BACKGROUND AND OBJECTIVE: We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). METHODS: Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD...... applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. RESULTS: Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis...... and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We...

  9. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    . They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  10. Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease

    Science.gov (United States)

    Kocks, Jan Willem H; van den Berg, Jan Willem K; Kerstjens, Huib AM; Uil, Steven M; Vonk, Judith M; de Jong, Ynze P; Tsiligianni, Ioanna G; van der Molen, Thys

    2013-01-01

    Background Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society. Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation. This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes. Methods Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital. In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study. Results All patient-reported outcomes showed a distinct pattern of improvement. In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure. Health status and gender predicted time to next exacerbation. Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score. In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar. Conclusion Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD. PMID:23766644

  11. Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

    Science.gov (United States)

    Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

    2005-01-01

    Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

  12. Evaluation of ocular acupuncture on cerebral infarction with cerebral blood flow perfusion imaging

    International Nuclear Information System (INIS)

    Li Yuge; Gao Qinyi; Wang Shuang; Zhao Yong

    2008-01-01

    To evaluate the immediate effect of ocular acupuncture on patients, an method of SPECT image of cerebral blood flow daily stress test was established. 10 patients diagnosed as cerebral infarction by CT or MRI were tested. They all received 99 Tc m -ECD SPECT imaging at twice before and after ocular acupuncture. By means of image subtraction technique and semi-quantitative method of regional interesting area, the change of regional cerebral blood flow was observed between the two images. Under restful state perfusion of cerebral blood flow in 18 foci was low at the frontal lobe, the cerebellum, the basal ganglia and temporal lobe. After ocular acupuncture, the perfusions were obviously increased in 16 foci among them and the reactivity of the frontal lobe and the cerebellum to ocular acupuncture was higher, the average improvement rate of which was 55.15% and 53.06% respectively, lower in the basal ganglia and temporal lobe, the average improvement rate was 31.79% and 36.67% respectively. 99 Tc m -ECD SPECT cerebral perfusion image has some significant clinic value for evaluating the effect of ocular acupuncture to treating cerebral infarction. (authors)

  13. Study of cerebral vascular diseases with radioisotopes in cerebral atherosclerotical subjects and/for subjects with sequelae of cerebral stroke, before and after use of the association piracetam-dihydroergotoxine

    International Nuclear Information System (INIS)

    Lara, P.F.; Ferreira, A.; Paulillo, L.F.; Cukierman, M.

    1985-01-01

    Twently subjects with cerebral sclerosis and/or sequelas of cerebral stroke were studied, before and after use of piracetam-dihydroergotoxine. We performed the complete hemispheric cerebral blood flow and cerebral scintigraphy, beyond clinical and neurological examination. Scintigraphies were unchanged. Cerebral circulation times, or both hemispheres, diminished. This occurred, probably, in relation with metabolic effects of both pharmaceutical drugs. The alpha sympatolytic and modulatory effects of dihydroergotoxine should be considered. (author) [pt

  14. Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study.

    Science.gov (United States)

    Wang, Zhang; Singh, Richa; Miller, Bruce E; Tal-Singer, Ruth; Van Horn, Stephanie; Tomsho, Lynn; Mackay, Alexander; Allinson, James P; Webb, Adam J; Brookes, Anthony J; George, Leena M; Barker, Bethan; Kolsum, Umme; Donnelly, Louise E; Belchamber, Kylie; Barnes, Peter J; Singh, Dave; Brightling, Christopher E; Donaldson, Gavin C; Wedzicha, Jadwiga A; Brown, James R

    2018-04-01

    Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon. We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium. The microbiome composition was similar among centres and between stable and exacerbations except for a small significant decrease of Veillonella at exacerbations. The abundance of Moraxella was negatively associated with bacterial alpha diversity. Microbiomes were distinct between exacerbations associated with bacteria versus eosinophilic airway inflammation. Dysbiosis at exacerbations, measured as significant within subject deviation of microbial composition relative to baseline, was present in 41% of exacerbations. Dysbiosis was associated with increased exacerbation severity indicated by a greater fall in forced expiratory volume in one second, forced vital capacity and a greater increase in CAT score, particularly in exacerbations with concurrent eosinophilic inflammation. There was a significant difference of temporal variability of microbial alpha and beta diversity among centres. The variation of beta diversity significantly decreased in those subjects with frequent historical exacerbations. Microbial dysbiosis is a feature of some exacerbations and its presence, especially in concert with eosinophilic inflammation, is associated with more severe exacerbations indicated by a greater fall in lung function. Results, NCT01620645. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

  15. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    Directory of Open Access Journals (Sweden)

    Orlando G. Povoas Barsottini

    2004-09-01

    Full Text Available Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis. We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL. She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of neuropathy and current treatment of AL.A amiloidose é uma síndrome caracterizada pela deposição no meio extracelular de material protéico altamente insolúvel e que pode afetar vários órgãos. Pode ocorrer como doença generalizada e pode ser idiopática (amiloidose primária. Descrevemos o caso de mulher de 48 anos com neuropatia axonal associada a proteinúria na qual a investigação final resultou no diagnóstico de amiloidose primária (AL. Foi submetida a transplante autólogo de medula óssea sem complicações. Discutiremos aspectos relacionados ao diagnóstico da neuropatia e do tratamento atual da AL.

