Science.gov

Sample records for advanced fabry disease

  1. Fabry disease.

    PubMed

    Schiffmann, Raphael

    2015-01-01

    Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy. As a result, patients have a markedly increased risk of developing ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction and chronic kidney disease. Virtually all complications of Fabry disease are non-specific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. Recent studies suggested a much higher incidence of mutations of the GLA gene, suggesting that this disorder is under-diagnosed. However, some of the gene variants may be benign. Although the etiology of Fabry disease has been known for many years, the mechanism by which the accumulating α-D-galactosyl moieties cause this multi organ disorder has only recently been studied and is yet to be completely elucidated. Specific therapy for Fabry disease has been developed in the last few years but its role in the management of the disorder is still being investigated. Fortunately, standard 'non-specific' medical and surgical therapy is effective in slowing deterioration or compensating for organ failure in patients with Fabry disease. PMID:26564084

  2. Fabry disease

    PubMed Central

    2010-01-01

    Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs

  3. Fabry Disease

    MedlinePlus

    ... kidneys may become progressively impaired, leading to renal failure. Other signs include decreased sweating, fever, and gastrointestinal ... of complications from strokes, heart disease, or kidney failure. What research is being done? The mission of ...

  4. Paediatric Fabry disease.

    PubMed

    Ellaway, Carolyn

    2016-01-01

    Fabry disease is a rare, progressive X-linked inborn error of the glycosphingolipid metabolic pathway. Mutations of the GLA gene result in deficiency of the lysosomal enzyme, α-galactosidase A (α-Gal A) with accumulation of glycosphingolipids, particularly globotriaosylceramide (GL3) in the vascular endothelium of various tissues. Accumulation of GL3 eventually leads to life threatening renal, cardiac and cerebrovascular complications typically in the third to fifth decades of life. The first signs and symptoms of classic Fabry disease however appear in childhood but diagnosis is often delayed. The symptoms most commonly experienced in childhood include neuropathic pain, gastrointestinal dysfunction, hyperhidrosis and heat intolerance. Timely diagnosis is important as early treatment with enzyme replacement therapy reduces GL3 accumulation, can stabilize disease progression and potentially prevent irreversible organ damage. Physicians should be familiar with the signs and symptoms of Fabry disease in childhood and be particularly vigilant for unusual or non-specific but recurrent or episodic symptoms. PMID:26835405

  5. Genetics Home Reference: Fabry disease

    MedlinePlus

    ... National Organization for Rare Disorders (NORD) National Tay-Sachs & Allied Diseases Association, Inc. Resource list from the ... Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, ...

  6. Renal involvement in Fabry disease.

    PubMed

    Abensur, Hugo; Reis, Marlene Antônia Dos

    2016-06-01

    Every cell in the human body has globotriaosylceramide accumulation (Gb3) in Fabry disease due to the mutation in gene of the enzyme α-galactosidase A. It is a disease linked to sex. The main clinical features are: cutaneous angiokeratomas; acroparestesias and early strokes; decreased sweating and heat intolerance; ocular changes; myocardial hypertrophy, arrhythmias; gastrointestinal disorders and renal involvement. Renal involvement occurs due to Gb3 accumulation in all types of renal cells. Therefore, patients may present glomerular and tubular function disorders. Podocytes are particularly affected, with pedicels effacement and development of proteinuria. The diagnosis is made by detection of reduced plasma or leukocyte α-galactosidase activity and genetic study for detecting the α-galactosidase gene mutation. Treatment with enzyme replacement contributes to delay the progression of kidney disease, especially if initiated early. PMID:27438980

  7. The Renal History of Fabry Disease.

    PubMed

    Gaggl, Martina; El-Hadi, Sarah; Aigner, Christof; Sunder-Plassmann, Gere

    2016-02-01

    In 1898 William Anderson and Johannes Fabry described the red-purple maculopapular skin lesions characteristic for Fabry disease and also mentioned the presence of proteinuria. Four decades later Maximiliaan Ruiter concluded that angiokeratoma corporis diffusum is the cutaneous manifestation of an inherited systemic internal disease. In 1947 autopsy findings of two cases who died from uraemia revealed sclerosis of glomeruli. At this time the presence of a thesaurismosis was also considered. The first renal needle biopsy in 1958 showed vacuolation and distension of the cells of the glomerular tufts and distal tubules suggestive of a storage disorder. The ability to concentrate the urine was also impaired in these patients. Sweely und Klionsky in 1963 demonstrated that the major storage component is a trihexoside. As of 1967 Roscoe Brady finally described the deficiency of the enzyme ceramidetrihexosidase/-galactosidase A characteristic in patients with Fabry disease. PMID:26913882

  8. Preselective gene therapy for Fabry disease

    PubMed Central

    Qin, Gangjian; Takenaka, Toshihiro; Telsch, Kimberly; Kelley, Leslie; Howard, Tazuko; Levade, Thierry; Deans, Robert; Howard, Bruce H.; Malech, Harry L.; Brady, Roscoe O.; Medin, Jeffrey A.

    2001-01-01

    Fabry disease is a lipid storage disorder resulting from mutations in the gene encoding the enzyme α-galactosidase A (α-gal A; EC 3.2.1.22). We previously have demonstrated long-term α-gal A enzyme correction and lipid reduction mediated by therapeutic ex vivo transduction and transplantation of hematopoietic cells in a mouse model of Fabry disease. We now report marked improvement in the efficiency of this gene-therapy approach. For this study we used a novel bicistronic retroviral vector that engineers expression of both the therapeutic α-gal A gene and the human IL-2Rα chain (huCD25) gene as a selectable marker. Coexpression of huCD25 allowed selective immunoenrichment (preselection) of a variety of transduced human and murine cells, resulting in enhanced intracellular and secreted α-gal A enzyme activities. Of particular significance for clinical applicability, mobilized CD34+ peripheral blood hematopoietic stem/progenitor cells from Fabry patients have low-background huCD25 expression and could be enriched effectively after ex vivo transduction, resulting in increased α-gal A activity. We evaluated effects of preselection in the mouse model of Fabry disease. Preselection of transduced Fabry mouse bone marrow cells elevated the level of multilineage gene-corrected hematopoietic cells in the circulation of transplanted animals and improved in vivo enzymatic activity levels in plasma and organs for more than 6 months after both primary and secondary transplantation. These studies demonstrate the potential of using a huCD25-based preselection strategy to enhance the clinical utility of ex vivo hematopoietic stem/progenitor cell gene therapy of Fabry disease and other disorders. PMID:11248095

  9. Multiple parapelvic cysts in Fabry disease.

    PubMed

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis. PMID:27061865

  10. Multiple parapelvic cysts in Fabry disease.

    PubMed

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.

  11. Electrocardiographic Changes and Arrhythmia in Fabry Disease

    PubMed Central

    Namdar, Mehdi

    2016-01-01

    Fabry disease is an X-chromosome-linked lysosomal storage disease characterized by a deficient activity or, in most males, absence of the enzyme α-galactosidase A (a-Gal A) leading to systemic, primary lysosomal accumulation of globotriaosylceramide (Gb3) (1). Recent literature refers to an overall birth prevalence of 1:40,000–170,000; however, such data do not allow an estimation on an actual patient number suffering from Fabry disease (2). Multisystem morbidity commonly develops in childhood and, with progression of the disease, life-threatening complications often occur in adulthood, including renal failure, cardiovascular dysfunction, neuropathy, and stroke (3–6). Life expectancy is reduced by an average of 15 years in female patients and 20 years in male patients (7, 8). The pathognomonic Gb3 accumulation has been repeatedly observed over the past decades by many groups in vascular endothelial and smooth muscle cells, cardiomyocytes, cardiac conduction tissue, and valvular fibroblasts (3). Although incompletely described, it is likely that inflammatory and neurohormonal mechanisms are involved in subsequent cellular and vascular dysfunction, leading to tissue ischemia, hypertrophy, and fibrosis (9). Furthermore, recently published works on cardiomyocyte dysfunction and conduction tissue involvement have suggested that cardiac dysfunction may reflect increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death, and accelerated conduction with prolonged refractoriness and electric instability (10, 11). PMID:27047943

  12. Electrocardiographic Changes and Arrhythmia in Fabry Disease.

    PubMed

    Namdar, Mehdi

    2016-01-01

    Fabry disease is an X-chromosome-linked lysosomal storage disease characterized by a deficient activity or, in most males, absence of the enzyme α-galactosidase A (a-Gal A) leading to systemic, primary lysosomal accumulation of globotriaosylceramide (Gb3) (1). Recent literature refers to an overall birth prevalence of 1:40,000-170,000; however, such data do not allow an estimation on an actual patient number suffering from Fabry disease (2). Multisystem morbidity commonly develops in childhood and, with progression of the disease, life-threatening complications often occur in adulthood, including renal failure, cardiovascular dysfunction, neuropathy, and stroke (3-6). Life expectancy is reduced by an average of 15 years in female patients and 20 years in male patients (7, 8). The pathognomonic Gb3 accumulation has been repeatedly observed over the past decades by many groups in vascular endothelial and smooth muscle cells, cardiomyocytes, cardiac conduction tissue, and valvular fibroblasts (3). Although incompletely described, it is likely that inflammatory and neurohormonal mechanisms are involved in subsequent cellular and vascular dysfunction, leading to tissue ischemia, hypertrophy, and fibrosis (9). Furthermore, recently published works on cardiomyocyte dysfunction and conduction tissue involvement have suggested that cardiac dysfunction may reflect increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death, and accelerated conduction with prolonged refractoriness and electric instability (10, 11). PMID:27047943

  13. Fabry's disease: An ultrastructural study of nerve biopsy

    PubMed Central

    Gayathri, N.; Yasha, T. C.; Kanjalkar, Makarand; Agarwal, Santosh; Sagar, B. K. Chandrashekar; Santosh, Vani; Shankar, S. K.

    2008-01-01

    Fabry's disease, an X linked recessive disorder caused by the deficiency of α-galactosidase A (α-gal A), leads to progressive accumulation of glycosphingolipids. We report this rare disease in a 19-year-old boy who presented with angiokeratomas, paresthesia and corneal opacities, and nerve biopsy revealed by electron microscopy lamellated inclusions in the smooth muscle, perineurial and endothelial cells characteristic of Fabry's disease. PMID:19893666

  14. A Case of Cerebral Aneurysmal Subarachnoid Hemorrhage in Fabry's Disease

    PubMed Central

    Chang, Youn Hyuk

    2013-01-01

    We report an unusual case of cerebral aneurysmal subarachnoid hemorrage (SAH) with Fabry's disease. A 42-year-old woman presented with aneurysmal SAH originated from a saccular aneurysm of the right posterior communicating artery. The patient was treated by an endovascular coil embolization of aneurysm. Postoperatively the patient recovered favorably without any neurological deficit. During her admission, the patient had a sign of proteinuria in urine analysis. The pathologic findings of kidney needle biopsy implied nephrosialidosis (mucolipidosis of lysosomal stroage disease), which is consistent with a Fabry's disease. It is uncommon that Fabry's disease is presented with aneurysmal SAH, especially in middle-aged patients, but could be a clinical concern. Further investigations are needed to reveal risk factors, vascular anatomy, and causative mechanisms of Fabry's disease with aneurysmal SAH. PMID:23634271

  15. Experiences of Being Heterozygous for Fabry Disease: a Qualitative Study.

    PubMed

    von der Lippe, Charlotte; Frich, Jan C; Harris, Anna; Solbrække, Kari Nyheim

    2016-10-01

    Little is known about the experiences of women with Fabry disease. The aim of this study was to explore women's experiences of being heterozygous for Fabry disease. We used an explorative qualitative study design and selected ten Norwegian women who were known heterozygous for Fabry disease to participate. We conducted in-depth semi-structured interviews and analyzed the interviews using inductive thematic analysis. We found that learning about one's heterozygous status may be devastating for some. However, for most of the participants, heterozygous status, as well as doctors' acceptance of symptoms in women heterozygous for Fabry disease, provided an explanation and relief. Although many women did not consider themselves ill, they wished to be acknowledged as more than "just carriers." The participants were grateful for enzyme replacement therapy, although it had its burdens regarding time, planning, and absences from school or work. Women with Fabry disease felt that the lack of knowledge among healthcare professionals about Fabry disease was frustrating and worrisome. These findings suggest that healthcare professionals should acknowledge the different ways women react to their diagnosis, and be aware of the personal costs of receiving treatment. PMID:26948256

  16. Experiences of Being Heterozygous for Fabry Disease: a Qualitative Study.

    PubMed

    von der Lippe, Charlotte; Frich, Jan C; Harris, Anna; Solbrække, Kari Nyheim

    2016-10-01

    Little is known about the experiences of women with Fabry disease. The aim of this study was to explore women's experiences of being heterozygous for Fabry disease. We used an explorative qualitative study design and selected ten Norwegian women who were known heterozygous for Fabry disease to participate. We conducted in-depth semi-structured interviews and analyzed the interviews using inductive thematic analysis. We found that learning about one's heterozygous status may be devastating for some. However, for most of the participants, heterozygous status, as well as doctors' acceptance of symptoms in women heterozygous for Fabry disease, provided an explanation and relief. Although many women did not consider themselves ill, they wished to be acknowledged as more than "just carriers." The participants were grateful for enzyme replacement therapy, although it had its burdens regarding time, planning, and absences from school or work. Women with Fabry disease felt that the lack of knowledge among healthcare professionals about Fabry disease was frustrating and worrisome. These findings suggest that healthcare professionals should acknowledge the different ways women react to their diagnosis, and be aware of the personal costs of receiving treatment.

  17. Pituitary function and morphology in Fabry disease.

    PubMed

    Maione, Luigi; Tortora, Fabio; Modica, Roberta; Ramundo, Valeria; Riccio, Eleonora; Daniele, Aurora; Belfiore, Maria Paola; Colao, Annamaria; Pisani, Antonio; Faggiano, Antongiulio

    2015-11-01

    Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications.

  18. Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis

    PubMed Central

    Zar-Kessler, Claire; Karaa, Amel; Sims, Katherine Bustin; Clarke, Virginia; Kuo, Braden

    2016-01-01

    Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical. PMID:27366228

  19. Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis.

    PubMed

    Zar-Kessler, Claire; Karaa, Amel; Sims, Katherine Bustin; Clarke, Virginia; Kuo, Braden

    2016-07-01

    Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical. PMID:27366228

  20. Cardiac device implantation in Fabry disease

    PubMed Central

    Sené, Thomas; Lidove, Olivier; Sebbah, Joel; Darondel, Jean-Marc; Picard, Hervé; Aaron, Laurent; Fain, Olivier; Zenone, Thierry; Joly, Dominique; Charron, Philippe; Ziza, Jean-Marc

    2016-01-01

    Abstract The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD. Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P < 0.05). Considering the high frequency of ACAs requiring CD implantation and the risk of sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype

  1. Atypical patterns of cardiac involvement in Fabry disease.

    PubMed

    Coughlan, J J; Elkholy, K; O'Brien, J; Kiernan, T

    2016-01-01

    A 58-year-old woman was referred to our cardiology service with chest pain, exertional dyspnoea and palpitations on a background of known Fabry disease diagnosed with genetic testing in 1994. ECG showed sinus rhythm, shortened PR interval, widespread t wave inversion, q waves in the lateral leads and left ventricular hypertrophy (LVH). Coronary angiogram showed only mild atheroma. Transthoracic echocardiogram showed anterolateral LVH and reduced left ventricular cavity size in keeping with Fabry cardiomyopathy. Cardiac MRI demonstrated asymmetric hypertrophy with evidence of diffuse myocardial fibrosis in the maximally hypertrophied segments from base to apex with late gadolinium enhancement in the anterior and anteroseptal walls. This was quite an atypical appearance for Fabry cardiomyopathy. This case highlights the heterogeneity of patterns of cardiac involvement that may be associated with this rare X-linked lysosomal disorder. PMID:26989114

  2. [Gaucher's and Fabry's diseases: biochemical and genetic aspects].

    PubMed

    Caillaud, Catherine; Poenaru, Livia

    2002-01-01

    Gaucher and Fabry's diseases are lysosomal storage disorders. They are due to glucocerebrosidase or alpha galactosidase deficiency, respectively. Gaucher disease, transmitted as an autosomal recessive trait, is frequent among Ashkenazi Jews. Cloning of the gene has allowed the characterization of few common mutations. Some of them have a prognosis value, in favour of either a non neurological form (type 1) or more severe forms (types 2 and 3). There mutations were found in 70% of the alleles, the other alleles carrying private mutations. Fabry disease is transmitted as an X-linked recessive trait. Genetic counselling in at-risk families relies on the detection of carrier females. As the alpha galactosidase gene shows various mutations, the establishment of phenotype-genotype correlations is limited. These two diseases, well defined at the biochemical and genetic level, are good models of inherited diseases for the development of specific therapies.

  3. Fabry disease presenting with sudden hearing loss and otosclerosis: a case report

    PubMed Central

    2012-01-01

    Introduction Fabry disease is an X-linked lysosomal storage disorder resulting in a multiple-system disorder with a wide spectrum of physical signs and symptoms, predominantly affecting the central and peripheral nervous systems, skin, heart, kidneys, and eyes. Case presentation We describe the case of a 26-year-old European Caucasian man who had Fabry disease and who presented with episodic sudden unilateral hearing loss and was treated with glucocorticoids, pentoxifylline, hyperbaric oxygen, and fluoride because of concomitant audiometric evidence of otosclerosis. This case demonstrates the partial and transient beneficial effect of standard treatment for sudden hearing loss not related to Fabry disease and analyzes the possible connection between typical Fabry disease inner-ear lesions and otosclerosis. Whereas hearing loss has been described in connection with Fabry disease, otosclerosis-associated hearing loss in Fabry disease has not yet been described. Conclusions Although progressive hearing loss in patients with Fabry disease seems to be influenced by replacement therapy, few data concerning treatment of sudden hearing loss are available. The lack of literature concerning the pathogenesis of the otological involvement in Fabry disease makes it impossible to identify a connection between the latter and otosclerosis. Therefore, this report may help to reinforce the importance of a thorough evaluation of hearing in patients with Fabry disease and may be of help with therapeutic decision-making. PMID:22507244

  4. Fabry's Disease: Case Series and Review of Literature

    PubMed Central

    Wani, Muzaffar Maqsood; Khan, Imran; Bhat, Riyaz Ahmad; Ahmad, Muzaffar

    2016-01-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare cause of end-stage renal disease. It classically affects males whereas 10–15% of female heterozygote carriers are affected depending on localization. Both the FD and its association with ESRD is rare. With this background, this case series of five patient's along with the review of literature is presented here. PMID:27398254

  5. Fabry's Disease: Case Series and Review of Literature.

    PubMed

    Wani, Muzaffar Maqsood; Khan, Imran; Bhat, Riyaz Ahmad; Ahmad, Muzaffar

    2016-01-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare cause of end-stage renal disease. It classically affects males whereas 10-15% of female heterozygote carriers are affected depending on localization. Both the FD and its association with ESRD is rare. With this background, this case series of five patient's along with the review of literature is presented here. PMID:27398254

  6. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease.

    PubMed

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-10-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients. PMID:27679722

  7. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease

    PubMed Central

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-01-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R2 = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients. PMID:27679722

  8. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease.

    PubMed

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-10-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

  9. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease

    PubMed Central

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-01-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R2 = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

  10. [Foam cell nephropathy in heterozygous female with Fabry's disease].

    PubMed

    Vera-Sempere, F J; García, A; Sánchez, M A; Moll, J L; Pérez, A

    2002-01-01

    We describe the clinical and pathological characteristics of a 49 year-old heterozygous female carrier of Anderson-Fabry's disease. Light microscopy and ultrastructural study of a renal biopsy showed the presence of foam cell nephropathy and galactosylceramide deposits affecting podocytes, the parietal epithelium of Bowman's capsule and the distal tubular cells, endothelial cells and medullary interstitial elements. Retrospectively, the presence of storage disease was confirmed in a hysterectomy specimen obtained two years previously. Our observation shows that heterozygotes for this disorder can not only carry and transmit the disease but may also develop pathological deposits in various organs. A renal biopsy from these carriers allows precise identification of the disease, facilitates adequate genetic counseling and gives the option of enzyme replacement therapy in patients who have pathological deposits.

  11. [Treatment of Fabry disease: Successes, failures, and expectations].

    PubMed

    Lidove, Olivier; Barbey, Frédéric; Joly, Dominique

    2016-04-01

    Fabry disease, an X-linked lysosomal storage disease, results from α-galactosidase A deficiency. Two different recombinant enzyme treatments (algalsidase alpha agalsidase beta) have been available since 2001 to treat a disease that affects not only men but also women. Enzyme replacement therapy promotes cell clearance of susbtrate, and improves some clinical parameters (heart, kidney damage, pain, quality of life). However, there is no proven efficacy to date on central nervous system lesions, on cardiac morbidity and mortality, nor on renal damage beyond a certain stage (proteinuria>1g/day and/or estimated glomerular filtration rate<60mL/min/1.73m(2)). In this review, we discuss the potential benefit of an early intervention, the vascular protective measures to be associated with enzyme therapy and their rationale, and some alternative treatments under development, such as chaperones and substrate molecules inhibitors. PMID:26968478

  12. [Treatment of Fabry disease: Successes, failures, and expectations].

    PubMed

    Lidove, Olivier; Barbey, Frédéric; Joly, Dominique

    2016-04-01

    Fabry disease, an X-linked lysosomal storage disease, results from α-galactosidase A deficiency. Two different recombinant enzyme treatments (algalsidase alpha agalsidase beta) have been available since 2001 to treat a disease that affects not only men but also women. Enzyme replacement therapy promotes cell clearance of susbtrate, and improves some clinical parameters (heart, kidney damage, pain, quality of life). However, there is no proven efficacy to date on central nervous system lesions, on cardiac morbidity and mortality, nor on renal damage beyond a certain stage (proteinuria>1g/day and/or estimated glomerular filtration rate<60mL/min/1.73m(2)). In this review, we discuss the potential benefit of an early intervention, the vascular protective measures to be associated with enzyme therapy and their rationale, and some alternative treatments under development, such as chaperones and substrate molecules inhibitors.

  13. Fabry's disease as a differential diagnosis of MS.

    PubMed

    Callegaro, D; Kaimen-Maciel, D R

    2006-01-01

    Fabry's disease is a genetically inherited error of glycosphingolipid metabolism that results from the defective activity of the lysosomal enzyme alpha-galactosidase A (alpha-GalA). The enzymatic defect, caused by an X-linked recessive genes, leads to progressive deposition of neutral glycosphingolipids (predominantly globotriaosylceramide), with terminal alpha-galactosyl moieties, in most visceral tissues and fluids of the body. Cerebrovascular manifestations result from multifocal small-vessel involvement and may include thromboses, basilar arterial ischaemia and aneurysm, seizures, paroxystic hemiplegia or hemianaesthesia, vestibular disorders and frank cerebral haemorrhage. Severe neurological signs may be present without evidence of major thrombosis and are presumably due to multifocal small-vessel occlusive disease. Vascular ischaemia and lipid deposition in peripheral nerves may cause conduction abnormalities (slowed conduction velocities and distal latency). Sensory neurons in spinal ganglia and small myelinated and unmyelinated fibers are affected preferentially. PMID:16420782

  14. Mitochondrial DNA haplogroups may influence Fabry disease phenotype.

    PubMed

    Simoncini, C; Chico, L; Concolino, D; Sestito, S; Fancellu, L; Boadu, W; Sechi, G P; Feliciani, C; Gnarra, M; Zampetti, A; Salviati, A; Scarpelli, M; Orsucci, D; Bonuccelli, U; Siciliano, G; Mancuso, M

    2016-08-26

    While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls. Haplogroups H and I, and haplogroup cluster HV were significantly more frequent in patients than controls. However, no correlation with gender, age of onset, organ involvement was observed. Our study seems to provide some evidence of a contribution of mitochondrial variation in FD pathogenesis, at least in Italy. PMID:27365132

  15. The Psychosocial Impact of Fabry Disease on Pediatric Patients.

    PubMed

    Bugescu, Nicolle; Naylor, Paige E; Hudson, Kyr; Aoki, Christa D; Cordova, Matthew J; Packman, Wendy

    2016-09-01

    Fabry disease (FD) is a multisystemic disease that has previously been reported to result in poorer quality of life and psychosocial functioning in impacted adults. However, prior to the current study, limited data were available on the impact of FD in children and adolescents. Therefore, the present study examined the differences of quality of life, psychosocial functioning, and depression in children with FD as compared with a healthy sample. Results indicated that children with FD were experiencing poorer quality of life than their healthy counterparts. Notably, results consistently identified adolescents with FD as more heavily impacted than younger children, although not to the same degree as adults with FD as reported in previous studies. Therefore, adolescence may be a critical point in the development of individuals with FD during which effective multidisciplinary interventions could be utilized to prevent poor quality of life and psychosocial functioning in adulthood. PMID:27617155

  16. Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease

    PubMed Central

    Üçeyler, Nurcan; Homola, György A.; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

    2014-01-01

    A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity. PMID:24475221

  17. Increased arterial diameters in the posterior cerebral circulation in men with Fabry disease.

    PubMed

    Uçeyler, Nurcan; Homola, György A; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

    2014-01-01

    A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males-females; normal-impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity.

  18. [Atypical symptoms of Fabry's disease: sudden bilateral deafness, lymphoedema and Lown-Ganong-Levine syndrome].

    PubMed

    Undas, Anetta; Ryś, Donata; Wegrzyn, Wojciech; Musiał, Jacek

    2002-11-01

    A 40-year-old man with Fabry disease, confirmed by decreased leukocyte alpha-galactosidase A activity in 2001, complained of sudden bilateral deafness, as evidenced by clinical history and audiometry. Magnetic resonance of the brain revealed features typical of Fabry disease. Other clinical manifestations of the disease included: angiokeratoma, mild proteinuria with normal renal function, lymphoedema of the lower limbs, pre-excitation syndrome, myocardial hypertrophy.

  19. Enzyme enhancers for the treatment of Fabry and Pompe disease.

    PubMed

    Lukas, Jan; Pockrandt, Anne-Marie; Seemann, Susanne; Sharif, Muhammad; Runge, Franziska; Pohlers, Susann; Zheng, Chaonan; Gläser, Anne; Beller, Matthias; Rolfs, Arndt; Giese, Anne-Katrin

    2015-03-01

    Lysosomal storage disorders (LSD) are a group of heterogeneous diseases caused by compromised enzyme function leading to multiple organ failure. Therapeutic approaches involve enzyme replacement (ERT), which is effective for a substantial fraction of patients. However, there are still concerns about a number of issues including tissue penetrance, generation of host antibodies against the therapeutic enzyme, and financial aspects, which render this therapy suboptimal for many cases. Treatment with pharmacological chaperones (PC) was recognized as a possible alternative to ERT, because a great number of mutations do not completely abolish enzyme function, but rather trigger degradation in the endoplasmic reticulum. The theory behind PC is that they can stabilize enzymes with remaining function, avoid degradation and thereby ameliorate disease symptoms. We tested several compounds in order to identify novel small molecules that prevent premature degradation of the mutant lysosomal enzymes α-galactosidase A (for Fabry disease (FD)) and acid α-glucosidase (GAA) (for Pompe disease (PD)). We discovered that the expectorant Ambroxol when used in conjunction with known PC resulted in a significant enhancement of mutant α-galactosidase A and GAA activities. Rosiglitazone was effective on α-galactosidase A either as a monotherapy or when administered in combination with the PC 1-deoxygalactonojirimycin. We therefore propose both drugs as potential enhancers of pharmacological chaperones in FD and PD to improve current treatment strategies.

  20. Enzyme enhancers for the treatment of Fabry and Pompe disease.

    PubMed

    Lukas, Jan; Pockrandt, Anne-Marie; Seemann, Susanne; Sharif, Muhammad; Runge, Franziska; Pohlers, Susann; Zheng, Chaonan; Gläser, Anne; Beller, Matthias; Rolfs, Arndt; Giese, Anne-Katrin

    2015-03-01

    Lysosomal storage disorders (LSD) are a group of heterogeneous diseases caused by compromised enzyme function leading to multiple organ failure. Therapeutic approaches involve enzyme replacement (ERT), which is effective for a substantial fraction of patients. However, there are still concerns about a number of issues including tissue penetrance, generation of host antibodies against the therapeutic enzyme, and financial aspects, which render this therapy suboptimal for many cases. Treatment with pharmacological chaperones (PC) was recognized as a possible alternative to ERT, because a great number of mutations do not completely abolish enzyme function, but rather trigger degradation in the endoplasmic reticulum. The theory behind PC is that they can stabilize enzymes with remaining function, avoid degradation and thereby ameliorate disease symptoms. We tested several compounds in order to identify novel small molecules that prevent premature degradation of the mutant lysosomal enzymes α-galactosidase A (for Fabry disease (FD)) and acid α-glucosidase (GAA) (for Pompe disease (PD)). We discovered that the expectorant Ambroxol when used in conjunction with known PC resulted in a significant enhancement of mutant α-galactosidase A and GAA activities. Rosiglitazone was effective on α-galactosidase A either as a monotherapy or when administered in combination with the PC 1-deoxygalactonojirimycin. We therefore propose both drugs as potential enhancers of pharmacological chaperones in FD and PD to improve current treatment strategies. PMID:25409744

  1. Light- and electron-microscopic histochemistry of Fabry's disease.

    PubMed Central

    Faraggiana, T.; Churg, J.; Grishman, E.; Strauss, L.; Prado, A.; Bishop, D. F.; Schuchman, E.; Desnick, R. J.

    1981-01-01

    A histochemical study was performed on light- and electron-microscopic level in a case of Fabry's disease. The patient underwent kidney transplantation for renal failure and died of heart failure 6 months later. Patient's tissues were studied at the light- and electron-microscopic levels with various embedding and staining techniques for lipids and carbohydrates. Two peroxidase-labeled lectins (from Ricinus communis and from Bandeiraea simplicifolia) known to have affinity for alpha- and beta-D-galactose, were strongly reactive with the storage material on frozen sections. The ultrahistochemical and extraction tests showed that the typical granules had a variable reactivity and morphologic characteristics in different cells, probably reflecting different composition. A small number of typical deposits were also observed in the transplanted kidney. This is the first reported case of recurrence of the storage disease in the allograft. Of interest was also the fact that the patient's blood inhibited normal alpha-galactosidase activity, suggesting a possible inhibitor-related mechanism in the pathogenesis of the recurrence. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 PMID:6786101

  2. Fabry's disease: an example of cardiorenal syndrome type 5.

    PubMed

    Sharma, Aashish; Sartori, Marco; Zaragoza, Jose J; Villa, Gianluca; Lu, Renhua; Faggiana, Elena; Brocca, Alessandra; Di Lullo, Luca; Feriozzi, Sandro; Ronco, Claudio

    2015-11-01

    Cardiorenal syndrome type 5 (CRS-5) includes conditions where there is a simultaneous involvement of the heart and kidney from a systemic disorder. This is a bilateral organ cross talk. Fabry's disease (FD) is a devastating progressive inborn error of metabolism with lysosomal glycosphingolipid deposition in variety of cell types, capillary endothelial cells, renal, cardiac and nerve cells. Basic effect is absent or deficient activity of lysosomal exoglycohydrolase a-galactosidase A. Renal involvement consists of proteinuria, isosthenuria, altered tubular function, presenting in second or third decade leading to azotemia and end-stage renal disease in third to fifth decade mainly due to irreversible changes to glomerular, tubular and vascular structures, especially highlighted by podocytes foot process effacement. Cardiac involvement consists of left ventricular hypertrophy, right ventricular hypertrophy, arrhythmias (sinus node and conduction system impairment), diastolic dysfunction, myocardial ischemia, infarction, transmural replacement fibrosis, congestive heart failure and cardiac death. Management of FD is based on enzymatic replacement therapy and control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors-and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statin to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias). PMID:26232292

  3. The management and treatment of children with Fabry disease: A United States-based perspective.

    PubMed

    Hopkin, Robert J; Jefferies, John L; Laney, Dawn A; Lawson, Victoria H; Mauer, Michael; Taylor, Matthew R; Wilcox, William R

    2016-02-01

    Fabry disease is an inherited X-linked disorder that presents during childhood in male and female patients. Young patients may initially experience pain, hypohidrosis, and gastrointestinal symptoms. Other manifestations of Fabry disease, such as renal and cardiac disease, manifest later in adolescence or adulthood. In the pediatric population, renal damage is typically subclinical and identifiable only through biopsy. Specialists from the United States with expertise in Fabry disease convened during 2013-2014 in order to develop these consensus guidelines about the management and treatment of children with Fabry disease. The presence of symptoms in boys and girls of any age is an indication to begin therapy. Early treatment before the onset of potentially irreversible vital organ pathology is ideal. Asymptomatic children with Fabry mutations should be followed closely for the development of renal, cardiac, neurological, or gastrointestinal signs, symptoms, or laboratory changes, which would warrant treatment initiation. A comprehensive care plan should be implemented by the treating physicians to guide the management of children with Fabry disease. PMID:26546059

  4. Agalsidase benefits renal histology in young patients with Fabry disease.

    PubMed

    Tøndel, Camilla; Bostad, Leif; Larsen, Kristin Kampevold; Hirth, Asle; Vikse, Bjørn Egil; Houge, Gunnar; Svarstad, Einar

    2013-01-01

    The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.

  5. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

    PubMed Central

    2013-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness is unclear. Methods Renal, cardiac, and cerebral outcomes were prospectively studied in males and females with Fabry disease treated with ERT. Additionally, the occurrence of major cardiac events, stroke, end-stage renal disease and death was compared to a natural history (NH) cohort meeting treatment criteria. Results Of 75 patients on ERT (median treatment duration 5.2 years, range 0.05-11.0), prospective follow-up was available for 57 adult patients (30 males) and 6 adolescents. Renal function declined in males (-3.4 ml/min/1.73 m2 per year, SE 0.2; p < 0.001) despite ERT, but followed the normal course in females (-0.8 ml/min/1.73 m2 per year, SE 0.3; p = 0.001). Cardiac mass increased during ERT in males (+ 1.2 gram/m2.7, SE 0.3; p < 0.001), but remained stable in females (-0.3 gram/m2.7 per year, SE 0.4; p = 0.52). ERT did not prevent the occurrence of cerebral white matter lesions. Comparison of ERT treated to untreated patients revealed that the odds to develop a first complication increased with age (OR 1.05 (95% CI: 1.0-1.1) per year, p = 0.012). For development of a first or second complication the odds declined with longer treatment duration (OR 0.81 (95% CI: 0.68-0.96) per year of ERT, p = 0.015;OR 0.52 (0.31-0.88), p = 0.014 respectively). Conclusions Long term ERT does not prevent disease progression, but the risk of developing a first or second complication declines with increasing treatment duration. ERT in advanced Fabry disease seems of doubtful benefit. PMID:23531228

  6. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

    PubMed Central

    Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

    2016-01-01

    Background Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. Trial registration number NCT00196742. PMID:26993266

  7. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    PubMed

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take

  8. Fabry disease, respiratory symptoms, and airway limitation – a systematic review

    PubMed Central

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    Background Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. Materials and method A systematic literature search was performed using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic. The remaining 27 articles were relevant for this review. Results The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory examinations are seldom performed. Pulmonary function tests primarily show obstructive airway limitation, but a few articles also report of patients with restrictive limitation and a mixture of both. No significant association has been found between smoking and the development of symptoms or spirometry abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed by high-resolution CT has not been significantly correlated with lung spirometry. Conclusion Consistent findings have not been shown in the current literature. Pulmonary function tests and registration of symptoms showed various results; however, there is a trend towards obstructive airway limitation in patients with Fabry disease. Further studies are needed to evaluate pathogenesis, progression, and the effects of treatment. PMID:26557248

  9. p.R301X Mutation and Variable Phenotypic Appearance of Fabry Disease

    PubMed Central

    Ozelsancak, Ruya; Uyar, Bulent

    2016-01-01

    Patient: Male, 39 Final Diagnosis: Fabry disease Symptoms: Acropareshesia • fatique Medication: — Clinical Procedure: Gene analysis Specialty: Metabolic Disorders and Diabetics Objective: Rare disease Background: Fabry disease is an X-linked disorder. Due to deficiency of the enzyme α-galactosidase A, neutral glycosphingolipids (primarily globotriaosylceramide) progressively accumulate within lysosomes of cells in various organ systems, resulting in a multi-system disorder, affecting both men and women. Misdiagnosis and delayed diagnosis are common because of the nature of Fabry disease. Case Report: We report a case of Fabry disease with a p.R301X (c.901 C>T) mutation in a 39-year-old man who was being treated for chronic sclerosing glomerulonephritis for 2 years. Family screening tests showed that the proband’s mother, sister, and daughter had the same mutation with different phenotypes. Levels of α-galactosidase A were low in the proband and his mother and sister. Cornea verticillata and heart involvement were present in multiple family members. Agalsidase alfa treatment was started in patients where indicated. Conclusions: Pedigree analysis is still a powerful, readily available tool to identify individuals at risk for genetic diseases and allows earlier detection and management of disease. PMID:27156739

  10. Cardiomyopathy and response to enzyme replacement therapy in a male mouse model for Fabry disease.

    PubMed

    Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G; Jaisser, Frederic

    2012-01-01

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3-4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose.

  11. Fabry disease and Factor V Leiden: a potent vascular risk combination.

    PubMed

    Tchan, M; Sillence, D

    2011-05-01

    A 45-year-old man with heterozygous Factor V Leiden presented with his third cerebrovascular accident despite being on warfarin at a therapeutic international normalized ratio. Subsequent investigation revealed a second genetic diagnosis of Fabry disease. He then had an acute myocardial infarction whilst on aspirin and warfarin. PMID:21605293

  12. Novel tools for extraction and validation of disease-related mutations applied to Fabry disease.

    PubMed

    Kuipers, Remko; van den Bergh, Tom; Joosten, Henk-Jan; Lekanne dit Deprez, Ronald H; Mannens, Marcel Mam; Schaap, Peter J

    2010-09-01

    Genetic disorders are often caused by nonsynonymous nucleotide changes in one or more genes associated with the disease. Specific amino acid changes, however, can lead to large variability of phenotypic expression. For many genetic disorders this results in an increasing amount of publications describing phenotype-associated mutations in disorder-related genes. Keeping up with this stream of publications is essential for molecular diagnostics and translational research purposes but often impossible due to time constraints: there are simply too many articles to read. To help solve this problem, we have created Mutator, an automated method to extract mutations from full-text articles. Extracted mutations are crossreferenced to sequence data and a scoring method is applied to distinguish false-positives. To analyze stored and new mutation data for their (potential) effect we have developed Validator, a Web-based tool specifically designed for DNA diagnostics. Fabry disease, a monogenetic gene disorder of the GLA gene, was used as a test case. A structure-based sequence alignment of the alpha-amylase superfamily was used to validate results. We have compared our data with existing Fabry mutation data sets obtained from the HGMD and Swiss-Prot databases. Compared to these data sets, Mutator extracted 30% additional mutations from the literature.

  13. Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model

    PubMed Central

    Lakomá, Jarmila; Rimondini, Roberto; Ferrer Montiel, Antonio; Donadio, Vincenzo; Liguori, Rocco

    2016-01-01

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(−/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(−/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(−/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(−/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(−/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(−/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life. PMID:27531673

  14. Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model.

    PubMed

    Lakomá, Jarmila; Rimondini, Roberto; Ferrer Montiel, Antonio; Donadio, Vincenzo; Liguori, Rocco; Caprini, Marco

    2016-01-01

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(-/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(-/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(-/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(-/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(-/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(-/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life. PMID:27531673

  15. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    PubMed

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed.

  16. Development of a model system for neuronal dysfunction in Fabry disease.

    PubMed

    Kaneski, Christine R; Brady, Roscoe O; Hanover, John A; Schueler, Ulrike H

    2016-09-01

    Fabry disease is a glycosphingolipid storage disorder that is caused by a genetic deficiency of the enzyme alpha-galactosidase A (AGA, EC 3.2.1.22). It is a multisystem disease that affects the vascular, cardiac, renal, and nervous systems. One of the hallmarks of this disorder is neuropathic pain and sympathetic and parasympathetic nervous dysfunction. The exact mechanism by which changes in AGA activity result in change in neuronal function is not clear, partly due to of a lack of relevant model systems. In this study, we report the development of an in vitro model system to study neuronal dysfunction in Fabry disease by using short-hairpin RNA to create a stable knock-down of AGA in the human cholinergic neuronal cell line, LA-N-2. We show that gene-silenced cells show specifically reduced AGA activity and store globotriaosylceramide. In gene-silenced cells, release of the neurotransmitter acetylcholine is significantly reduced, demonstrating that this model may be used to study specific neuronal functions such as neurotransmitter release in Fabry disease. PMID:27471012

  17. MALDI-TOF and cluster-TOF-SIMS imaging of Fabry disease biomarkers

    NASA Astrophysics Data System (ADS)

    Touboul, David; Roy, Sandrine; Germain, Dominique P.; Chaminade, Pierre; Brunelle, Alain; Laprevote, Olivier

    2007-02-01

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism, in which a partial or total deficiency of [alpha]-galactosidase A, a lysosomal enzyme, results in the progressive accumulation of neutral glycosphingolipids (globotriaosylceramide and digalactosylceramide) in most fluids and tissues of the body. Few information is available about the composition and distribution in tissues of the accumulated glycosphingolipids species. Mass spectrometry imaging is an innovative technique, which can provide pieces of information about the distribution of numerous biological compounds, such as lipids, directly on the tissue sections. MALDI-TOF and cluster-TOF-SIMS imaging approaches were used to study the localization of lipids (cholesterol, cholesterol sulfate, vitamin E, glycosphingolipids ...) on skin and kidney sections of patients affected by the Fabry disease. Numerous information on pathophysiology were enlightened by both techniques.

  18. Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

    PubMed

    Hirashio, S; Taguchi, T; Naito, T; Maki, K; Ogata, S; Taniyama, K; Taniguchi, Y; Yorioka, N

    2009-05-01

    A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

  19. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)

    PubMed Central

    Hoffmann, B; d Garcia; Mehta, A; Beck, M; Widmer, U; Ricci, R; on, b

    2005-01-01

    Background: Fabry disease is an X linked lysosomal storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A. This leads to accumulation of globotriaosylceramide in nearly all tissues, including the blood vessels, kidney, myocardium, and nervous system. Symptoms often begin in childhood and include acroparaesthesia, with burning or tingling pain that spreads from the extremities to more proximal sites. Aims: This study set out to evaluate pain and its influence on quality of life in patients with Fabry disease receiving enzyme replacement therapy (ERT) with agalsidase alfa. Methods: Data were obtained from the Fabry Outcome Survey. Pain was measured using the Brief Pain Inventory (BPI), and health-related quality of life (HRQoL) was documented with the European Quality of Life Questionnaire (EQ-5D). Results: The mean (SD) score for "pain at its worst" on the BPI prior to ERT was 5.1 (2.7). One year after commencement of ERT, this had improved by 0.5, and improved by a further 0.6 after 2 years (p<0.05). Similar statistically significant improvements were seen for "pain on average" and "pain now" after 2 years of ERT. The mean HRQoL utility score prior to ERT was 0.66 (0.32). After 12 months of treatment with agalsidase alfa, this had improved to 0.74 (0.26; p<0.05); this improvement was maintained after 2 years. Conclusions: ERT with agalsidase alfa significantly reduces pain and improves quality of life in patients with Fabry disease. PMID:15744039

  20. Infrared imaging microscopy of bone: Illustrations from a mouse model of Fabry disease

    PubMed Central

    Boskey, Adele L.; Goldberg, Michel; Kulkarni, Ashok; Gomez, Santiago

    2006-01-01

    Bone is a complex tissue whose composition and properties vary with age, sex, diet, tissue type, health and disease. In this review, we demonstrate how infrared spectroscopy and infrared spectroscopic imaging can be applied to the study of these variations. A specific example of mice with Fabry disease (a lipid storage disease) is presented in which it is demonstrated that the bones of these young animals, while showing typical spatial variation in mineral content, mineral crystal size, and collagen maturity, do not differ from the bones of age- and sex-matched wild type animals. PMID:16697974

  1. Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

    NASA Astrophysics Data System (ADS)

    Boutin, Michel; Auray-Blais, Christiane

    2015-03-01

    Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

  2. Nature and frequency of mutations in the [alpha]-galactosidase A gene that cause Fabry disease

    SciTech Connect

    Eng, C.M.; Resnick-Silverman, L.A.; Niehaus, D.J.; Astrin, K.H.; Desnick, R.J. )

    1993-12-01

    To determine the nature and frequency of the molecular lesions causing the classical and milder-variant Fabry phenotypes, and for precise carrier detection in Fabry families, the [alpha]-Gal A transcripts or genomic sequences from unrelated Fabry hemizygotes were analyzed. In patients with the classical phenotype, 18 new mutations were identified: N34S, C56G, W162R, R227Q, R227X, D264V, D266V, S297F, D313Y, G328A, W340X, E398X, IVS2+2, IVS5[delta]-2,3, 773[delta]2, 954[delta]5, 1016[delta]11, and 1123[delta]53. Unrelated asymptomatic or mildly affected patients with symptoms confined to the heart had a missense mutation, N215S, that expressed residual enzymatic activity. Related, moderately affected patients with late-onset cardiac and pulmonary manifestations had a small deletion, 1208[delta]3, that predicted the in-frame deletion of arginine 404 near the terminus of the 429 residue enzyme polypeptide. In addition, five small gene rearrangements involving exonic sequences were identified in unrelated classically affected patients. Two small deletions and one small duplication had short direct repeats at their respective breakpoint junctions and presumably resulted from slipped mispairing. A deletion occurred at a potential polymerase [alpha] arrest site, while the breakpoints of another deletion occurred at an inverted tetranucleotide repeat. Screening of unrelated Fabry patients with allele-specific oligonucleotides for seven mutations revealed that these were private, with the notable exception of N215S, R227Q, and R227X, which were each found in several unrelated families from different ethnic backgrounds. The CpG dinucleotide at codon 227 was the most common site of mutation, having been altered in 5% of the 148 unrelated Fabry alleles. These studies revealed that most [alpha]-Gal A lesions were private, that codon 227 was a mutational hot spot, and that certain mutations predicted a milder disease phenotype. 40 refs., 8 figs., 3 tabs.

  3. Molecular damage in Fabry disease: characterization and prediction of alpha-galactosidase A pathological mutations.

    PubMed

    Riera, Casandra; Lois, Sergio; Domínguez, Carmen; Fernandez-Cadenas, Israel; Montaner, Joan; Rodríguez-Sureda, Victor; de la Cruz, Xavier

    2015-01-01

    Loss-of-function mutations of the enzyme alpha-galactosidase A (GLA) causes Fabry disease (FD), that is a rare and potentially fatal disease. Identification of these pathological mutations by sequencing is important because it allows an early treatment of the disease. However, before taking any treatment decision, if the mutation identified is unknown, we first need to establish if it is pathological or not. General bioinformatic tools (PolyPhen-2, SIFT, Condel, etc.) can be used for this purpose, but their performance is still limited. Here we present a new tool, specifically derived for the assessment of GLA mutations. We first compared mutations of this enzyme known to cause FD with neutral sequence variants, using several structure and sequence properties. Then, we used these properties to develop a family of prediction methods adapted to different quality requirements. Trained and tested on a set of known Fabry mutations, our methods have a performance (Matthews correlation: 0.56-0.72) comparable or better than that of the more complex method, Polyphen-2 (Matthews correlation: 0.61), and better than those of SIFT (Matthews correl.: 0.54) and Condel (Matthews correl.: 0.51). This result is validated in an independent set of 65 pathological mutations, for which our method displayed the best success rate (91.0%, 87.7%, and 73.8%, for our method, PolyPhen-2 and SIFT, respectively). These data confirmed that our specific approach can effectively contribute to the identification of pathological mutations in GLA, and therefore enhance the use of sequence information in the identification of undiagnosed Fabry patients. PMID:25382311

  4. High Variability of Fabry Disease Manifestations in an Extended Italian Family

    PubMed Central

    Cammarata, Giuseppe; Fatuzzo, Pasquale; Rodolico, Margherita Stefania; Colomba, Paolo; Sicurella, Luigi; Iemolo, Francesco; Zizzo, Carmela; Bartolotta, Caterina; Duro, Giovanni

    2015-01-01

    Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL). The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease. PMID:25977923

  5. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    PubMed

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future. PMID:27576727

  6. Discontinuation of enzyme replacement therapy in Fabry disease in the Dutch cohort.

    PubMed

    Arends, Maarten; Linthorst, Gabor E; Hollak, Carla E; Biegstraaten, Marieke

    2016-02-01

    Fabry disease (FD) is a progressive, multi-organ, lysosomal storage disease. Enzyme replacement therapy (ERT) is available for the treatment of the disease. While the reasons to initiate ERT have been frequently discussed, discontinuation of ERT is rarely reported. In this paper we describe our experiences with stopping ERT in FD. From 1999 through 2015, twenty-one patients discontinued ERT. These patients were generally older and more severely affected in comparison those who continued ERT. The reason to discontinue ERT switched from death or terminal illness in the first years towards treatment failure in more recent years. Three cases are described in more detail. We conclude that discontinuation of ERT should or may be considered in subgroups of FD patients although further studies on the effectiveness of ERT in subgroups of patients and the course of the disease after discontinuation of ERT are needed. PMID:26654842

  7. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    PubMed

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  8. Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease

    PubMed Central

    Ashe, Karen M; Budman, Eva; Bangari, Dinesh S; Siegel, Craig S; Nietupski, Jennifer B; Wang, Bing; Desnick, Robert J; Scheule, Ronald K; Leonard, John P; Cheng, Seng H; Marshall, John

    2015-01-01

    Fabry disease, an X-linked glycosphingolipid storage disorder, is caused by the deficient activity of α-galactosidase A (α-Gal A). This results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide (GL-3) and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid, lyso-GL-3), leading to kidney, heart, and cerebrovascular disease. To complement and potentially augment the current standard of care, biweekly infusions of recombinant α-Gal A, the merits of substrate reduction therapy (SRT) by selectively inhibiting glucosylceramide synthase (GCS) were examined. Here, we report the development of a novel, orally available GCS inhibitor (Genz-682452) with pharmacological and safety profiles that have potential for treating Fabry disease. Treating Fabry mice with Genz-682452 resulted in reduced tissue levels of GL-3 and lyso-GL-3 and a delayed loss of the thermal nociceptive response. Greatest improvements were realized when the therapeutic intervention was administered to younger mice before they developed overt pathology. Importantly, as the pharmacologic profiles of α-Gal A and Genz-682452 are different, treating animals with both drugs conferred the greatest efficacy. For example, because Genz-682452, but not α-Gal A, can traverse the blood–brain barrier, levels of accumulated glycosphingolipids were reduced in the brain of Genz-682452–treated but not α-Gal A–treated mice. These results suggest that combining substrate reduction and enzyme replacement may confer both complementary and additive therapeutic benefits in Fabry disease. PMID:25938659

  9. Lysosomal delivery of therapeutic enzymes in cell models of Fabry disease.

    PubMed

    Marchesan, D; Cox, T M; Deegan, P B

    2012-11-01

    The success of enzymatic replacement in Gaucher disease has stimulated development of targeted protein replacement for other lysosomal disorders, including Anderson-Fabry disease, which causes fatal cardiac, cerebrovascular and renal injury: deficiency of lysosomal α-Galactosidase A induces accumulation of glycosphingolipids. Endothelial cell storage was the primary endpoint in a clinical trial that led to market authorization. Two α-Galactosidase A preparations are licensed worldwide, but fatal outcomes persist, with storage remaining in many tissues. We compare mechanisms of uptake of α -Galactosidase A into cells relevant to Fabry disease, in order to investigate if the enzyme is targeted to the lysosomes in a mannose-6-phosphate receptor dependent fashion, as generally believed. α -Galactosidase A uptake was examined in fibroblasts, four different endothelial cell models, and hepatic cells in vitro. Uptake of europium-labeled human α -Galactosidase A was measured by time-resolved fluorescence. Ligand-specific uptake was quantified in inhibitor studies. Targeting to the lysosome was determined by precipitation and by confocal microscopy. The quantity and location of cation-independent mannose-6-phosphate receptors in the different cell models were investigated using confocal microscopy. Uptake and delivery of α -Galactosidase A to lysosomes in fibroblasts is mediated by the canonical mannose-6-phosphate receptor pathway, but in endothelial cells in vitro this mechanism does not operate. Moreover, this observation is supported by a striking paucity of expression of cation independent mannose-6-phosphate receptors on the plasma membrane of the four endothelial cell models and by little delivery of enzyme to lysosomes, when compared with fibroblasts. If these observations are confirmed in vivo, alternative mechanisms will be needed to explain the ready clearance of storage from endothelial cells in patients undergoing enzyme replacement therapy. PMID:22450713

  10. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    PubMed

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety

  11. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    PubMed Central

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  12. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease.

    PubMed

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11-12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11-12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11-12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  13. Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease.

    PubMed

    Lemansky, P; Bishop, D F; Desnick, R J; Hasilik, A; von Figura, K

    1987-02-15

    The synthesis and processing of the human lysosomal enzyme alpha-galactosidase A was examined in normal and Fabry fibroblasts. In normal cells, alpha-galactosidase A was synthesized as an Mr = 50,500 precursor, which contained phosphate groups in oligosaccharide chains cleavable by endoglucosaminidase H. The precursor was processed via ill-defined intermediates to a mature Mr 46,000 form. Processing was complete within 3-7 days after synthesis. In the presence of NH4Cl and in I-cell fibroblasts, the majority of newly synthesized alpha-galactosidase A was secreted as an Mr = 52,000 form. For comparison, the processing and stability of alpha-galactosidase A were examined in fibroblasts from five unrelated patients with Fabry disease, which is caused by deficient alpha-galactosidase A activity. In one cell line, synthesis of immunologically cross-reacting polypeptides was not detectable. In another, the synthesis, processing, and stability of alpha-galactosidase A was indistinguishable from that in normal fibroblasts. In a third Fabry cell line, the mutation retarded the maturation of alpha-galactosidase A. Finally, in two cell lines, alpha-galactosidase A polypeptides were synthesized that were rapidly degraded following delivery to lysosomes. These results clearly indicate that Fabry disease comprises a heterogeneous group of mutations affecting synthesis, processing, and stability of alpha-galactosidase A. PMID:3029062

  14. Novel α-Galactosidase A Mutation (K391E) in a Young Woman With Severe Cardiac and Renal Manifestations of Fabry Disease.

    PubMed

    Wakakuri, Hiroaki; Nakamura, Shunichi; Utsumi, Kouichi; Shimizu, Wataru; Yasutake, Masahiro

    2016-09-28

    Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-β after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function. As early therapy is crucial for preventing life-threatening sequelae, clinicians should consider Fabry disease in young patients presenting with cardiac and renal disease without any likely causes. PMID:27593536

  15. Novel α-Galactosidase A Mutation (K391E) in a Young Woman With Severe Cardiac and Renal Manifestations of Fabry Disease.

    PubMed

    Wakakuri, Hiroaki; Nakamura, Shunichi; Utsumi, Kouichi; Shimizu, Wataru; Yasutake, Masahiro

    2016-09-28

    Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-β after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function. As early therapy is crucial for preventing life-threatening sequelae, clinicians should consider Fabry disease in young patients presenting with cardiac and renal disease without any likely causes.

  16. [Heart involvement in Anderson-Fabry disease: Italian recommendations for diagnostic, follow-up and therapeutic management].

    PubMed

    Pieruzzi, Federico; Pieroni, Maurizio; Zachara, Elisabetta; Marziliano, Nicola; Morrone, Amelia; Cecchi, Franco

    2015-11-01

    Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations of the GLA gene that encodes alpha-galactosidase A. It is characterized by a multisystemic involvement: the renal, neurological, heart, cochleovestibular and cutaneous systems are the most damaged. Morbidity and mortality of Anderson-Fabry disease depend on renal insufficiency, heart failure and nervous system involvement. Left ventricular hypertrophy is the most common cardiac manifestation followed by conduction system disease, valve dysfunction, and arrhythmias. Mild to moderate left ventricular hypertrophy may simulate a non-obstructive hypertrophic cardiomyopathy. Management of Anderson-Fabry disease starting from the diagnosis of cardiac involvement, the prevention of complications, the therapeutic aspects, up to appropriate clinical follow-up, requires a multidisciplinary approach. According to recent management guidelines, only few evidence-based data are available to guide the clinical and therapeutic approach to this rare disease. An Italian Board, composed by nephrologists, cardiologists, geneticists, pediatricians and neurologists has been established in order to approve by consensus a diagnostic and therapeutic management protocol. The authors report the results of this cardiologic management consensus. PMID:26571477

  17. [Globosides as key players in the pathophysiology of Shiga toxin-associated acute kidney failure and Fabry disease].

    PubMed

    Porubsky, S

    2014-11-01

    Globosides and their isomeric counterparts isoglobosides belong to the class of neutral glycosphingolipids with an as yet undefined physiological function. In the pathogenesis of human diseases, globosides play an important role as cellular receptors for Shiga toxins which are produced by certain strains of S. dysenteriae and E. coli. In order to elucidate the pathogenesis of Shiga toxin-associated kidney failure, we studied human kidney biopsies and animal models. Our work showed that in patients suffering from Shiga toxin-elicited kidney failure, no complement activation could be demonstrated by immunohistochemical analysis of kidney biopsies. Therefore, complement activation is unlikely to play a major role in mediating thrombotic microangiopathy on exposure to Shiga toxin. Moreover, analysis of the human biopsies and of a murine model of Shiga toxin-associated disease pinpointed acute tubular damage as an important and previously neglected contributor to acute kidney failure in patients infected with Shiga toxin-producing E. coli. Furthermore, globosides play a decisive role in the pathogenesis of Fabry disease which results from a decreased or absent activity of the lysosomal enzyme α-galactosidase A. The results on transgenic mice showed that in vital organs, such as the heart, kidneys and liver, it was possible to revert the phenotype of Fabry disease by eliminating the synthesis of globosides. This implicates that substrate reduction therapy through inhibition of globosides might represent a new therapeutic option for Fabry disease, all the more so as globosides seem to be dispensable.

  18. Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development

    PubMed Central

    Biko, Lydia; Hose, Dorothea; Hofmann, Lukas; Sommer, Claudia

    2016-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease. Conclusions Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain. PMID:27145802

  19. Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients

    PubMed Central

    Müller, Karen B.; Galdieri, Luciano C.; Pereira, Vanessa G.; Martins, Ana M.; D’Almeida, Vânia

    2012-01-01

    Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle. PMID:22888289

  20. Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: lessons from Gaucher, GM1-gangliosidosis and Fabry diseases.

    PubMed

    Sánchez-Fernández, Elena M; García Fernández, José M; Mellet, Carmen Ortiz

    2016-04-25

    Lysosomal storage disorders (LSDs) are often caused by mutations that destabilize native folding and impair the trafficking of enzymes, leading to premature endoplasmic reticulum (ER)-associated degradation, deficiencies of specific hydrolytic functions and aberrant storage of metabolites in the lysosomes. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) are available for a few of these conditions, but most remain orphan. A main difficulty is that virtually all LSDs involve neurological decline and neither proteins nor the current SRT drugs can cross the blood-brain barrier. Twenty years ago a new therapeutic paradigm better suited for neuropathic LSDs was launched, namely pharmacological chaperone (PC) therapy. PCs are small molecules capable of binding to the mutant protein at the ER, inducing proper folding, restoring trafficking and increasing enzyme activity and substrate processing in the lysosome. In many LSDs the mutated protein is a glycosidase and the accumulated substrate is an oligo- or polysaccharide or a glycoconjugate, e.g. a glycosphingolipid. Although it might appear counterintuitive, substrate analogues (glycomimetics) behaving as competitive glycosidase inhibitors are good candidates to perform PC tasks. The advancements in the knowledge of the molecular basis of LSDs, including enzyme structures, binding modes, trafficking pathways and substrate processing mechanisms, have been put forward to optimize PC selectivity and efficacy. Moreover, the chemical versatility of glycomimetics and the variety of structures at hand allow simultaneous optimization of chaperone and pharmacokinetic properties. In this Feature Article we review the advancements made in this field in the last few years and the future outlook through the lessons taught by three archetypical LSDs: Gaucher disease, GM1-gangliosidosis and Fabry disease. PMID:27043200

  1. Late onset variants in Fabry disease: Results in high risk population screenings in Argentina

    PubMed Central

    Serebrinsky, G.; Calvo, M.; Fernandez, S.; Saito, S.; Ohno, K.; Wallace, E.; Warnock, D.; Sakuraba, H.; Politei, J.

    2015-01-01

    Background Screening for Fabry disease (FD) in high risk populations yields a significant number of individuals with novel, ultra rare genetic variants in the GLA gene, largely without classic manifestations of FD. These variants often have significant residual α-galactosidase A activity. The establishment of the pathogenic character of previously unknown or rare variants is challenging but necessary to guide therapeutic decisions. Objectives To present 2 cases of non-classical presentations of FD with renal involvement as well as to discuss the importance of high risk population screenings for FD. Results Our patients with non-classical variants were diagnosed through FD screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage. Conclusions Screening programs for FD in high risk populations are important as FD is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations. PMID:26937405

  2. Postmortem diagnosis of Fabry disease with acromegaly and a unique vasculopathy.

    PubMed

    Takao, Masaki; Mori, Taisuke; Orikasa, Hideki; Oh, Haengphil; Suzuki, Kinuko; Koto, Atsuo; Yamazaki, Kazuto

    2007-09-01

    A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.

  3. Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease.

    PubMed

    Chiba, Yasunori; Sakuraba, Hitoshi; Kotani, Masaharu; Kase, Ryoichi; Kobayashi, Kazuo; Takeuchi, Makoto; Ogasawara, Satoshi; Maruyama, Yutaka; Nakajima, Tasuku; Takaoka, Yuki; Jigami, Yoshifumi

    2002-12-01

    A mammalian-like sugar moiety was created in glycoprotein by Saccharomyces cerevisiae in combination with bacterial alpha-mannosidase to produce a more economic enzyme replacement therapy for patients with Fabry disease. We introduced the human alpha-galactosidase A (alpha-GalA) gene into an S. cerevisiae mutant that was deficient in the outer chains of N-linked mannan. The recombinant alpha-GalA contained both neutral (Man(8)GlcNAc(2)) and acidic ([Man-P](1-2)Man(8)GlcNAc(2)) sugar chains. Because an efficient incorporation of alpha-GalA into lysosomes of human cells requires mannose-6-phosphate (Man-6-P) residues that should be recognized by the specific receptor, we trimmed down the sugar chains of the alpha-GalA by a newly isolated bacterial alpha-mannosidase. Treatment of the alpha-GalA with the alpha-mannosidase resulted in the exposure of a Man-6-P residue on a nonreduced end of oligosaccharide chains after the removal of phosphodiester-linked nonreduced-end mannose. The treated alpha-GalA was efficiently incorporated into fibroblasts derived from patients with Fabry disease. The uptake was three to four times higher than that of the nontreated alpha-GalA and was inhibited by the addition of 5 mM Man-6-P. Incorporated alpha-GalA was targeted to the lysosome, and hydrolyzed ceramide trihexoside accumulated in the Fabry fibroblasts after 5 days. This method provides an effective and economic therapy for many lysosomal disorders, including Fabry disease.

  4. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    PubMed

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients. PMID:27225851

  5. Interconversion of the Specificities of Human Lysosomal Enzymes Associated with Fabry and Schindler Diseases

    SciTech Connect

    Tomasic, Ivan B.; Metcalf, Matthew C.; Guce, Abigail I.; Clark, Nathaniel E.; Garman, Scott C.

    2010-09-03

    The human lysosomal enzymes {alpha}-galactosidase ({alpha}-GAL, EC 3.2.1.22) and {alpha}-N-acetylgalactosaminidase ({alpha}-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of {alpha}-GAL and {alpha}-NAGAL. The engineered {alpha}-GAL (which we call {alpha}-GALSA) retains the antigenicity of {alpha}-GAL but has acquired the enzymatic specificity of {alpha}-NAGAL. Conversely, the engineered {alpha}-NAGAL (which we call {alpha}-NAGAL{sup EL}) retains the antigenicity of {alpha}-NAGAL but has acquired the enzymatic specificity of the {alpha}-GAL enzyme. Comparison of the crystal structures of the designed enzyme {alpha}-GAL{sup SA} to the wild-type enzymes shows that active sites of {alpha}-GAL{sup SA} and {alpha}-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.

  6. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    PubMed

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

  7. Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry.

    PubMed

    Lavoie, Pamela; Boutin, Michel; Abaoui, Mona; Auray-Blais, Christiane

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by the absence or reduction of the enzyme α-galactosidase A activity. Currently, globotriaosylsphingosine (lyso-Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso-Gb3 and seven structurally related analogs. A solid-phase extraction process is performed, then lyso-Gb3 and its analogs are analyzed simultaneously with an internal standard by ultra-performance liquid chromatography (UPLC) coupled to a tandem mass spectrometry (MS/MS) system. This methodology can be useful for the diagnosis of Fabry patients, including patients with cardiac variant mutations, but also to monitor the efficacy of therapeutic interventions, considering that lyso-Gb3 analogs are more elevated than lyso-Gb3 itself in urine. © 2016 by John Wiley & Sons, Inc.

  8. Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry.

    PubMed

    Lavoie, Pamela; Boutin, Michel; Abaoui, Mona; Auray-Blais, Christiane

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by the absence or reduction of the enzyme α-galactosidase A activity. Currently, globotriaosylsphingosine (lyso-Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations. This unit describes a multiplex methodology targeting the analysis of urinary lyso-Gb3 and seven structurally related analogs. A solid-phase extraction process is performed, then lyso-Gb3 and its analogs are analyzed simultaneously with an internal standard by ultra-performance liquid chromatography (UPLC) coupled to a tandem mass spectrometry (MS/MS) system. This methodology can be useful for the diagnosis of Fabry patients, including patients with cardiac variant mutations, but also to monitor the efficacy of therapeutic interventions, considering that lyso-Gb3 analogs are more elevated than lyso-Gb3 itself in urine. © 2016 by John Wiley & Sons, Inc. PMID:27367162

  9. Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey.

    PubMed

    Huzmeli, Can; Candan, Ferhan; Alaygut, Demet; Bagci, Gokhan; Akkaya, Lale; Bagci, Binnur; Sozmen, Eser Yıldırım; Kurtulgan, Hande Kucuk; Kayatas, Mansur

    2016-08-01

    Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF. PMID:27105876

  10. Serum-Mediated Inhibition of Enzyme Replacement Therapy in Fabry Disease.

    PubMed

    Lenders, Malte; Stypmann, Jörg; Duning, Thomas; Schmitz, Boris; Brand, Stefan-Martin; Brand, Eva

    2016-01-01

    Fabry disease (FD) is a progressive multisystemic disorder, treatable with recombinant enzyme replacement therapy (agalsidase). However, recent studies suggest an endogenous inhibition of agalsidase in patients with FD, as reported for other lysosomal storage diseases. To assess the clinical consequences of serum-mediated agalsidase inhibition in affected patients, we determined the agalsidase inhibition status of 168 patients (68 male) with FD and compared outcomes of inhibition-positive patients with those of inhibition-negative patients. The assessment included clinical events during time on agalsidase, determination of renal and cardiac function, and evaluation of FD-related symptoms. The frequency of serum-mediated agalsidase inhibition was 40% in agalsidase-treated males. Inhibition did not depend on the compound initially used (agalsidase-α or -β). Agalsidase inhibition was associated with higher lyso-globotriaosylceramide levels and worse disease severity scores in patients. Compared with agalsidase inhibition-negative men, agalsidase inhibition-positive men showed greater left ventricular mass (P=0.02) and substantially lower renal function (difference in eGFR of about -30 ml/min per 1.73 m(2); P=0.04), which was confirmed by a longitudinal 5-year retrospective analysis. Additionally, affected patients presented more often with FD-typical symptoms, such as diarrhea, fatigue, and neuropathic pain, among others. Therefore, patients with poor clinical outcome on agalsidase should be tested for agalsidase inhibition. Future studies are warranted to determine if affected patients with FD benefit from acute reduction of anti-agalsidase antibodies or long-term immune modulation therapies to suppress agalsidase inhibition and to identify mechanisms that minimize antibody generation against agalsidase.

  11. Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey.

    PubMed

    Huzmeli, Can; Candan, Ferhan; Alaygut, Demet; Bagci, Gokhan; Akkaya, Lale; Bagci, Binnur; Sozmen, Eser Yıldırım; Kurtulgan, Hande Kucuk; Kayatas, Mansur

    2016-08-01

    Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

  12. Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke

    PubMed Central

    Kilarski, Laura L.; Rutten-Jacobs, Loes C. A.; Bevan, Steve; Baker, Rob; Hassan, Ahamad; Hughes, Derralynn A.; Markus, Hugh S.

    2015-01-01

    Background and Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. Methods Caucasian patients with lacunar infarction, aged ≤70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI’s and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. Results Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade ≥2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. Conclusion CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected. PMID:26305465

  13. Advancement of Optical Component Control for an Imaging Fabry-Perot Interferometer

    NASA Technical Reports Server (NTRS)

    Larar, Allen M.; Cook, William B.; Flood, Michael A.; Campbell, Joel F.; Boyer, Charles M.

    2009-01-01

    Risk mitigation activities associated with a prototype imaging Fabry-Perot Interferometer (FPI) system are continuing at the NASA Langley Research Center. The system concept and technology center about enabling and improving future space-based atmospheric composition missions, with a current focus on observing tropospheric ozone around 9.6 micron, while having applicability toward measurement in different spectral regions and other applications. Recent activities have focused on improving an optical element control subsystem to enable precise and accurate positioning and control of etalon plates; this is needed to provide high system spectral fidelity critical for enabling the required ability to spectrally-resolve atmospheric line structure. The latest results pertaining to methodology enhancements, system implementation, and laboratory characterization testing will be reported

  14. Advanced Interrogation of Fiber-Optic Bragg Grating and Fabry-Perot Sensors with KLT Analysis.

    PubMed

    Tosi, Daniele

    2015-10-29

    The Karhunen-Loeve Transform (KLT) is applied to accurate detection of optical fiber sensors in the spectral domain. By processing an optical spectrum, although coarsely sampled, through the KLT, and subsequently processing the obtained eigenvalues, it is possible to decode a plurality of optical sensor results. The KLT returns higher accuracy than other demodulation techniques, despite coarse sampling, and exhibits higher resilience to noise. Three case studies of KLT-based processing are presented, representing most of the current challenges in optical fiber sensing: (1) demodulation of individual sensors, such as Fiber Bragg Gratings (FBGs) and Fabry-Perot Interferometers (FPIs); (2) demodulation of dual (FBG/FPI) sensors; (3) application of reverse KLT to isolate different sensors operating on the same spectrum. A simulative outline is provided to demonstrate the KLT operation and estimate performance; a brief experimental section is also provided to validate accurate FBG and FPI decoding.

  15. Advanced Interrogation of Fiber-Optic Bragg Grating and Fabry-Perot Sensors with KLT Analysis

    PubMed Central

    Tosi, Daniele

    2015-01-01

    The Karhunen-Loeve Transform (KLT) is applied to accurate detection of optical fiber sensors in the spectral domain. By processing an optical spectrum, although coarsely sampled, through the KLT, and subsequently processing the obtained eigenvalues, it is possible to decode a plurality of optical sensor results. The KLT returns higher accuracy than other demodulation techniques, despite coarse sampling, and exhibits higher resilience to noise. Three case studies of KLT-based processing are presented, representing most of the current challenges in optical fiber sensing: (1) demodulation of individual sensors, such as Fiber Bragg Gratings (FBGs) and Fabry-Perot Interferometers (FPIs); (2) demodulation of dual (FBG/FPI) sensors; (3) application of reverse KLT to isolate different sensors operating on the same spectrum. A simulative outline is provided to demonstrate the KLT operation and estimate performance; a brief experimental section is also provided to validate accurate FBG and FPI decoding. PMID:26528975

  16. Advanced Interrogation of Fiber-Optic Bragg Grating and Fabry-Perot Sensors with KLT Analysis.

    PubMed

    Tosi, Daniele

    2015-01-01

    The Karhunen-Loeve Transform (KLT) is applied to accurate detection of optical fiber sensors in the spectral domain. By processing an optical spectrum, although coarsely sampled, through the KLT, and subsequently processing the obtained eigenvalues, it is possible to decode a plurality of optical sensor results. The KLT returns higher accuracy than other demodulation techniques, despite coarse sampling, and exhibits higher resilience to noise. Three case studies of KLT-based processing are presented, representing most of the current challenges in optical fiber sensing: (1) demodulation of individual sensors, such as Fiber Bragg Gratings (FBGs) and Fabry-Perot Interferometers (FPIs); (2) demodulation of dual (FBG/FPI) sensors; (3) application of reverse KLT to isolate different sensors operating on the same spectrum. A simulative outline is provided to demonstrate the KLT operation and estimate performance; a brief experimental section is also provided to validate accurate FBG and FPI decoding. PMID:26528975

  17. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.

    PubMed

    Pan, Xiaoxia; Ouyang, Yan; Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  18. Unravelling the mechanism of action of enzyme replacement therapy in Fabry disease.