  16. Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and 123I-IMP with acetazolamide test

    International Nuclear Information System (INIS)

    Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi; Suematsu, Katsumi.

    1989-01-01

    To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl 123 I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25∼50% stenosis), and severe degree(50%cerebral vasodilatory capacity was preserved at the normal level during the period of vasospasm. In eight patients with asymptomatic vasospasm (moderate degree), a transient limitation of cerebral vasodiratory capacity was observed between the 6th and 16th day after a rupture of the cerebral aneurysm. In five patients with symptomatic vasospasm resulting in reversible ischemia, a marked limitation of cerebral vasodilatory capacity was noted between the 7th and 15th day, and a delayed recovery of cerebral vasodilatory capacity was observed. This reversibility of cerebral vasodilatory capacity in patients with cerebral vasospasm suggests that a local decrease of purfusion pressure due to cerebral vasospasm causes compensatory vasodilation of intraparenchymal arteries and the vasodilatory reaction to acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.)

  17. The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

    Science.gov (United States)

    Lambert, Katrina A; Prendergast, Luke A; Dharmage, Shyamali C; Tang, Mimi; O'Sullivan, Molly; Tran, Thomas; Druce, Julian; Bardin, Philip; Abramson, Michael J; Erbas, Bircan

    2017-10-11

    It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

  18. Can resistive breathing injure the lung? Implications for COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Vassilakopoulos T

    2016-09-01

    Full Text Available Theodoros Vassilakopoulos, Dimitrios Toumpanakis Pulmonary and Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Greece Abstract: In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction. The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. Keywords: resistive breathing, COPD, mechanotransduction, bronchoconstriction, inflammation

  19. Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

    Science.gov (United States)

    Pichiorri, Floriana; Vicenzini, Edoardo; Gilio, Francesca; Giacomelli, Elena; Frasca, Vittorio; Cambieri, Chiara; Ceccanti, Marco; Di Piero, Vittorio; Inghilleri, Maurizio

    2012-08-01

    To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe

  20. Pulmonary Exacerbation Score in Cystlc Fibrosis Patients: Reliability and Validity Testing

    OpenAIRE

    Keller, F.

    2016-01-01

    Background: Lung disease in cystic fibrosis (CF) is characterized by recurrent pulmonary exacerbations (PEs), but consensus on diagnostic criteria for PE is lacking. The use of a consistent definition of PE as an outcome measure in CF clinical trials would allow meaningful comparison across centers. The aim of this study was to assess the reliability and validity of a simplified version of the Seattle Pulmonary Exacerbation Score (SPEX). Materials and Methods: A cross-sectional observational ...

  1. Inverse relationship between nonadherence to original GOLD treatment guidelines and exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    Foda HD

    2017-01-01

    Full Text Available Hussein D Foda,1,2 Anthony Brehm,1,2 Karen Goldsteen,3 Norman H Edelman2,4 1Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Medical Center, Northport, 2Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, Stony Brook University Medical Center, Stony Brook, NY, 3MPH Program, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 4Department of Preventative Medicine and Program in Public Health, Stony Brook University Medical Center, Stony Brook, NY, USA Background: Prescriber disagreement is among the reasons for poor adherence to COPD treatment guidelines; it is yet not clear whether this leads to adverse outcomes. We tested whether undertreatment according to the original Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines led to increased exacerbations.Methods: Records of 878 patients with spirometrically confirmed COPD who were followed from 2005 to 2010 at one Veterans Administration (VA Medical Center were analyzed. Analysis of variance was performed to assess differences in exacerbation rates between severity groups. Logistic regression analysis was performed to assess the relationship between noncompliance with guidelines and exacerbation rates.Findings: About 19% were appropriately treated by guidelines; 14% overtreated, 44% undertreated, and in 23% treatment did not follow any guideline. Logistic regression revealed a strong inverse relationship between undertreatment and exacerbation rate when severity of obstruction was held constant. Exacerbations per year by GOLD stage were significantly different from each other: mild 0.15, moderate 0.27, severe 0.38, very severe 0.72, and substantially fewer than previously reported.Interpretation: The guidelines were largely not followed. Undertreatment predominated but, contrary to expectations, was associated with fewer exacerbations. Thus, clinicians were likely

  2. Efficacy of a self-management plan in exacerbations for patients with advanced COPD

    Directory of Open Access Journals (Sweden)

    Sánchez-Nieto JM

    2016-08-01

    Full Text Available Juan Miguel Sánchez-Nieto,1,2 Rubén Andújar-Espinosa,3 Roberto Bernabeu-Mora,1,2 Chunshao Hu,1 Beatriz Gálvez-Martínez,1 Andrés Carrillo-Alcaraz,1 Carlos Federico Álvarez-Miranda,3 Olga Meca-Birlanga,1 Eva Abad-Corpa4 1Division of Pneumology, Hospital Morales Meseguer, 2University of Murcia, 3Division of Pneumology, Hospital Arrixaca, Murcia, 4Department of Professional Development Unit, Murcia, Spain Background: Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD.Methods: Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality.Results: After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04 and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40

  3. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

  4. COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

    Directory of Open Access Journals (Sweden)

    Pasquale MK

    2016-01-01

    Full Text Available Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy & Execution, Humana Inc., Louisville, KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA Background: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC or COPD assessment test (CAT score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.Methods: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis­eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart. The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.Results: Among a total of 1,159 members who returned the