    PubMed

    Ko, Younhee; Lee, CheolHo; Moon, Myeong Hee; Hong, Geu-Ru; Cheon, Chong-Kun; Lee, Jin-Sung

    2016-02-01

    Fabry disease (FD) is a rare X-linked recessive glycosphingolipid-storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Intravenous enzyme replacement therapy (ERT) has been used to supplement deficient enzyme activity in patients with FD. Despite its clinical effect and manifestations, clear criteria for the clinical effectiveness and cost-effectiveness of ERT have not been well established. In this study, we investigated the pharmacodynamic actions and short-term effects of ERT in patients with FD through direct molecular profiling from blood samples of patients before and after ERT. Based on this comparison, we observed that immune/inflammation-related pathways and growth factor-related pathways such as innate/adaptive immune pathway, lymphocyte proliferation and leukocyte proliferation were actively regulated under ERT. We also found that TINAGL1, DAAM2, CDK5R1 and MYO5B known to be related with clinical symptoms of FD showed increased levels after ERT, leading to the amelioration of clinical manifestations. Especially the catabolic process-related genes, including USP15 and ERUN1, showed direct increasing after ERT in vivo in male patients. These results suggest that male patients with FD respond more actively to ERT than do female patients with FD. Pathway analysis revealed that oxidative phosphorylation pathway-related genes are downregulated under ERT. ERT has a role to protect the proteins from oxidative damage and such deactivation of oxidative phosphorylation is one of direct pharmacodynamic actions of ERT. These results extended our understanding of the pathophysiology of ERT. To our knowledge, this is the first study to observe the molecular basis for the mechanism of ERT in vivo through the comprehensive comparison of transcriptome study with next-generation sequencing data. PMID:26490183

  19. Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

    PubMed Central

    Wang, Zhaohui; Ren, Hong; Shen, Pingyan; Wang, Weiming; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Chen, Xiaonong; Zhang, Wen; Yang, Li; Li, Xiao; Xu, Jing; Chen, Nan

    2016-01-01

    Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. PMID:27560961

  20. Enzymatic diagnosis of Fabry disease using a fluorometric assay on dried blood spots: An alternative methodology.

    PubMed

    Caudron, Eric; Prognon, Patrice; Germain, Dominique P

    2015-12-01

    Fabry disease (FD, OMIM#301500) is an X-linked lysosomal storage disorder caused by the functional deficiency of α-galactosidase A, a lysosomal enzyme. A method to screen for FD in large populations has been developed using a fluorometric assay of α-galactosidase A activity in dried blood spots (DBS) on filter paper. However, results can be influenced by quenching of fluorescence by haemoglobin which, together with small sample size, may result in a low light emission signal. An alternative, simple and sensitive fluorometric assay was developed for the determination of α-galactosidase A activity in DBS. The assay uses 4-methylumbelliferyl-α-d-galactose as an artificial substrate. To minimize the risk of false-positives, zinc sulfate was used for protein precipitation to stop the enzymatic reaction and eliminate interfering species (hemoglobin). Samples from 209 individuals (60 hemizygotes, 68 heterozygotes, and 81 controls) were tested to establish reference values for the assay. The mean α-galactosidase A activity of the 81 controls was 9.1 ± 3.3 μmol h(-1) L(-1) (mean ± SD). All 60 hemizygotes affected with FD had AGAL activities below 1.7 μmol h(-1) L(-1) (0.2 ± 0.3 μmol h(-1) L(-1)). For the 68 heterozygous females, AGAL activity ranged from 0 to 12.6 μmol h(-1) L(-1) (3.5 ± 2.7 μmol h(-1) L(-1)). Two-thirds of the female patients could be identified using the enzymatic assay and a cut-off level of 40% of the median control value (<3.4 μmol h(-1) L(-1)). Our fluorometric assay using zinc sulfate protein precipitation was shown to have similar sensitivity and robustness while reducing the risk of false positive results due to quenching of 4-MU fluorescence by haemoglobin. PMID:26520229

  1. Cardiac Troponin I: A Valuable Biomarker Indicating the Cardiac Involvement in Fabry Disease

    PubMed Central

    Giese, Anne Kathrin; Eichler, Sabrina; Sieweke, Nicole; Speth, Maria; Bauer, Timm; Hamm, Christian

    2016-01-01

    Objectives Assessment of the clinical severity of Fabry disease (FD), an X-linked, rare, progressive disorder based on a genetic defect in alpha-galactosidase is challenging, especially regarding cardiac involvement. The aim of the study was to evaluate the diagnostic value of cardiac troponin I (cTnI) in discriminating FD patients with cardiac involvement in a large FD patient cohort. Methods cTnI levels were measured with a contemporary sensitive assay in plasma samples taken routinely from FD patients. The assay was calibrated to measure cTnI levels ≥0.01 ng/ml. Elevated cTnI values (cut-off ≥0.04 ng/ml) were correlated with clinical data. Results cTnI was assessed in 62 FD patients (median age: 47 years, males: 36%). Elevated cTnI levels were detected in 23 (37%) patients. Patients with a cTnI elevation were older (median 55 years versus 36 years, p<0.001). Elevated cTnI levels were associated with the presence of a LVH (16/23 versus 1/39; OR 65.81, CI: 6.747–641.859; p<0.001). In almost all patients with a left ventricular hypertrophy (LVH) elevated cTnI levels were detected (16/17, 94%). Absolute cTnI levels in patients with LVH were higher than in those without (median 0.23 ng/ml versus 0.02 ng/ml; p<0.001). A cTnI level <0.04ng/ml had a high negative predictive value regarding the presence of a LVH (38/39, 97%). In a control group of non-FD patients (n = 17) with LVH (due to hypertension) none showed cTnI levels ≥0.01 ng/ml. Conclusions Elevated cTnI levels are common in FD patients, reflecting cardiac involvement. FD patients might benefit from a continuous cTnI monitoring. PMID:27322070

  2. Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease.

    PubMed

    Ziegler, Robin J; Li, Chester; Cherry, Maribeth; Zhu, Yunxiang; Hempel, Donna; van Rooijen, Nico; Ioannou, Yiannis A; Desnick, Robert J; Goldberg, Mark A; Yew, Nelson S; Cheng, Seng H

    2002-05-20

    Systemic administration of recombinant adenoviral vectors for gene therapy of chronic diseases such as Fabry disease can be limited by dose-dependent toxicity. Because administration of a high dose of Ad2/CMVHI-alpha gal encoding human alpha-galactosidase A results in expression of supraphysiological levels of the enzyme, we sought to determine whether lower doses would suffice to correct the enzyme deficiency and lysosomal storage abnormality observed in Fabry mice. Reducing the dose of Ad2/CMVHI-alpha gal by 10-fold (from 10(11) to 10(10) particles/mouse) resulted in a greater than 200-fold loss in transgene expression. In Fabry mice, the reduced expression of alpha-galactosidase A, using the lower dose of Ad2/CMVHI-alpha gal, was associated with less than optimal clearance of the accumulated glycosphingolipid (GL-3) from the affected lysosomes. It was determined that this lack of linearity in dose response was not due to an inability to deliver the recombinant viral vectors to the liver but rather to sequestration, at least in part, of the viral vectors by the Kupffer cells. This lack of correlation between dose and expression levels could be obviated by supplementing the low dose of Ad2/CMVHI-alpha gal with an unrelated adenoviral vector or by depleting the Kupffer cells before administration of Ad2/CMVHI-alpha gal. Prior removal of the Kupffer cells, using clodronate liposomes, facilitated the use of a 100-fold lower dose of Ad2/CMVHI-alpha gal (10(9) particles/mouse) to effect the nearly complete clearance of GL-3 from the affected organs of Fabry mice. These results suggest that practical strategies that minimize the interaction between the recombinant adenoviral vectors and the reticuloendothelial system (RES) may improve the therapeutic window of this vector system. In this regard, we showed that pretreatment of mice with gamma globulins also resulted in significantly enhanced adenovirus-mediated transduction and expression of alpha-galactosidase A in the

  3. Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.

    PubMed

    Boutin, Michel; Lavoie, Pamela; Abaoui, Mona; Auray-Blais, Christiane

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb3 and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley & Sons, Inc.

  4. Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.

    PubMed

    Boutin, Michel; Lavoie, Pamela; Abaoui, Mona; Auray-Blais, Christiane

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the multiplex analysis of lyso-Gb3 and its 6 analogs in plasma. The samples are prepared by solid phase extraction using mixed-mode strong cation exchange (MCX) cartridges. An in-house synthesized N-glycinated lyso-Gb3 derivative was used for the internal standard. The limits of detection (LODs) measured for lyso-Gb3 and its analogs ranged from 0.06 to 0.29 nM. © 2016 by John Wiley & Sons, Inc. PMID:27367163

  5. Advanced Coats' disease.

    PubMed Central

    Haik, B G

    1991-01-01

    Advanced Coats' disease and retinoblastoma can both present with the triad of a retinal detachment, the appearance of a subretinal mass, and dilated retinal vessels. Thus, even the most experienced observer may not be able to differentiate these entities on ophthalmoscopic findings alone. Coats' disease is the most common reason for which eyes are enucleated with the misdiagnosis of retinoblastoma. Ultrasonography is the auxiliary diagnostic test most easily incorporated into the clinical examination, and can be utilized repeatedly without biologic tissue hazard. Ultrasonically identifiable features allowing differentiation between Coats' disease and retinoblastoma include the topography and character of retinal detachment and presence or absence of subretinal calcifications. Ultrasonography is of lesser use in poorly calcified retinoblastoma and in detecting optic nerve or extraocular extension in heavily calcified retinoblastoma. CT is perhaps the single most valuable test because of its ability to: (a) delineate intraocular morphology, (b) quantify subretinal densities, (c) identify vascularities within the subretinal space through the use of contrast enhancement, and (d) detected associated orbital or intracranial abnormalities. Optimal computed tomographic studies, however, require multiple thin slices both before and after contrast introduction and expose the child to low levels of radiation if studies are repeated periodically. MR imaging is valuable for its multiplanar imaging capabilities, its superior contrast resolution, and its ability to provide insights into the biochemical structure and composition of tissues. It is limited in its ability to detect calcium, which is the mainstay of ultrasonic and CT differentiation. Aqueous LDH and isoenzyme levels were not valuable in distinguishing between Coats' disease and retinoblastoma. The value of aqueous NSE levels in the differentiation of advanced Coats' disease and exophytic retinoblastoma deserves

  6. [The nephropathy in the Anderson-Fabry disease: new recommendations for the diagnosis, the follow-up and the therapy].

    PubMed

    Mignani, Renzo; Gallieni, Maurizio; Feriozzi, Sandro; Pisani, Antonio; Marziliano, Nicola; Morrone, Amelia

    2015-01-01

    Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations of the GLA gene that encodes alpha-galactosidase A. It is a characterized by the involvement of several systems: renal, neurological, hearth, cochleovestibular and cutaneous systems are the most involved. Despite recent studies have provided new insights in the this disease, there are still lacks and discrepancies among all insiders regarding the diagnosis, clinical and therapeutic management. Enzyme replacement have been demonstrated to improve the course of the disease, especially when the diagnosis is early. There are still some debates on diagnosis and management of patients, in particular in the heterozygote female and the start of enzyme replacement. Thus, an Italian board, composed by nephrologists, cardiologists, genetics, pediatricians and neurologists has been established in order to approve through a consensus a diagnostic and therapeutic Italian management. Authors report the renal clinical and therapeutic management, a useful tool either for expert physicians or for those with a few experience in the diagnosis and management of this disease.

  7. Advances in tropical diseases.

    PubMed

    Ramos-E-Silva, M; Silveira Lima, T

    2011-10-01

    There are six diseases that WHO considers as the major threat in developing countries, leprosy, filariasis, malaria, schistosomiasis, Chagas disease and leishmaniasis; and of these only malaria does not present skin lesions. These diseases are among the so called tropical diseases found in countries of tropical climate, usually infections and infestations considered exotic and rare in European and North American countries. It is extremely important for doctors of all countries to be able to provide correct pre travel counseling and to make early diagnosis and treatment, thus avoiding dissemination of these dieases to non endemic areas. The authors review some important tropical diseases seen in Brazil, as paracoccidiodomycosis, lobomycosis, myiasis, tungiasis, and cutaneous schistosomiasis and discuss new information about them. PMID:21956272

  8. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease

    PubMed Central

    den-Haan, Helena; Pérez-Sánchez, Horacio; Del Prete, Rosita; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Andreotti, Giuseppina

    2016-01-01

    Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. PMID:27788225

  9. Sudoscan as a noninvasive tool to assess sudomotor dysfunction in patients with Fabry disease: results from a case-control study.

    PubMed

    Sahuc, Pauline; Chiche, Laurent; Dussol, Bertrand; Pouget, Jean; Franques, Jérôme

    2016-01-01

    Hypohidrosis is a frequent and early symptom in patients with Fabry disease. Studies have reported improved sweating in patients treated with enzyme-replacement therapy. A new method, Sudoscan, has been developed that is noninvasive, is quantitative, and can quickly evaluate sweat gland function. It is based on the electrochemical reaction between sweat chlorides and stainless-steel electrodes in contact with the palms and soles. The aim of our study was to evaluate the Sudoscan as a tool to assess sudomotor dysfunction in patients with Fabry disease. Consecutive patients were prospectively recruited who had a diagnosis of Fabry disease, which had been confirmed genetically and/or by measurement of α-galactosidase activity in leukocytes. Healthy controls, matched (1:1) for age and sex, were also enrolled. Test results were expressed immediately as electrochemical skin conductance (ESC, µS) for hands and feet. Sudomotor dysfunction was considered absent, moderate, or severe if the ESC measured on the feet was >60 µS, between 60 and 40 µS, or <40 µS, respectively. Among the 18 patients, 11 had hypohidrosis or anhidrosis. Hand and feet ESCs were significantly lower in patients compared to their controls (P=0.0015 and P=0.0047, respectively). Among patients, 8/18 (44.5%) had a sudomotor dysfunction, moderate in three and severe in five cases. Hand and feet ESCs were significantly lower in those with hypohidrosis/anhidrosis compared to those without (P=0.0014 and P=0.0056, respectively). This study showed that Sudoscan provided a quick, noninvasive, and quantitative measurement of sudomotor function in Fabry disease patients. PMID:26893567

  10. Distributions of Globotriaosylceramide Isoforms, and Globotriaosylsphingosine and Its Analogues in an α-Galactosidase A Knockout Mouse, a Model of Fabry Disease.

    PubMed

    Sueoka, Hideaki; Aoki, Mikio; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

    2015-01-01

    Fabry disease is caused by deficient activity of α-galactosidase A (GLA) and characterized by systemic accumulation of glycosphingolipids, substrates of the enzyme. To gain insight into the pathogenesis of Fabry disease based on accumulated substrates, we examined the tissue and plasma distributions of globotriaosylceramide (Gb3) isoforms, and globotriaosylsphingosine (lyso-Gb3) and its analogues in a GLA knockout mouse, a model of Fabry disease, by means of liquid chromatography-mass spectrometry and nano-liquid chromatography-tandem mass spectrometry, respectively. The results revealed that the contents of these substrates in the liver, kidneys, heart, and plasma of GLA knockout mice were apparently higher than in those of wild-type ones, and organ specificity in the accumulation of Gb3 isoforms was found. Especially in the kidneys, accumulation of a large amount of Gb3 isoforms including hydroxylated residues was found. In the GLA knockout mice, the proportion of hydrophobic Gb3 isoforms was apparently higher than that in the wild-type mice. On the other hand, hydrophilic residues were abundant in plasma. Unlike that of Gb3, the concentration of lyso-Gb3 was high in the liver, and the lyso-Gb3/Gb3 ratio in plasma was significantly higher than those in the organs. The concentration of lyso-Gb3 was apparently higher than those of its analogues in the organs and plasma from both the GLA knockout and wild-type mice. This information will be useful for elucidating the basis of Fabry disease. PMID:26661087

  11. Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y

    PubMed Central

    Oder, Daniel; Üçeyler, Nurcan; Liu, Dan; Hu, Kai; Petritsch, Bernhard; Sommer, Claudia; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter

    2016-01-01

    Objectives The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function. Setting and participants In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included. Primary and secondary outcome measures Cardiac, nephrological, neurological, laboratory and quality of life data. Results AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain −21.6±1.9%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter. Conclusions The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD. PMID:27059467

  12. Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

    PubMed

    Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

    2016-01-01

    We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta.

  13. Mutant alpha-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin.

    PubMed

    Ishii, Satoshi; Chang, Hui-Hwa; Kawasaki, Kunito; Yasuda, Kayo; Wu, Hui-Li; Garman, Scott C; Fan, Jian-Qiang

    2007-09-01

    Fabry disease is a lysosomal storage disorder caused by the deficiency of alpha-Gal A (alpha-galactosidase A) activity. In order to understand the molecular mechanism underlying alpha-Gal A deficiency in Fabry disease patients with residual enzyme activity, enzymes with different missense mutations were purified from transfected COS-7 cells and the biochemical properties were characterized. The mutant enzymes detected in variant patients (A20P, E66Q, M72V, I91T, R112H, F113L, N215S, Q279E, M296I, M296V and R301Q), and those found mostly in mild classic patients (A97V, A156V, L166V and R356W) appeared to have normal K(m) and V(max) values. The degradation of all mutants (except E59K) was partially inhibited by treatment with kifunensine, a selective inhibitor of ER (endoplasmic reticulum) alpha-mannosidase I. Metabolic labelling and subcellular fractionation studies in COS-7 cells expressing the L166V and R301Q alpha-Gal A mutants indicated that the mutant protein was retained in the ER and degraded without processing. Addition of DGJ (1-deoxygalactonojirimycin) to the culture medium of COS-7 cells transfected with a large set of missense mutant alpha-Gal A cDNAs effectively increased both enzyme activity and protein yield. DGJ was capable of normalizing intracellular processing of mutant alpha-Gal A found in both classic (L166V) and variant (R301Q) Fabry disease patients. In addition, the residual enzyme activity in fibroblasts or lymphoblasts from both classic and variant hemizygous Fabry disease patients carrying a variety of missense mutations could be substantially increased by cultivation of the cells with DGJ. These results indicate that a large proportion of mutant enzymes in patients with residual enzyme activity are kinetically active. Excessive degradation in the ER could be responsible for the deficiency of enzyme activity in vivo, and the DGJ approach may be broadly applicable to Fabry disease patients with missense mutations.

  14. Mutant α-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin

    PubMed Central

    Ishii, Satoshi; Chang, Hui-Hwa; Kawasaki, Kunito; Yasuda, Kayo; Wu, Hui-Li; Garman, Scott C.; Fan, Jian-Qiang

    2007-01-01

    Fabry disease is a lysosomal storage disorder caused by the deficiency of α-Gal A (α-galactosidase A) activity. In order to understand the molecular mechanism underlying α-Gal A deficiency in Fabry disease patients with residual enzyme activity, enzymes with different missense mutations were purified from transfected COS-7 cells and the biochemical properties were characterized. The mutant enzymes detected in variant patients (A20P, E66Q, M72V, I91T, R112H, F113L, N215S, Q279E, M296I, M296V and R301Q), and those found mostly in mild classic patients (A97V, A156V, L166V and R356W) appeared to have normal Km and Vmax values. The degradation of all mutants (except E59K) was partially inhibited by treatment with kifunensine, a selective inhibitor of ER (endoplasmic reticulum) α-mannosidase I. Metabolic labelling and subcellular fractionation studies in COS-7 cells expressing the L166V and R301Q α-Gal A mutants indicated that the mutant protein was retained in the ER and degraded without processing. Addition of DGJ (1-deoxygalactonojirimycin) to the culture medium of COS-7 cells transfected with a large set of missense mutant α-Gal A cDNAs effectively increased both enzyme activity and protein yield. DGJ was capable of normalizing intracellular processing of mutant α-Gal A found in both classic (L166V) and variant (R301Q) Fabry disease patients. In addition, the residual enzyme activity in fibroblasts or lymphoblasts from both classic and variant hemizygous Fabry disease patients carrying a variety of missense mutations could be substantially increased by cultivation of the cells with DGJ. These results indicate that a large proportion of mutant enzymes in patients with residual enzyme activity are kinetically active. Excessive degradation in the ER could be responsible for the deficiency of enzyme activity in vivo, and the DGJ approach may be broadly applicable to Fabry disease patients with missense mutations. PMID:17555407

  15. A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance.

    PubMed

    van der Tol, L; Smid, B E; Poorthuis, B J H M; Biegstraaten, M; Deprez, R H Lekanne; Linthorst, G E; Hollak, C E M

    2014-01-01

    Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the significance of GLA gene variants and to calculate the prevalence of definite classical and uncertain cases. We searched PubMed and Embase for screening studies on FD. We collected data on screening methods, clinical, biochemical and genetic assessments. The pooled prevalence of identified subjects and those with a definite diagnosis of classical FD were calculated. As criteria for a definite diagnosis, we used the presence of a GLA variant, absent or near-absent leukocyte enzyme activity and characteristic features of FD. Fifty-one studies were selected, 45 in high-risk and 6 in newborn populations. The most often used screening method was an enzyme activity assay. Cut-off values comprised 10-55% of the mean reference value for men and up to 80% for women. Prevalence of GLA variants in newborns was 0.04%. In high-risk populations the overall prevalence of individuals with GLA variants was 0.62%, while the prevalence of a definite diagnosis of FD was 0.12%. The majority of identified individuals in high-risk and newborn populations harbour GVUS or neutral variants in the GLA gene. To determine the pathogenicity of a GVUS in an individual, improved diagnostic criteria are needed. We propose a diagnostic algorithm to approach the individual with an uncertain diagnosis. PMID:23922385

  16. Reduced Right Ventricular Native Myocardial T1 in Anderson-Fabry Disease: Comparison to Pulmonary Hypertension and Healthy Controls

    PubMed Central

    Pagano, Joseph J.; Chow, Kelvin; Khan, Aneal; Michelakis, Evangelos; Paterson, Ian; Oudit, Gavin Y.; Thompson, Richard B.

    2016-01-01

    Aims Anderson-Fabry disease (AFD) is characterized by progressive multiorgan accumulation of intracellular sphingolipids due to α-galactosidase A enzyme deficiency, resulting in progressive ventricular hypertrophy, heart failure, arrhythmias, and death. Decreased native (non-contrast) left ventricular (LV) T1 (longitudinal relaxation time) with MRI discriminates AFD from healthy controls or other presentations of concentric hypertrophy, but the right ventricle (RV) has not been studied. The aims of the current study were to evaluate native RV T1 values in AFD, with a goal of better understanding the pathophysiology of RV involvement. Methods and Results Native T1 values were measured in the inferior RV wall (RVI), interventricular septum (IVS), and inferior LV (LVI) in patients with AFD, patients with pulmonary hypertension, who provided an alternative RV pathological process for comparison, and healthy controls. A minimum wall thickness of 4 mm was selected to minimize partial volume errors in tissue T1 analysis. T1 analysis was performed in 6 subjects with AFD, 6 subjects with PH, and 21 controls. Native T1 values were shorter (adjusted p<0.05 for all comparisons), independent of location, in subjects with AFD (RVI-T1 = 1096±49 ms, IVS-T1 = 1053±41 ms, LVI-T1 = 1072±44 ms) compared to both PH (RVI-T1 = 1239±41 ms, IVS-T1 = 1280±123 ms, LVI-T1 = 1274±57 ms) and HC (IVS-T1 = 1180±60 ms, LVI-T1 = 1183±45 ms). RVI measurements were not possible in controls due to insufficient wall thickness. Conclusion Native T1 values appear similarly reduced in the left and right ventricles of individuals with AFD and RV wall thickening, suggesting a common pathology. In contrast, individuals with PH and thickened RVs showed increased native T1 values in both ventricles, suggestive of fibrosis. PMID:27305064

  17. Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene.

    PubMed Central

    Redonnet-Vernhet, I; Ploos van Amstel, J K; Jansen, R P; Wevers, R A; Salvayre, R; Levade, T

    1996-01-01

    We describe two female monozygotic (MZ) twins heterozygous for Fabry disease, an X linked disorder resulting from the deficient activity of alpha-galactosidase A. While one of the twins was clinically affected, the other was asymptomatic. Enzymatic assay of alpha-galactosidase in blood leucocytes, skin fibroblasts, Epstein-Barr virus transformed lymphoid cell lines, and hair follicles of the twins and their parents confirmed the heterozygous status of the twins and indicated that Fabry disease had occurred as a result of a de novo mutation. The son of the unaffected twin sister was shown to be hemizygous. Molecular analysis of the alpha-galactosidase A gene permitted the identification of an as yet undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn substitution at codon 231. Single strand conformation polymorphism (SSCP) analysis again showed the heterozygous status of the twins and a normal pattern in their parents. The basis for the discordant expression of this d novo mutation in the twins was investigated by studying their X inactivation status. Analysis of the inactive X specific methylation at the androgen receptor gene showed unbalanced inactivation in the twins' fibroblasts and in opposite directions. While the maternally derived X chromosome was preferentially active in the asymptomatic twin, the paternal X chromosome was active in the other, affected twin and was found in her hemizygotic nephew. These data suggest that the paternal X chromosome carries the de novo alpha-galactosidase A mutation and that uneven X inactivation is the underlying mechanism for disease expression in this novel female MZ twin pair. This is the first documented case of female twins discordant for Fabry disease. Images PMID:8863162

  18. A comprehensive Fabry-related pain questionnaire for adult patients.

    PubMed

    Üçeyler, Nurcan; Magg, Barbara; Thomas, Phillip; Wiedmann, Silke; Heuschmann, Peter; Sommer, Claudia

    2014-11-01

    Pain may be the earliest symptom in Fabry disease and presents with a distinct phenotype including triggerable pain attacks, evoked pain, pain crises, and chronic pain. Current pain questionnaires do not reflect the special phenotype of Fabry disease-associated pain, which hampers its systematic evaluation as the basis of correct diagnosis and effective treatment. A questionnaire specifically designed to assess Fabry disease-associated pain is thus urgently needed. At the Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Germany, we developed and validated the first face-to-face Fabry Pain Questionnaire (FPQ) for adult patients. The initial version of the FPQ was tested in a pilot study with 20 consecutive Fabry disease patients. The performance of the revised FPQ was assessed in a first (n=56) and second (n=20) validation phase in consecutive Fabry disease patients. For this, patients were interviewed at baseline and 2 weeks later. We determined the test-retest reliability and validity of the FPQ in comparison to data obtained with the Neuropathic Pain Symptom Inventory. The FPQ contains 15 questions on the 4 pain phenotypes of Fabry disease (pain attacks, pain crises, evoked pain, chronic pain) in childhood and adulthood, on pain development during life with and without enzyme replacement therapy, and on everyday life impairment due to pain. This first disease-specific questionnaire is a valuable tool for baseline and follow-up assessment of pain in Fabry disease patients and may guide treatment in this distinct pain phenotype.

  19. Accurate quantification of sphingosine-1-phosphate in normal and Fabry disease plasma, cells and tissues by LC-MS/MS with (13)C-encoded natural S1P as internal standard.

    PubMed

    Mirzaian, Mina; Wisse, Patrick; Ferraz, Maria J; Marques, André R A; Gabriel, Tanit L; van Roomen, Cindy P A A; Ottenhoff, Roelof; van Eijk, Marco; Codée, Jeroen D C; van der Marel, Gijsbert A; Overkleeft, Herman S; Aerts, Johannes M

    2016-08-01

    We developed a mass spectrometric procedure to quantify sphingosine-1-phosphate (S1P) in biological materials. The use of newly synthesized (13)C5 C18-S1P and commercial C17-S1P as internal standards rendered very similar results with respect to linearity, limit of detection and limit of quantitation. Caution is warranted with determination of plasma S1P levels. Earlier it was reported that S1P is elevated in plasma of Fabry disease patients. We investigated this with the improved quantification. No clear conclusion could be drawn for patient plasma samples given the lack of uniformity of blood collection and plasma preparation. To still obtain insight, plasma and tissues were identically collected from α-galactosidase A deficient Fabry mice and matched control animals. No significant difference was observed in plasma S1P levels. A significant 2.3 fold increase was observed in kidney of Fabry mice, but not in liver and heart. Comparative analysis of S1P in cultured fibroblasts from normal subjects and classically affected Fabry disease males revealed no significant difference. In conclusion, accurate quantification of S1P in biological materials is feasible by mass spectrometry using the internal standards (13)C5 C18-S1P or C17-S1P. Significant local increases of S1P in the kidney might occur in Fabry disease as suggested by the mouse model. PMID:27221202

  20. Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

    PubMed

    Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells. PMID:26971403

  1. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  2. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  3. NASA Bioreactors Advance Disease Treatments

    NASA Technical Reports Server (NTRS)

    2009-01-01

    the body. Experiments conducted by Johnson scientist Dr. Thomas Goodwin proved that the NASA bioreactor could successfully cultivate cells using simulated microgravity, resulting in three-dimensional tissues that more closely approximate those in the body. Further experiments conducted on space shuttle missions and by Wolf as an astronaut on the Mir space station demonstrated that the bioreactor s effects were even further expanded in space, resulting in remarkable levels of tissue formation. While the bioreactor may one day culture red blood cells for injured astronauts or single-celled organisms like algae as food or oxygen producers for a Mars colony, the technology s cell growth capability offers significant opportunities for terrestrial medical research right now. A small Texas company is taking advantage of the NASA technology to advance promising treatment applications for diseases both common and obscure.

  4. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  5. Advances in inflammatory bowel diseases in children.

    PubMed

    Michail, S; Ramsy, M; Soliman, E

    2012-06-01

    Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition that burdens the lives of many children around the world. It is characterized by chronic gastrointestinal inflammation. Crohn's disease (CD), ulcerative colitis and IBD-unknown are the three types of this disease. The management of children with inflammatory bowel disease is complex and requires skill, knowledge and experience with current advances in the field. Over the past several years, there have been a number of achievements and progress made in the care and management of this disorder. The diagnostic tools have greatly improved. The therapeutic armamentarium has expanded. The genetics of IBD has become more detailed and the role of the gut microbiome has been better defined. The evolution of biological agents has revolutionized the way we approach this disease. This review highlights the recent advances in pediatric inflammatory bowel disease and provides an overview for clinicians caring for children with this disorder. PMID:22555319

  6. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    PubMed Central

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

  7. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    PubMed

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids. PMID:26873218

  8. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    PubMed

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

  9. Advances in identifying beryllium sensitization and disease.

    PubMed

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.

  10. Advances in Identifying Beryllium Sensitization and Disease

    PubMed Central

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and l940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true “gold standard” for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms. PMID:20195436

  11. Advances in microfluidics in combating infectious diseases.

    PubMed

    Tay, Andy; Pavesi, Andrea; Yazdi, Saeed Rismani; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-01-01

    One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed. PMID:26854743

  12. Genetic Disorders with Dyshidrosis: Ectodermal Dysplasia, Incontinentia Pigmenti, Fabry Disease, and Congenital Insensitivity to Pain with Anhidrosis.

    PubMed

    Wataya-Kaneda, Mari

    2016-01-01

    Sweating is regulated by various neurohormonal mechanisms. A disorder in any part of the sweating regulatory pathways, such as the thermal center, neurotransmitters in the central to peripheral nerve, innervation of periglandular neurotransmission, and sweat secretion in the sweat gland itself, induces dyshidrosis. Therefore, hereditary disorders with dyshidrosis result from a variety of causes. These diseases have characteristic symptoms derived from each pathogenesis besides dyshidrosis. The information in this chapter is useful for the differential diagnosis of representative genetic disorders with dyshidrosis. PMID:27584961

  13. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  14. Scientifically advanced solutions for chestnut ink disease.

    PubMed

    Choupina, Altino Branco; Estevinho, Letícia; Martins, Ivone M

    2014-05-01

    On the north regions of Portugal and Spain, the Castanea sativa Mill. culture is extremely important. The biggest productivity and yield break occurs due to the ink disease, the causal agent being the oomycete Phytophthora cinnamomi. This oomycete is also responsible for the decline of many other plant species in Europe and worldwide. P. cinnamomi and Phytophthora cambivora are considered, by the generality of the authors, as the C. sativa ink disease causal agents. Most Phytophthora species secrete large amounts of elicitins, a group of unique highly conserved proteins that are able to induce hypersensitive response (HR) and enhances plant defense responses in a systemic acquired resistance (SAR) manner against infection by different pathogens. Some other proteins involved in mechanisms of infection by P. cinnamomi were identified by our group: endo-1,3-beta-glucanase (complete cds); exo-glucanase (partial cds) responsible by adhesion, penetration, and colonization of host tissues; glucanase inhibitor protein (GIP) (complete cds) responsible by the suppression of host defense responses; necrosis-inducing Phytophthora protein 1 (NPP1) (partial cds); and transglutaminase (partial cds) which inducts defense responses and disease-like symptoms. In this mini-review, we present some scientifically advanced solutions that can contribute to the resolution of ink disease.

  15. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

    PubMed Central

    Goker-Alpan, Ozlem; Longo, Nicola; McDonald, Marie; Shankar, Suma P; Schiffmann, Raphael; Chang, Peter; Shen, Yinghua; Pano, Arian

    2016-01-01

    Background Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. Methods In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=−0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (−3.3, 3.7) g/m2.7; midwall fractional shortening, −0.62% (−2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (−11.4, 11.7) mL/min/1.73 m2; urine protein, −1.8 (−6.0, 2.4) mg/dL; urine microalbumin, 0.6 (−0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), −5.71 (−10.8, −0.6) nmol/mL; urinary Gb3, −1,403.3 (−3,714.0, 907.4) nmol/g creatinine

  16. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    PubMed

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. PMID:23702393

  17. Holographic Fabry-Perot spectrometer.

    PubMed

    Martínez-Matos, O; Rodrigo, José A; Vaveliuk, P; Calvo, M L

    2011-02-15

    We propose a spectrum analyzer based on the properties of a hologram recorded with the field transmitted by a Fabry-Perot etalon. The spectral response of this holographic Fabry-Perot spectrometer (HFPS) is analytically investigated in the paraxial approximation and compared with a conventional Fabry-Perot etalon of similar characteristics. We demonstrate that the resolving power is twice increased and the free spectral range (FSR) is reduced to one-half. The proposed spectrometer could improve the operational performance of the etalon because it can exhibit high efficiency and it would be insensible to environmental conditions such as temperature and vibrations. Our analysis also extends to another variant of the HFPS based on holographic multiplexing of the transmitted field of a Fabry-Perot etalon. This device increases the FSR, keeping the same HFPS performance.

  18. Recent Advances in Autoimmune Thyroid Diseases

    PubMed Central

    Yoo, Won Sang

    2016-01-01

    Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs. PMID:27586448

  19. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy. PMID:27521115

  20. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

  1. Preliminary Fabry Perot testing - 1986

    SciTech Connect

    Benner, D.E.

    1987-04-30

    Fabry Perot interferometry is a method of determining instantaneous velocities of an object in motion. The interferometer system is composed of the Fabry Perot interferometer, a laser, an electronic streak camera, and several focusing lenses. The first tests discussed were done on exploding bridgewire devices. During these tests, several system parameters were changed. These changes did not seem to affect the data, which appeared to be consistent. The second tests performed focused on slapper-type devices. It was determined that sandblasted, vapor-deposited aluminum on the slapper material would be required to yield quality data. Streak camera failure prevented much data from being collected. An effort is being made to replace the current streak camera. After it is replaced, a Fabry Perot and velocity interferometry system for any reflector comparison will be made. The results will be published as the conclusion to this report.

  2. Preliminary Fabry Perot testing - 1986

    NASA Astrophysics Data System (ADS)

    Benner, D. E.

    1987-04-01

    Fabry Perot interferometry is a method of determining instantaneous velocities of an object in motion. The interferometer system is composed of the Fabry Perot interferometer, a laser, an electronic streak camera, and several focusing lenses. The first tests discussed were done on exploding bridgewire devices. During these tests, several system parameters were changed. These changes did not seem to affect the data, which appeared to be consistent. The second tests performed focused on slapper-type devices. It was determined that sandblasted, vapor-deposited aluminum on the slapper material would be required to yield quality data. Streak camera failure prevented much data from being collected. An effort is being made to replace the current streak camera. After it is replaced, a Fabry Perot and velocity interferometry system for any reflector comparison will be made. The results will be published as the conclusion to this report.

  3. Recent advances in echocardiography for valvular heart disease

    PubMed Central

    Hahn, Rebecca

    2015-01-01

    Echocardiography is the imaging modality of choice for the assessment of patients with valvular heart disease. Echocardiographic advancements may have particular impact on the assessment and management of patients with valvular heart disease. This review will summarize the current literature on advancements, such as three-dimensional echocardiography, strain imaging, intracardiac echocardiography, and fusion imaging, in this patient population. PMID:26594349

  4. Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

    PubMed

    Putko, Brendan N; Wen, Kevin; Thompson, Richard B; Mullen, John; Shanks, Miriam; Yogasundaram, Haran; Sergi, Consolato; Oudit, Gavin Y

    2015-03-01

    Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden. Anderson-Fabry disease is an X-linked disorder, and genetic testing is critical for the diagnosis of AFD in women. Echocardiography with strain imaging and cardiac magnetic resonance imaging using late enhancement and T1 mapping are important imaging tools. The current therapy for AFD is enzyme replacement therapy (ERT), which can reverse or prevent AFD progression, while gene therapy and the use of molecular chaperones represent promising novel therapies for AFD. Anderson-Fabry cardiomyopathy is an important and potentially reversible cause of heart failure that involves LVH, increased susceptibility to arrhythmias and valvular regurgitation. Genetic testing and cardiac MRI are important diagnostic tools, and AFD cardiomyopathy is treatable if ERT is introduced early.

  5. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  6. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented. PMID:24262965

  7. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented.

  8. [Huntington's disease--advances in gene mapping].

    PubMed

    Nakamura, S

    1993-09-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. It is inherited in an autosomal dominant fashion. The genetic defect causing HD was assigned to chromosome 4 in 1983 using polymorphic DNA markers in humans. Thereafter, a location cloning approach was pursued to isolate and characterize the HD gene. Recently, the Huntington's disease collaborative research group has isolated a new gene, IT 15, in 4p 16.3. IT 15 contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from disease families. The (CAG)n repeat appears to be located within the coding sequence of a predicted 348 kd protein that is unrelated to any known gene.