  5. Predicting high risk of exacerbations in bronchiectasis: the E-FACED score

    Directory of Open Access Journals (Sweden)

    Martinez-Garcia MA

    2017-01-01

    Full Text Available Martinez-Garcia MA,1,2 Athanazio RA,3 Girón R,4 Máiz-Carro L,5 de la Rosa D,6 Olveira C,7 de Gracia J,2,8 Vendrell M,9 Prados-Sánchez C,10 Gramblicka G,11 Corso Pereira M,12 Lundgren FL,13 Fernandes De Figueiredo M,14 Arancibia F,15 Rached SZ3 1Pulmonary Service, Polytechnic and University La Fe Hospital, Valencia, Spain; 2CIBERes, CIBER de Enfermedades Respiratorias. Madrid. Spain; 3Pulmonary Division, Heart Institute (Incor, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; 4Pneumology Service, Hospital La Princesa, 5Pneumology Service, Hospital Ramón y Cajal, Madrid, 6Pneumology Unit, Hospital Plató, Barcelona, 7Pneumology, Málaga Regional University Hospital, Instituto de Biomedicina de Málaga (IBIMA, Málaga University, Spain; 8Pneumology Service, Hospital Vall d’Hebron, Barcelona, 9Bronchiectasis Group IDIBGI, Dr. Trueta University Hospital. UdG. Ciberes CB06/06/0030, 10Unidad de Fibrosis Quística y Bronquiectasias. Hospital Universitario La Paz. Madrid. Spain; 11Pneumology Service, Hospital del Tórax Dr A Cetrángolo, Buenos Aires, Argentina; 12Pneumology Service, Universidade Estadual de Campinas UNICAMP, Sao Paulo, 13Pneumology Service, Hospital Octávio de Freitas, Recife, 14Pneumology Service, Hospital de Messejana, Fortaleza, Brazil; 15Pneumology Service, Instituto Nacional del Tórax, Santiago de Chile, Chile Background: Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients.Objective: Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality.Methods: The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three

  6. A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations

    DEFF Research Database (Denmark)

    Singh, Dave; Kampschulte, Jorg; Wedzicha, Jadwiga A

    2013-01-01

    -primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology. FORWARD is therefore...

  7. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy.

    Science.gov (United States)

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-10-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation ( SO 2 ) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin ( HbR ) and a decrease in SO 2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow ( CBF ) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- ( HbO 2 ) and total hemoglobin ( HbT ). In addition HbO 2 , HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO 2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

  8. Psychopathological dimensions in subjects with hereditary ATTR V30M amyloidosis and their relation with life events due to the disease.

    Science.gov (United States)

    Lopes, Alice; Fonseca, Isabel; Sousa, Alexandra; Rodrigues, Carla; Branco, Margarida; Coelho, Teresa; Sequeiros, Jorge; Freitas, Paula

    2018-03-01

    Chronic physical illness has been associated with emotional distress. Chronic diseases may change usual family patterns with economic, social and family losses. Hereditary ATTR V30M amyloidosis is a rare, fatal inherited systemic amyloidosis, with chronic evolution and beginning in adulthood. To evaluate psychopathological dimensions and how they correlated with disease-related life events, 209 symptomatic and asymptomatic carriers, participated in the study. Sociodemographic and Family and Personal History Disease questionnaires and brief symptom inventory (BSI) were applied. BSI indices, global severity index (GSI), positive symptom index (PSI) and positive symptom total (PST) scored higher than general population. Independent predictors for GSI >0.83 were female sex (OR = 3.46, p = .005) and being symptomatic carriers (OR = 3.03, p = .039). Independent predictors of a PST >26.99 were female sex (OR = 3.74, p = .012) symptomatic carrier (OR = 5.32, p = .025), age between 15 and 24 years at affected parent's death (OR = 5.26, p = .04). Independent predictors of a PSI >1.56 were being asymptomatic carrier (OR = 6.3, p = .036); to have children (OR = 3.19, p = .043) and have ≤14 years at parent's disease onset (OR = 6.39, p = .05). Results point to an important vulnerability of this population for psychological distress and psychiatric disease. Early life events related to disease, being sick and sex are associated with psychopathological distress.

  9. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Chin-Yi Cheng

    2016-01-01

    Full Text Available Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs, including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

  10. Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

    Science.gov (United States)

    Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

    2014-01-01

    Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

  11. Therapeutic interventions in cerebral palsy.

    Science.gov (United States)

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

  12. Nanomedicine in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Balakrishnan B

    2013-11-01

    Full Text Available Bindu Balakrishnan,1 Elizabeth Nance,1 Michael V Johnston,2 Rangaramanujam Kannan,3 Sujatha Kannan1 1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University; Baltimore, MD, USA; 2Department of Neurology and Pediatrics, Kennedy Krieger Institute, Baltimore, MD, USA; 3Department of Ophthalmology, Center for Nanomedicine, Johns Hopkins University, Baltimore, MD, USA Abstract: Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. Keywords: dendrimer, cerebral palsy, neuroinflammation, nanoparticle, neonatal brain injury, G4OH-PAMAM