  9. Advances in the prevention of Alzheimer's Disease

    PubMed Central

    Mangialasche, Francesca; Kivipelto, Miia

    2015-01-01

    Alzheimer's disease (AD), the leading cause of dementia, has reached epidemic proportions, with major social, medical and economical burdens. With no currently available curative treatments, both the World Health Organization and the G8 Dementia Summit recently identified dementia and AD prevention as a major public health priority. Dementia and AD have a wide range of risk factors (genetic, vascular/metabolic and lifestyle-related), which often co-occur and thus interact with each other. Previous intervention efforts aimed at preventing dementia and AD focused on the management of single risk factors, with relatively modest findings. Also, the effect of risk factors depends on age at exposure, indicating that the timing of preventive interventions needs to be carefully considered. In view of the complex multifactorial nature of AD, as well as its long pre-clinical (asymptomatic) phase, interventions simultaneously targeting multiple risk factors and disease mechanisms at an early stage of the disease are most likely to be effective. Three large European multidomain prevention trials have been launched with the goal of preventing cognitive decline, dementia and AD in older adults with different risk profiles. Pharmacological trials are also shifting towards prevention of Alzheimer dementia, by targeting at-risk individuals prior to the onset of cognitive symptoms. The current review will summarize and discuss the evidence on risk and protective factors from observational studies, ongoing lifestyle-related and pharmacological randomized controlled trials (RCTs), as well as future directions for dementia and AD prevention. PMID:26097723

  10. Biomarkers in inflammatory bowel disease: current practices and recent advances.

    PubMed

    Iskandar, Heba N; Ciorba, Matthew A

    2012-04-01

    Crohn's disease and ulcerative colitis represent the two main forms of the idiopathic chronic inflammatory bowel diseases (IBD). Currently available blood and stool based biomarkers provide reproducible, quantitative tools that can complement clinical assessment to aid clinicians in IBD diagnosis and management. C-reactive protein and fecal based leukocyte markers can help the clinician distinguish IBD from noninflammatory diarrhea and assess disease activity. The ability to differentiate between forms of IBD and predict risk for disease complications is specific to serologic tests including antibodies against Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic proteins. Advances in genomic, proteomic, and metabolomic array based technologies are facilitating the development of new biomarkers for IBD. The discovery of novel biomarkers, which can correlate with mucosal healing or predict long-term disease course has the potential to significantly improve patient care. This article reviews the uses and limitations of currently available biomarkers and highlights recent advances in IBD biomarker discovery. PMID:22424434

  11. Advanced alveolar echinococcosis disease associated with Budd–Chiari syndrome

    PubMed Central

    Soyer, Vural; Ara, Cengiz; Yaylak, Faik; Sarıcı, Barış; Ozsoy, Mustafa; Koç, Okay; Yılmaz, Sezai

    2015-01-01

    Introduction Alveolar echinococceal disease of the liver is rare. Echinococcus multilocularis is responsible for the development of the related clinical conditions. Advanced disease may result with serious complications such as end stage liver disease and Budd–Chiari syndrome. Presentation of case In this presentation, a 28 years-old woman who was a case with advanced alveolar echinococcosis complicated with a Budd–Chiari syndrome and was performed successful living donor liver transplantation, has been demonstrated with clinical and radiological images. Discussion Initially there may be no clinical evidence of the disease in humans for years. Severity and fatality are the significant characteristics of the natural history. Extension to the surrounding tissues and metastasis of the parasitic mass may be observed. Prevention is essential in disease control. Serologic assay may identify the parasite. However, early diagnosis is rare. Staging is based on radiologic imaging. Some patients with advanced disease may require surgery. Hepatic resection and liver transplantation are accepted procedures in selected patients. Conclusion The importance of early diagnosis to prevent advanced complications such as development of Budd–Chiari syndrome and metastasis has been underlined. PMID:25600725

  12. Recent advances in small bowel diseases: Part II

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all areas of gastroenterology and hepatology, in 2009 and 2010 there were many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed, and the important advances in basic science as well as clinical applications were considered. In Part II we review six topics: absorption, short bowel syndrome, smooth muscle function and intestinal motility, tumors, diagnostic imaging, and cystic fibrosis. PMID:22807605

  13. α-Galactosidase A expressed in the salivary glands partially corrects organ biochemical deficits in the fabry mouse through endocrine trafficking.

    PubMed

    Passineau, Michael J; Fahrenholz, Timothy; Machen, Laurie; Zourelias, Lee; Nega, Katherine; Paul, Rachel; MacDougall, Mary J; Mamaeva, Olga; Steet, Richard; Barnes, Jarrod; Kingston, H M; Benza, Raymond L

    2011-03-01

    Fabry disease is caused by an X-linked deficiency of the lysosomal enzyme α-galactosidase A (GLA) and has been treated successfully with enzyme replacement therapy (ERT). Gene therapy has been proposed as an alternative to ERT due to the presumed advantages of continuous, endogenous production of the therapeutic enzyme. GLA production in the liver and its therapeutic efficacy in the Fabry mouse have been demonstrated previously with various viral vector systems. In consideration of the potential advantages of using the salivary glands as endogenous GLA biosynthesis sites, we explored the feasibility of this approach in the Fabry mouse. GLA -/0 or -/- mice received an adenoviral vector (2 × 10(10) or 1 × 10(9) viral particles) expressing GLA to the right submandibular gland via oral cannulation of the submandibular duct. Four days later, animals were sacrificed; saliva, plasma, kidney, liver, and brain were collected and assayed using ELISA, Western blot, and a GLA enzymatic activity assay using both traditional fluorescence methods and isotope dilution mass spectrometry by following the U.S. EPA Method 6800. GLA activity was significantly elevated in the serum and liver of both treatment groups, and improvement in the kidney was marginally significant (P < 0.069) in the high-dose group. Notably, we found that liver and salivary gland produce different glycoforms of the GLA transgene. Only small numbers of adenoviral genomes were observed in the livers of treated animals, but in four of 14 in the high-dose groups, liver levels of adenovirus exceeded 20 copies/μg, indicating that the sequestration in the salivary gland was imperfect at high doses. Taken together, these results indicate that the salivary gland-based gene therapy for Fabry disease is promising, and further studies with advanced viral vector gene delivery systems (e.g., adeno-associated virus) for long-term treatment appear to be warranted. PMID:20858137

  14. Kidney disease in children: latest advances and remaining challenges.

    PubMed

    Bertram, John F; Goldstein, Stuart L; Pape, Lars; Schaefer, Franz; Shroff, Rukshana C; Warady, Bradley A

    2016-03-01

    To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients.

  15. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  16. Advances in diagnostic testing for gastroesophageal reflux disease.

    PubMed

    Gawron, Andrew J; Hirano, Ikuo

    2010-08-14

    Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology. PMID:20698036

  17. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  18. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  19. Advances in environmental and occupational diseases 2004.

    PubMed

    Frew, Anthony J

    2005-06-01

    2004 was another good year for publications on environmental and occupational disorders in our journal. The major focus is clearly on the environment and particularly on environmental risk factors for sensitization and asthma. There is a growing consensus that exposure to pets is good, provided there is enough of it. Low levels enhance sensitization, and higher levels protect against the consequences of that sensitization. Following on from previous work on cockroaches, we now see allergy to feral mice as an emergent problem--at least we now have the tools to study this properly. Emphasis seems to be swinging away from the outdoor environment as a cause of allergic disease and toward the indoor environment, which is, after all, where most of us spend most of our lives. New techniques for studying isocyanate allergy might kindle a revival of interest in the mechanisms of occupational asthma caused by low-molecular-weight compounds. But for all types of occupational allergy, prevention remains key, and it is good to see that comprehensive programs of allergen reduction can pay off in reduced rates of latex allergy in health care workers. Further work in the area of recombinant allergens is welcome but needs soon to be translated into new diagnostic and therapeutic strategies. This sector of allergy research remains vibrant, and the editors will continue to welcome outstanding contributions in this area.

  20. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  1. Testosterone in men with advanced liver disease: abnormalities and implications.

    PubMed

    Sinclair, Marie; Grossmann, Mathis; Gow, Paul J; Angus, Peter W

    2015-02-01

    Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials. PMID:25087838

  2. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    PubMed Central

    Chakraborty, Sandip; Kumar, Amit; Tiwari, Ruchi; Rahal, Anu; Malik, Yash; Dhama, Kuldeep; Pal, Amar; Prasad, Minakshi

    2014-01-01

    Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses. PMID:25028620

  3. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  4. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID:27553994

  5. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD.

  6. Recent advances in small bowel diseases: Part I

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician. PMID:22807604

  7. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

    Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

  8. Laboratory Diagnosis of Lyme Disease - Advances and Challenges

    PubMed Central

    Marques, Adriana R.

    2015-01-01

    Synopsis Lyme disease is the most common tick-borne illness in the United States and Europe. Culture for B. burgdorferi is not routinely available. PCR can be helpful in synovial fluid of patients with Lyme arthritis. The majority of laboratory tests performed for the diagnosis of Lyme disease are based on detection of the antibody responses against B. burgdorferi in serum. The sensitivity of antibody-based tests increases with the duration of the infection, and patients who present very early in their illness are more likely to have a negative result. Patients with erythema migrans should receive treatment based on the clinical diagnosis. The current Centers for Disease Control and Prevention recommendations for serodiagnosis of Lyme disease is a 2-tiered algorithm, an initial enzyme immunoassay (EIA) followed by separate IgM and IgG Western blots if the first EIA test result is positive or borderline. The IgM result is only relevant for patients with illness duration of less than a month. While the 2-tier algorithm works well for later stages of the infection, it has low sensitivity during early infection. A major advance has been the discovery of VlsE and its C6 peptide as markers of antibody response in Lyme disease. Specificity is extremely important in Lyme disease testing, as the majority of tests are being performed in situations with low likelihood of the disease, a situation where a positive result is more likely to be a false positive. Current assays do not distinguish between active and inactive infection, and patients may continue to be seropositive for years. There is a need to simplify the testing algorithm for Lyme disease, improving sensitivity in early disease while still maintaining high specificity and providing information about the stage of infection. The development of a point of care assay and biomarkers for active infection would be major advances for the field. PMID:25999225

  9. [Research advances in pediatric nonalcoholic fatty liver disease].

    PubMed

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  10. [Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives].

    PubMed

    Chacón-Camacho, Óscar Francisco; Astorga-Carballo, Aline; Zenteno, Juan Carlos

    2015-01-01

    Gene therapy is a promising new therapeutic strategy that could provide a novel and more effective way of targeting hereditary ophthalmological diseases. The eye is easily accessible, highly compartmentalized, and an immune-privileged organ that gives advantages as an ideal gene therapy target. Recently, important advances in the availability of various intraocular vector delivery routes and viral vectors that are able to efficiently transduce specific ocular cell types have been described. Gene therapy has advanced in some retinal inherited dystrophies; in this way, preliminary success is now being reported for the treatment of Leber congenital amaurosis (LCA). This review will provide an update in the field of gene therapy for the treatment of ocular inherited diseases.

  11. Recent advances in understanding of chronic kidney disease

    PubMed Central

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed. PMID:26937272

  12. Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.

    PubMed

    Biancini, Giovana Brondani; Jacques, Carlos Eduardo; Hammerschmidt, Tatiane; de Souza, Heryk Motta; Donida, Bruna; Deon, Marion; Vairo, Filippo Pinto; Lourenço, Charles Marques; Giugliani, Roberto; Vargas, Carmen Regla

    2016-10-01

    Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase - GPx - and normal glutathione reductase - GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO(.)) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO(.) equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD. PMID:27458128

  13. Biomolecules damage and redox status abnormalities in Fabry patients before and during enzyme replacement therapy.

    PubMed

    Biancini, Giovana Brondani; Jacques, Carlos Eduardo; Hammerschmidt, Tatiane; de Souza, Heryk Motta; Donida, Bruna; Deon, Marion; Vairo, Filippo Pinto; Lourenço, Charles Marques; Giugliani, Roberto; Vargas, Carmen Regla

    2016-10-01

    Fabry disease (FD) is caused by deficient activity of the lysosomal enzyme α-galactosidase A. Its substrates, mainly globotriaosylceramide (Gb3), accumulate and seem to induce other pathophysiological findings of FD. Once enzyme replacement therapy (ERT) is not completely efficient on preventing disease progress in FD patients, elucidating the underlying mechanisms in FD pathophysiology is essential to the development of additional therapeutic strategies. We investigated 58 Fabry patients (23 male and 35 female) subdivided into two groups (at diagnosis and during long-term ERT) and compared them to healthy individuals. Fabry patients at diagnosis presented altered glutathione (GSH) metabolism (higher GSH levels, lower glutathione peroxidase - GPx - and normal glutathione reductase - GR - activities), higher lipid peroxidation levels (thiobarbituric acid reactive species - TBARS - and malondialdehyde - MDA), nitric oxide (NO(.)) equivalents and urinary Gb3. Fabry patients on ERT presented GSH metabolism similar to controls, although lipid peroxidation and urinary levels of NO(.) equivalents remained higher whereas Gb3 levels were lower than at diagnosis but still higher than controls. These data demonstrated that redox impairment occurs in Fabry patients before and after ERT, probably as a consequence of Gb3 accumulation, providing targets to future therapy approaches using antioxidants in combination with ERT in FD.

  14. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients

    NASA Astrophysics Data System (ADS)

    Alharbi, Fahad J.; Geberhiwot, Tarekegn; Hughes, Derralynn A.; Ward, Douglas G.

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish.

  15. [Integrated care for patients with advanced chronic obstructive pulmonary disease].

    PubMed

    Jassem, Ewa; Górecka, Dorota; Krakowiak, Piotr; Kozielski, Jerzy; Słomiński, J Marek; Krajnik, Małgorzata; Fal, Andrzej M

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease).

  16. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  17. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  18. [Advances in prenatal diagnosis of congenital heart diseases].

    PubMed

    Muner-Hernando, Marta; Gil-Mira, Mar; Zapardiel, Ignacio

    2013-06-01

    Congenital heart diseases are the most frequent abnormalities at the time of delivery. Their importance lays in the fact that they represent 46% of neonatal deaths and they are cause of a high morbidity rate. However, an early diagnosis is difficult. The aim of this revision is to give an update on the advances in the prenatal diagnosis of congenital heart diseases and their advantages compared to conventional sonography. The introduction of new technology in the detection of congenital heart diseases has improved the acquisition of better images in terms of resolution and quality. However, there is a lack of large studies to prove its benefits in non-selected population, although preliminary studies seem to give faithful results.

  19. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  20. Congenital heart disease in Mexico: advances of the regionalization project.

    PubMed

    Calderón-Colmenero, Juan; Cervantes-Salazar, Jorge; Curi-Curi, Pedro; Ramírez-Marroquín, Samuel

    2013-04-01

    Consistent with the mission of the World Society for Pediatric and Congenital Heart Surgery to promote health care for children with congenital heart disease all around the world, a Mexican Association of Specialists in Congenital Heart Disease (abbreviated in Spanish as AMECC) was created in Mexico in 2008. Our efforts were coordinated with those of the National Health Secretary with the objective being implementation of a national plan for regionalization of care for patients with congenital heart disease. To improve our knowledge related to technologic and human resources for management of congenital heart disease, we developed a national survey. Finally, a national database was created for collecting all Mexican centers' information related to congenital heart disease care in order to quantify the advances related to the proposed plans. The database utilized international consensus nomenclature. The aim of this article is to show the sequence of our actions in relation to direct accomplishments and the current status of congenital heart disease care in Mexico. This article emphasizes the main aspects of these actions: regionalization project implementation, national survey results, and cardiovascular pediatric surgical database creation. Knowledge of outcomes related to successful actions would be useful for those countries that face similar challenges and may lead them to consider adoption of similar measures with the respective adjustments to their own reality.

  1. Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy

    PubMed Central

    Krämer, Johannes; Bijnens, Bart; Störk, Stefan; Ritter, Christian O.; Liu, Dan; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2015-01-01

    Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy. PMID:26600044

  2. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  3. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively.

  4. DNA damage in Fabry patients: An investigation of oxidative damage and repair.

    PubMed

    Biancini, Giovana Brondani; Moura, Dinara Jaqueline; Manini, Paula Regina; Faverzani, Jéssica Lamberty; Netto, Cristina Brinckmann Oliveira; Deon, Marion; Giugliani, Roberto; Saffi, Jenifer; Vargas, Carmen Regla

    2015-06-01

    Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported. However, DNA damage by oxidative species in FD has not yet been studied. We investigated basal DNA damage, oxidative DNA damage, DNA repair capacity, and reactive species generation in Fabry patients and controls. To measure oxidative damage to purines and pyrimidines, the alkaline version of the comet assay was used with two endonucleases, formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). To evaluate DNA repair, a challenge assay with hydrogen peroxide was performed. Patients presented significantly higher levels of basal DNA damage and oxidative damage to purines. Oxidative DNA damage was induced in both DNA bases by H2O2 in patients. Fabry patients presented efficient DNA repair in both assays (with and without endonucleases) as well as significantly higher levels of oxidative species (measured by dichlorofluorescein content). Even if DNA repair be induced in Fabry patients (as a consequence of continuous exposure to oxidative species), the repair is not sufficient to reduce DNA damage to control levels. PMID:26046974

  5. Advances in nanotechnology for the management of coronary artery disease.

    PubMed

    Rhee, June-Wha; Wu, Joseph C

    2013-02-01

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix.

  6. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson's Disease.

    PubMed

    Fauser, Mareike; Löhle, Matthias; Ebersbach, Georg; Odin, Per; Fuchs, Gerd; Jost, Wolfgang H; Chaudhuri, K Ray; Koch, Rainer; Storch, Alexander

    2015-01-01

    Nonmotor symptoms (NMS) fluctuate in conjunction with motor oscillations in advanced Parkinson's disease (PD), though little is known about the variability of NMS fluctuations in individual patients. We aimed to assess within-patient variability in frequency and severity of NMS during a series of five patient-perceived motor On and Off periods in 38 fluctuating PD patients from the multicenter NonMotorFluctuations in PD study using a visual analogue scale. NMS frequency and severity appeared moderately variable in both motor states within individual patients. Symptom severity ranges between motor states showed high variability and were larger in motor Off states for most NMS. PMID:26639660

  7. [Advances in the researches of lutein and alzheimer's disease].

    PubMed

    Xu, Xianrong; Lin, Xiaoming

    2015-05-01

    Lutein, a kind of oxycarotenoid, can pass the blood brain barrier and preferentially accumulate in the human brain, which is the most abundant carotenoid in human brain. Evidence from multiple studies suggested that lutein was closely related to age-related cognitive decline and risk of Alzheimer's disease (AD) in human. Dietary, plasma and brain concentrations of lutein were negatively associated with age-related cognitive decline. Lutein concentrations in plasma and brain were significantly lower in AD patients than those of health control. In human brain, lutein was the sole carotenoid which consistently associated with a range of cognitive function measures. In elderly women, lutein supplement can improve the cognitive function. In this article, we systematically reviewed the literature on the role of lutein in age-related cognitive decline and alzheimer's disease and its possible mechanisms. It may prove some benefit information for the advanced research and prevention of AD.

  8. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

    Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity. PMID:19302045

  9. Methodological advances in drug discovery for Chagas disease

    PubMed Central

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  10. Impaired phospholipid-related signal transduction in advanced Huntington's disease.

    PubMed

    Puri, B K

    2001-09-01

    The aim of this study was to test the hypothesis that Huntington's disease is associated with impaired phospholipid-related signal transduction using the niacin skin flush test. This is the first reported use of this test in this patient group. The response to topical aqueous methyl nicotinate solution was recorded at 5 min intervals over 20 min in six in-patients with advanced (stage III) Huntington's disease and in 14 age- and sex-matched normal individuals with no history of this or any other major neurological disorder. The volumetric niacin response (VNR) (mean +/- S.E.M.) in the patients with Huntington's disease, 16.3 +/- 2.6 mol x s x l(-1), was significantly lower than the mean VNR of 28.3 +/- 2.1 mol x s x l(-1) in the control group (P = 0.004). These results are consistent with the conclusion that Huntington's disease may be associated with an abnormality of neuronal membrane fatty acid metabolism, possibly as a consequence of an as yet unidentified action of huntingtin.

  11. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  12. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  13. Polymer Drug Conjugates: Recent Advancements in Various Diseases.

    PubMed

    Singh, Jasbir; Desai, Sapna; Yadav, Snehlata; Narasimhan, Balasubramanian; Kaur, Harmeet

    2016-01-01

    During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status. PMID:26898741

  14. Strained layer Fabry-Perot device

    DOEpatents

    Brennan, Thomas M.; Fritz, Ian J.; Hammons, Burrell E.

    1994-01-01

    An asymmetric Fabry-Perot reflectance modulator (AFPM) consists of an active region between top and bottom mirrors, the bottom mirror being affixed to a substrate by a buffer layer. The active region comprises a strained-layer region having a bandgap and thickness chosen for resonance at the Fabry-Perot frequency. The mirrors are lattice matched to the active region, and the buffer layer is lattice matched to the mirror at the interface. The device operates at wavelengths of commercially available semiconductor lasers.

  15. Analysis of Fabry-Perot Velocimeter Records

    SciTech Connect

    Avara, G

    2001-08-03

    Program demonstration and user instructions are presented for FabryVB5. This computer program was created for use in analyzing Fabry-Perot interferometer records that detail the velocity time histories of fast moving surfaces. Graphical curves representing peak fringe positions and fiducial timing dots are extracted from a digitized film record or from a CCD digital image. An analysis is demonstrated on a sample velocimeter record along with some mathematical formula and routine operations. Routines used to analyze calibration records on streak camera distortions are illustrated in an appendix. This is a Microsoft Visual Basic{trademark} version for the PC.

  16. Advances in stem cell therapy for cardiovascular disease (Review).

    PubMed

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  17. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  18. CAP--advancing the evaluation of preclinical Alzheimer disease treatments.

    PubMed

    Reiman, Eric M; Langbaum, Jessica B; Tariot, Pierre N; Lopera, Francisco; Bateman, Randall J; Morris, John C; Sperling, Reisa A; Aisen, Paul S; Roses, Allen D; Welsh-Bohmer, Kathleen A; Carrillo, Maria C; Weninger, Stacie

    2016-01-01

    If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiation and performance of preclinical AD trials. In this article, we note some of the current challenges, opportunities and emerging strategies in preclinical AD treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a convening, harmonizing and consensus-building initiative to help stakeholders advance AD prevention research with rigour, care and maximal impact-and we demonstrate the impact of CAP on the goals and design of new preclinical AD trials.

  19. Recent advancement of therapeutic endoscopy in the esophageal benign diseases.

    PubMed

    Bechara, Robert; Inoue, Haruhiro

    2015-05-16

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  20. Recent advancement of therapeutic endoscopy in the esophageal benign diseases

    PubMed Central

    Bechara, Robert; Inoue, Haruhiro

    2015-01-01

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  1. Research advances in esophageal diseases: bench to bedside

    PubMed Central

    di Pietro, Massimiliano

    2013-01-01

    Over the last year, significant steps have been made toward understanding the pathogenesis of esophageal diseases and translating this knowledge to clinical practice. Gastroesophageal reflux disease (GERD) is the most common outpatient diagnosis in gastroenterology and has a high prevalence in the general population. As many as 40% of patients with GERD have incomplete response to medical therapy, and the pathophysiological mechanisms underlying lack of response are now better understood. Novel medical and minimally invasive interventions are available to optimize management of GERD. Esophageal cancer, regardless of the histological subtype, has among the worst survival statistics among all malignancies. Taking advantage of technological advances in genome sequencing, the mutational spectra in esophageal cancer are now emerging, offering novel avenues for targeted therapies. Early diagnosis is another strand for improving survival. While genome-wide association studies are providing insights into genetic susceptibility, novel approaches to early detection of cancer are being devised through the use of biomarkers applied to esophageal samples and as part of imaging technologies. Dysmotility and eosinophilic esophagitis are the differential diagnoses in patients with dysphagia. New pathophysiological classifications have improved the management of motility disorders. Meanwhile, exciting progress has been made in the endoscopic management of these conditions. Eosinophilic esophagitis is still a relatively new entity, and the pathogenesis remains poorly understood. However, it is now clear that an allergic reaction to food plays an important role, and dietary interventions as well as biologic agents to block the inflammatory cascade are novel, promising fields of clinical research. PMID:24167725

  2. Advances in pleural disease management including updated procedural coding.

    PubMed

    Haas, Andrew R; Sterman, Daniel H

    2014-08-01

    Over 1.5 million pleural effusions occur in the United States every year as a consequence of a variety of inflammatory, infectious, and malignant conditions. Although rarely fatal in isolation, pleural effusions are often a marker of a serious underlying medical condition and contribute to significant patient morbidity, quality-of-life reduction, and mortality. Pleural effusion management centers on pleural fluid drainage to relieve symptoms and to investigate pleural fluid accumulation etiology. Many recent studies have demonstrated important advances in pleural disease management approaches for a variety of pleural fluid etiologies, including malignant pleural effusion, complicated parapneumonic effusion and empyema, and chest tube size. The last decade has seen greater implementation of real-time imaging assistance for pleural effusion management and increasing use of smaller bore percutaneous chest tubes. This article will briefly review recent pleural effusion management literature and update the latest changes in common procedural terminology billing codes as reflected in the changing landscape of imaging use and percutaneous approaches to pleural disease management.

  3. Advances in the treatment of cognitive impairment in Parkinson's disease.

    PubMed

    Goldman, Jennifer G; Weintraub, Daniel

    2015-09-15

    Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges.

  4. Optical tests of the LUTIN Fabry-Pérot prototype

    NASA Astrophysics Data System (ADS)

    Giovannelli, L.; Berrilli, F.; Del Moro, D.; Greco, V.; Piazzesi, R.; Sordini, A.; Stangalini, M.

    2014-12-01

    The soLar group University of Tor vergata fabry-perot INterferometer (LUTIN) is a narrow band filter based on an optical cavity resonator with Capacitance-Stabilised Etalon (CSE) control. The prototype, developed at the University of Rome Tor Vergata, is part of the study for the narrow band channel of the ADvanced Astronomy for HELIophysics (ADAHELI) mission designed to investigate the dynamics of solar atmosphere as part of the Italian Space Agency (ASI) Small Missions program. We developed the electro-mechanical control for the optical cavity, necessary for the tuning and the gap control of the instrument. We present the measures of the microroughness of the optical plates, performed with a Zygo interferometer, and the instrument spectral stability behaviour in on-optical-bench open-air mode. The measures refer to the upgraded version of the LUTIN prototype, which mounts the new λ/60 optical plates.

  5. Chronic advanced liver disease and impotence: cause and effect?

    PubMed

    Cornely, C M; Schade, R R; Van Thiel, D H; Gavaler, J S

    1984-01-01

    The prevalence of impotence is increased in males who chronically abuse alcohol. Further, impotence may occur in the absence of liver disease in such men. In contrast, no data is available concerning the prevalence of impotence in nonalcoholic men with advanced liver disease. To investigate the relationship between alcohol and impotence in cirrhotic men, a self-administered questionnaire was completed by male alcoholic cirrhotics admitted to the medical service as well as by nonalcoholic cirrhotic liver transplant candidates admitted to the medical and surgical services of Presbyterian-University Hospital. Each participant was asked whether or not he had experienced impotence and if so, to report the frequency and duration of his impotence. The frequency of impotence was recorded on a weighted scale with four gradations: 4 = always; 3 = usually; 2 = sometimes; 1 = seldom. In addition, measures of hepatic injury and function as well as measures of the functional integrity of the hypothalamic-pituitary-gonadal axis for each subject evaluated were obtained. Fourteen of the 20 alcoholics with cirrhosis and 10 of the 40 nonalcoholic liver transplant candidates with cirrhosis reported a history of impotence. The association between impotence and alcohol abuse was significant. The impotence index developed by multiplying the frequency by the duration of impotency for each individual demonstrated a more severe degree of impotence in the alcoholics as compared to the nonalcoholics (p less than 0.01). The alcoholics also had lower plasma levels of testosterone and greater plasma levels of gonadotropins as compared to the nonalcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Recent Advances in Traditional Chinese Medicine for Kidney Disease.

    PubMed

    Zhong, Yifei; Menon, Madhav C; Deng, Yueyi; Chen, Yiping; He, John Cijiang

    2015-09-01

    Because current treatment options for chronic kidney disease (CKD) are limited, many patients seek out alternative therapies such as traditional Chinese medicine. However, there is a lack of evidence from large clinical trials to support the use of traditional medicines in patients with CKD. Many active components of traditional medicine formulas are undetermined and their toxicities are unknown. Therefore, there is a need for research to identify active compounds from traditional medicines and understand the mechanisms of action of these compounds, as well as their potential toxicity, and subsequently perform well-designed, randomized, controlled, clinical trials to study the efficacy and safety of their use in patients with CKD. Significant progress has been made in this field within the last several years. Many active compounds have been identified by applying sophisticated techniques such as mass spectrometry, and more mechanistic studies of these compounds have been performed using both in vitro and in vivo models. In addition, several well-designed, large, randomized, clinical trials have recently been published. We summarize these recent advances in the field of traditional medicines as they apply to CKD. In addition, current barriers for further research are also discussed. Due to the ongoing research in this field, we believe that stronger evidence to support the use of traditional medicines for CKD will emerge in the near future.

  7. Extrinsic Fabry-Perot ultrasonic detector

    NASA Astrophysics Data System (ADS)

    Kidwell, J. J.; Berthold, John W., III

    1996-10-01

    We characterized the performance of a commercial fiber optic extrinsic Fabry-Perot interferometer for use as an ultrasonic sensor, and compared the performance with a standard lead zirconate titanate (PZT) detector. The interferometer was unstabilized. The results showed that the fiber sensor was about 12 times less sensitive than the PZT detector. Ultrasonic frequency response near 100 kHz was demonstrated. We describe the design of the fiber sensor, the details of the tests performed, and potential applications.

  8. An Archetype Semi-Ring Fabry-Perot (SRFP) Resonator

    NASA Technical Reports Server (NTRS)

    Taghavi-Larigani, Shervin; VanZyl, Jakob

    2009-01-01

    We introduce and demonstrate the generation of a novel resonator, termed Semi-Ring Fabry-Perot (SRFP), that exhibits unique features, such as, its use of one plane mirror, allowing the SRFP to be easily fabricated as a symmetrical device. In addition to its unique features, it exhibits advantages of ring and Fabry-Perot resonators: 1) compared to a ring resonator that only allows a transmitted intensity, the Semi-Ring Fabry-Perot (SRFP) supports standing waves, allowing both a reflected and transmitted intensity; 2) the reflected light spectrum of the SRFP resonator is much narrower than similar Fabry-Perot, implying higher finesse.

  9. Striped Fabry-Perots: Improved efficiency for velocimetry

    SciTech Connect

    McMillan, C.; Steinmetz, L.

    1990-07-01

    Removing a narrow stripe of the reflective coating from the input mirror of a Fabry-Perot interferometer can dramatically increase the amount of light transmitted through the system; we have observed gains in excess of 50 when we compare a conventional Fabry-Perot with the striped Fabry-Perot under similar lighting conditions. The stripe affects the distribution of light in the Fabry-Perot peaks causing them to be lower in the center of the pattern. We examine this distribution, and discuss its application in analyzing velocities. 6 refs., 6 figs., 1 tab.

  10. Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from Fabry mice.

    PubMed

    Meng, Xing-Li; Day, Taniqua S; McNeill, Nathan; Ashcraft, Paula; Frischmuth, Thomas; Cheng, Seng H; Liu, Zhi-Ping; Shen, Jin-Song; Schiffmann, Raphael

    2016-05-01

    Fabry disease is caused by deficient activity of α-galactosidase A and subsequent intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Vascular endothelial cells may play important roles in disease pathogenesis, and are one of the main target cell types in therapeutic interventions. In this study, we generated immortalized aortic endothelial cell lines from a mouse model of Fabry disease. These cells retained endothelial cell-specific markers and functions. Gb3 expression level in one of these clones (referred to as FMEC2) was highly susceptible to culture media, and appeared to be regulated by glucosylceramide synthase. Results also showed that Gb3 could be upregulated by hydrocortisone. FMEC2 express the mannose 6-phosphate receptor and sortilin but not the mannose receptor. Uptake studies suggested that sortilin plays a role in the binding and internalization of mammalian cell-produced α-galactosidase A. Moss-aGal (a plant-made enzyme) was endocytosed by FMEC2 via a receptor other than the aforementioned receptors. In conclusion, this study suggests that glucosylceramide synthase and hydrocortisone may play important roles in modulating Gb3 levels in Fabry mouse aortic endothelial cells, and that endocytosis of recombinant α-galactosidase A involves a combination of multiple receptors depending on the properties of the enzyme. PMID:26960552

  11. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.

  12. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. PMID:27592075

  13. Advances in imaging to allow personalized medicine in Crohn's disease.

    PubMed

    Neurath, Markus F

    2015-08-01

    Crohn's disease is a destructive inflammatory bowel disease of unknown origin that may lead to various complications such as strictures, stenosis, fistulas and colitis-associated neoplasias. However, the course of the disease varies substantially among patients and disease behaviour may also change with time. At diagnosis behaviour is inflammatory in the majority of patients, while penetrating or structuring behaviour become more prominent at later time points. Thus, medication in Crohn's disease needs frequent optimization over time. Therefore, new strategies for prediction of response to therapy are urgently needed. Here, recent advantages in imaging techniques for personalized medicine in Crohn's disease are reviewed. Such advantages include ultrasonography, computed tomography, magnetic resonance imaging and new endoscopic approaches such as molecular endoscopy. It is expected that these novel techniques will lead to marked improvements in the assessment of disease behaviour and the prediction of response to clinical therapy with biologicals. PMID:26002559

  14. An economic Fabry-Perot wavelength reference

    NASA Astrophysics Data System (ADS)

    Fżrész, Gábor; Glenday, Alex; Latham, Christian

    2014-07-01

    Precision radial velocity (PRV) measurements are key in studying exoplanets, and so are wavelength calibrators in PRV instruments. ThAr lamps offer an affordable but somewhat limited solution for the visible passband. Laser frequency combs are ideal calibrators, except the (still) narrow wavelength coverage and large price tag. White light Fabry-Perot (FP) calibrators offer frequency-comb like properties in a more affordable and less complicated package1. Using a commercial solid FP etalon and off-the shelf components we have constructed an economic FP calibrator suitable for observatories on a smaller budget.

  15. Endorectal MRI of Prostate Cancer: Incremental Prognostic Importance of Gross Locally Advanced Disease

    PubMed Central

    Muglia, Valdair F.; Westphalen, Antonio C.; Wang, Zhen J.; Kurhanewicz, John; Carroll, Peter R.; Coakley, Fergus V.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment. PMID:22109291

  16. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  17. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  18. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling

    PubMed Central

    Escobar, Luis E.; Craft, Meggan E.

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  19. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

  20. The Fabry-Perot interferometer prototype for the ADAHELI solar small mission

    NASA Astrophysics Data System (ADS)

    Berrilli, Francesco; Cocciolo, Martina; Giovannelli, Luca; Del Moro, Dario; Giannattasio, Fabio; Piazzesi, Roberto; Stangalini, Marco; Egidi, Alberto; Cavallini, Fabio; Greco, Vincenzo; Selci, Stefano

    2011-10-01

    ADAHELI ADvanced Astronomy for HELIophysics is a solar satellite designed to investigate the fast dynamics of the solar photosphere and chromosphere performing visible and NIR broad-band and monochromatic observations of selected atomic lines. ADAHELI is an Italian Space Agency (ASI) project, approved for a feasibility study within the ASI Small Missions call. ISODY Interferometer for SOlar DYnamics is a Gregorian telescope and its focal plane suite (FPS). The FPS is composed of a high-resolution fast acquisition system, based upon a tandem of Fabry-Pérot interferometers operating in the visible and NIR regions on selected solar atmospheric lines, a broad band channel, and a correlation tracker used as image stabilization system. In this contribution we describe the Fabry-Pérot étalon prototype, based on the capacitance-stabilised concept, realized in our laboratory to perform preliminary mechanical and optical tests with a view to a future Fabry-Pérot étalon prototype for space application.

  1. Advancing the understanding of autism disease mechanisms through genetics

    PubMed Central

    de la Torre-Ubieta, Luis; Won, Hyejung; Stein, Jason L; Geschwind, Daniel H

    2016-01-01

    Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. PMID:27050589

  2. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  3. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD.

  4. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  5. Polycystic liver diseases: advanced insights into the molecular mechanisms.

    PubMed

    Perugorria, Maria J; Masyuk, Tatyana V; Marin, Jose J; Marzioni, Marco; Bujanda, Luis; LaRusso, Nicholas F; Banales, Jesus M

    2014-12-01

    Polycystic liver diseases are genetic disorders characterized by progressive bile duct dilatation and/or cyst development. The large volume of hepatic cysts causes different symptoms and complications such as abdominal distension, local pressure with back pain, hypertension, gastro-oesophageal reflux and dyspnea as well as bleeding, infection and rupture of the cysts. Current therapeutic strategies are based on surgical procedures and pharmacological management, which partially prevent or ameliorate the disease. However, as these treatments only show short-term and/or modest beneficial effects, liver transplantation is the only definitive therapy. Therefore, interest in understanding the molecular mechanisms involved in disease pathogenesis is increasing so that new targets for therapy can be identified. In this Review, the genetic mechanisms underlying polycystic liver diseases and the most relevant molecular pathways of hepatic cystogenesis are discussed. Moreover, the main clinical and preclinical studies are highlighted and future directions in basic as well as clinical research are indicated.

  6. [Advances on pharmacokinetics of traditional Chinese medicine under disease states].

    PubMed

    Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin

    2015-01-01

    In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

  7. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  8. Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor.

    PubMed

    Fan, J Q; Ishii, S; Asano, N; Suzuki, Y

    1999-01-01

    Fabry disease is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal alpha-galactosidase A (alpha-Gal A), resulting in renal failure along with premature myocardial infarction and strokes. No effective treatment of this disorder is available at present. Studies of residual activities of mutant enzymes in many Fabry patients showed that some of them had kinetic properties similar to those for normal alpha-Gal A, but were significantly less stable, especially in conditions of neutral pH (refs. 3-5). The biosynthetic processing was delayed in cultured fibroblasts of a Fabry patient, and the mutant protein formed an aggregate in endoplasmic reticulum, indicating that the enzyme deficiency in some mutants was mainly caused by abortive exit from the endoplasmic reticulum, leading to excessive degradation of the enzyme. We report here that 1-deoxy-galactonojirimycin (DGJ), a potent competitive inhibitor of alpha-Gal A, effectively enhanced alpha-Gal A activity in Fabry lymphoblasts, when administrated at concentrations lower than that usually required for intracellular inhibition of the enzyme. DGJ seemed to accelerate transport and maturation of the mutant enzyme. Oral administration of DGJ to transgenic mice overexpressing a mutant alpha-Gal A substantially elevated the enzyme activity in some organs. We propose a new molecular therapeutic strategy for genetic metabolic diseases of administering competitive inhibitors as 'chemical chaperons' at sub-inhibitory intracellular concentrations. PMID:9883849

  9. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  10. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  11. Isolation and characterization of microsatellite loci in Quercus fabri (Fagaceae).

    PubMed

    Xiao, Z Z; Chen, W W; Bao, W; Wang, R; Li, Y Y

    2016-01-01

    Quercus fabri is a pioneer species of secondary succession in evergreen broadleaved forests in China. In this study, we isolated and developed 12 polymorphic and 2 monomorphic microsatellite loci for Q. fabri using the biotin-streptavidin capture method. We characterized 12 polymorphic loci in 52 individuals from two populations. The number of alleles per locus ranged from 3 to 23. The observed and expected heterozygosities per locus were 0.033-0.773 and 0.138-0.924, respectively. These microsatellite loci will facilitate the studies on genetic variation, mating system, and gene flow of Q. fabri. PMID:27420954

  12. Advances in pediatric rhabdomyosarcoma characterization and disease model development.

    PubMed

    O'Brien, D; Jacob, A G; Qualman, S J; Chandler, D S

    2012-01-01

    Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades.

  13. Advances in the Urinary Exosomes in Renal Diseases.

    PubMed

    Chen, Pei-Pei; Qin, Yan; Li, Xue-Mei

    2016-08-01

    Cells secrete around 30-100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations. PMID:27594162

  14. Advances in pediatric rhabdomyosarcoma characterization and disease model development

    PubMed Central

    Brien, Dennis O’; Jacob, Aishwarya G.; Qualman, Stephen J.; Chandler, Dawn S.

    2014-01-01

    Summary Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor Xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades. PMID:22127592

  15. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and

  16. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  17. Fabry-Perot resonance of water waves.

    PubMed

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  18. Fabry-Perot resonance of water waves

    NASA Astrophysics Data System (ADS)

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  19. Recent advances in the cell biology of polycystic kidney disease.

    PubMed

    Smyth, Brendan J; Snyder, Richard W; Balkovetz, Daniel F; Lipschutz, Joshua H

    2003-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial disorder, crossing multiple ethnicities as well as organ systems. The goal of understanding and, ultimately, curing ADPKD has fostered collaborative efforts among many laboratories, mustered on by the opportunity to probe fundamental cellular biology. Here we review what is known about ADPKD including well-accepted data such as the identification of the causative genes and the fact that PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the "two-hit hypothesis," and somewhat confusing information regarding polycystin-1 and -2 localization and protein interactions. Special attention is paid to the recently discovered role of the cilium in polycystic kidney disease and the model it suggests. Studying ADPKD is important, not only as an evaluation of a multisystem disorder that spans a lifetime, but as a testament to the achievements of modern biology and medicine.

  20. New advances on glial activation in health and disease

    PubMed Central

    Lee, Kim Mai; MacLean, Andrew G

    2015-01-01

    In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development. Future therapies for CNS infection, injury, and neurodegenerative disease are now aimed at targeting astrocyte responses to such insults including astrocyte activation, astrogliosis and other morphological changes, and innate and adaptive immune responses. PMID:25964871

  1. Conventional and advanced MR imaging in infantile Refsum disease.

    PubMed

    Kılıç, Mustafa; Karlı-Oğuz, Kader; Haliloğlu, Göknur; Topçu, Meral; Wanders, Ronald James; Coşkun, Turgay

    2015-01-01

    We report magnetic resonance (MR) imaging findings including diffusion-weighted imaging and proton MR spectroscopy findings in a patient with infantile Refsum disease. The initial diagnosis was made on the basis of history, clinical findings and biochemical studies. Bilateral and symmetrical involvement of the peritrigonal white matter, centrum semiovale, thalami, corpus callosum and corticospinal tracts as assessed by increased T2 signal was highly suggestive of a peroxisomal disorder. Facilitated diffusion was observed in diseased parenchyma. Long echo-time (TE: 270 ms) MRS showed decreased N-acetyl-aspartate/creatine and elevated choline/creatine and lactate; short echo-time MRS (TE: 30 ms) revealed increased myoinositol at 3.56 ppm and lipid peaks at 0.9 and 1.3 ppm. A major contribution to the differential diagnosis came from MR imaging and proton MRS, as discussed in this report.

  2. Advances in diagnosis and management of salivary gland diseases.

    PubMed

    Rice, D H

    1984-02-01

    Salivary glands may be involved in a wide variety of diseases, which may be broadly grouped into (1) inflammatory, (2) noninflammatory, nonneoplastic and (3) neoplastic categories. Most inflammatory and noninflammatory, nonneoplastic diseases should be managed conservatively and symptomatically. The common exceptions are first-arch branchialcleft cysts and calculi. Neoplastic lesions always require resection if that is feasible. For benign tumors, simple excision with a cuff of normal tissue around it will usually suffice. The prevailing trend for treatment of malignant neoplasms is conservatism. No longer is the facial nerve routinely sacrificed. The resection done is dictated by the tumor size and the facial nerve is spared unless directly invaded. Postoperative radiation therapy is increasingly used.

  3. Psychosocial correlates of survival in advanced malignant disease?

    PubMed

    Cassileth, B R; Lusk, E J; Miller, D S; Brown, L L; Miller, C

    1985-06-13

    Prospective studies of the general population have isolated specific social and psychological factors as independent predictors of longevity. This study assesses the ability of these factors, plus two others said to influence survival in patients with cancer, to predict survival and the time to relapse after a diagnosis of cancer. Patients with unresectable cancers (n = 204) were followed to determine the length of survival. Patients with Stage I or II melanoma or Stage II breast cancer (n = 155) were followed to determine the time to relapse. Analysis of data on these 359 patients indicates that social and psychological factors individually or in combination do not influence the length of survival or the time to relapse (P less than 0.10). The specific diagnosis (F = 2.0, P = 0.06), performance status (F = 0.66, P = 0.62), extent of disease (F = 1.12, P = 0.89), and therapy (F = 1.08, P = 0.35) were also unrelated to the psychosocial factors studied. Although these factors may contribute to the initiation of morbidity, the biology of the disease appears to predominate and to override the potential influence of life-style and psychosocial variables once the disease process is established.

  4. Why musical memory can be preserved in advanced Alzheimer's disease.

    PubMed

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  5. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  6. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use.

  7. Advance in the pathogenesis and treatment of Wilson disease

    PubMed Central

    2012-01-01

    Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need. PMID:23210912

  8. Advances in metal-induced oxidative stress and human disease.

    PubMed

    Jomova, Klaudia; Valko, Marian

    2011-05-10

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  9. Advances in Gene Therapy for Diseases of the Eye

    PubMed Central

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-01-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future. PMID:27178388

  10. Advances in Gene Therapy for Diseases of the Eye.

    PubMed

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-08-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future.

  11. Advances in chest drain management in thoracic disease

    PubMed Central

    George, Robert S.

    2016-01-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  12. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  13. Advances in kinase inhibition: treating rheumatic diseases and beyond

    PubMed Central

    Gadina, Massimo

    2014-01-01

    Purpose of review Kinases inhibitors are now used for the treatment of autoimmune diseases. Here are reviewed the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders. Recent findings Similarly to p38 inhibitors, Syk inhibitors have not fulfilled the expectations of researchers and clinicians and will likely not be used therapeutically in autoimmunity. BTK inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Jak inhibitors have revealed that besides T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated. Summary First generation pan-Jak inhibitors can be useful for a wide variety of pathologies. They act on innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner. PMID:24419749

  14. Therapeutic advances in the treatment of Peyronie's disease.

    PubMed

    Yafi, F A; Pinsky, M R; Sangkum, P; Hellstrom, W J G

    2015-07-01

    Peyronie's disease (PD) is an under-diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration-approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon-alpha-2B, however, their use is considered off-label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD-associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non-responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

  15. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  16. Advances in Diagnosis and Management of Celiac Disease

    PubMed Central

    Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.

    2015-01-01

    Celiac disease is an autoimmune disorder induced by dietary gluten in genetically predisposed individuals. It has a prevalence of ∼1% in many populations worldwide. New diagnoses have increased substantially, due to increased awareness, better diagnostic tools, and probable, real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing non-dietary therapies. PMID:25662623

  17. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

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

    PubMed

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

    2015-07-01

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

  19. Fabry-Perot MEMS Accelerometers for Advanced Seismic Imaging

    SciTech Connect

    Chisum, Brad

    2015-05-31

    This report summarizes the technical achievements that occurred over the duration of the project. On November 14th, 2014, Lumedyne Technologies Incorporated was acquired. As a result of the acquisition, the work toward seismic imaging applications was suspended indefinitely. This report captures the progress achieved up to that time.

  20. Advances in Susceptibility Genetics of Intervertebral Degenerative Disc Disease

    PubMed Central

    Zhang, Yin'gang; Sun, Zhengming; Liu, Jiangtao; Guo, Xiong

    2008-01-01

    The traditional view that the etiology of lumbar disc herniation is primarily due to age, gender, occupation, smoking and exposure to vehicular vibration dominated much of the last century. Recent research indicates that heredity may be largely responsible for the degeneration as well as herniation of intervertebral discs. Since 1998, genetic influences have been confirmed by the identification of several genes forms associated with disc degeneration. These researches are paving the way for a better understanding of the biologic mechanisms. Now, many researchers unanimously agree that lumbar disc herniation appears to be similar to other complex diseases, whose etiology has both environmental and hereditary influence, each with a part of contribution and relative risk. Then addressing the etiological of lumbar disc herniation, it is important to integrate heredity with the environment factors. For the purpose of this review, we have limited our discussion to several susceptibility genes associated with disc degeneration. PMID:18781226

  1. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances.

  2. Advances in Surgical Treatment of Congenital Airway Disease.

    PubMed

    Ragalie, William S; Mitchell, Michael E

    2016-01-01

    Tracheobronchomalacia (TBM) is frequently present in infants and children with congenital heart disease (CHD). Infants with CHD and TBM appear to do worse than those without TBM. The principle of operative intervention for TBM is to improve function of the airway and clinical status. When indicated, conventional surgical options include tracheostomy, aortopexy, tracheoplasty, and anterior tracheal suspension. There is no consensus on the optimal treatment of severe tracheobonchomalacia, which can be associated with a mortality rate as high as 80%. Congenital tracheal stenosis is also frequently associated with CHD (vascular rings, atrioventricular canal defects, and septal defects) and may require concomitant repair. Repair of tracheal stenosis is often associated with distal TBM. This article addresses new techniques that can be performed in corrective surgery for both TBM and congenital tracheal stenosis. PMID:27568138

  3. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  4. Recent advances in understanding cardiac contractility in health and disease

    PubMed Central

    MacLeod, Ken T.

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  5. Gamma radiation resistant Fabry-Perot fiber optic sensors

    NASA Astrophysics Data System (ADS)

    Liu, Hanying; Miller, Don W.; Talnagi, Joseph

    2002-08-01

    The Nuclear Regulatory Commission (NRC) in 1998 completed a study of emerging technologies that could be applicable to measurement systems in nuclear power plants [H. M. Hashemian [et al.], "Advanced Instrumentation and Maintenance Technologies for Nuclear Power Plants," NUREG/CR-5501 (1998)]. This study concluded that advanced fiber optic sensing technology is an emerging technology that should be investigated. It also indicated that there had been very little research related to performance evaluation of fiber optic sensors in nuclear plant harsh environments, although substantial research has been performed on nuclear radiation effects on optical fibers in the last two decades. A type of Fabry-Perot fiber optic temperature sensor, which is manufactured by Fiso Technologies in Canada, is qualified to be a candidate for potential applications in nuclear radiation environment due to its unique signal processing technique and its resistance to power loss. The gamma irradiation effects on this type of sensors are investigated in this article. Two sensors were irradiated in a gamma irradiation field and one of them was irradiated up to a total gamma dose of 133 Mrad. The sensor on-line performance was monitored during each gamma irradiation test. Furthermore, the sensor static and dynamic performance before and after each irradiation test were evaluated according to the Standard ISA-dS67.06.01 ("Performance Monitoring for Nuclear Safety-Related Instrument Channels in Nuclear Power Plants", Standard ISA-dS67.06.01, Draft 7, Instrument Society of America, 1999). Although several abnormal phenomena were observed, analysis shows that gamma irradiation is not accredited to the abnormal behavior, which implies that this type of sensor is suitable to a gamma irradiation environment with a high gamma dose.

  6. X-ray imaging in advanced studies of ophthalmic diseases

    SciTech Connect

    Antunes, Andrea; Safatle, Angelica M. V.; Barros, Paulo S. M.; Morelhao, Sergio L.

    2006-07-15

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength {lambda}=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  7. X-ray imaging in advanced studies of ophthalmic diseases.

    PubMed

    Antunes, Andrea; Safatle, Angélica M V; Barros, Paulo S M; Morelhão, Sérgio L

    2006-07-01

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength lambda=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  8. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    PubMed Central

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  9. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD. PMID:27708720

  10. Charles Fabry métrologue

    NASA Astrophysics Data System (ADS)

    Bouchareine, P.

    We describe the two main experimental results obtained by Charles Fabry in fundamental metrology. First, the measurement of the volume of a quartz cube was achieved with Macé de Lépinay, conducting to an enhanced value of the ratio between one "litre" and one cubic decimetre. The probably most important experimental result is the second measurement of the "metre" in optical wavelengths, made in "Conservatoire des arts et métiers”, some years after the first one achieved by Albert Michelson with Jean-René Benoît in the "Bureau international des poids et mesures" in Sèvres. We compare the two experimental devices and processes, the results and their uncertainties. The very good agreement between the two interferometrists was an argument to convince the international community that an atomic wavelength is a better standard for lengths measurements than the platinum Prototype, and lead to the two new definitions of the "mètre" in 1960 and1983. Nous décrivons les deux principaux résultats obtenus par Charles Fabry en métrologie fondamentale. Tout d'abord la mesure du volume d'un cube de quartz a été faite avec Macé de Lépinay, conduisant à une meilleure valeur du rapport du litre au décimètre cube. Le résultat expérimental le plus significatif est probablement la mesure du mètre en longueurs d'onde lumineuses, effectuée au Conservatoire des arts et métiers, quelques années après la première mesure de ce type faite par Albert Michelson avec Jean-René Benoît au Bureau international des poids et mesures à Sèvres. Nous comparons les deux dispositifs expérimentaux et leur exploitation, les résultats et leurs incertitudes. Le très bon accord entre les deux expérimentateurs fut décisif pour convaincre la communauté internationale que la longueur d'onde d'une radiation atomique est un meilleur étalon pour les mesures de longueur que le Prototype international en platine iridié, et conduisit aux deux nouvelles définitions du mètre de 1960

  11. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals.

  12. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals. PMID:27040400

  13. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  14. Recent advances in herbal medicines treating Parkinson's disease.

    PubMed

    Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

    2013-01-01

    Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated.

  15. Building a multicenter telehealth network to advance chronic disease management.

    PubMed

    Khairat, Saif; Wijesinghe, Namal; Wolfson, Julian; Scott, Rob; Simkus, Ray

    2014-01-01

    The use of telehealth solutions has proved to improve clinical management of chronic diseases, expand access to healthcare services and clinicians, and reduce healthcare-related costs. The project aims at improving Heart Failure (HF) management through the utilization of a Telemedicine and Personal Health Records systems that will assist HF specialist in Colombo, Sri Lanka to monitor and consult with remote HF patients. A telehealth network will be built at an international site that connects five remote telehealth clinics to a central clinic at a major University Hospital in Sri Lanka where HF specialists are located. In this study, 200 HF patients will be recruited for nine months, 100 patients will be randomly selected for the treatment group and the other 100 will be selected for the control group. Pre, mid, and post study surveys will be conducted to assess the efficacy and satisfaction levels of patients with both care models. Moreover, clinical outcomes will be collected to evaluate the impact of the intervention on the treatment patients compared to control patients. The research aims at enhancing Heart Failure management through eliminating current health challenges and healthcare-related financial burdens.

  16. Eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease

    SciTech Connect

    Straus, D.J.; Myers, J.; Passe, S.

    1980-07-15

    Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age > 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations; (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

  17. [Social and health impact of advanced chronic kidney disease].

    PubMed

    Górriz Teruel, J L; Otero González, A

    2008-01-01

    The prevalence of CKD in Spain is 11%, with a high rate of associated vascular risk factors and a progressive increase in the number of patients requiring kidney replacement therapy, estimated at 5-8% annually. This has made CKD one of the leading health, social and economic problems for the health care systems of all developed countries. Kidney replacement therapy, although adequate, is not optimal for solving this clinical problem. The key aspects of the problem are: The increase in the number of patients with CKD due to: Early vascular injury as a result of the inflammatory process associated with CKD. Aging of the population, although CKD may be more dependent on comorbidities than age "per se", and prevalence may therefore not have the expected increase. The epidemic of type 2 diabetes mellitus. CKD is the major vascular risk factor both in the general and hypertensive population or patients with established vascular injury. The estimated cost of care of stage 1-4 CKD per year can be 1.6-2.4 times more than kidney replacement therapy. The approach to this serious social and health problem is based on: Early detection and diagnosis of CKD by estimation of glomerular filtration rate and assessment of associated risk factors. Establishment of treatment goals for control of cardiovascular risk factors (blood pressure, dyslipidemia, diabetes mellitus,) and albuminuria to reduce the rate of progression of kidney disease. Joint approach to problem by primary care physicians and other specialists caring for patients at high cardiovascular risk. Establishment of criteria for referral to nephrology departments.

  18. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease.

    PubMed

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  19. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease

    PubMed Central

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  20. Genomic and metabolomic advances in the identification of disease and adverse event biomarkers.

    PubMed

    Mendrick, Donna L; Schnackenberg, Laura

    2009-10-01

    Incomplete knowledge of tissue pathogenesis is hampering the identification of biomarkers for the appropriate therapeutic targets to prevent or inhibit disease processes, and the prediction and diagnosis of injury due to disease and adverse events of drug therapy. The revolution in genomics and metabolomics, combined with advanced bioinformatics and computational methods for mining such large, complex data sets, are beginning to provide critical insights into tissue injury. Such results will move us closer to the promise of personalized medicine.

  1. Fabry-Perot observations of comet Austin

    NASA Technical Reports Server (NTRS)

    Schultz, David; Scherb, F.; Roesler, F. L.; Li, G.; Harlander, J.; Roberts, T. P. P.; Vandenberk, D.; Nossal, S.; Coakley, M.; Oliversen, Ronald J.

    1990-01-01

    Preliminary results of a program to observe Comet Austin (1990c1) from 16 April to 4 May and from 11 May to 27 May 1990 using the West Auxiliary of the McMath Solar Telescope on Kitt Peak, Arizona were presetned. The observations were made with a 15 cm duel-etalon Fabry-Perot scanning and imaging spectrometer with two modes of operation: a high resolution mode with a velocity resolution of 1.2 km/s and a medium resolution mode with a velocity resolution 10 km/s. Scanning data was obtained with an RCA C31034A photomultiplier tube and imaging data was obtained with a Photometrics LN2 cooled CCD camera with a 516 by 516 Ford chip. The results include: (1) information on the coma outflow velocity from high resolution spectral profiles of (OI)6300 and NH2 emissions, (2) gaseous water production rates from medium resolution observation of (OI)6300, (3) spectra of H2O(+) emissions in order to study the ionized component of the coma, (4) spatial distribution of H2O(+) emission features from sequences of velocity resolved images (data cubes), and (5) spatial distribution of (OI)6300 and NH2 emissions from medium resolution images. The field of view on the sky was 10.5 arcminutes in diameter. In the imaging mode the CCD was binned 4 by 4 resulting in 7.6 sec power pixel and a subarray readout for a field of view of 10.5 min.

  2. Surface Plasmons in Fabry-Perot Microcavities

    NASA Astrophysics Data System (ADS)

    Gregory, Stephen

    2000-05-01

    We have developed a technique for creating a tunable Fabry-Perot microcavity by flattening a tunneling microscope tip to create a mirror which is then opposed to a semitransparent metal-film mirror. The latter is deposited on a glass prism through which light can be directed into the cavity and which transmits light emitted by the cavity. With this arrangement we can reproducibly investigate behavior as the mirror separation is tuned down to contact. The modes usually associated with optical cavities are free-space solutions of Maxwell's equations and are populated by photons. However, in a microscopic cavity we must also consider near-field phenomena such as surface-plasmons at the surfaces of the mirrors. These can be excited by a laser beam incident on the prism at an appropriate angle. Surface-plasmon solutions include coupled modes involving both mirrors, which are radially confined in the microcavity. We are studying interconversion of photons and surface-plasmons and the lifetimes of both types of excitations, in particular as these are modified by cavity quantum electrodynamic effects.

  3. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery.

    PubMed

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  4. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  5. Identifying human disease genes: advances in molecular genetics and computational approaches.

    PubMed

    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  6. Advances in the diagnosis and management of inflammatory bowel disease: challenges and uncertainties.

    PubMed

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990-2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  7. Advances in the Diagnosis and Management of Inflammatory Bowel Disease: Challenges and Uncertainties

    PubMed Central

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  8. The Care Needs of Community-Dwelling Seniors Suffering from Advanced Chronic Obstructive Pulmonary Disease

    ERIC Educational Resources Information Center

    Wilson, Donna M.; Ross, Carolyn; Goodridge, Donna; Davis, Penny; Landreville, Alison; Roebuck, Kim

    2008-01-01

    Aim: This study was undertaken to determine the care needs of Canadian seniors living at home with advanced chronic obstructive pulmonary disease (COPD). Background: COPD is a leading cause of morbidity and mortality worldwide. Although hospitalizations for illness exacerbations and end-stage care may be common, most persons with COPD live out…

  9. Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Review of: “Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science”. Elizabeth W. Davdison. 2006. The University of Arizona Press, Tucson, AZ. 208 pp. Dr. Davidson links many of the accomplishments in invertebrate pathology to subsequent successes in the l...

  10. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 23 commercially available peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2014 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to soilborne diseases. Among the 16 runner entries evaluated, Tamrun OL11...

  11. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

  12. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease

    PubMed Central

    Grove, J; Daly, A; Bassendine, M; Gilvarry, E; Day, C

    2000-01-01

    BACKGROUND—The factors determining why less than 10% of heavy drinkers develop advanced alcoholic liver disease (ALD) remain elusive, although genetic factors may be important. Interleukin 10 (IL-10) is an important cytokine with anti-inflammatory, anti-immune, and antifibrotic functions. Several polymorphisms have been identified in the IL-10 promoter and recent evidence suggests that some of these may have functional effects on IL-10 secretion.
AIMS—To test the hypothesis that IL-10 promoter region polymorphisms are associated with susceptibility to ALD.
METHODS—The allele frequencies for the two single base pair substitutions at positions −627 (C→A) and −1117 (A→G) in the IL-10 promoter were determined in 287 heavy drinkers with biopsy proved advanced ALD, 107 heavy drinkers with no evidence of liver disease or steatosis only on biopsy, and 227 local healthy volunteers.
RESULTS—At position −627, 50% of patients with advanced ALD had a least one A allele compared with 33% of controls (p<0.0001) and 34% of drinkers with no or mild disease (p=0.017). At position −1117, the slight excess of the A allele in drinkers with advanced disease was because of linkage disequilibrium between the A alleles at the two sites.
CONCLUSIONS—Among heavy drinkers, possession of the A allele at position −627 in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the −627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.


Keywords: ethyl alcohol; cirrhosis; interleukin 10; genetic polymorphism PMID:10716685

  13. Advances in understanding and treating liver diseases during pregnancy: A review

    PubMed Central

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-01-01

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients. PMID:25954092

  14. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival. PMID:23339016

  15. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.

  16. Fabrication of Fabry-Perot Interferometer Sensors and Characterization of their Performances for Aircraft Inspection

    NASA Technical Reports Server (NTRS)

    Pendergrass, LeRuth Q.

    1995-01-01

    This work provides the information for fabricating Fabry-Perot Interferometer sensors and their performances. The Fabry-Perot Interferometer sensors developed here will be used for the detection of flaws in aircraft structures. The sequel also contains discussion of the experimental setups for the Ultrasonic technique and the Fabry-Perot Interferometer.

  17. A review of advances in the study of diseases of fish: 1954-1964

    USGS Publications Warehouse

    Post, G.

    1965-01-01

    STUDY OF DISEASE IN ANIMALS, INCLUDING MAN, has progressed rapidly in the past decade. Looking back, we find amazing success in the study of man's diseases and possibly only a little less success in studies of diseases of domesticated homeothermic animals. We who are interested in the poikilothermic animals may feel at times that we have not advanced so rapidly in our field. The reason for this may be closely associated with economics. The market for drugs and therapeutic agents is greater for domestic livestock than for cultured fishes. A larger income is derived from rearing domestic livestock. Therefore, more public funds are available for study of diseases of man and domestic livestock, while such funds are limited for the study of diseases of fish. The Federal and State fish-cultural systems, as well as colleges and universities, have been most active in research on fish disease and probably will continue to be so.

  18. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    PubMed

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need.

  19. Atmospheric temperature sensing with a multiorder Fabry-Perot interferometer.

    PubMed

    Wang, J; Drayson, S R; Hayes, P B

    1989-12-01

    A Fabry-Perot interferometer has a periodic response. By matching the free spectral range of a Fabry-Perot interferometer (FPI) with the period of the CO(2) spectrum, considerable advantages of throughput and spectral resolution can be achieved, leading to high spectral resolution and vertical resolution for atmospheric temperature sounders. In this paper, the concept of a high resolution multiorder Fabry-Perot interferometer using portions of the 15-microm and 4.3-microm bands of CO(2)for the purpose of atmospheric temperature sounding is discussed. Suitable sounding spectral positions, FPI free spectral range, and weighting functions are calculated. An effective spectral resolution of 0.02 cm(-1) can be achieved by the proposed sounder with a FPI finess of ~100 which is within the present state-of-the-art technology in the infrared region, leading to considerable improvement in the vertical resolution of the atmospheric temperature sounder. PMID:20555996

  20. Fabry-Pérot interferometry for long range displacement sensing.

    PubMed

    Thurner, Klaus; Braun, Pierre-François; Karrai, Khaled

    2013-09-01

    We investigate different optical configurations of a low-finesse Fabry-Pérot interferometer used for displacement sensing. The different configurations of the Fabry-Pérot cavity are selected in order to achieve large measurement ranges and angular alignment tolerances and to make the interferometer applicable for targets of various reflectivity ranges. The possible working ranges and angular alignment tolerances are characterized with respect to the interference contrast which is a measure for the signal quality. The use of a confocal arrangement enables a measurement range of up to about 0.4 m, or to work with an angular tolerance of more than ±0.2°. In order to predict the optical response of arbitrary configurations of the Fabry-Pérot interferometer, we introduce a simulation method based on the Airy formula and the fiber optic coupling efficiency.

  1. The South Pole Imaging Fabry Perot Interferometer (SPIFI)

    NASA Technical Reports Server (NTRS)

    Stacey, G. J.; Bradford, C. M.; Swain, M. R.; Jackson, J. M.; Bolato, A. D.; Davidson, J. A.; Savage, M.

    1996-01-01

    The design and construction of the South Pole imaging Fabry-Perot interferometer (SPIFI) is reported. The SPIFI is a direct detection imaging spectrometer for use in the far infrared and submillimeter bands accessible to the 1.7 m telescope at the South Pole, and in the submillimeter bands accessible to the 15 m James Clerk Maxwell Telescope (JCMT), HI. It employs a 5 x 5 silicon bolometer array and three cryogenic Fabry Perot interferometers in series in order to achieve velocity resolutions of between 300 km/s and 30 km/s over the entire field of view with a resolution of up to 1 km/s at the center pixel. The scientific justification for the instrument is discussed, considering the spectral lines available to SPIFI. The optical path, the cryogenic Fabry-Perot, the adiabatic demagnetization refrigerator and the detector array are described. The instrument's sensitivity is presented and compared with coherent systems.

  2. Novel tunable Fabry-Perot filters for FBG sensing system

    NASA Astrophysics Data System (ADS)

    Wu, Wei; Tong, Xinglin; Liu, Xin; Chen, Ting

    2008-12-01

    Tunable filters with a wide tunable rang have been found wide applications and be the key component in fiber optical communication system and fiber sensor system. It is hard to fabricate a fiber Fabry-Perot tunable filter. In this paper, the principles of Fabry-Perot filter is introduced, and a novel tunable Fabry-Perot filter is designed and fabricated. The fabricated process of the tunable filter is described and the transmission spectrum of tunable F-P filter in experiment is given and discussed. The tunable F-P filter has the advantages of simple structure, low modulated voltage and cost effectiveness. The filter can be applied to wavelength interrogation in fiber Bragg grating (FBG) sensing system to detect the drift of the fiber Bragg wavelength.

  3. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

    PubMed Central

    2011-01-01

    Background Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients. Methods The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed. Results All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5 - 29.2) after 1 year of shortage (p = 0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. Conclusions No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage

  4. Vibration-induced elastic deformation of Fabry-Perot cavities

    SciTech Connect

    Chen Lisheng; Hall, John L.; Ye Jun; Yang Tao; Zang Erjun; Li Tianchu

    2006-11-15

    We perform a detailed numerical analysis of Fabry-Perot cavities used for state-of-the-art laser stabilization. Elastic deformation of Fabry-Perot cavities with various shapes and mounting methods is quantitatively analyzed using finite-element analysis. We show that with a suitable choice of mounting schemes it is feasible to minimize the susceptibility of the resonator length to vibrational perturbations. This investigation offers detailed information on stable optical cavities that may benefit the development of ultrastable optical local oscillators in optical atomic clocks and precision measurements probing the fundamental laws of physics.

  5. Sapphire-fiber-based intrinsic Fabry-Perot interferometer

    NASA Technical Reports Server (NTRS)

    Wang, Anbo; Gollapudi, Sridhar; Murphy, Kent A.; May, Russell G.; Claus, Richard O.

    1992-01-01

    A sapphire optical fiber intrinsic Fabry-Perot interferometric sensor is demonstrated. A length of multimode sapphire fiber that functions as a Fabry-Perot cavity is spliced to a silica single-mode fiber. The interferometric signals of this sensor are produced by the interference between the reflection from the silica-sapphire fiber splice and the reflection from the free end face of the sapphire fiber. This sensor has been demonstrated for temperature measurement. A resolution of 0.2 C has been obtained over a measurement range of 310 C to 976 C.

  6. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  7. Advanced therapeutic endoscopist and inflammatory bowel disease: Dawn of a new role

    PubMed Central

    Modha, Kunjam; Navaneethan, Udayakumar

    2014-01-01

    Endoscopy plays a key role in the diagnosis and treatment of patients with inflammatory bowel disease (IBD). Colonoscopy has been traditionally used in the diagnosis of IBD and helps in determination of an important end point in patient management, “mucosal healing”. However, the involvement of an advanced endoscopist has expanded with innovations in therapeutic and newer imaging techniques. Endoscopists are increasingly being involved in the management of anastomotic and small bowel strictures in these patients. The advent of balloon enteroscopy has helped us access areas not deemed possible in the past for dilations. An advanced endoscopist also plays an integral part in managing ileal pouch-anal anastomosis complications including management of pouch strictures and sinuses. The use of rectal endoscopic ultrasound has been expanded for imaging of perianal fistulae in patients with Crohn’s disease and appears much more sensitive than magnetic resonance imaging and exam under anesthesia. Advanced endoscopists also play an integral part in detection of dysplasia by employing advanced imaging techniques. In fact the paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology with pancolonic chromoendoscopy becoming the main imaging modality for neoplasia surveillance in IBD patients in most institutions. Advanced endoscopists are also called upon to diagnose primary sclerosing cholangitis (PSC) and also offer options for endoscopic management of strictures through endoscopic retrograde cholangiopancreatography (ERCP). In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization which assesses the presence of chromosomal aneuploidy (abnormality in chromosome number) are established initial diagnostic techniques in the investigation of patients with biliary strictures. Thus advanced

  8. Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities

    PubMed Central

    Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi

    2013-01-01

    Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context. PMID:23680886

  9. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

    PubMed

    Dubois, Bruno; Feldman, Howard H; Jacova, Claudia; Hampel, Harald; Molinuevo, José Luis; Blennow, Kaj; DeKosky, Steven T; Gauthier, Serge; Selkoe, Dennis; Bateman, Randall; Cappa, Stefano; Crutch, Sebastian; Engelborghs, Sebastiaan; Frisoni, Giovanni B; Fox, Nick C; Galasko, Douglas; Habert, Marie-Odile; Jicha, Gregory A; Nordberg, Agneta; Pasquier, Florence; Rabinovici, Gil; Robert, Philippe; Rowe, Christopher; Salloway, Stephen; Sarazin, Marie; Epelbaum, Stéphane; de Souza, Leonardo C; Vellas, Bruno; Visser, Pieter J; Schneider, Lon; Stern, Yaakov; Scheltens, Philip; Cummings, Jeffrey L

    2014-06-01

    In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. PMID:24849862

  10. Advances in the prevention of oral disease; the role of the International Association for Dental Research

    PubMed Central

    2015-01-01

    Abstract Background Since its foundation in 1920, prevention of oral disease has been a priority for the International Association for Dental Research (IADR) and the commitment of the organisation to the subject area is clearly expressed in its mission to improve oral health worldwide. The IADR has a current global membership of almost 11,000 people who share an interest in oral and craniofacial research. Contribution of IADR This paper provides an overview of the contribution of IADR to supporting research and associated activities in disease prevention, in disseminating knowledge and in advocating for better oral health for all citizens of the world. It looks back over time and summarises current supports. Two more recent initiatives in disease prevention are described in more detail, the Global Oral Health Inequalities Research Agenda (GOHIRA) and the proceedings at the 2013 World Conference on Preventive Dentistry (WCPD, 2013), a joint initiative between IADR and WHO. Through organisational structure, meetings, publications, scientific groups and networks and external relations, IADR has been at the forefront of advancing research for the prevention of oral diseases. Conclusions IADR is committed to ensuring research advances get disseminated and implemented and at the same time encourages and advocates for basic, clinical and translational research across disciplines so that we may uncover the major breakthrough in prevention of oral disease. PMID:26391001

  11. Dynamic tension EMG to characterize the effects of DBS treatment of advanced Parkinson's disease.

    PubMed

    Ruonala, V; Pekkonen, E; Rissanen, S; Airaksinen, O; Miroshnichenko, G; Kankaanpää, M; Karjalainen, P

    2014-01-01

    Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters. PMID:25570683

  12. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    PubMed

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  13. Managing uncertainty in advanced liver disease: a qualitative, multiperspective, serial interview study

    PubMed Central

    Kimbell, Barbara; Boyd, Kirsty; Kendall, Marilyn; Iredale, John; Murray, Scott A

    2015-01-01

    Objective To understand the experiences and support needs of people with advanced liver disease and those of their lay and professional carers to inform improvements in the supportive and palliative care of this rapidly growing but currently neglected patient group. Design Multiperspective, serial interviews. We conducted up to three qualitative in-depth interviews with each patient and lay carer over 12 months and single interviews with case-linked healthcare professionals. Data were analysed using grounded theory techniques. Participants Patients with advanced liver disease of diverse aetiologies recruited from an inpatient hepatology ward, and their lay carers and case-linked healthcare professionals nominated by the patients. Setting Primary and secondary care in South-East Scotland. Results 37 participants (15 patients, 11 lay and 11 professional carers) completed 51 individual and 13 joint patient-carer interviews. Nine patients died during the study. Uncertainty dominated experiences throughout the course of the illness, across patients’ considerable physical, psychological, social and existential needs and affected patients, lay carers and professionals. This related to the nature of the condition, the unpredictability of physical deterioration and prognosis, poor communication and information-sharing, and complexities of care. The pervasive uncertainty also shaped patients’ and lay carers’ strategies for coping and impeded care planning. While patients’ acute medical care was usually well coordinated, their ongoing care lacked structure and focus. Conclusions Living, dying and caring in advanced liver disease is dominated by pervasive, enduring and universally shared uncertainty. In the face of high levels of multidimensional patient distress, professionals must acknowledge this uncertainty in constructive ways that value its contribution to the person's coping approach. Pervasive uncertainty makes anticipatory care planning in advanced liver

  14. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  15. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  16. Advances in huntington disease drug discovery: novel approaches to model disease phenotypes.