  13. Cerebral involvement in a patient with Goodpasture's disease due to shortened induction therapy: a case report

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    Preul Christoph

    2009-11-01

    Full Text Available Abstract Introduction Goodpasture's disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear. Case presentation A 21-year-old Caucasian man with Goodpasture's disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patient's usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane antibodies were significantly reduced. Previous immunosuppressive therapy was performed without corticosteroids and terminated early after 3 months. The differential diagnostic considerations were cerebral vasculitis and posterior reversible encephalopathy syndrome. Vasculitis could be seen as an extrarenal manifestation of the underlying disease. Posterior reversible encephalopathy syndrome, on the other hand, can be triggered by immunosuppressive therapy and may appear without a hypertensive crisis. Conclusion A combination of central nervous system symptoms with a positive antiglomerular basement membrane test in a patient with Goodpasture's disease should immediately be treated as an acute exacerbation of the disease with likely cross-reactivity of antibodies with the choroid plexus. In our patient, a discontinuous strategy of immunosuppressive therapy may have favored recurrence of Goodpasture's disease.

  14. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard...... polysomnography. Unlike our previous study in man showing a highly significant 25% decrease in CMRO2 during deep sleep (stage 3-4) we found a modest but statistically significant decrease of 5% in CMRO2 during stage 2 sleep. Deep and light sleep are both characterized by an almost complete lack of mental activity....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  15. Cerebral fat embolism

    International Nuclear Information System (INIS)

    Sakamoto, Toshihisa; Sawada, Yusuke; Yukioka, Tetsuo; Nishide, Kazuyuki; Yoshioka, Toshiharu

    1982-01-01

    A case of cerebral fat embolism is reported. A 18-year-old patient with multiple bone fractures was in semiconma immediately after an injury. Brain CT showed no brain swelling or intracranial hematoma. Hypoxemia and alcoholemia were noted on admission, which returned to normal without improvement of consciousness level. In addition, respiratory symptoms with positive radiographic changes, tachycardia, pyrexia, sudden drop in hemoglobin level, and sudden thrombocytopenia developed. These symptoms were compatible with Gurd's criteria of systemic fat embolism. Eight days after injury, multiple low density areas appeared on CT and disappeared within the subsequent two weeks, and subdural effusion with cerebral atrophy developed. These CT findings were not considered due to cerebral trauma. Diagnosis of cerebral fat embolism was made. The subdural effusion was drained. Neurologic and pulmonary recoveries took place slowly and one month following the injury the patient became alert and exhibited fully coordinated limb movement. The CT scans of the present case well corresponded with hitherto reported pathological findings. Petechiae in the white matter must have developed on the day of injury, which could not be detected by CT examination. It is suggested that some petechial regions fused to purpuras and then gradually resolved when they were detected as multiple low density areas on CT. CT in the purpuras phase would have shown these lesions as high density areas. These lesions must have healed with formation of tiny scars and blood pigment which were demonstrated as the disappearance of multiple low density areas by CT examination. Cerebral atrophy and subsequent subdural effusion developed as a result of demyelination. The patient took the typical clinical course of cerebral fat embolism and serial CT scans served for its assessment. (author)

  16. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research.

    Science.gov (United States)

    Hill, Adam T; Haworth, Charles S; Aliberti, Stefano; Barker, Alan; Blasi, Francesco; Boersma, Wim; Chalmers, James D; De Soyza, Anthony; Dimakou, Katerina; Elborn, J Stuart; Feldman, Charles; Flume, Patrick; Goeminne, Pieter C; Loebinger, Michael R; Menendez, Rosario; Morgan, Lucy; Murris, Marlene; Polverino, Eva; Quittner, Alexandra; Ringshausen, Felix C; Tino, Gregory; Torres, Antoni; Vendrell, Montserrat; Welte, Tobias; Wilson, Rob; Wong, Conroy; O'Donnell, Anne; Aksamit, Timothy

    2017-06-01

    There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis. Copyright ©ERS 2017.

  17. Determining the diagnostic value of endogenous carbon monoxide in Chronic Obstructive Pulmonary Disease exacerbations

    International Nuclear Information System (INIS)

    Dogan, N. O.; Corbacioglu, S. K.; Bildik, F.; Kilicaslan, I.; Hakoglu, O.; Gunaydin, G. P.; Cevik, Y.; Ulker, V.; Gokcen, E.

    2014-01-01

    Objective: To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. Methods: The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. Results: There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p<0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95-2.00). The corresponding levels in Group 2 (1.8 (1.38-2.20)) and Group 3 (1.9 (1.5-3.0)) were higher than the controls (p<0.001 and p<0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 (1.10-1.55)) was observed (p<0.434). Conclusion: Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations. (author)

  18. Can a school-based hand hygiene program reduce asthma exacerbations among elementary school children?

    Science.gov (United States)

    Gerald, Joe K.; Zhang, Bin; McClure, Leslie A.; Bailey, William C.; Harrington, Kathy F.

    2012-01-01

    Background Viral upper respiratory infections have been implicated as a major cause of asthma exacerbations among school age children. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections but, effective hand washing practices are difficult to establish in schools. Objectives This randomized controlled trial evaluated whether a standardized regimen of hand washing plus alcohol-based hand sanitizer could reduce asthma exacerbations more than schools’ usual hand hygiene practices. Methods This was a two year, community-based, randomized controlled crossover trial. Schools were randomized to usual care then intervention (Sequence 1) or intervention then usual care (Sequence 2). Intervention schools were provided with alcohol-based hand sanitizer, hand soap, and hand hygiene education. The primary outcome was the proportion of students experiencing an asthma exacerbation each month. Generalized estimating equations were used to model the difference in the marginal rate of exacerbations between sequences while controlling for individual demographic factors and the correlation within each student and between students within each school. Results 527 students with asthma were enrolled among 31 schools. The hand hygiene intervention did not reduce the number of asthma exacerbations as compared to the schools’ usual hand hygiene practices (p=0.132). There was a strong temporal trend as both sequences experienced fewer exacerbations during Year 2 as compared to Year 1 (phand hygiene behaviors and resources in usual care schools. Therefore, these results should be viewed cautiously. PMID:23069487

  19. Exacerbations of COPD: quantifying the patient's perspective using discrete choice modelling.

    Science.gov (United States)

    Haughney, J; Partridge, M R; Vogelmeier, C; Larsson, T; Kessler, R; Ståhl, E; Brice, R; Löfdahl, C-G

    2005-10-01

    Patient-centred care is the current vogue in chronic obstructive pulmonary disease (COPD), but it is only recently that robust techniques have become available to determine patients' values and preferences. In this international cross-sectional study, patients' concerns and expectations regarding COPD exacerbations were explored using discrete choice modelling. A fractional factorial design was used to develop scenarios comprising a combination of levels for nine different attributes. In face-to-face interviews, patients were presented with paired scenarios and asked to choose the least preferable. Multinomial logit (with hierarchical Bayes) methods were used to estimate utilities. A total of 125 patients (82 males; mean age 66 yrs; 4.6 mean exacerbations.yr-1) were recruited. The attributes of exacerbations considered most important were impact on everyday life (20%), need for medical care (16%), number of future attacks (12%) and breathlessness (11%). The next most important attributes were speed of recovery, productive cough and social impact (all 9%), followed by sleep disturbance and impact on mood (both 7%). Importantly, analysis of utility shifts showed that patients most feared being hospitalised, housebound or bedridden. These issues were more important than symptom improvement. Strategies for the clinical management of chronic obstructive pulmonary disease should clearly address patients' concerns and focus on preventing and treating exacerbations to avoid these feared outcomes.

  20. Comparison of COPD Assessment Test and Clinical COPD Questionnaire to predict the risk of exacerbation

    Directory of Open Access Journals (Sweden)

    Jo YS

    2017-12-01

    Full Text Available Yong Suk Jo,1 Ho Il Yoon,2 Deog Kyeom Kim,3 Chul-Gyu Yoo,1 Chang-Hoon Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Background and objective: Guidelines recommend the use of simple but comprehensive tools such as COPD Assessment Test (CAT and Clinical COPD Questionnaire (CCQ to assess health status in COPD patients. We aimed to compare the ability of CAT and CCQ to predict exacerbation in COPD patients. Methods: We organized a multicenter prospective cohort study that included COPD patients. The relationships between CAT, CCQ, and other clinical measurements were analyzed by correlation analysis, and the impact of CAT and CCQ scores on exacerbation was analyzed by logistic regression analyses and receiver operating characteristic curve. Results: Among 121 COPD patients, CAT and CCQ score correlated with other symptom measures, lung function and exercise capacity as well. Compared with patients who did not experience exacerbation, those who experienced exacerbation (n=45; 38.2% exhibited more severe airflow limitation, were more likely to have a history of exacerbation in the year prior to enrollment, and demonstrated higher CAT scores. CCQ scores were not significantly associated with exacerbations. A CAT score of ≥15 was an independent risk factor for exacerbation (adjusted odds ratio [aOR], 2.40; 95% CI, 1.03–6.50; P=0.04. Furthermore, CAT scores of ≥15 demonstrated an increased predictive ability for exacerbation compared with currently accepted guidelines for the use of CAT (≥10 and CCQ (≥1 in the assessment of COPD

  1. Imaging findings and cerebral perfusion in arterial ischemic stroke due to transient cerebral arteriopathy in children; Achados de imagem e perfusao arterial cerebral em acidente vascular cerebral isquemico devido a arteriopatia transitoria em crianca

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa Junior, Alcino Alves, E-mail: alcinojr@uol.com.br [Departamento de Diagnostico por Imagem, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Ellovitch, Saada Resende de Souza [Neuropediatria, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Pincerato, Rita de Cassia Maciel [Hospital Samaritano, Sao Paulo, SP (Brazil)

    2012-04-15

    We report the case of a 4-year-old female child who developed an arterial ischemic stroke in the left middle cerebral artery territory, due to a proximal stenosis of the supraclinoid internal carotid artery, most probably related to transient cerebral arteriopathy of childhood. Computed tomography scan, magnetic resonance imaging, perfusion magnetic resonance and magnetic resonance angiography are presented, as well as follow-up by magnetic resonance and magnetic resonance angiography exams. Changes in cerebral perfusion and diffusion-perfusion mismatch call attention. As far as we know, this is the first report of magnetic resonance perfusion findings in transient cerebral arteriopathy. (author)

  2. Prediction of cerebral ischemia due to cerebral vasospasm in SAH using SPECT and sup 123 I-IMP with acetazolamide test