    PubMed

    Bard, Jonathan; Wall, Michael D; Lazari, Ovadia; Arjomand, Jamshid; Munoz-Sanjuan, Ignacio

    2014-02-01

    Huntington disease is a monogenic, autosomal dominant, progressive neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely correlates with expanded CAG repeat length. HD leads to extensive degeneration of the basal ganglia, hypothalamic nuclei, and selected cortical areas, and a wide range of molecular mechanisms have been implicated in disease pathology in animal or cellular models expressing mutated HTT (mHTT) proteins, either full-length or amino-terminal fragments. However, HD cellular models that recapitulate the slow progression of the disease have not been available due to the toxicity of overexpressed exogenous mHTT or to limitations with using primary cells for long-term studies. Most investigations of the effects of mHTT relied on cytotoxicity or aggregation end points in heterologous systems or in primary embryonic neuroglial cultures derived from HD mouse models. More innovative approaches are currently under active investigation, including screening using electrophysiological endpoints, as well as the recent use of primary blood mononuclear cells and of human embryonic stem cells derived from a variety of HD research participants. Here we describe how these cellular systems are being used to investigate HD biology as well as to identify mechanisms with therapeutic potential.

  17. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease

    PubMed Central

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  18. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease.

    PubMed

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  19. ‘Reality and desire’ in the care of advanced chronic kidney disease

    PubMed Central

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep Mª; Ortiz, Alberto

    2010-01-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process. PMID:25984045

  20. 'Reality and desire' in the care of advanced chronic kidney disease.

    PubMed

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep M; Ortiz, Alberto

    2010-10-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process.

  1. Silicon Carbide Mounts for Fabry-Perot Interferometers

    NASA Technical Reports Server (NTRS)

    Lindemann, Scott

    2011-01-01

    Etalon mounts for tunable Fabry- Perot interferometers can now be fabricated from reaction-bonded silicon carbide structural components. These mounts are rigid, lightweight, and thermally stable. The fabrication of these mounts involves the exploitation of post-casting capabilities that (1) enable creation of monolithic structures having reduced (in comparison with prior such structures) degrees of material inhomogeneity and (2) reduce the need for fastening hardware and accommodations. Such silicon carbide mounts could be used to make lightweight Fabry-Perot interferometers or could be modified for use as general lightweight optical mounts. Heretofore, tunable Fabry-Perot interferometer structures, including mounting hardware, have been made from the low-thermal-expansion material Invar (a nickel/iron alloy) in order to obtain the thermal stability required for spectroscopic applications for which such interferometers are typically designed. However, the high mass density of Invar structures is disadvantageous in applications in which there are requirements to minimize mass. Silicon carbide etalon mounts have been incorporated into a tunable Fabry-Perot interferometer of a prior design that originally called for Invar structural components. The strength, thermal stability, and survivability of the interferometer as thus modified are similar to those of the interferometer as originally designed, but the mass of the modified interferometer is significantly less than the mass of the original version.

  2. A Fabry-Perot Solid Etalon for Teaching.

    ERIC Educational Resources Information Center

    Bruce, P. J.; And Others

    1986-01-01

    Describes a solid etalon Fabry-Perot interferometer, discussing free spectral range, instrumental finesse, and temperature effects. Provides schematic of temperature control/display circuit. Explains use of 100 millimeter camera lens and 10 power micrometer eyepiece for resolving rings and measure diameters. (JM)

  3. Development of the Fabry-Perot Spectrometer Application

    NASA Technical Reports Server (NTRS)

    Browne, Kathryn

    2015-01-01

    Methane is a greenhouse gas with global warming effects 20 times more detrimental than carbon dioxide. Currently, only aircraft missions measure methane and do not provide continuous monitoring, This presentation will cover the Fabry-Perot spectrometer which will provide continuous monitoring of methane. It will also cover the development of the software used to extract and process the data the spectrometer collects.

  4. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

    PubMed

    Tarsy, Daniel

    2012-06-01

    In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.

  5. GPs’ views on managing advanced chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss EM; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-01-01

    Background Chronic kidney disease (CKD) has become a significant part of the GP’s workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. Aim To explore GPs’ views of managing patients with advanced CKD and referral to secondary care. Design and setting Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Method Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. Results GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient’s interests. Conclusion GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. PMID:26120137

  6. Predictive and preventive strategies to advance the treatments of cardiovascular and cerebrovascular diseases: the Ukrainian context

    PubMed Central

    2012-01-01

    Despite great efforts in treatments of cardiovascular diseases, the field requires innovative strategies because of high rates of morbidity, mortality and disability, indicating evident deficits in predictive vascular diagnosis and individualized treatment approaches. Talking about the vascular system, currently, physicians are not provided with integrated medical approaches to diagnose and treat vascular diseases. Only an individual global approach to the analysis of all segments in the vascular system of a patient allows finding the optimal way for vascular disease treatment. As for the existing methodology, there is a dominance of static methods such as X-ray contrast angiography and magnetic resonance imaging in angiomode. Taking into account the world experience, this article deals with innovative strategies, aiming at predictive diagnosis in vascular system, personalization of the biomedical treatment approaches, and targeted prevention of individual patient cohorts. Clinical examples illustrate the advances in corresponding healthcare sectors. Recommendations are provided to promote the field. PMID:23083430

  7. [Research advances on role of microRNAs in congenital heart diseases].

    PubMed

    Yan, Hua-Lin; Hua, Yi-Min

    2014-10-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, which mainly regulate gene expression through post-transcriptional process. They are highly conserved, tissue-specific and highly specific in miRNA-binding on 3'-untranslated regions. MicroRNAs have been identified as crucial regulators in myocardial cell proliferation, differentiation and apoptosis, migration of cardiac neural crest cells, cardiac morphogenesis and cardiac patterning processes, which may provide a new insight into the research on developmental mechanism of congenital heart diseases. The research on miRNAs in congenital heart diseases includes clinical research and animal experiments. This article reviews two types of research advances, the mechanism of congenital heart diseases, and the current status and limitation of the domestic reports.

  8. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  9. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    PubMed Central

    Scanlon, Samantha A; Murray, Joseph A

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions. PMID:22235174

  10. Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease.

    PubMed

    Davis, Ira D; Ho, Martin; Hupertz, Vera; Avner, Ellis D

    2003-10-01

    Childhood PKD encompasses the diagnoses of AR and ADPKD, glomerulocystic disease, and syndromes such as tuberous sclerosis or Jeune's syndrome. Given the fact that a majority of PKD children with ESRD carry the diagnosis of ARPKD, natural history studies assessing the long-term prognosis of PKD patients following renal transplantation must focus on morbidity and mortality issues related to complications from congenital hepatic fibrosis. Using the NAPRTCS registry, we analyzed the patient and graft survival rates of 203 PKD patients and 7044 non-PKD patients undergoing renal transplantation between 1987 and 2001. Deceased PKD patients, all with a diagnosis of ARPKD, were further identified and characterized using a special questionnaire submitted to the principal investigators. Overall graft and patient survival rates were not significantly different between PKD and non-PKD patients. No differences in rates of acute rejection or time to first rejection were noted between PKD and non-PKD patients. The relative risk of living longer than 3 yr in the PKD patients was not significantly different from non-PKD patients (RR = 0.70, p = 0.28). Sepsis was identified as a likely factor in the cause of death in nine (64%) ARPKD patients and was comfirmed with a positive blood culture in four patients. Despite similar graft and patient survival rates among PKD and non-PKD children following renal transplantation, our results suggest that ARPKD transplant recipients appear to be at increased risk for sepsis that may be related to hepatic fibrosis and ascending cholangitis. The utility of early liver transplantation in ARPKD patients with significant hepatobiliary disease is discussed.

  11. Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

    PubMed

    Imai, Kazuo; Maeda, Takuya; Sayama, Yusuke; Osa, Morichika; Mikita, Kei; Kurane, Ichiro; Miyahira, Yasushi; Kawana, Akihiko; Miura, Sachio

    2015-10-01

    Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan.

  12. Optical enhancement of a Fabry-Perot interferometer for low luminance measurements

    SciTech Connect

    Dave, H.H.; Dave, J.H.; Allen, J.E. Jr.; Herrero, F.A.

    1994-12-31

    A high-quality, large numerical aperture Fresnel zone device is being developed to enhance the performance of a Fabry-Perot interferometer (FPI) system. As predicted by the theory, the contributions from the successive interference fringes transmitted by this multiple Fresnel aperture increase the throughput of the FPI system many fold. This versatile optical element can also function as a lens, an aperture and a filter resulting in a very compact system. For a given FPI resolution, a dramatic increase in the throughput and significant reduction in the instrument size attained by this experimental approach offers broad possibilities for major scientific advances for faint radiation measurements in several areas including astronomy, remote sensing of the atmosphere, X-ray microscopy, plasma research, and neutron imaging.

  13. Optical cavity characterization of the Tor Vergata Fabry-Pérot interferometer

    NASA Astrophysics Data System (ADS)

    Giovannelli, Luca; Berrilli, Francesco; Del Moro, Dario; Greco, Vincenzo; Piazzesi, Roberto; Sordini, Andrea; Stangalini, Marco

    2014-08-01

    We report the first optical and control performances of the Tor Vergata Fabry-Ṕerot interferometer prototype designed and realized in the framework of the ADvanced Astronomy for HELIophysics (ADAHELI) solar mission project. The characterization of the the coated surfaces of the two plates defining the optical cavity has been carried out with a Zygo interferometer able to measure the microroughness and global curvature of the cavity. The peak-to-valley errors are compliant with the manufacturer specifications and correspond to λ/70 and λ/80 @632.8 nm respectively. In addition, we present a first estimate of the interferometer spectral stability in stable open-air condition. A spectral uncertainty equal to 0.95 pm is found as the typical RMS over one hour of the passband central wavelength position.

  14. Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms.

    PubMed

    Pokuri, Venkata K; Nourkeyhani, Houman; Betsy, Bodie; Herbst, Laurie; Sikorski, Marcus; Spangenthal, Edward; Fabiano, Andrew; George, Saby

    2015-07-01

    The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.

  15. Advances and challenges in biosensor-based diagnosis of infectious diseases

    PubMed Central

    Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

    2014-01-01

    Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

  16. [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

    PubMed

    Nakai, Kentaro

    2016-09-01

    Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID:27561348

  17. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease.

    PubMed

    Vos, Frederiek E; Schollum, John B; Walker, Robert J

    2011-12-01

    Diabetic nephropathy is the most common aetiology of end-stage kidney disease (ESKD). Strict glycaemic control reduces the development and progression of diabetes-related complications, and there is evidence that improved metabolic control improves outcomes in diabetic subjects with advanced chronic kidney disease (CKD). Glycaemic control in people with kidney disease is complex. Changes in glucose and insulin homeostasis may occur as a consequence of loss of kidney function and dialysis. The reliability of measures of long-term glycaemic control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in the setting of CKD and ESKD is questioned. Despite the altered character of diabetes in CKD, current guidelines for diabetes management are not specifically adjusted to this patient group. The validity of indicators of longer term glycaemic control has been the focus of increased recent research. This review discusses the current understanding of commonly used indicators of metabolic control (HbA1c, fructosamine, glycated albumin) in the setting of advanced CKD (Stages 4 and 5, glomerular filtration rate <30 mL/min/1.73m(2)).

  18. Subcutaneous nephrovesical bypass: Treatment for ureteral obstruction in advanced metastatic disease

    PubMed Central

    WANG, YUNYAN; WANG, GONGCHENG; HOU, PEIJIN; ZHUANG, HAIJUN; YANG, XIAOSONG; GU, SHUO; WANG, HENGBING; JI, LU; XU, ZONGYUAN; MENG, JUNSONG

    2015-01-01

    The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 μmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL. PMID:25435997

  19. Is gardening a stimulating activity for people with advanced Huntington's disease?

    PubMed

    Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

    2014-11-01

    This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD.

  20. Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients

    PubMed Central

    da Costa, Thiago Alvares; Silva, Marcelo José Barbosa; Alves, Polyanna Miranda; Chica, Javier Emílio Lazo; Barcelos, Emilio Zorzo; Giani, Max Antonio Alves; Garlet, Gustavo Pompermaier; da Silva, João Santana; Rodrigues Júnior, Virmondes; Rodrigues, Denise Bertulucci Rocha; Cardoso, Cristina Ribeiro de Barros

    2015-01-01

    Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression. PMID:26063981

  1. Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease.

    PubMed

    Cáceres-Redondo, María T; Carrillo, Fátima; Lama, María J; Huertas-Fernández, Ismael; Vargas-González, Laura; Carballo, Manuel; Mir, Pablo

    2014-03-01

    The short-term benefits of levodopa/carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) are well documented, but the long-term benefits are still uncertain. The aim of this study was to investigate the motor and cognitive outcome of LCIG treatment in advanced PD after a follow-up period of at least 24 months. We assessed 29 patients with advanced PD who started LCIG infusion at our centre between 2007 and 2013. Motor fluctuations, parkinsonian symptoms, activities of daily living and impact on quality of life were evaluated. We also investigated the cognitive outcome using a battery of neuropsychological tests. All adverse events were recorded. Of the 29 PD patients who initiated LCIG, 16 patients reached the follow-up evaluation (24 months), after a mean time period of 32.2 ± 12.4 months. Six patients did not fulfil the 24-month follow-up visit and were evaluated after a mean time period of 8.6 ± 5.4 months. Seven patients discontinued the treatment before the scheduled visit. "Off" time and "On" dyskinesia duration were significantly reduced. LCIG improved quality of life and non motor symptoms, despite overall unchanged total levodopa doses prior to LCIG beginning. Motor and cognitive decline were detected. A relatively high number of adverse events occurred during the follow-up, above all, technical problems with the infusion device and mild problems related with gastrostomy. There were four cases of peripheral neuropathy (PN), 2 of which were considered serious. Our data confirm that LCIG is beneficial in the long-term treatment of advanced PD patients despite a decline in cognitive functions in a subgroup of patients, probably due to disease progression. PN in patients with LCIG may be more frequent than the published date suggest. PMID:24477490

  2. Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-10-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC)  ≤  5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6  ±  1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was  ≥  0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC  ≤  1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

  3. The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-12-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

  4. Advances in Urine Microscopy.

    PubMed

    Becker, Gavin J; Garigali, Giuseppe; Fogazzi, Giovanni B

    2016-06-01

    Urine microscopy is an important tool for the diagnosis and management of several conditions affecting the kidneys and urinary tract. In this review, we describe the automated instruments, based either on flow cytometry or digitized microscopy, that are currently in use in large clinical laboratories. These tools allow the examination of large numbers of samples in short periods. We also discuss manual urinary microscopy commonly performed by nephrologists, which we encourage. After discussing the advantages of phase contrast microscopy over bright field microscopy, we describe the advancements of urine microscopy in various clinical conditions. These include persistent isolated microscopic hematuria (which can be classified as glomerular or nonglomerular on the basis of urinary erythrocyte morphology), drug- and toxin-related cystalluria (which can be a clue for the diagnosis of acute kidney injury associated with intrarenal crystal precipitation), and some inherited conditions (eg, adenine phosphoribosyltransferase deficiency, which is associated with 2,8-dihydroxyadenine crystalluria, and Fabry disease, which is characterized by unique urinary lamellated fatty particles). Finally, we describe the utility of identifying "decoy cells" and atypical malignant cells, which can be easily done with phase contrast microscopy in unfixed samples. PMID:26806004

  5. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  6. Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.

    PubMed

    Naylor, Mary D; Karlawish, Jason H; Arnold, Steven E; Khachaturian, Ara S; Khachaturian, Zaven S; Lee, Virginia M-Y; Baumgart, Matthew; Banerjee, Sube; Beck, Cornelia; Blennow, Kaj; Brookmeyer, Ron; Brunden, Kurt R; Buckwalter, Kathleen C; Comer, Meryl; Covinsky, Kenneth; Feinberg, Lynn Friss; Frisoni, Giovanni; Green, Colin; Guimaraes, Renato Maia; Gwyther, Lisa P; Hefti, Franz F; Hutton, Michael; Kawas, Claudia; Kent, David M; Kuller, Lewis; Langa, Kenneth M; Mahley, Robert W; Maslow, Katie; Masters, Colin L; Meier, Diane E; Neumann, Peter J; Paul, Steven M; Petersen, Ronald C; Sager, Mark A; Sano, Mary; Schenk, Dale; Soares, Holly; Sperling, Reisa A; Stahl, Sidney M; van Deerlin, Vivianna; Stern, Yaakov; Weir, David; Wolk, David A; Trojanowski, John Q

    2012-09-01

    To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article. PMID:22959699

  7. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  8. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  9. Fabry in the older patient: Clinical consequences and possibilities for treatment.

    PubMed

    Lidove, Olivier; Barbey, Frédéric; Niu, Dau-Ming; Brand, Eva; Nicholls, Kathleen; Bizjajeva, Svetlana; Hughes, Derralynn A

    2016-08-01

    Baseline demographic and phenotypic characteristics of patients aged ≥50years in the Fabry Outcome Survey (Shire; data extracted June 2014) were compared with younger adults to investigate potential factors influencing treatment decisions in later life. Age groups were defined using age at treatment initiation or at FOS entry for untreated patients: 18-49 (n=1344; 49.5% male; 64.6% received agalsidase alfa enzyme replacement therapy [ERT]); 50-64 (n=537; 35.4% male; 74.3% treated); 65-74 (n=137; 32.1% male; 68.6% treated); and ≥75years (n=26; 26.9% male; 50.0% treated). Successive age groups showed higher median age at first symptom and diagnosis. Median alpha-galactosidase A activity, measured as percentage activity of the midpoint of the normal range, was much greater in females than males of all groups except ≥75years (33.4% in females; 27.8% in males). Patients aged ≥75years showed greater values than patients aged 18-49years for median left ventricular mass indexed to height (62.7 vs 42.4g/m(2.7)), mean ventricular wall thickness (15.0 vs 10.0mm) and prevalence of hypertension (57.7% vs 21.8%), and lower median estimated glomerular filtration rate (Modification of Diet in Renal Disease: 65.6 vs 98.5mL/min/1.73m(2)). Larger proportions in the groups aged ≥50 exhibited cardiac and/or cerebrovascular manifestations compared with patients aged 18-49years. The smaller proportion of patients receiving ERT aged ≥75years compared with the younger groups might reflect relatively milder disease burden or physician/patient reluctance to initiate/continue ERT at this age. Further studies are needed to increase knowledge of Fabry disease and ERT in later life. PMID:27221354

  10. Fabry-Perot interferometer utilized for displacement measurement in a large measuring range

    SciTech Connect

    Wang, Yung-Cheng; Shyu, Lih-Horng; Chang, Chung-Ping

    2010-09-15

    The optical configuration of a Fabry-Perot interferometer is uncomplicated. This has already been applied in different measurement systems. For the displacement measurement with the Fabry-Perot interferometer, the result is significantly influenced by the tilt angles of the measurement mirror in the interferometer. Hence, only for the rather small measuring range, the Fabry-Perot interferometer is available. The goal of this investigation is to enhance the measuring range of Fabry-Perot interferometer by compensating the tilt angles. To verify the measuring characteristic of the self-developed Fabry-Perot interferometer, some comparison measurements with a reference standard have been performed. The maximum deviation of comparison experiments is less than 0.3 {mu}m in the traveling range of 30 mm. The experimental results show that the Fabry-Perot interferometer is highly stable, insensitive to environment effects, and can meet the measuring requirement of the submicrometer order.

  11. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer. PMID:25898957

  12. Advances in Microfluidic PCR for Point-of-Care Infectious Disease Diagnostics

    PubMed Central

    Park, Seungkyung; Zhang, Yi; Lin, Shin; Wang, Tza-Huei; Yang, Samuel

    2011-01-01

    Global burdens from existing or emerging infectious diseases emphasize the need for point-of-care (POC) diagnostics to enhance timely recognition and intervention. Molecular approaches based on PCR methods have made significant inroads by improving detection time and accuracy but are still largely hampered by resource-intensive processing in centralized laboratories, thereby precluding their routine bedside- or field-use. Microfluidic technologies have enabled miniaturization of PCR processes onto a chip device with potential benefits including speed, cost, portability, throughput, and automation. In this review, we provide an overview of recent advances in microfluidic PCR technologies and discuss practical issues and perspectives related to implementing them into infectious disease diagnostics. PMID:21741465

  13. Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review.

    PubMed

    Staudt, Michael D; Di Sebastiano, Andrea R; Xu, Hu; Jog, Mandar; Schmid, Susanne; Foster, Paula; Hebb, Matthew O

    2016-01-01

    Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) offer a potential class of cytoprotective pharmacotherapeutics that may complement dopamine (DA) replacement and CBT strategies in PD. Chronic NTF delivery may be an integral goal of CBT, with grafts consisting of autologous drug-producing (e.g., DA, NTF) cells that are capable of integration and function in the host brain. In this mini-review, we outline the past experience and recent advances in NTF technology and CBT as promising and integrated approaches for the treatment of PD. PMID:26330171

  14. Current Updates on Therapeutic Advances in the Management of Cardiovascular Diseases.

    PubMed

    Jabir, Nasimudeen R; Siddiqui, Ali Nasir; Firoz, Chelapram Kandy; Ashraf, Ghulam Md; Zaidi, Syed Kashif; Khan, Mohd Shahnawaz; Shakil, Shazi; Alama, Mohammed Nabil; Kamal, Mohammad Amjad; Tabrez, Shams

    2016-01-01

    Despite the significant advances in the medical research and treatment methods, the rate of mortality associated with cardiovascular disease (CVD) is continuously rising and it remains the leading cause of death worldwide. There are several treatment methods for CVD and associated complications that have been considered till now. The current treatment methods cannot produce rapid cure, but could prevent or reduce the progression of this devastating disease. In the current article, we have summarized the use of various pharmacological agents viz. HMG-CoA reductase inhibitors (statins), antihypertensive, thrombolytic and anticoagulation agents that are currently being used for the management of CVD which targets different biochemical or molecular events. Based on our article, more research in this field is advocated which will provide the rapid and effective treatment methods in order to avoid fatal complications associated with CVD. PMID:26601967

  15. Epigenetic regulation of mitochondrial function in neurodegenerative disease: New insights from advances in genomic technologies.

    PubMed

    Devall, Matthew; Roubroeks, Janou; Mill, Jonathan; Weedon, Michael; Lunnon, Katie

    2016-06-20

    The field of mitochondrial epigenetics has received increased attention in recent years and changes in mitochondrial DNA (mtDNA) methylation has been implicated in a number of diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis. However, current publications have been limited by the use of global or targeted methods of measuring DNA methylation. In this review, we discuss current findings in mitochondrial epigenetics as well as its potential role as a regulator of mitochondria within the brain. Finally, we summarize the current technologies best suited to capturing mtDNA methylation, and how a move towards whole epigenome sequencing of mtDNA may help to advance our current understanding of the field. PMID:26876477

  16. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  17. Cardioproteomics: advancing the discovery of signaling mechanisms involved in cardiovascular diseases

    PubMed Central

    Cui, Ziyou; Dewey, Shannamar; Gomes, Aldrin V

    2011-01-01

    Cardioproteomics (Cardiovascular proteomics) is fast becoming an indispensible technique in deciphering changes in signaling pathways that occur in cardiovascular diseases (CVDs). The quality and availability of the instruments and bioinformatics software used for cardioproteomics continues to improve, and these techniques are now available to most cardiovascular researchers either directly or indirectly via university core centers. The heart and aorta are specialized tissues which present unique challenges to investigate. Currently, the diverse range of proteomic techniques available for cardiovascular research makes the choice of the best method or best combination of methods for the disease parameter(s) being investigated as important as the equipment used. This review focuses on proteomic techniques and their applications which have advanced our understanding of the signaling mechanisms involved in CVDs at the levels of protein complex/protein-protein interaction, post-translational modifications and signaling induced protein changes. PMID:22254205

  18. Curvature sensor based on a Fabry-Perot interferometer

    NASA Astrophysics Data System (ADS)

    Monteiro, Catarina; Ferreira, Marta S.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-05-01

    A curvature sensor based on a Fabry-Perot interferometer is proposed. A capillary tube of silica is fusion spliced between two single mode fibers, producing a Fabry-Perot cavity. The light propagates in air, when passing through the capillary tube. Two different cavities are subjected to curvature and temperature. The cavity with shorter length shows insensitivity to both measurands. The larger cavity shows two operating regions for curvature measurement, where a linear response is shown, with a maximum sensitivity of 18.77pm/m-1 for the high curvature radius range. When subjected to temperature, the sensing head produces a similar response for different curvature radius, with a sensitivity of 0.87pm/°C.

  19. Fiber optic, Fabry-Perot high temperature sensor

    NASA Technical Reports Server (NTRS)

    James, K.; Quick, B.

    1984-01-01

    A digital, fiber optic temperature sensor using a variable Fabry-Perot cavity as the sensor element was analyzed, designed, fabricated, and tested. The fiber transmitted cavity reflection spectra is dispersed then converted from an optical signal to electrical information by a charged coupled device (CCD). A microprocessor-based color demodulation system converts the wavelength information to temperature. This general sensor concept not only utilizes an all-optical means of parameter sensing and transmitting, but also exploits microprocessor technology for automated control, calibration, and enhanced performance. The complete temperature sensor system was evaluated in the laboratory. Results show that the Fabry-Perot temperature sensor has good resolution (0.5% of full seale), high accuracy, and potential high temperature ( 1000 C) applications.

  20. Hollow-core fiber Fabry-Perot photothermal gas sensor.

    PubMed

    Yang, Fan; Tan, Yanzhen; Jin, Wei; Lin, Yuechuan; Qi, Yun; Ho, Hoi Lut

    2016-07-01

    A highly sensitive, compact, and low-cost trace gas sensor based on photothermal effect in a hollow-core fiber Fabry-Perot interferometer (FPI) is described. The Fabry-Perot sensor is fabricated by splicing a piece of hollow-core photonic bandgap fiber (HC-PBF) to single-mode fiber pigtails at both ends. The absorption of a pump beam in the hollow core results in phase modulation of probe beam, which is detected by the FPI. Experiments with a 2 cm long HC-PBF with femtosecond laser drilled side-holes demonstrated a response time of less than 19 s and noise equivalent concentration (NEC) of 440 parts-per-billion (ppb) using a 1 s lock-in time constant, and the NEC goes down to 117 ppb (2.7×10-7 in absorbance) by using 77 s averaging time.

  1. Principle and applications of Faraday-Fabry-Perot cavity

    NASA Astrophysics Data System (ADS)

    Di, Nan; Zhao, Jianlin

    2010-10-01

    A Faraday-Fabry-Perot (FFP) cavity, composed of an Fabry-Perot (FP) cavity and a piece of Faraday magneto-optical material, is presented. The principle of FFP cavity and its polarization modulation effect are described by use of optical matrix analysis. The result shows that the Faraday rotation is able to be magnified by more than two orders of magnitude in resonant FFP cavity, while different elliptically polarized lights are obtained in non-resonant cavity. Furthermore two novel applications, that is, optical isolator based on passive FFP cavity (FOI) and Faraday-Zeeman dual-frequency laser (FZDL) based on active FFP cavity whose eigen modes operate as circularly polarized lights and whose frequency difference can be adjusted continuously by magnetic field, are introduced. The principles, typical parameters and performance characteristics are analyzed in both applications.

  2. Hollow-core fiber Fabry-Perot photothermal gas sensor.

    PubMed

    Yang, Fan; Tan, Yanzhen; Jin, Wei; Lin, Yuechuan; Qi, Yun; Ho, Hoi Lut

    2016-07-01

    A highly sensitive, compact, and low-cost trace gas sensor based on photothermal effect in a hollow-core fiber Fabry-Perot interferometer (FPI) is described. The Fabry-Perot sensor is fabricated by splicing a piece of hollow-core photonic bandgap fiber (HC-PBF) to single-mode fiber pigtails at both ends. The absorption of a pump beam in the hollow core results in phase modulation of probe beam, which is detected by the FPI. Experiments with a 2 cm long HC-PBF with femtosecond laser drilled side-holes demonstrated a response time of less than 19 s and noise equivalent concentration (NEC) of 440 parts-per-billion (ppb) using a 1 s lock-in time constant, and the NEC goes down to 117 ppb (2.7×10-7 in absorbance) by using 77 s averaging time. PMID:27367092

  3. Incidence and Predictors of 30-Day Readmission Among Patients Hospitalized for Advanced Liver Disease

    PubMed Central

    BERMAN, KENNETH; TANDRA, SWETA; FORSSELL, KATE; VUPPALANCHI, RAJ; BURTON, JAMES R.; NGUYEN, JAMES; MULLIS, DEVONNE; KWO, PAUL; CHALASANI, NAGA

    2011-01-01

    BACKGROUND & AIMS The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients, but it has not been studied adequately for patients with advanced liver disease. We investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days. METHODS We analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008. Patients with elective admission and recipients of liver transplants were not included. During the study period, there were 447 patients and a total of 554 eligible admissions. Multivariate analyses were performed to identify variables associated with 30-day readmission and to examine its relationship with mortality at 90 days. RESULTS The 30-day readmission rate was 20%. After adjusting for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.09; P = .002), the presence of diabetes (OR, 1.78; 95% CI, 1.07–2.95; P = .027), and male sex (OR, 1.73; 95% CI, 1.03–2.89; P = .038). After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not (26.8% vs 9.8%; OR, 2.6; 95% CI, 1.36 –5.02; P = .004). CONCLUSIONS Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge; these patients have a higher 90-day mortality rate than those who are not readmitted in 30 days. These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis. PMID:21092762

  4. Orthogonal Fabry-Pérot sensors for photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Ellwood, R.; Ogunlade, O.; Zhang, E. Z.; Beard, P. C.; Cox, B. T.

    2016-03-01

    Fabry-Pérot (FP) sensors have been used to produce in-vivo photoacoustic images of exquisite quality. However, for simplicity of construction FP sensors are produced in a planar form. Planar sensors suffer from a limited detection aperture, due to their planarity. We present a novel sensor geometry that allowed a greater field of view by placing a second sensor orthogonal to the first. This captured data from the deeper lying regions of interest and mitigated the limited view.

  5. Micromachined Tunable Fabry-Perot Filters for Infrared Astronomy

    NASA Technical Reports Server (NTRS)

    Barclay, Richard; Bier, Alexander; Chen, Tina; DiCamillo, Barbara; Deming, Drake; Greenhouse, Matthew; Henry, Ross; Hewagama, Tilak; Jacobson, Mindy; Loughlin, James; Krebs, Carolyn A. (Technical Monitor)

    2002-01-01

    Micromachined Fabry-Perot tunable filters with a large clear aperture (12.5 to 40 mm) are being developed as an optical component for wide-field imaging 1:1 spectroscopy. This program applies silicon micromachining fabrication techniques to miniaturize Fabry-Perot filters for astronomical science instruments. The filter assembly consists of a stationary etalon plate mated to a plate in which the etalon is free to move along the optical axis on silicon springs attached to a stiff silicon support ring. The moving etalon is actuated electrostatically by electrode pairs on the fixed and moving etalons. To reduce mass, both etalons are fabricated by applying optical coatings to a thin freestanding silicon nitride film held flat in drumhead tension rather than to a thick optical substrate. The design, electro-mechanical modeling, fabrication, and initial results will be discussed. The potential application of the miniature Fabry-Perot filters will be briefly discussed with emphasis on the detection of extra-solar planets.

  6. Recent advance in the molecular genetics of Wilson disease and hereditary hemochromatosis.

    PubMed

    Lv, Tingxia; Li, Xiaojin; Zhang, Wei; Zhao, Xinyan; Ou, Xiaojuan; Huang, Jian

    2016-10-01

    Metabolic liver diseases such as Wilson disease (WD) and hereditary hemochromatosis (HH) possess complicated pathogenesis and typical hereditary characteristics with the hallmarks of a deficiency in metal metabolism. Mutations in genes encoding ATPase, Cu + transporting, beta polypeptide (ATP7B) and hemochromatosis (HFE) or several non-HFE genes are considered to be causative for WD and HH, respectively. Although the identification of novel mutations in ATP7B for WD and HFE or the non-HFE genes for HH has increased, especially with the application of whole genome sequencing technology in recent years, the biological function of the identified mutations, as well as genotype-phenotype correlations remain to be explored. Further analysis of the causative gene mutation would be critical to clarify the mechanisms underlying specific disease phenotypes. In this review, we therefore summarize the recent advances in the molecular genetics of WD and HH including the updated mutation spectrums and the correlation between genotype and phenotype, with an emphasis on biological functional studies of the individual mutations identified in WD and HH. The weakness of the current functional studies and analysis for the clinical association of the individual mutation was also discussed. These works are essential for the understanding of the association between genotypes and phenotypes of these inherited metabolic liver diseases.

  7. Inherited retinal diseases in dogs: advances in gene/mutation discovery

    PubMed Central

    Miyadera, Keiko

    2015-01-01

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed. PMID:26120276

  8. Recent advances in the application of metabolomics to Alzheimer’s Disease

    PubMed Central

    Trushina, Eugenia; Mielke, Michelle M.

    2013-01-01

    The pathophysiological changes associated with Alzheimer’s Disease (AD) begin decades before the emergence of clinical symptoms. Understanding the early mechanisms associated with AD pathology is, therefore, especially important for identifying disease-modifying therapeutic targets. While the majority of AD clinical trials to date have focused on anti-amyloid-beta (Aβ) treatments, other therapeutic approaches may be necessary. The ability to monitor changes in cellular networks that include both Aβ and non-Aβ pathways is essential to advance our understanding of the etiopathogenesis of AD and subsequent development of cognitive symptoms and dementia. Metabolomics is a powerful tool that detects perturbations in the metabolome, a pool of metabolites that reflects changes downstream of genomic, transcriptomic and proteomic fluctuations, and represents an accurate biochemical profile of the organism in health and disease. The application of metabolomics could help to identify biomarkers for early AD diagnosis, to discover novel therapeutic targets, and to monitor therapeutic response and disease progression. Moreover, given the considerable parallel between mouse and human metabolism, the use of metabolomics provides ready translation of animal research into human studies for accelerated drug design. In this review, we will summarize current progress in the application of metabolomics in both animal models and in humans to further understanding of the mechanisms involved in AD pathogenesis. PMID:23816564

  9. Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

    PubMed

    Oliveira, Cláudia; Ribeiro, António J; Veiga, Francisco; Silveira, Isabel

    2016-05-01

    Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far. PMID:27305810

  10. Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

    PubMed

    Oliveira, Cláudia; Ribeiro, António J; Veiga, Francisco; Silveira, Isabel

    2016-05-01

    Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far.

  11. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  12. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  13. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  14. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

    PubMed Central

    Maan, Raoel; van der Meer, Adriaan J.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID:27006761

  15. Dietary Advanced Glycation End Products and Their Role in Health and Disease12

    PubMed Central

    Uribarri, Jaime; del Castillo, María Dolores; de la Maza, María Pía; Filip, Rosana; Gugliucci, Alejandro; Luevano-Contreras, Claudia; Macías-Cervantes, Maciste H; Markowicz Bastos, Deborah H; Medrano, Alejandra; Menini, Teresita; Portero-Otin, Manuel; Rojas, Armando; Sampaio, Geni Rodrigues; Wrobel, Kazimierz; Wrobel, Katarzyna; Garay-Sevilla, Ma Eugenia

    2015-01-01

    Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1–3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research. PMID:26178030

  16. Advances in translational bioinformatics facilitate revealing the landscape of complex disease mechanisms

    PubMed Central

    2014-01-01

    Advances of high-throughput technologies have rapidly produced more and more data from DNAs and RNAs to proteins, especially large volumes of genome-scale data. However, connection of the genomic information to cellular functions and biological behaviours relies on the development of effective approaches at higher systems level. In particular, advances in RNA-Seq technology has helped the studies of transcriptome, RNA expressed from the genome, while systems biology on the other hand provides more comprehensive pictures, from which genes and proteins actively interact to lead to cellular behaviours and physiological phenotypes. As biological interactions mediate many biological processes that are essential for cellular function or disease development, it is important to systematically identify genomic information including genetic mutations from GWAS (genome-wide association study), differentially expressed genes, bidirectional promoters, intrinsic disordered proteins (IDP) and protein interactions to gain deep insights into the underlying mechanisms of gene regulations and networks. Furthermore, bidirectional promoters can co-regulate many biological pathways, where the roles of bidirectional promoters can be studied systematically for identifying co-regulating genes at interactive network level. Combining information from different but related studies can ultimately help revealing the landscape of molecular mechanisms underlying complex diseases such as cancer. PMID:25559210

  17. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study

    PubMed Central

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m2 and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox’s analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46–1.91) and 1% (HR = 1.01, 95% CI: 1.01–1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  18. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review.