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji; Wada, Keiji; Takeda, Rihei; Usami, Takashi; Hashimoto, Ikuo; Shimazaki, Mitsuteru; Tanaka, Chiharu; Nakamura, Jun-ichi (Nakamura Memorial Hospital, Sapporo (Japan)); Suematsu, Katsumi

    1989-11-01

    To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl {sup 123}I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types; mild degree (25%>stenosis), moderate degree (25{approx}50% stenosis), and severe degree(50%cerebral vasodilatory capacity was preserved at the normal level during the period of vasospasm. In eight patients with asymptomatic vasospasm (moderate degree), a transient limitation of cerebral vasodiratory capacity was observed between the 6th and 16th day after a rupture of the cerebral aneurysm. In five patients with symptomatic vasospasm resulting in reversible ischemia, a marked limitation of cerebral vasodilatory capacity was noted between the 7th and 15th day, and a delayed recovery of cerebral vasodilatory capacity was observed. This reversibility of cerebral vasodilatory capacity in patients with cerebral vasospasm suggests that a local decrease of purfusion pressure due to cerebral vasospasm causes compensatory vasodilation of intraparenchymal arteries and the vasodilatory reaction to acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm. (J.P.N.).

  3. Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE* systematic review

    DEFF Research Database (Denmark)

    Papadopoulos, N G; Christodoulou, I; Rohde, G

    2011-01-01

    and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most...... and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02505.x. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections...

  4. The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis.

    Science.gov (United States)

    Martin, Amber L; Marvel, Jessica; Fahrbach, Kyle; Cadarette, Sarah M; Wilcox, Teresa K; Donohue, James F

    2016-04-16

    This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George's Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations. A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance. Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant. The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships

  5. Monitoring of cerebral haemodynamics in newborn infants

    DEFF Research Database (Denmark)

    Liem, K Djien; Greisen, Gorm

    2010-01-01

    The most important cerebrovascular injuries in newborn infants, particularly in preterm infants, are cerebral haemorrhage and ischemic injury. The typical cerebral vascular anatomy and the disturbance of cerebral haemodynamics play important roles in the pathophysiology. The term 'cerebral haemod...

  6. Recovery of cerebral blood flow in unilateral chronic subdural hematoma. The correlation with cerebral re-expansion in elders

    International Nuclear Information System (INIS)

    Nemoto, Akio

    2003-01-01

    CT and SPECT were used to investigate the relationship between cerebral re-expansion and changes in cerebral blood flow underneath hematoma in elderly patients after surgery for chronic unilateral subdural hematoma. I studied 22 patients with mild hematoma, aged 43 to 82 years (mean 67 years). The patients were placed in either Group A (under 70 years) or Group B (70 years or over) to observe postoperative changes. CT and SPECT examinations were conducted before surgery and 1, 7 and 30 days after surgery, 4 times in total. Cerebral re-expansion was represented by the re-expansion rate (PER) comparing the pre- and postoperative thickness of the maximal hematoma in CT images. The rate of cerebral re-expansion was slowed in Group B (p<0.01). Cerebral re-expansion was characterized by biphasic, rapid or gradual re-expansion on postoperative day 1 with a significant difference between groups (p<0.01). Before surgery, cerebral blood flow on the affected side correlated with age (p<0.01), thougn blood flow was diminished in both groups. After surgery, cerebral blood flow on the affected side exceeded that on the unaffected side in Group A and transiently increased on postoperative day 1. Cerebral blood flow improved after surgery in both groups, with a significant difference in those changes over time (p<0.01). In both groups, cerebral re-expansion on postoperative days 7 and 30 correlated with cerebral blood flow on the affected side (p<0.05). The present results suggest that improvement in cerebral blood flow on the affected side is delayed in elderly patients, due to slower postoperative cerebral re-expansion. (author)

  7. Psychological Factors and Pain Exacerbation in Knee Osteoarthritis : A Web Based Case-Crossover Study

    NARCIS (Netherlands)

    Erfani, Tahereh; Keefe, Francis; Bennell, Kim; Chen, J; Makovey, J; Metcalf, B; Williams, A.D.; Zhang, Y; Hunter, David

    2015-01-01

    OBJECTIVES: The pain experienced by osteoarthritis (OA) patients is neither constant nor unchanging and patients experience episodes of pain exacerbations. Using an innovative web based case-crossover design, we evaluated whether psychological factors are risk factors for pain exacerbations in

  8. Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    Kiyoshi Sekiya

    2013-01-01

    Conclusions: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

  9. Studies of cerebral atrophy and regional cerebral blood flow in patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Kitamura, Shin

    1983-01-01

    Cerebral atrophy and regional cerebral blood flow (rCBF) of 25 patients with Parkinson's disease were studied. The rCBF was measured with the intra-arterial Xe-133 injection method. The results obtained were as follows: 1) Sixty four % of Parkinson's disease patients showed ventricular dilation, and 76% of Parkinson's disease patients showed cortical atrophy on the CT scan, but we had to allow for the effects of the natural aging process on these results. 2) No correlation was recognized either between cerebral atrophy and the severity of Parkinson's disease, or between cerebral atrophy and the duration of Parkinson's disease. 3) In Parkinson's disease patients, the mean rCBF was lower than that of normal control subjects. The difference was even more remarkable in older patients. Only 40% of Parkinson's disease patients showed hyperfrontal pattern. 4) There was no correlation either between the mean rCBF and the severity of Parkinson's disease, or between the mean rCBF and the duration of Parkinson's disease. There was no significant difference between the mean rCBF of Parkinson's disease patients receiving levodopa and that of untreated patients. 5) The mean rCBF decreased in patients with cerebral atrophy on the CT scan. 6) Parkinson's disease patients with intellectual impairment showed cerebral atrophy and a remarkable decrease of the mean rCBF. 7) The effect of aging on cerebral atrophy on the CT scan had to be allowed for, but judging from the decrease of the mean rCBF, the cerebral cortex is evidently involved in Parkinson's disease. 8) The rCBF decline in Parkinson's disease patients may be related with the diminished cortical metabolic rate due to a remote effect of striatal dysfunction and a disturbance of mesocortical dopaminergic pathways. (J.P.N.)

  10. Studies of cerebral atrophy and regional cerebral blood flow in patients with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Shin [Nippon Medical School, Tokyo

    1983-04-01

    Cerebral atrophy and regional cerebral blood flow (rCBF) of 25 patients with Parkinson's disease were studied. The rCBF was measured with the intra-arterial Xe-133 injection method. The results obtained were as follows: 1) Sixty four % of Parkinson's disease patients showed ventricular dilation, and 76% of Parkinson's disease patients showed cortical atrophy on the CT scan, but we had to allow for the effects of the natural aging process on these results. 2) No correlation was recognized either between cerebral atrophy and the severity of Parkinson's disease, or between cerebral atrophy and the duration of Parkinson's disease. 3) In Parkinson's disease patients, the mean rCBF was lower than that of normal control subjects. The difference was even more remarkable in older patients. Only 40% of Parkinson's disease patients showed hyperfrontal pattern. 4) There was no correlation either between the mean rCBF and the severity of Parkinson's disease, or between the mean rCBF and the duration of Parkinson's disease. There was no significant difference between the mean rCBF of Parkinson's disease patients receiving levodopa and that of untreated patients. 5) The mean rCBF decreased in patients with cerebral atrophy on the CT scan. 6) Parkinson's disease patients with intellectual impairment showed cerebral atrophy and a remarkable decrease of the mean rCBF. 7) The effect of aging on cerebral atrophy on the CT scan had to be allowed for, but judging from the decrease of the mean rCBF, the cerebral cortex is evidently involved in Parkinson's disease. 8) The rCBF decline in Parkinson's disease patients may be related with the diminished cortical metabolic rate due to a remote effect of striatal dysfunction and a disturbance of mesocortical dopaminergic pathways.

  11. Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

    Directory of Open Access Journals (Sweden)

    Dreyse J

    2015-03-01

    Full Text Available Jorge Dreyse,1 Orlando Díaz,1 Paula Repetto,2 Arturo Morales,1 Fernando Saldías,1 Carmen Lisboa11Department of Pulmonary Diseases, School of Medicine, 2School of Psychology, Pontificia Universidad Católica de Chile, Santiago, ChileBackground: In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD. However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1 and impairment of functional and clinical outcomes in ex-smoking COPD patients.Methods: A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire. Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis.Results: During follow-up, 419 (96% moderate acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation

  12. Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Poulsen, Nadia

    2017-01-01

    BACKGROUND: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response...... occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. METHODS: Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum...... in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo...

  13. Management and prevention of chronic obstructive pulmonary disease exacerbations: a state of the art review

    Directory of Open Access Journals (Sweden)

    Wedzicha Jadwiga A

    2009-08-01

    Full Text Available Abstract Exacerbations of chronic obstructive pulmonary disease (COPD are important events in the natural history of this prevalent and devastating condition. This review provides a concise, state of the art summary on prevention and management of exacerbations. Considerable new data underpins evidence in support of many preventative interventions, pharmacological and non-pharmacological, that are now available. Challenges remain in developing new approaches, and delivering those that already exist to the right patient at the right time. Management of an exacerbation remains stepwise according to clinical severity, but there is now additional focus on addressing comorbidities and taking the opportunity at acute events to optimise preventative strategies for the future. Ultimately, exacerbations are heterogeneous events in a heterogeneous disease, and an individualised approach is paramount.

  14. Cerebral blood measurements in cerebral vascular disease: methodological and clinical aspects

    International Nuclear Information System (INIS)

    Fieschi, C.; Lenzi, G.L.

    1982-01-01

    This paper is devoted mainly to studies performed on acute cerebral vascular disease with the invasive techniques for the measurement of regional cerebral blood flow (rCBF). The principles of the rCBF method are outlined and the following techniques are described in detail: xenon-133 inhalation method, xenon-133 intravenous method and emission tomography methods. (C.F.)