    PubMed

    de la Morena, M Teresa; Nelson, Robert P

    2014-04-01

    Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is

  19. Results of two different surgical techniques in the treatment of advanced-stage Freiberg's disease

    PubMed Central

    Özkul, Emin; Gem, Mehmet; Alemdar, Celil; Arslan, Hüseyin; Boğatekin, Ferit; Kişin, Bülent

    2016-01-01

    Background: Freiberg's disease is an osteochondrosis most commonly seen in adolescent women and characterized by pain, swelling and motion restriction in the second metatarsal. The early stages of this disease can be managed with semirigid orthoses, metatarsal bars and short leg walking cast. Number of operative methods are suggested which can be used depending on the pathophysiology of the disease, including abnormal biomechanics, joint congruence and degenerative process. We evaluated the outcomes of the patients with Freiberg's disease who were treated with dorsal closing-wedge osteotomy and resection of the metatarsal head. Patients and Methods: 16 patients (11 female, 5 male) with a mean age of 24.5 (range 13–49 years) years who underwent dorsal closing wedge osteotomy or resection of the metatarsal head were included in this retrospective study. Second metatarsal was affected in 13 and third metatarsal in three patients. According to the Smillie's classification system, ten patients had type IV osteonecrosis and six patients had type V. The results of the patients were evaluated using the lesser metatarsophalangeal-interphalangeal (LMPI) scale. Results: According to the LMPI scale, the postoperative scores for the osteotomy and excision groups were 86 (range 64–100) and 72.6 (range 60–85), respectively. In the osteotomy group, mean passive flexion restriction was 18° (range 0°–35°) and mean passive extension restriction was 12° (range 0°–25°). Mean metatarsal shortening was 2.2 mm (range 2–4 mm) in the osteotomy group as opposed to 9.8 mm (range 7–14 mm) in the excision group. Significant pain relief was obtained in both groups following the surgery. Conclusions: The decision of performing osteotomy or resection arthroplasty in the patients with advanced-stage Freiberg's disease should be based on the joint injury and the patients should be informed about the cosmetic problems like shortening which may arise from resection. PMID:26955180

  20. Advances in the Treatment of Aortic Valve Disease: is it Time for Companion Diagnostics?

    PubMed Central

    Hinton, Robert B.

    2014-01-01

    Purpose of the review Aortic valve disease (AVD) is a growing public health problem, and the pathogenesis underlying AVD is complex. The lack of durable bioprostheses and pharmacologic therapies remain central needs in care. The purpose of this review is to highlight recent clinical studies that impact the care of children with AVD and to explore ongoing translational research efforts. Recent findings Clinical studies have evaluated the durability of bioprosthetics and surgical strategies, tested statins during early disease, and identified new predictive biomarkers. Large animal models have demonstrated the effectiveness of a novel bioprosthetic scaffold. Mouse models of latent AVD have advanced our ability to elucidate natural history and perform preclinical studies that test new treatments in the context of early disease. Summary Current priorities for AVD patients include identifying new pharmacologic treatments and developing durable bioprostheses. Multidisciplinary efforts are needed that bridge pediatric and adult programs, bring together different types of expertise and leverage network and consortium resources. As our understanding of the underlying complex genetics is better defined, companion diagnostics may transform future clinical trials and ultimately improve the care of patients with AVD by promoting personalized medicine and early intervention. PMID:25089943

  1. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2013-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

  2. Recent advances in understanding the role of lamins in health and disease

    PubMed Central

    Reddy, Sita; Comai, Lucio

    2016-01-01

    Lamins are major components of the nuclear lamina, a network of proteins that supports the nuclear envelope in metazoan cells. Over the past decade, biochemical studies have provided support for the view that lamins are not passive bystanders providing mechanical stability to the nucleus but play an active role in the organization of the genome and the function of fundamental nuclear processes. It has also become apparent that lamins are critical for human health, as a large number of mutations identified in the gene that encodes for A-type lamins are associated with tissue-specific and systemic genetic diseases, including the accelerated aging disorder known as Hutchinson-Gilford progeria syndrome. Recent years have witnessed great advances in our understanding of the role of lamins in the nucleus and the functional consequences of disease-associated A-type lamin mutations. Many of these findings have been presented in comprehensive reviews. In this mini-review, we discuss recent breakthroughs in the role of lamins in health and disease and what lies ahead in lamin research. PMID:27803806

  3. Health, economic, psychological and social impact of educating carers of patients with advanced pulmonary disease (protocol).

    PubMed

    Sladek, R M; Jones, T; Phillips, P A; Luszcz, M; Rowett, D; Eckermann, S; Woodman, R J; Frith, P

    2011-09-01

    People with advanced pulmonary disease (APD), such as those with chronic obstructive pulmonary disease, have markedly impaired quality of life. Home Oxygen Therapy (HOT) itself is burdensome, although it often improves survival duration and quality of life in these patients. The exact burdens on informal caregivers of these patients are unknown. The central purpose of the pragmatic randomized controlled study described in this protocol is to determine the effectiveness of improving the skills and knowledge of carers of patients with APD who use HOT. Specifically we aimed to estimate the incremental impact of this carer intervention above usual care on health, economic, psychological and social domains for patient and carer dyads relative to the level of current burden. Eligible patients and their carers were recruited through three major hospitals, and randomized to an intervention or control group. The carers in the intervention group received two home-delivered education sessions based on the principles of academic detailing. Participants are currently being followed over 12 months. The primary outcome will be the proportion of patients surviving without a chronic obstructive pulmonary disease-related readmission / residential (non respite) care over 12 months. Carer secondary outcomes include perceived caregiver burden, level of expected and received social support, perceived level of mastery, self esteem, health related quality of life and disability, and ability to conduct domestic chores and household maintenance, social activities and provide service to others, and fatigue. Secondary patient outcomes include health related quality of life and disability, and current respiratory health status.

  4. Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

    PubMed Central

    Ponziani, Francesca Romana; Gerardi, Viviana; Pecere, Silvia; D’Aversa, Francesca; Lopetuso, Loris; Zocco, Maria Assunta; Pompili, Maurizio; Gasbarrini, Antonio

    2015-01-01

    Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial “fingerprint”, characterized by the reduced ratio of “good” to “potentially pathogenic” bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease. PMID:26604640

  5. Big data to smart data in Alzheimer's disease: Real-world examples of advanced modeling and simulation.

    PubMed

    Haas, Magali; Stephenson, Diane; Romero, Klaus; Gordon, Mark Forrest; Zach, Neta; Geerts, Hugo

    2016-09-01

    Many disease-modifying clinical development programs in Alzheimer's disease (AD) have failed to date, and development of new and advanced preclinical models that generate actionable knowledge is desperately needed. This review reports on computer-based modeling and simulation approach as a powerful tool in AD research. Statistical data-analysis techniques can identify associations between certain data and phenotypes, such as diagnosis or disease progression. Other approaches integrate domain expertise in a formalized mathematical way to understand how specific components of pathology integrate into complex brain networks. Private-public partnerships focused on data sharing, causal inference and pathway-based analysis, crowdsourcing, and mechanism-based quantitative systems modeling represent successful real-world modeling examples with substantial impact on CNS diseases. Similar to other disease indications, successful real-world examples of advanced simulation can generate actionable support of drug discovery and development in AD, illustrating the value that can be generated for different stakeholders. PMID:27327540

  6. Big data to smart data in Alzheimer's disease: Real-world examples of advanced modeling and simulation.

    PubMed

    Haas, Magali; Stephenson, Diane; Romero, Klaus; Gordon, Mark Forrest; Zach, Neta; Geerts, Hugo

    2016-09-01

    Many disease-modifying clinical development programs in Alzheimer's disease (AD) have failed to date, and development of new and advanced preclinical models that generate actionable knowledge is desperately needed. This review reports on computer-based modeling and simulation approach as a powerful tool in AD research. Statistical data-analysis techniques can identify associations between certain data and phenotypes, such as diagnosis or disease progression. Other approaches integrate domain expertise in a formalized mathematical way to understand how specific components of pathology integrate into complex brain networks. Private-public partnerships focused on data sharing, causal inference and pathway-based analysis, crowdsourcing, and mechanism-based quantitative systems modeling represent successful real-world modeling examples with substantial impact on CNS diseases. Similar to other disease indications, successful real-world examples of advanced simulation can generate actionable support of drug discovery and development in AD, illustrating the value that can be generated for different stakeholders.

  7. Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn's Disease.

    PubMed

    Wang, Kuan; Wu, Lu-Yi; Dou, Chuan-Zi; Guan, Xin; Wu, Huan-Gan; Liu, Hui-Rong

    2016-01-01

    To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD. PMID:27651792

  8. Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn's Disease

    PubMed Central

    Dou, Chuan-zi; Guan, Xin; Wu, Huan-gan

    2016-01-01

    To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD.

  9. Liver transplantation for chronic liver disease: advances and controversies in an era of organ shortages

    PubMed Central

    Prince, M; Hudson, M

    2002-01-01

    Since liver transplantation was first performed in 1968 by Starzl et al, advances in case selection, liver surgery, anaesthetics, and immunotherapy have significantly increased the indications for and success of this operation. Liver transplantation is now a standard therapy for many end stage liver disorders as well as acute liver failure. However, while demand for cadaveric organ grafts has increased, in recent years the supply of organs has fallen. This review addresses current controversies resulting from this mismatch. In particular, methods for increasing graft availability and difficulties arising from transplantation in the context of alcohol related cirrhosis, primary liver tumours, and hepatitis C are reviewed. Together these three indications accounted for 42% of liver transplants performed for chronic liver disease in the UK in 2000. Ethical frameworks for making decisions on patients' suitability for liver transplantation have been developed in both the USA and the UK and these are also reviewed. PMID:11884694

  10. Research Advance in Intestinal Mucosal Barrier and Pathogenesis of Crohn's Disease

    PubMed Central

    Dou, Chuan-zi; Guan, Xin; Wu, Huan-gan

    2016-01-01

    To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD. PMID:27651792

  11. Examining the Role of Gender in Career Advancement at the Centers for Disease Control and Prevention

    PubMed Central

    Roy, Kakoli; Gotway Crawford, Carol A.

    2010-01-01

    During the past decade, efforts to promote gender parity in the healing and public health professions have met with only partial success. We provide a critical update regarding the status of women in the public health profession by exploring gender-related differences in promotion rates at the nation's leading public health agency, the Centers for Disease Control and Prevention (CDC). Using personnel data drawn from CDC, we found that the gender gap in promotion has diminished across time and that this reduction can be attributed to changes in individual characteristics (e.g., higher educational levels and more federal work experience). However, a substantial gap in promotion that cannot be explained by such characteristics has persisted, indicating continuing barriers in women's career advancement. PMID:20075327

  12. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

    PubMed

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Bello, Alexander; Fernando, Lisa; Alimonti, Judie B; Fausther-Bovendo, Hugues; Wei, Haiyan; Aviles, Jenna; Hiatt, Ernie; Johnson, Ashley; Morton, Josh; Swope, Kelsi; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Pauly, Michael H; Velasco, Jesus; Pettitt, James; Olinger, Gene G; Whaley, Kevin; Xu, Bianli; Strong, James E; Zeitlin, Larry; Kobinger, Gary P

    2014-10-01

    Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

  13. Recent advances in understanding the biomolecular basis of chronic beryllium disease: a review.

    PubMed

    McCleskey, T Mark; Buchner, Virginia; Field, R William; Scott, Brian L

    2009-01-01

    In this review we summarize the work conducted over the past decade that has advanced our knowledge of pulmonary diseases associated with exposure to beryllium that has provided a molecular-based understanding of the chemistry, immunopathology, and immunogenetics of beryllium toxicity. Beryllium is a strong and lightweight metal that generates and reflects neutrons, resists corrosion, is transparent to X-rays, and conducts electricity. Beryllium is one of the most toxic elements on the periodic table, eliciting in susceptible humans (a) an allergic immune response known as beryllium sensitization (BeS); (b) acute beryllium disease, an acutely toxic, pneumonitis-like lung condition resulting from exposure to high beryllium concentrations that are rarely seen in modern industry; and (c) chronic beryllium disease (CBD) following either high or very low levels of exposure. Because of its exceptional strength, stability, and heat-absorbing capability, beryllium is used in many important technologies in the modern world. In the early 1940s, beryllium was recognized as posing an occupational hazard in manufacturing and production settings. Although acute beryllium disease is now rare, beryllium is an insidious poison with a latent toxicity and the risk of developing CBD persists. Chronic beryllium disease-a systemic granulomatous lung disorder caused by a specific delayed immune response to beryllium within a few months to several decades after exposure-has been called the "unrecognized epidemic". Although not a disease in itself, BeS, the innate immune response to beryllium identified by an abnormal beryllium lymphocyte proliferation test result, is a population-based predictor of CBD. Genetic susceptibility to CBD is associated with alleles of the major histocompatibility gene, human leukocyte antigen DP (HLA-DP) containing glutamic acid at the 69th position of the beta chain (HLA-DPbeta-E69). Other genes are likely to be involved in the disease process, and research on

  14. Mary S. Easton Center of Alzheimer's Disease Research at UCLA: advancing the therapeutic imperative.

    PubMed

    Cummings, Jeffrey L; Ringman, John; Metz, Karen

    2010-01-01

    The Mary S. Easton Center for Alzheimer's Disease Research (UCLA-Easton Alzheimer's Center) is committed to the "therapeutic imperative" and is devoted to finding new treatments for Alzheimer's disease (AD) and to developing technologies (biomarkers) to advance that goal. The UCLA-Easton Alzheimer's Center has a continuum of research and research-related activities including basic/foundational studies of peptide interactions; translational studies in transgenic animals and other animal models of AD; clinical research to define the phenotype of AD, characterize familial AD, develop biomarkers, and advance clinical trials; health services and outcomes research; and active education, dissemination, and recruitment activities. The UCLAEaston Alzheimer's Center is supported by the National Institutes on Aging, the State of California, and generous donors who share our commitment to developing new therapies for AD. The naming donor (Jim Easton) provided substantial funds to endow the center and to support projects in AD drug discovery and biomarker development. The Sidell-Kagan Foundation supports the Katherine and Benjamin Kagan Alzheimer's Treatment Development Program, and the Deane F. Johnson Alzheimer's Research Foundation supports the Deane F. Johnson Center for Neurotherapeutics at UCLA. The John Douglas French Alzheimer's Research Foundation provides grants to junior investigators in critical periods of their academic development. The UCLA-Easton Alzheimer's Center partners with community organizations including the Alzheimer's Association California Southland Chapter and the Leeza Gibbons memory Foundation. Collaboration with pharmaceutical companies, biotechnology companies, and device companies is critical to developing new therapeutics for AD and these collaborations are embraced in the mission of the UCLA-Easton Alzheimer's Center. The Center supports excellent senior 3 investigators and serves as an incubator for new scientists, agents, models, technologies

  15. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2004-07-01

    This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003. Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march. Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart. A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis. In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin. Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom.

  16. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year.

  17. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2015-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

  18. Gender difference in advanced HIV disease and late presentation according to European consensus definitions

    PubMed Central

    Jiang, Hongbo; Yin, Jieyun; Fan, Yunzhou; Liu, Jianhua; Zhang, Zhixia; Liu, Li; Nie, Shaofa

    2015-01-01

    Effectiveness of highly active antiretroviral therapy is limited for a large proportion of individuals living with HIV presenting for medical care at an advanced stage. Controversial results of gender differences in risk of late HIV diagnosis were reported among existing literatures. Therefore, we conducted this meta-analysis to synthesize a summary of gender differences in risk of advanced HIV disease (AHD) and late presentation (LP) according to European consensus definitions. Totally, 32 studies were included based on predetermined selection criteria. The pooled adjusted odds ratios of males presenting with AHD and LP compared with females were 1.73 (95% confidence interval [CI], 1.59–1.89) and 1.38 (95% CI, 1.18–1.62) with significant heterogeneity observed (I2 = 78.50%, and I2 = 85.60%, respectively). Subgroup analysis revealed that time lag, study location, number of patients, proportion of females, study design, number of adjusted variables might be potential source of heterogeneity. Sensitivity analysis showed robustness of the results. No publication bias was observed in studies on AHD or LP. The current meta-analysis indicated that males are at higher risk of AHD or LP compared with females. More attention should be paid to males to make sure early testing, diagnosis, and treatment, and ultimately improve individual and population health. PMID:26412578

  19. Conjugate Fabry-Perot cavity pair for improved astro-comb accuracy.

    PubMed

    Li, Chih-Hao; Chang, Guoqing; Glenday, Alexander G; Langellier, Nicholas; Zibrov, Alexander; Phillips, David F; Kärtner, Franz X; Szentgyorgyi, Andrew; Walsworth, Ronald L

    2012-08-01

    We propose a new astro-comb mode-filtering scheme composed of two Fabry-Perot cavities (coined "conjugate Fabry-Perot cavity pair"). Simulations indicate that this new filtering scheme makes the accuracy of astro-comb spectral lines more robust against systematic errors induced by nonlinear processes associated with power-amplifying and spectral-broadening optical fibers.

  20. Technical advance: liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease.

    PubMed

    Burwitz, Benjamin J; Reed, Jason S; Hammond, Katherine B; Ohme, Merete A; Planer, Shannon L; Legasse, Alfred W; Ericsen, Adam J; Richter, Yoram; Golomb, Gershon; Sacha, Jonah B

    2014-09-01

    Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease. PMID:24823811

  1. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-09-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).

  2. Technical Advance: Liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease

    PubMed Central

    Burwitz, Benjamin J.; Reed, Jason S.; Hammond, Katherine B.; Ohme, Merete A.; Planer, Shannon L.; Legasse, Alfred W.; Ericsen, Adam J.; Richter, Yoram; Golomb, Gershon; Sacha, Jonah B.

    2014-01-01

    Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease. PMID:24823811

  3. Advances in the Endoscopic Assessment of Inflammatory Bowel Diseases: Cooperation between Endoscopic and Pathologic Evaluations

    PubMed Central

    Cheon, Jae Hee

    2015-01-01

    Endoscopic assessment has a crucial role in the management of inflammatory bowel disease (IBD). It is particularly useful for the assessment of IBD disease extension, severity, and neoplasia surveillance. Recent advances in endoscopic imaging techniques have been revolutionized over the past decades, progressing from conventional white light endoscopy to novel endoscopic techniques using molecular probes or electronic filter technologies. These new technologies allow for visualization of the mucosa in detail and monitor for inflammation/dysplasia at the cellular or sub-cellular level. These techniques may enable us to alter the IBD surveillance paradigm from four quadrant random biopsy to targeted biopsy and diagnosis. High definition endoscopy and dye-based chromoendoscopy can improve the detection rate of dysplasia and evaluate inflammatory changes with better visualization. Dye-less chromoendoscopy, including narrow band imaging, iScan, and autofluorescence imaging can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies. Moreover, confocal laser endomicroscopy or endocytoscopy have can achieve real-time histology evaluation in vivo and have greater accuracy in comparison with histology. These new technologies could be combined with standard endoscopy or further histologic confirmation in patients with IBD. This review offers an evidence-based overview of new endoscopic techniques in patients with IBD. PMID:26018512

  4. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

  5. Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease

    PubMed Central

    Kuo, I-Ching; Lin, Hugo You-Hsien; Niu, Sheng-Wen; Hwang, Daw-Yang; Lee, Jia-Jung; Tsai, Jer-Chia; Hung, Chi-Chih; Hwang, Shang-Jyh; Chen, Hung-Chun

    2016-01-01

    Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3–4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%–7%, 7%–9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3–4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3–4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3–4 CKD but not in stage 5 CKD. PMID:26818011

  6. Pathogenesis of alcohol-induced liver disease: classical concepts and recent advances.

    PubMed

    Seth, Devanshi; Haber, Paul S; Syn, Wing-Kin; Diehl, Anna Mae; Day, Christopher P

    2011-07-01

    Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and physiological/cell signaling pathways include fibrinolysis, osteopontin, transforming growth factor-β-SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non-alcoholic steatohepatitis share common pathways and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy.

  7. Can an 86-year-old woman with advanced lung disease be a world class athlete?

    PubMed

    Guenette, Jordan A; Diane Lougheed, M; Webb, Katherine A; O'Donnell, Denis E

    2012-04-30

    We describe the case of an 86-year-old woman with advanced obstructive lung disease (forced expiratory volume in 1 s/forced vital capacity ratio (FEV(1)/FVC)=34%) who remains capable of superior athletic performance. Detailed pulmonary function testing was performed to characterize this patient's baseline respiratory impairment. An incremental symptom limited cycle exercise test was performed to characterize her sensory, ventilatory, cardiovascular and respiratory mechanical responses to exercise. Despite significant respiratory mechanical constraints, her peak cycle work rate and oxygen uptake were 177 and 175% predicted, respectively, and she achieved this while experiencing only moderate exertional dyspnea. She holds numerous world and national masters swim records despite her substantial objective respiratory impairment and continues to compete and set records to this day. We propose that lifelong participation in rigorous endurance training resulted in desensitization to dyspnea and has led to important cardiorespiratory adaptations that may have counterbalanced the known negative effects of obstructive lung disease on exercise performance and dyspnea.

  8. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-01-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2). PMID:27598108

  9. Sensitivity analysis of infectious disease models: methods, advances and their application.

    PubMed

    Wu, Jianyong; Dhingra, Radhika; Gambhir, Manoj; Remais, Justin V

    2013-09-01

    Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable of providing considerable insights over traditional methods. We investigate five global SA methods-scatter plots, the Morris and Sobol' methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method-and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design. PMID:23864497

  10. Multichannel Fabry-Perot spectrometer for infrared astronomy

    NASA Technical Reports Server (NTRS)

    Jennings, Donald E.; Boyle, R. J.

    1986-01-01

    A multichannel design which makes use of the radiation normally rejected in a Fabry-Perot spectrometer is described, with application to infrared astronomy. The present optical design minimizes the diameters of the etalon and optics. The use of spherical mirrors ensures that no radiation is lost through the entrance aperture, and the beams can be completely collimated at the etalon. Laboratory studies demonstrate that the ability to employ eight channels increases by a factor of four the flux integrated during a given time period compared with that of a single-channel instrument. The spectrometer is nondispersive, and the source can be imaged at each of several output spectral positions.

  11. Transformation optics with Fabry-Pérot resonances

    PubMed Central

    Sadeghi, M. M.; Li, Sucheng; Xu, Lin; Hou, Bo; Chen, Huanyang

    2015-01-01

    Transformation optics is a powerful tool to design various novel devices, such as invisibility cloak. Fantastic effects from this technique are usually accompanied with singular mappings, resulting in challenging implementations and narrow bands of working frequencies. Here in this article, Fabry-Pérot resonances in materials of extreme anisotropy are used to design various transformation optical devices that are not only easy to realize but also work well for a set of resonant frequencies (multiple frequencies). As an example, a prototype of a cylindrical concentrator is fabricated for microwaves. PMID:25726924

  12. Holographic liquid crystal polarization grating with Fabry-Perot structure.

    PubMed

    Sakamoto, Moritsugu; Yamaguchi, Haruki; Noda, Kohei; Sasaki, Tomoyuki; Kawatsuki, Nobuhiro; Ono, Hiroshi

    2016-03-15

    A holographic liquid crystal polarization grating with a Fabry-Perot structure was developed. Because of its resonant structure, the device offers high levels of control of the diffraction properties of incident-polarized light beams, depending on the resonance conditions. The diffracted light beams are emitted in both the reflection and transmission directions, and the device thus works as a multibranch polarization grating with double optical paths, unlike a conventional polarization grating. These device features were experimentally demonstrated and were also explained theoretically.

  13. Transformation optics with Fabry-Pérot resonances

    NASA Astrophysics Data System (ADS)

    Sadeghi, M. M.; Li, Sucheng; Xu, Lin; Hou, Bo; Chen, Huanyang

    2015-03-01

    Transformation optics is a powerful tool to design various novel devices, such as invisibility cloak. Fantastic effects from this technique are usually accompanied with singular mappings, resulting in challenging implementations and narrow bands of working frequencies. Here in this article, Fabry-Pérot resonances in materials of extreme anisotropy are used to design various transformation optical devices that are not only easy to realize but also work well for a set of resonant frequencies (multiple frequencies). As an example, a prototype of a cylindrical concentrator is fabricated for microwaves.

  14. Holographic liquid crystal polarization grating with Fabry-Perot structure.

    PubMed

    Sakamoto, Moritsugu; Yamaguchi, Haruki; Noda, Kohei; Sasaki, Tomoyuki; Kawatsuki, Nobuhiro; Ono, Hiroshi

    2016-03-15

    A holographic liquid crystal polarization grating with a Fabry-Perot structure was developed. Because of its resonant structure, the device offers high levels of control of the diffraction properties of incident-polarized light beams, depending on the resonance conditions. The diffracted light beams are emitted in both the reflection and transmission directions, and the device thus works as a multibranch polarization grating with double optical paths, unlike a conventional polarization grating. These device features were experimentally demonstrated and were also explained theoretically. PMID:26977643

  15. Stable fiber-based Fabry-Perot cavity

    SciTech Connect

    Steinmetz, T.; Colombe, Y.; Hunger, D.; Haensch, T. W.; Balocchi, A.; Warburton, R. J.; Reichel, J.

    2006-09-11

    The development of a fiber-based, tunable optical cavity with open access is reported. The cavity is of the Fabry-Perot type and is formed with miniature spherical mirrors positioned on the end of single- or multimode optical fibers by a transfer technique, which involves lifting a high-quality mirror from a smooth convex substrate, either a ball lens or microlens. The cavities typically have a finesse of {approx}1000 and a mode volume of 600 {mu}m{sup 3}. The detection of small ensembles of cold Rb atoms guided through such a cavity on an atom chip is demonstrated.

  16. Microlens optical fiber Fabry-Pérot tunable filter

    NASA Astrophysics Data System (ADS)

    Tang, Caijie; Jiang, Yi

    2009-11-01

    An optical fiber Fabry-Pérot tunable filter is constructed by fixing two microlensed mirror-coated fibers to the opposite ends of a piezoelectric transducer. A tunable filter with a free spectral range of 70 nm, a finesse of 175, an insertion loss of 1.05 dB, and a tuning frequency exceeding 1 kHz has been experimentally demonstrated. The filter is easy to construct at a low cost, and it is anticipated that it will be used in fiber-optic sensing systems, spectrometers, and tunable optical fiber lasers.

  17. Dieulafoy's lesion-like bleeding: an underrecognized cause of upper gastrointestinal hemorrhage in patients with advanced liver disease.

    PubMed

    Akhras, Jamil; Patel, Pragnesh; Tobi, Martin

    2007-03-01

    Dieulafoy's lesion is a gastrointestinal submucosal artery that ruptures into the lumen causing massive hemorrhage. Until recently, failure to diagnose and treat patients endoscopically may have necessitated blind gastrectomy. Because arteriolar spider nevi abound in patients with liver disease and bleeding from such lesions has been described in the upper gastrointestinal tract, we reviewed our experience to determine whether a diagnosis of advanced liver disease could facilitate recognition and treatment of this type of arterial bleeding. Endoscopy records from 1991 to 1996 for all cases of upper gastrointestinal bleeding at our institution were reviewed. Dieulafoy's lesion-like bleeding was defined as arterial-type bleeding with no evidence of mucosal ulceration or erosions. Advanced liver disease was defined as signs of portal hypertension and/or cirrhosis or infiltrative liver disease. Dieulafoy's lesion-like bleeding was the cause in 6 of 4569 cases (0.13%). Five patients with Dieulafoy's lesion-like gastrointestinal hemorrhage had advanced liver disease compared with 954 of 4569 of all patients endoscoped for gastrointestinal hemorrhage for the period evaluated (OR = 19.04; 95% CI 2.1-900.8; p < 0.002 by Fisher's exact test). Dieulafoy's lesion-like bleeding was treated successfully with epinephrine injection and endoscopic cauterization in 5 of 6 patients with 1 patient requiring surgery. No other clinical associations were evident. Dieulafoy's lesion-like bleeding occurs more commonly in patients with advanced liver disease and should be included as a potential cause for bleeding in advanced liver disease and aggressively sought.

  18. Effect of levodopa‐carbidopa intestinal gel on dyskinesia in advanced Parkinson's disease patients

    PubMed Central

    Fung, Victor S. C.; Boyd, James T.; Slevin, John T.; Hall, Coleen; Chatamra, Krai; Eaton, Susan; Benesh, Janet A.

    2016-01-01

    ABSTRACT Objective The purpose of this study was to assess the effect of levodopa‐carbidopa intestinal gel (carbidopa‐levodopa enteral suspension) in advanced Parkinson's disease patients with troublesome dyskinesia. Methods Post hoc analyses of patient data from a 12‐week, randomized, double‐blind study and a 54‐week open‐label study were performed. Efficacy was assessed in the subgroup of patients defined by ≥1 hour of “on” time with troublesome dyskinesia at baseline as recorded in Parkinson's disease symptom diaries (double blind: n = 11 levodopa‐carbidopa intestinal gel, n = 12 oral levodopa‐carbidopa; open label: n = 144 levodopa‐carbidopa intestinal gel). The changes in “off” time, “on” time with and without troublesome dyskinesia, and the overall safety and tolerability of levodopa‐carbidopa intestinal gel were analyzed. Results Although not significantly different from oral levodopa treatment (P > .05) in the double‐blind study, levodopa‐carbidopa intestinal gel treatment resulted in a reduction from baseline in “on” time with troublesome dyskinesia (mean [standard deviation] hours: baseline = 3.1 [1.7], change from baseline to final = −1.8 [1.8], P = .014), increase in “on” time without troublesome dyskinesia (baseline = 7.4 [2.2], change = 4.4 [3.6], P = .004), and decrease in “off” time (baseline = 5.5 [1.3], change = −2.7 [2.8], P = .015). Similar trends were found in the open‐label study. An increase in levodopa‐carbidopa intestinal gel dose was not significantly correlated with increased “on” time with troublesome dyskinesia in either study (double blind: r = −.073, P = .842; open label: r = −0.001, P = .992). Adverse events were usually mild to moderate in severity and related to the gastrointestinal procedure. Conclusion Our exploratory analyses suggest that optimizing levodopa delivery with levodopa

  19. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease.

    PubMed

    Knowles, Michael R; Daniels, Leigh Anne; Davis, Stephanie D; Zariwala, Maimoona A; Leigh, Margaret W

    2013-10-15

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.

  20. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2009-02-01

    This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams.

  1. Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

    PubMed

    Valldeoriola, Francesc; Pilleri, Manuela; Tolosa, Eduardo; Molinuevo, José L; Rumià, Jordi; Ferrer, Enric

    2002-01-01

    Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.

  2. Effect of Bicarbonate Supplementation on Renal Function and Nutritional Indices in Predialysis Advanced Chronic Kidney Disease

    PubMed Central

    Jeong, Jiwon; Kwon, Soon Kil

    2014-01-01

    Current practice guidelines recommend alkali therapy in patients with chronic kidney disease (CKD) and metabolic acidosis to prevent complications. This study aims to investigate the effect of oral sodium bicarbonate supplementation on the progression of renal function and nutritional indices in patients with predialysis advanced CKD. Forty patients with predialysis stage 5 CKD(estimated glomerular filtration rate, eGFR <15mL/min per 1.73m2) and 40 patients with stage 4 CKD (eGFR 15 to 30mL/min per 1.73m2) who had a total CO2 less than 22mEq/L were assigned into the bicarbonate treatment group or control group for 12 months. In stage 4 CKD, there were significant differences in the changes of eGFR during the study between the treatment group and the control group (-2.30±4.49 versus -6.58±6.32mL/min/1.73m2, p<0.05). However, in stage 5 CKD, there were no significant differences in the change of eGFR during the study between the two groups (-2.10±2.06 versus -3.23±1.95mL/min/1.73 m2).There were no significant differences in the changes of nutritional indices such as albumin, prealbumin, transferrin, total lymphocyte count (TLC), and Ondodera's prognostic nutritional index (OPNI) during the study between the two groups. In stage 5 CKD, there were significant differences in the changes of TLC and OPNI between the two groups. In conclusion, our results demonstrate that bicarbonate supplementation slows the rate of decline of renal function in stage 4 CKD and improves nutritional indices in stage 5 CKD. Alkali therapy in advanced CKD may have beneficial effect on renal function and malnutrition. PMID:25606047

  3. Hydrocarbon gas detection with microelectromechanical Fabry-Perot interferometer

    NASA Astrophysics Data System (ADS)

    Mannila, Rami; Tuohiniemi, Mikko; Mäkynen, Jussi; Näkki, Ismo; Antila, Jarkko

    2013-05-01

    VTT Technical Research Centre of Finland has developed microelectromechanical (MEMS) Fabry-Perot interferometer (FPI) for hydrocarbon measurements. Fabry-Perot interferometer is a structure where is two highly reflective surfaces separated by a tunable air gap. The MEMS FPI is a monolithic device, i.e. it is made entirely on one substrate in a batch process, without assembling separate pieces together. The gap is adjusted by moving the upper mirror with electrostatic force, so there are no actual moving parts. The manufactured MEMS FPIs have been characterized. The tuning wavelength range of the MEMS FPI is 2.8-3.5 μm and its spectral resolution is 50-60 nm. VTT has designed and manufactured a handheld size demonstrator device based on the technology presented in this abstract. This device demonstrates gas detecting by measuring cigarette lighter gas and various plastic materials transmission spectra. The demonstrator contains light source, gas cell, MEMS FPI, detector and control electronics. It is connected to a laptop by USB connection, additional power supply or connection is not needed.

  4. Atmospheric spectra from a multiplex Fabry-Perot interferometer

    SciTech Connect

    Snell, H.E.; Cook, W.B.; Hays, P.B.

    1994-12-31

    Remote sensing of major and minor constituents in the earth`s atmosphere is of great importance to the study of climate and global change. Because much of remote sensing involves placing instrumentation in environments that are not easily accessible, such as balloons, spacecraft, or remote field stations, it is usually necessary that the instrumentation be compact, lightweight, and rugged. This paper describes the development of a new type of remote sensing instrument the authors have chosen to call the Multiplex Fabry-Perot Interferometer (MFPI). They will present atmospheric spectra obtained with the working prototype instrument. The MFPI is a Fabry-Perot interferometer for which the etalon plate separation is changed over a large optical distance during a measurement. When the resulting interferogram is Fourier transformed the multiple reflections within the etalon cavity produce a spectrum analogous to that which would be produced by an array of Michelson interferometers. However, for high spectral resolution measurements the scan distance required by the MFPI is much less than for the comparable Michelson. The MFPI will be ideal for remote sensing applications where weight, size, and mechanical reliability are primary considerations.

  5. The IRAF Fabry-Perot analysis package: Ring fitting

    NASA Technical Reports Server (NTRS)

    Shopbell, P. L.; Bland-Hawthorn, J.; Cecil, G.

    1992-01-01

    As introduced at ADASSI, a Fabry-Perot analysis package for IRAF is currently under development as a joint effort of ourselves and Frank Valdes of the IRAF group. Although additional portions of the package were also implemented, we report primarily on the development of a robust ring fitting task, useful for fitting the calibration rings obtained in Fabry-Perot observations. The general equation of an ellipse is fit to the shape of the rings, providing information on ring center, ellipticity, and position angle. Such parameters provide valuable information on the wavelength response of the etalon and the geometric stability of the system. Appropriate statistical weighting is applied to the pixels to account for increasing numbers with radius, the Lorentzian cross-section, and uneven illumination. The major problems of incomplete, non-uniform, and multiple rings are addressed with the final task capable of fitting rings regardless of center, cross-section, or completion. The task requires only minimal user intervention, allowing large numbers of rings to be fit in an extremely automated manner.

  6. Fiber-coupled short Fabry-Perot resonators

    SciTech Connect

    Stone, J.; Marcuse, D. )

    1989-05-01

    Fabry-Perot resonators intended as filters in wavelength-multiplexed optical communications systems may have to be very short (on the order of 10 {mu}m) in order to increase their free spectral range. Short, yet tunable cavities can be designed as air gaps between two fibers placed in close proximity with highly reflecting mirrors deposited on their ends. However, an air-gap resonator with plane mirrors between closely spaced fiber ends may yield low throughout because of the poor match between the modes of typical single-mode fibers and the resonant mode in the air-gap cavity. The throughput can be improved by confining the resonant mode by means of a hollow dielectric tube placed inside the resonator. This paper compares short fiber-coupled Fabry-Parot resonators with and without an inserted hollow dielectric waveguide and derives expressions for their transmission losses. The authors show that the throughput of both types of resonator can be improved significantly by using a special fiber with large mode size to couple to the resonator. The special fiber is then spliced to a conventional single-mode fiber. They conclude that the resonator with an inserted hollow dielectric waveguide offers increased throughput for resonators with high finesse.

  7. [Skin and chronic kidney disease].