  15. CT classification and clinical prognosis of cerebral infarction in the area of middle cerebral artery

    International Nuclear Information System (INIS)

    Konno, Jyoji

    1983-01-01

    Computerized tomographies (CT) were repeatedly scanned on 70 patients with cerebral infarction in the middle cerebral artery. Low density area (LDA) was measured with HounFsfield's Unit (HU) and studied on the progressive changes. Classification of LDA was attempted and studied on correlation with mass effect, contrast enhancement, angiographical findings, clinical symptoms and prognosis. It was considered that important points of diagnosis of cerebral infarction were timing of examination of CT and determination of LDA with HUF. It was also thought that CT classification of LDA was usefull to estimate prognosis of the patients with cerebral infarction. (author)

  16. Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    van Geffen WH

    2018-04-01

    Full Text Available Wouter H van Geffen,1,2 Huib AM Kerstjens2 1Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands; 2Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands Background: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD (AECOPD, but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. Methods: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state at least 42 days later: inspiratory capacity (IC, body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. Results: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05±0.11 L and increased again during resolution by 15.6%±23.1% or 0.28±0.08 L (mean ± standard error of the mean, p<0.01. Testing of metronome-paced changes in IC was feasible, and it decreased by 0.74±0.06 L at admission, similarly to at stable state. Clinical COPD Questionnaire score was 3.7±0.2 at admission and improved by 1.7±0.2 points (p<0.01, and the Borg dyspnea score improved by 2.2±0.5 points from 4.4±0.4 at admission (p<0.01. Conclusion: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase. Keywords: COPD, exacerbations of COPD, static hyperinflation, dynamic hyperinflation, severe acute exacerbations of COPD, COPD exacerbation, chronic obstructive pulmonary disease

  17. TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Song Min

    2011-08-01

    Full Text Available Abstract Background Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD, are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs, a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it is unknown if TLR4 signaling is involved in initiation of Aβ deposition as well as activation and recruitment of microglia at the early stage of AD. Here, we investigated the role of TLR4 signaling and microglial activation in early stages using 5-month-old AD mouse models when Aβ deposits start. Methods Microglial activation and amyloid deposition in the brain were determined by immunohistochemistry in the AD models. Levels of cerebral soluble Aβ were determined by ELISA. mRNA levels of cytokines and chemokines in the brain and Aβ-stimulated monocytes were quantified by real-time PCR. Cognitive functions were assessed by the Morris water maze. Results While no difference was found in cerebral Aβ load between AD mouse models at 5 months with and without TLR4 mutation, microglial activation in a TLR4 mutant AD model (TLR4M Tg was less than that in a TLR4 wild-type AD model (TLR4W Tg. At 9 months, TLR4M Tg mice had increased Aβ deposition and soluble Aβ42 in the brain, which were associated with decrements in cognitive functions and expression levels of IL-1β, CCL3, and CCL4 in the hippocampus compared to TLR4W Tg mice. TLR4 mutation diminished Aβ-induced IL-1β, CCL3, and CCL4 expression in monocytes. Conclusion This is the first demonstration of TLR4

  18. Fine particulate pollution and asthma exacerbations.

    Science.gov (United States)

    Bouazza, Naïm; Foissac, Frantz; Urien, Saik; Guedj, Romain; Carbajal, Ricardo; Tréluyer, Jean-Marc; Chappuy, Hélène

    2017-12-19

    As the results from epidemiological studies about the impact of outdoor air pollution on asthma in children are heterogeneous, our objective was to investigate the association between asthma exacerbation in children and exposure to air pollutants. A database of 1 264 585 paediatric visits during the 2010-2015 period to the emergency rooms from 20 emergency departments (EDs) of 'Assistance Publique Hôpitaux de Paris (APHP)', the largest hospital group in Europe, was used. A total of 47 107 visits were classified as asthma exacerbations. Concentration of air pollutants (nitrogen dioxide, ozone, fine particulate matter (PM) with an aerodynamic diameter smaller than 10  µm (PM 10 ) and 2.5 µm (PM 2.5 )), as well as meteorological data, evolution of respiratory syncytial virus infection and pollen exposition, were collected on an hourly or daily basis for the same period using institutional databases. To assess the association between air pollution and asthma, mixed-effects quasi-Poisson regression modelling was performed. The only compound independently associated with ED visits for asthma was PM 2.5 (Ppollutants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study

    Science.gov (United States)

    Müllerová, Hana; Shukla, Amit; Hawkins, Adam; Quint, Jennifer

    2014-01-01

    Objectives To evaluate risk factors associated with exacerbation frequency in primary care. Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts. Design Retrospective observational cohort study. Setting Electronic medical records database (England and Wales). Participants 58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink. Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted. Outcome measures Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics. Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models. Results During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none). Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer). Conclusions Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. PMID:25524545

  20. Classification of Exacerbation Frequency in the COPDGene Cohort Using Deep Learning with Deep Belief Networks.

    Science.gov (United States)

    Ying, Jun; Dutta, Joyita; Guo, Ning; Hu, Chenhui; Zhou, Dan; Sitek, Arkadiusz; Li, Quanzheng

    2016-12-21

    This study aims to develop an automatic classifier based on deep learning for exacerbation frequency in patients with chronic obstructive pulmonary disease (COPD). A threelayer deep belief network (DBN) with two hidden layers and one visible layer was employed to develop classification models and the models' robustness to exacerbation was analyzed. Subjects from the COPDGene cohort were labeled with exacerbation frequency, defined as the number of exacerbation events per year. 10,300 subjects with 361 features each were included in the analysis. After feature selection and parameter optimization, the proposed classification method achieved an accuracy of 91.99%, using a 10-fold cross validation experiment. The analysis of DBN weights showed that there was a good visual spatial relationship between the underlying critical features of different layers. Our findings show that the most sensitive features obtained from the DBN weights are consistent with the consensus showed by clinical rules and standards for COPD diagnostics. We thus demonstrate that DBN is a competitive tool for exacerbation risk assessment for patients suffering from COPD.