    PubMed

    Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

    2014-01-01

    Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process. PMID:25315722

  8. Levodopa-Induced Modifications of Prosody and Comprehensibility in Advanced Parkinson's Disease as Perceived by Professional Listeners

    ERIC Educational Resources Information Center

    De Letter, Miet; Santens, Patrick; Estercam, Irina; Van Maele, Georges; De Bodt, Marc; Boon, Paul; Van Borsel, John

    2007-01-01

    The prosodic aspects of hypokinetic dysarthria in Parkinson's disease (PD) have been the focus of numerous reports. Few data on the effects of levodopa on prosody, more specifically on the effects on the variability of prosodic characteristics such as pitch, loudness and speech rate, are available in advanced PD. The relation between these…

  9. Factors associated with presentation to care with advanced HIV disease in Brussels and Northern France: 1997-2007

    PubMed Central

    2011-01-01

    Background Our objective was to determine the frequency and determinants of presentation to care with advanced HIV disease in patients who discover their HIV diagnosis at this stage as well as those with delayed presentation to care after HIV diagnosis in earlier stages. Methods We collected data on 1,819 HIV-infected patients in Brussels (Belgium) and Northern France from January 1997 to December 2007. "Advanced HIV disease" was defined as CD4 count <200/mm3 or clinically-defined AIDS at study inclusion and was stratified into two groups: (a) late testing, defined as presentation to care with advanced HIV disease and HIV diagnosis ≤6 months before initiation of HIV care; and (b) delayed presentation to care, defined as presentation to care with advanced HIV disease and HIV diagnosis >6 months before initiation of HIV care. We used multinomial logistic regression to determine the factors associated with delayed presentation to care and late testing. Results Of the 570 patients initiating care with advanced HIV disease, 475 (83.3%) were tested late and 95 (16.7%) had delayed presentation to care. Risk factors for delayed presentation to care were: age 30-50 years, injection drug use, and follow-up in Brussels. Risk factors for late testing were: sub-Saharan African origin, male gender, and older age. HIV transmission through heterosexual contact was associated with an increased risk of both delayed presentation to care and late testing. Patients who initiated HIV care in 2003-2007 were less likely to have been tested late or to have a delayed presentation to care than patients who initiated care before 2003. Conclusion A considerable proportion of HIV-infected patients present to care with advanced HIV disease. Late testing, rather than a delay in initiating care after earlier HIV testing, is the main determinant of presentation to care with advanced HIV disease. The factors associated with delay presentation to care differ from those associated with late testing

  10. Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study of 32 patients

    PubMed Central

    de Bie, R M A; Schuurman, P; Bosch, D; de Haan, R J; Schmand, B; Speelman, J

    2001-01-01

    OBJECTIVES—In a randomised trial to study the efficacy of unilateral pallidotomy in patients with advanced Parkinson's disease, patients having pallidotomy within 1 month after randomisation were compared with patients having pallidotomy 6 months after the primary outcome assessment. Of the 37 patients enrolled 32 had a unilateral pallidotomy. The follow up study of these patients is presented to report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural effects; (4) relation between lesion location and outcome; and (5) preoperative patient characteristics predictive for good outcome.
METHODS—Outcome measures were the motor section of the unified Parkinson's disease rating scale (UPDRS), levodopa induced dyskinesias, disability, quality of life, and a comprehensive neuropsychological assessment. Multivariate logistic regression was used to identify preoperative patient characteristics independently associated with good outcome.
RESULTS—Off phase assessment showed a reduction in parkinsonism from 49 to 36.5 points on the UPDRS 6 months after surgery. Improvements were also demonstrated for activities of daily living and quality of life. In the on phase dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three patients had major permanent adverse effects. Besides worsening of verbal fluency after left sided surgery, systematic cognitive deterioration was not detected. Patients taking less than 1000 levodopa equivalent units (LEU)/day were more likely to improve.
CONCLUSIONS—The positive effects of unilateral pallidotomy are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day were most likely to improve.

 PMID:11511714

  11. Advance Care Planning and Goals of Care Communication in Older Adults with Cardiovascular Disease and Multi-Morbidity.

    PubMed

    Lum, Hillary D; Sudore, Rebecca L

    2016-05-01

    This article provides an approach to advance care planning (ACP) and goals of care communication in older adults with cardiovascular disease and multi-morbidity. The goal of ACP is to ensure that the medical care patients receive is aligned with their values and preferences. In this article, the authors outline common benefits and challenges to ACP for older adults with cardiovascular disease and multimorbidity. Recognizing that these patients experience diverse disease trajectories and receive care in multiple health care settings, the authors provide practical steps for multidisciplinary teams to integrate ACP into brief clinic encounters.

  12. [Structural characteristics of Abies fabri forests at the upper reach of Yangtze River].

    PubMed

    Gao, Jiarong; Zhang, Dongsheng; Niu, Jianzhi; Yu, Xinxiao; Zhang, Wenjing

    2003-01-01

    The structural characteristics of Abies fabri forest under different succession stages in Gongga Mountains at the upper reach of Yangtze River were studied. The results showed that in the mature Abies fabri forest, there existed abundant seeds and a few saplings of Abies fabri younger than 20 years, but only Abies fabri was the dominant regeneration species. In the poplar-fir mixed forest, the height growth of poplar and birch was very fast during first 30 years, and poplar and birch dominated rapidly over the canopy. Abies fabri had a lower growth rate and a strong shade-tolerance in its first growth stage, and could replace other tree species gradually. The cycle of mud-rock flow occurrence was above 100 years in the Gongga montane areas from elevation of 2800 to 3200 m. After mud-rock flow, poplar and birch often occurred and dominated, and there were only a small number of Abies fabri saplings in slash. Under natural condition, to recover Abies fabri forest would demand a long time, but this process could be controlled and improved by human activities.

  13. Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review.

    PubMed

    Volkmann, Jens; Albanese, Alberto; Antonini, Angelo; Chaudhuri, K Ray; Clarke, Carl E; de Bie, Rob M A; Deuschl, Günther; Eggert, Karla; Houeto, Jean-Luc; Kulisevsky, Jaime; Nyholm, Dag; Odin, Per; Østergaard, Karen; Poewe, Werner; Pollak, Pierre; Rabey, Jose Martin; Rascol, Olivier; Ruzicka, Evzen; Samuel, Michael; Speelman, Hans; Sydow, Olof; Valldeoriola, Francesc; van der Linden, Chris; Oertel, Wolfgang

    2013-11-01

    Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine. PMID:23287972

  14. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified.

  15. Invited review: Stem cells and muscle diseases: advances in cell therapy strategies.

    PubMed

    Negroni, Elisa; Gidaro, Teresa; Bigot, Anne; Butler-Browne, Gillian S; Mouly, Vincent; Trollet, Capucine

    2015-04-01

    Despite considerable progress to increase our understanding of muscle genetics, pathophysiology, molecular and cellular partners involved in muscular dystrophies and muscle ageing, there is still a crucial need for effective treatments to counteract muscle degeneration and muscle wasting in such conditions. This review focuses on cell-based therapy for muscle diseases. We give an overview of the different parameters that have to be taken into account in such a therapeutic strategy, including the influence of muscle ageing, cell proliferation and migration capacities, as well as the translation of preclinical results in rodent into human clinical approaches. We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so far [CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), muscle-derived stem cells (MuStem), embryonic stem cells (ES) and induced pluripotent stem cells (iPS)]. Finally, we provide an update of ongoing clinical trials using cell therapy strategies.

  16. Pulmonary hypertension in adults with congenital heart disease and Eisenmenger syndrome: current advanced management strategies.

    PubMed

    D'Alto, Michele; Diller, Gerhard-Paul

    2014-09-01

    The presence of pulmonary arterial hypertension (PAH) increases morbidity and reduces survival in patients with congenital heart disease (CHD). PAH-CHD is a heterogeneous condition, depending on the type of the underlying defect and previous repair strategies. There is growing evidence of the benefits of PAH-specific therapy in the PAH-CHD population, but despite recent advances mortality rates remain relatively high. In the last years, an increasing focus has been placed on patients with PAH-CHD and net left-to-right shunt. Currently, there are limited data to guide the management of these patients and uncertainty on the cut-off values for eventual defect closure. Pregnancy conveys significant risks in PAH-CHD patients: appropriate counselling and care, including psychological support and a multidisciplinary team, should be part of the routine management of women with PAH-CHD of reproductive age. Some subgroups, such as patients with Down's syndrome, Fontan circulation and 'segmental' pulmonary hypertension, present particular challenges in terms of management and therapy. The current review focuses on contemporary treatment strategies in PAH-CHD patients with particular emphasis on challenging patient groups and conditions.

  17. Home Palliative Care for Patients with Advanced Chronic Kidney Disease: Preliminary Results

    PubMed Central

    Teruel, José L.; Rexach, Lourdes; Burguera, Victor; Gomis, Antonio; Fernandez-Lucas, Milagros; Rivera, Maite; Diaz, Alicia; Collazo, Sergio; Liaño, Fernando

    2015-01-01

    Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. At the end of 2011, we began a program based on the care and monitoring of these patients by Primary Care Teams. ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor and nurse, under the coordination of the Palliative Care Unit and the Nephrology Department. During 2012, 2013, and 2014, 76 patients received treatment in this program (mean age: 81 years; mean Charlson age-comorbidity index: 10, and mean glomerular filtration rate: 12.4 mL/min/1.73 m2). The median patient follow-up time (until death or until 31 December 2014) was 165 days. During this period, 51% of patients did not have to visit the hospital’s emergency department and 58% did not require hospitalization. Forty-eight of the 76 patients died after a median time of 135 days in the program; 24 (50%) died at home. Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care Teams. PMID:27417813

  18. Imaging Multimodalities for Dissecting Alzheimer's Disease: Advanced Technologies of Positron Emission Tomography and Fluorescence Imaging

    PubMed Central

    Shimojo, Masafumi; Higuchi, Makoto; Suhara, Tetsuya; Sahara, Naruhiko

    2015-01-01

    The rapid progress in advanced imaging technologies has expanded our toolbox for monitoring a variety of biological aspects in living subjects including human. In vivo radiological imaging using small chemical tracers, such as with positron emission tomography, represents an especially vital breakthrough in the efforts to improve our understanding of the complicated cascade of neurodegenerative disorders including Alzheimer's disease (AD), and it has provided the most reliable visible biomarkers for enabling clinical diagnosis. At the same time, in combination with genetically modified animal model systems, the most recent innovation of fluorescence imaging is helping establish diverse applications in basic neuroscience research, from single-molecule analysis to animal behavior manipulation, suggesting the potential utility of fluorescence technology for dissecting the detailed molecular-based consequence of AD pathophysiology. In this review, our primary focus is on a current update of PET radiotracers and fluorescence indicators beneficial for understanding the AD cascade, and discussion of the utility and pitfalls of those imaging modalities for future translational research applications. We will also highlight current cutting-edge genetic approaches and discuss how to integrate individual technologies for further potential innovations. PMID:26733795

  19. Renal histology in polycystic kidney disease with incipient and advanced renal failure.

    PubMed

    Zeier, M; Fehrenbach, P; Geberth, S; Möhring, K; Waldherr, R; Ritz, E

    1992-11-01

    Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure.

  20. Drugs of abuse that mediate advanced glycation end product formation: a chemical link to disease pathology.

    PubMed

    Treweek, Jennifer B; Dickerson, Tobin J; Janda, Kim D

    2009-05-19

    Nicotine and methamphetamine are frequently abused in modern society, despite the increasing evidence of their addictive, neuropharmacological, and toxic effects. Tobacco, the most widely abused substance, is the leading cause of preventable death in the United States, killing nearly half a million Americans annually. A methamphetamine epidemic has also spread during the past decade; severe neurotoxicity and addictiveness contribute to the drug's notoriety. Although the majority of research on these two drugs is of pharmacological and neurobiological motivation, further study of these molecules from a chemical perspective may provide novel mechanistic insight into either their addictive potential or their pathological effects. For example, nicotine and methamphetamine share a common structural feature, a secondary amine, suggesting that these molecules could possess similar (or analogous) in vivo reactivity. Discoveries concerning the synthetic requirements for aqueous aldol catalysis and the feasibility of the enamine mechanism under physiological conditions have given rise to the hypothesis that ingested molecules, such as abused drugs, could participate in reactions utilizing an enamine intermediate in vivo. The chemical reactivity of exogenous drugs with amine functionalities was initially examined in the context of the Maillard reaction, or nonenzymatic browning. The heating of reducing sugars with amino acids yields a brown solution; studies of this reaction were originally applied to food chemistry for the production of distinct flavors and aromas. Further research has since revealed numerous instances in which the in vivo production of advanced glycation end products (AGEs) through the Maillard reaction contribute to the pathology of disease states. Specifically, the modification of long-lived proteins by glycation and glycoxidation and the accumulation of these AGEs compromise the original function of such proteins and change the mechanical properties of

  1. [Advance in diagnosis and treatment of psycho-cardiological abnormality of patients with coronary heart disease with traditional Chinese medicines].

    PubMed

    Yuan, Rong; Wang, Jiel; Liu, Wei

    2015-02-01

    To discuss the etiology, pathogenesis, therapies and prescriptions of psycho-cardiological abnormality of patients with coronary heart disease. According to the advance in modern diagnosis and treatment, the authors believed that psycho-cardiological abnormality of patients with coronary heart disease is closely related with mental stresses, like anxiety, depression and insomnia. It is mostly caused by emotional injury and expressed in heart, liver, spleen and kidney. The pathogenesis is heart-liver hyperactivity, yin deficiency in heart and kidney, and insufficiency in heart and spleen. The full recognition of etiology and pathogenesis of psycho-cardiological abnormality of patients with coronary heart disease and the combined treatment of disease and syndromes are of great significance to reduce mental stress and other risk factors, prevent and treat coronary heart disease and improve prognosis.

  2. A novel Michelson Fabry-Perot hybrid interference sensor based on the micro-structured fiber

    NASA Astrophysics Data System (ADS)

    Zhang, Yaxun; Zhang, Yu; Wang, Zhenzhen; Liu, Zhihai; Wei, Yong; Zhao, Enming; Yang, Xinghua; Zhang, Jianzhong; Yang, Jun; Yuan, Libo

    2016-09-01

    We propose and demonstrate a novel Michelson Fabry-Perot hybrid fiber interference sensor. By integrating a Michelson interferometer in a two-core fiber and a Fabry-Perot interferometer in a micro silica-capillary, we produce the Michelson Fabry-Perot hybrid interference sensor. Owing to the structure characteristic of the micro-structured fiber, this hybrid fiber interference sensor can achieve the measurement of the axial strain and radial bending simultaneously. The measurement sensitivity of the axial train is 0.015 nm/με and the measurement sensitivity of the radial bending is 1.393 nm/m-1.

  3. Focused ion beam post-processing of optical fiber Fabry-Perot cavities for sensing applications.

    PubMed

    André, Ricardo M; Pevec, Simon; Becker, Martin; Dellith, Jan; Rothhardt, Manfred; Marques, Manuel B; Donlagic, Denis; Bartelt, Hartmut; Frazão, Orlando

    2014-06-01

    Focused ion beam technology is combined with chemical etching of specifically designed fibers to create Fabry-Perot interferometers. Hydrofluoric acid is used to etch special fibers and create microwires with diameters of 15 μm. These microwires are then milled with a focused ion beam to create two different structures: an indented Fabry-Perot structure and a cantilever Fabry-Perot structure that are characterized in terms of temperature. The cantilever structure is also sensitive to vibrations and is capable of measuring frequencies in the range 1 Hz - 40 kHz.

  4. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results.

    PubMed

    Fernandez, Hubert H; Standaert, David G; Hauser, Robert A; Lang, Anthony E; Fung, Victor S C; Klostermann, Fabian; Lew, Mark F; Odin, Per; Steiger, Malcolm; Yakupov, Eduard Z; Chouinard, Sylvain; Suchowersky, Oksana; Dubow, Jordan; Hall, Coleen M; Chatamra, Krai; Robieson, Weining Z; Benesh, Janet A; Espay, Alberto J

    2015-04-01

    Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma-level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day "off" time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, "on" time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks. PMID:25545465

  5. Comparative Effectiveness of Early versus Conventional Timing of Dialysis Initiation in Advanced Chronic Kidney Disease

    PubMed Central

    Crews, Deidra C.; Scialla, Julia J.; Boulware, L. Ebony; Navaneethan, Sankar D.; Nally, Joseph V.; Liu, Xiaobo; Arrigain, Susana; Schold, Jesse D.; Ephraim, Patti L.; Jolly, Stacey E.; Sozio, Stephen M.; Michels, Wieneke M.; Miskulin, Dana C.; Tangri, Navdeep; Shafi, Tariq; Wu, Albert W.; Bandeen-Roche, Karen

    2014-01-01

    Background Previous observational studies examining outcomes associated with the timing of dialysis initiation in the US have often been limited by lead time and survivor bias. Study Design Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis initiation in advanced chronic kidney disease (CKD). The analysis employed inverse probability weighting to account for an individual’s contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy [i.e. dialysis was initiated early, or estimated glomerular filtration rate (eGFR) fell below 10 ml/min per 1.73 m2]. Setting & Participants CKD patients who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005 and at least two estimated eGFRs in the range of 20 to 30 ml/min per 1.73m2 measured at least 180 days apart. Predictors Timing of dialysis initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis initiation ≥10 ml/min per 1.73m2) or later (eGFR < 10), and was time-varying. Outcomes Death from any cause occurring from the time that eGFR was equal to 20 ml/min per 1.73m2 through September 15, 2009. Results The study population consisted of 652 patients meeting inclusion criteria. The majority of the study population (71.3%) did not initiate dialysis during follow up. Patients who did not initiate dialysis (n=465) were older, more likely to be Caucasian, and had more favorable laboratory profiles than those who initiated. Overall, 146 initiated early, and 80 had eGFR fall below 10 ml/min per 1.73 m2. Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival

  6. Intrinsic Fabry-Perot optical fiber sensors and their multiplexing

    DOEpatents

    Wang, Anbo

    2007-12-11

    An intrinsic Fabry-Perot optical sensor includes a thin film sandwiched between two fiber ends. When light is launched into the fiber, two reflections are generated at the two fiber/thin film interfaces due to a difference in refractive indices between the fibers and the film, giving rise to the sensor output. In another embodiment, a portion of the cladding of a fiber is removed, creating two parallel surfaces. Part of the evanescent fields of light propagating in the fiber is reflected at each of the surfaces, giving rise to the sensor output. In a third embodiment, the refractive index of a small portion of a fiber is changed through exposure to a laser beam or other radiation. Interference between reflections at the ends of the small portion give rise to the sensor output. Multiple sensors along a single fiber are multiplexed using an optical time domain reflectometry method.

  7. Photoacoustic imaging using an 8-beam Fabry-Perot scanner

    NASA Astrophysics Data System (ADS)

    Huynh, Nam; Ogunlade, Olumide; Zhang, Edward; Cox, Ben; Beard, Paul

    2016-03-01

    The planar Fabry Perot (FP) photoacoustic scanner has been shown to provide exquisite high resolution 3D images of soft tissue structures in vivo to depths up to approximately 10mm. However a significant limitation of current embodiments of the concept is low image acquisition speed. To increase acquisition speed, a novel multi-beam scanner architecture has been developed. This enables a line of equally spaced 8 interrogation beams to be scanned simultaneously across the FP sensor and the photoacoustic signals detected in parallel. In addition, an excitation laser operating at 200Hz was used. The combination of parallelising the detection and the high pulse repetition frequency (PRF) of the excitation laser has enabled dramatic reductions in image acquisition time to be achieved. A 3D image can now be acquired in 10 seconds and 2D images at video rates are now possible.

  8. Fiber Fabry-Perot interferometer for curvature sensing

    NASA Astrophysics Data System (ADS)

    Monteiro, Catarina S.; Ferreira, Marta S.; Silva, Susana O.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-07-01

    A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature.

  9. Millimeter-long fiber Fabry-Perot cavities.

    PubMed

    Ott, Konstantin; Garcia, Sebastien; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-05-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5 mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

  10. Fourier transform spectrometer based on Fabry-Perot interferometer.

    PubMed

    Al-Saeed, Tarek A; Khalil, Diaa A

    2016-07-10

    We analyze the Fourier transform spectrometer based on a symmetric/asymmetric Fabry-Perot interferometer. In this spectrometer, the interferogram is obtained by recording the intensity as a function of the interferometer length. Then, we recover the spectrum by applying the discrete Fourier transform (DFT) directly on the interferogram. This technique results in spectral harmonic overlap and fictitious wavenumber components outside the original spectral range. For this purpose, in this work, we propose a second method to recover the spectrum. This method is based on expanding the DFT of the interferogram and the spectrum by a Haar or box function. By this second method, we recovered the spectrum and got rid of the fictitious spectral components and spectral harmonic overlap.

  11. Analysis and design of tunable fiber Fabry-Perot filter

    NASA Astrophysics Data System (ADS)

    Qi, Haibing; Yu, Yonglin

    2008-12-01

    The effective reflectivity of planar tunable filter fiber Fabry-Perot (TF-FFP) caused by coupling losses would led to the change of tuning range and the full width half maximum (FWHM) in the process of gap distance tuning. The general transfer function expression of FFP is developed by Gaussian beams model and coupling losses. A method that is by appropriate unsymmetrical reflectivity of fiber end can increase the tuning range and reduce the FWHM is proposed, the obtained parameters may be useful for the analysis and design of other TF-FFP. At last the initial gap position and reflectivities of both ends of TF-FFP are designed theoretically for C-band and C+L-band respectively.

  12. HTS Fabry-Perot resonators for the far infrared

    NASA Astrophysics Data System (ADS)

    Keller, Philipp; Prenninger, Martin; Pechen, Evgeny V.; Renk, Karl F.

    1996-06-01

    We report on far infrared (FIR) Fabry-Perot resonators (FPR) with high temperature superconductor (HTS) thin films as mirrors. For the fabrication of FPR we use two parallel MgO plates covered with YBa2Cu3O7-delta thin films on adjacent sides. We have measured the far-infrared transmissivity at 10 K with a Fourier transform infrared spectrometer. Very sharp resonances can be observed for frequencies below 6 THz where the MgO is transparent. The finesse (width of the first order resonance) is comparable to the FPR with metallic meshes as reflectors that are applied in the FIR spectroscopy and astronomy. We have also shown that thin films of gold are not adequate substitute to HTS thin films and not suitable for the fabrication of high-quality FPR due to the ohmic losses.

  13. Fabry-Perot observations of Comet Halley H2O(+)

    NASA Astrophysics Data System (ADS)

    Scherb, F.; Magee-Sauer, K.; Roesler, F. L.; Harlander, J.

    1990-07-01

    Fabry-Perot scanning spectrometer observations of Comet Halley's H2O(+) emissions have yielded 6158.64 and 6158.85 A spin doublet data at distances in the range of 0 to 2 million km from the comet heat in the antisunward direction. Cometary plasma outflow velocities were ascertained on the basis of the emissions' Doppler shifts, yielding results that were mostly but not exclusively consistent with the plasma's constant antisunward acceleration; the acceleration varied from night to night of observations over a 30-300 cm/sec range. The unusual plasma kinematics of December 14-15, 1985, and January 10, 1986, may be associated with the tail-disconnection activity observed by others.

  14. Millimeter-long fiber Fabry-Perot cavities.

    PubMed

    Ott, Konstantin; Garcia, Sebastien; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-05-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5 mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem. PMID:27137597

  15. Micromachined fiber optic Fabry-Perot underwater acoustic probe

    NASA Astrophysics Data System (ADS)

    Wang, Fuyin; Shao, Zhengzheng; Hu, Zhengliang; Luo, Hong; Xie, Jiehui; Hu, Yongming

    2014-08-01

    One of the most important branches in the development trend of the traditional fiber optic physical sensor is the miniaturization of sensor structure. Miniature fiber optic sensor can realize point measurement, and then to develop sensor networks to achieve quasi-distributed or distributed sensing as well as line measurement to area monitoring, which will greatly extend the application area of fiber optic sensors. The development of MEMS technology brings a light path to address the problems brought by the procedure of sensor miniaturization. Sensors manufactured by MEMS technology possess the advantages of small volume, light weight, easy fabricated and low cost. In this paper, a fiber optic extrinsic Fabry-Perot interferometric underwater acoustic probe utilizing micromachined diaphragm collaborated with fiber optic technology and MEMS technology has been designed and implemented to actualize underwater acoustic sensing. Diaphragm with central embossment, where the embossment is used to anti-hydrostatic pressure which would largely deflect the diaphragm that induce interferometric fringe fading, has been made by double-sided etching of silicon on insulator. By bonding the acoustic-sensitive diaphragm as well as a cleaved fiber end in ferrule with an outer sleeve, an extrinsic Fabry-Perot interferometer has been constructed. The sensor has been interrogated by quadrature-point control method and tested in field-stable acoustic standing wave tube. Results have been shown that the recovered signal detected by the sensor coincided well with the corresponding transmitted signal and the sensitivity response was flat in frequency range from 10 Hz to 2kHz with the value about -154.6 dB re. 1/μPa. It has been manifest that the designed sensor could be used as an underwater acoustic probe.

  16. Tunable Fabry-Pérot interferometer with subwavelength grating reflectors for MWIR microspectrometers

    NASA Astrophysics Data System (ADS)

    Meinig, Marco; Kurth, Steffen; Seifert, Mario; Hiller, Karla; Wecker, Julia; Ebermann, Martin; Neumann, Norbert; Gessner, Thomas

    2016-04-01

    This report presents recent advances in the design and fabrication of a tunable Fabry-Pérot interferometer (FPI) with subwavelength grating (SWG) reflectors, as well as measurement results and applications. The FPI is designed as wavelength selecting element for highly miniaturized mid-wave infrared spectrometers. The optical resonator of the FPI is built between two highly reflecting mirrors. The mirrors are integrated in a supporting MEMS structure with one electrostatically movable and one fixed mirror carrier. The FPI is fabricated in a bulk micromachining batch process on wafer level from two silicon substrates. The substrates are bonded together with an intermediate SU-8 layer. The reflectors are made of aluminum subwavelength gratings, structured on a thin LP-Si3N4 membrane by nanoimprint lithography. The subwavelength structures build a frequency selective surface with high reflectance and low absorbance in a defined spectral range. Simulations and optimization of the design were done using finite element method with a 3D EM frequency domain solver. Comparison of simulation results and measurements of fabricated reflectors and FPIs are in very good agreement. The FPIs are used in the 5th interference order and can be tuned from 3.5 μm to 2.9 μm electrically. The measured maximum transmittance is between 70 % and 50 % and the measured FWHM bandwidth is lower than 50 nm. The new subwavelength grating reflectors can be integrated in a MEMS batch process more cost-efficient than previously used reflectors of dielectric layer stacks.

  17. Application of advanced cytometric and molecular technologies to minimal residual disease monitoring

    NASA Astrophysics Data System (ADS)

    Leary, James F.; He, Feng; Reece, Lisa M.

    2000-04-01

    Minimal residual disease monitoring presents a number of theoretical and practical challenges. Recently it has been possible to meet some of these challenges by combining a number of new advanced biotechnologies. To monitor the number of residual tumor cells requires complex cocktails of molecular probes that collectively provide sensitivities of detection on the order of one residual tumor cell per million total cells. Ultra-high-speed, multi parameter flow cytometry is capable of analyzing cells at rates in excess of 100,000 cells/sec. Residual tumor selection marker cocktails can be optimized by use of receiver operating characteristic analysis. New data minimizing techniques when combined with multi variate statistical or neural network classifications of tumor cells can more accurately predict residual tumor cell frequencies. The combination of these techniques can, under at least some circumstances, detect frequencies of tumor cells as low as one cell in a million with an accuracy of over 98 percent correct classification. Detection of mutations in tumor suppressor genes requires insolation of these rare tumor cells and single-cell DNA sequencing. Rare residual tumor cells can be isolated at single cell level by high-resolution single-cell cell sorting. Molecular characterization of tumor suppressor gene mutations can be accomplished using a combination of single- cell polymerase chain reaction amplification of specific gene sequences followed by TA cloning techniques and DNA sequencing. Mutations as small as a single base pair in a tumor suppressor gene of a single sorted tumor cell have been detected using these methods. Using new amplification procedures and DNA micro arrays it should be possible to extend the capabilities shown in this paper to screening of multiple DNA mutations in tumor suppressor and other genes on small numbers of sorted metastatic tumor cells.

  18. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    PubMed Central

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

  19. Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy

    PubMed Central

    Kaku, Yoshio; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Hirai, Keiji; Hoshino, Taro; Mori, Honami; Yoshida, Izumi; Morishita, Yoshiyuki; Tabei, Kaoru

    2015-01-01

    Background The following calcium (Ca) correction formula (Payne) is conventionally used for serum Ca estimation: corrected total Ca (TCa) (mg/dl) = TCa (mg/dl) + [4 – albumin (g/dl)]; however, it is inapplicable to advanced chronic kidney disease (CKD) patients. Methods 1,922 samples in CKD G4 + G5 patients and 341 samples in CKD G5D patients were collected. Levels of TCa (mg/day), ionized Ca2+ (iCa2+) (mmol/l) and other clinical parameters were measured. We assumed the corrected TCa to be equal to eight times the iCa2+ value (measured corrected TCa). We subsequently performed stepwise multiple linear regression analysis using the clinical parameters. Results The following formula was devised from multiple linear regression analysis. For CKD G4 + G5 patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 4 × (7.4 – pH) + 0.1 × (6 – P) + 0.22. For CKD G5D patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 0.1 × (6 – P) + 0.05 × (24 – HCO3-) + 0.35. Receiver operating characteristic analysis showed the high values of the area under the curve of approximated corrected TCa for the detection of measured corrected TCa ≥8.4 mg/dl and ≤10.4 mg/dl for each CKD sample. Both intraclass correlation coefficients for each CKD sample demonstrated superior agreement using the new formula compared to the previously reported formulas. Conclusion Compared to other formulas, the approximated corrected TCa values calculated from the new formula for patients with CKD G4 + G5 and CKD G5D demonstrates superior agreement with the measured corrected TCa. PMID:26557841

  20. Advanced glycation end products and the progressive course of renal disease.

    PubMed

    Heidland, A; Sebekova, K; Schinzel, R

    2001-10-01

    In experimental and human diabetic nephropathy (DN), it has been shown that advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and pentosidine, accumulate with malondialdehyde in glomerular lesions in relation to disease severity and in the presence of an upregulated receptor for AGE (RAGE) in podocytes. Toxic effects of AGEs result from structural and functional alterations in plasma and extracellular matrix (ECM) proteins, in particular, from cross-linking of proteins and interaction of AGEs with their receptors and/or binding proteins. In mesangial and endothelial cells, the AGE-RAGE interaction caused enhanced formation of oxygen radicals with subsequent activation of nuclear factor-kappaB and release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). In tubular cells, incubation with AGE albumin was followed by stimulation of the mitogen-activating protein (MAP) kinase pathway and its downstream target, the activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein kinase C activity, decreased cell proliferation, and impaired protein degradation rate, in part caused by decreased cathepsin activities. The pathogenic relevance of AGEs was further verified by in vivo experiments in euglycemic rats and mice by the parenteral administration of AGE albumin, leading in the glomeruli to TGF-beta1 overproduction, enhanced gene expression of ECM proteins, and morphological lesions similar to those of DN. Evidence for the pathogenic relevance of AGEs in DN also comes from experimental studies in which the formation and/or action of AGEs was modulated by aminoguanidine, OPB-9195, pyridoxamine, soluble RAGEs, serine protease trypsin, and antioxidants, resulting in improved cell and/or renal function.

  1. Self-Reported Pain and Disease Symptoms Persist in Juvenile Idiopathic Arthritis Despite Treatment Advances

    PubMed Central

    Bromberg, Maggie H.; Connelly, Mark; Anthony, Kelly K.; Gil, Karen M.; Schanberg, Laura E.

    2014-01-01

    Objective To use electronic diaries (e-diaries) to determine whether pain, stiffness, and fatigue continue to be common, disabling symptoms in children with juvenile idiopathic arthritis (JIA) despite the use of aggressive treatments in contemporary medical management. Methods Fifty-nine children with JIA (ages 8–18 years) provided ratings of pain, stiffness, and fatigue intensity and functional limitations using a smartphone e-diary 3 times each day for 1 month. Medication information was collected via parent report and checked for accuracy by chart review. Descriptive analyses were conducted to determine typical symptom intensity, frequency, and variability. Multilevel modeling was used to analyze associations between symptoms and functional outcomes and between medication use and symptom intensity. Results Children reported moments of pain in 66% of e-diary entries. No children were entirely pain-free across the reporting period. In 31% of all e-diary entries the visual analog scale score for pain was >40 (high pain intensity), with 86% of children reporting a high level of pain at least once during the study period. The mean ratings of pain, stiffness, and fatigue intensity were in the mild-to-moderate range. Medication class was not a reliable predictor of differences in symptom intensity, even though 79% of children were prescribed a disease-modifying antirheumatic drug and 47% were prescribed a biologic agent. Moments of higher pain intensity and higher stiffness intensity were each uniquely predictive of higher concurrent functional limitations. Conclusion Self-reported pain, stiffness, and fatigue continue to be common in children with JIA, despite contemporary advances in treatment strategies, including use of biologic agents. These findings are surprisingly consistent with previous results from research using daily paper diaries in the pre-biologics era. There remains a pressing and ongoing need to optimize pain and symptom management in JIA. PMID

  2. [Advances on Extrocorporeal Photochemotherapy in the Treatment of Chronic Graft-Versus-Host Disease].

    PubMed

    Chen, Run-Zhe; Chen, Bao-An; Cheng, Jian

    2015-08-01

    Chronic graft-versus-host disease (cGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is also one of the major causes of patients' death following transplantation. Recently, extracorporeal photochemotherapy (ECP) has shown a considerable efficacy in cGVHD treatment, which is based on the infusion of autologous peripheral blood mononuclear cells collected by aphesis, incubated with the photoactivable drug 8-methoxypsoralen (8-MOP) and UV-A irradiation. The therapeutic effect of ECP is mainly achieved by the induction of cell apoptosis, influencing the function of dendritic cells and the induction of immune tolerance. ECP has many advantages in the treatment of cGVHD, such as no increasing the risk of infection in patients, unaffecting the graft-versus-leukemia effect, nearly no side effect and so on. Many medical centers have done a lot of research on the treatment of cGVHD in both children and adults by using ECP and achieved good results. CD19(+) CD21(-) B lymphocytes, serum BAFF and serum TNFα can be used to measure and early evaluate the efficacy of ECP treatment. The effect of ECP is associated with many factors, and certain complications may occur during the treatment. At present, the application of ECP treatment is limited by the unclear mechanisms, varying treatment cycles in different studies, and small number of patients in clinical research. In the near future, with deeper basic research, increasing the case number and standard clinical treatment, ECP will have a more extensive application prospects. This review focuses mainly on the clinical advances of ECP in the treatment of cGVHD. PMID:26314474

  3. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    PubMed Central

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

  4. A high-finesse fiber optic Fabry-Perot interferometer based magnetic-field sensor

    NASA Astrophysics Data System (ADS)

    Chen, Feifei; Jiang, Yi; Gao, Hongchun; Jiang, Lan

    2015-08-01

    A high-finesse extrinsic Fabry-Perot interferometric sensor for the measurement of weak dc magnetic fields is demonstrated. The Fabry-Perot cavity is formed by aligning the fiber end-face and the TbDyFe rod end-face, and each end-face is coated by a mirror with a micro-lens. The length of the TbDyFe rod is changed by the variation of an applied dc magnetic field, leading a change of the Fabry-Perot cavity length. By interrogating the white-light interferometric spectrum, the wavelength of the resonant peak is tracked and the length of the Fabry-Perot cavity is obtained. The sensor exhibits a high sensitivity of 1510 nm/mT with a magnetic resolution of 25 nT.

  5. Uses of Fabry-Perot velocimeters in studies of high explosives detonation

    SciTech Connect

    Breithaupt, R.D.; Tarver, C.M.

    1990-08-27

    The Fabry Perot has become an important and valuable tool by which explosive performance information can be obtained relatively easily and inexpensively. Principle uses of the Fabry Perot have been free surface, and particle velocity measurements in one dimensional studies of explosive performance. In the cylinder test, it has been very useful to resolve early wall motions. We have refined methods of characterizing new explosives i.e. equation of state, C-J pressure, via the cylinder shot, flat plate, and particle velocity techniques. All of these use Fabry Perot as one of the principle diagnostics. Each of these experimental techniques are discussed briefly and some of the results obtained. Modeling developed to fit Fabry-Perot results are described along with future testing.

  6. Demonstrations Using a Fabry-Perot. I. Multiple-Slit Interference

    ERIC Educational Resources Information Center

    Roychoudhuri, Chandrasekhar

    1975-01-01

    Describes a demonstration technique for showing multiple-slit interference patterns with the use of a Fabry-Perot etalon and a laser beam. A simple derivation of the analytical expression for such fringes is presented. (Author/CP)

  7. Method and apparatus for a Fabry-Perot multiple beam fringe sensor

    NASA Technical Reports Server (NTRS)

    James, Kenneth A. (Inventor); Quick, William H. (Inventor); Strahan, Virgil H. (Inventor)

    1986-01-01

    A method and, in one embodiment of the invention, the resulting apparatus for implementing a unique multiple beam fringe sensor that is adapted to be interfaced with a low cost, compact fiber optic transmission system in order to provide an accurate digital representation of a physical parameter (e.g. temperature) of a remote sample. The sensor is fabricated so as to include a Fabry-Perot gap formed between the ends of two mated optical fibers. By examining the optical characteristics of light that is transmitted through the Fabry-Perot sensor gap, an indication of gap width can be ascertained. Accordingly, a change in Fabry-Perot sensor gap width is related to a change in the particular physical parameter to be measured. In another embodiment of the invention, a second unique multiple beam fringe sensor having a Fabry-Perot gap is disclosed that is also adapted to provide an accurate digital representation of a physical parameter (e.g. temperature) of a remote sample. The sensor may be fabricated in two segments. A fiber containing segment includes each of a driving optical fiber for supplying incident light signals to the Fabry-Perot gap and a sensing optical fiber for receiving output light signals that have been transmitted twice through the Fabry-Perot gap, the optical characteristics of which output signals provide an indication of the parameter to be sensed. A transducer segment includes the Fabry-Perot gap formed therein and means responsive to the physical parameter for changing the width of the Fabry-Perot gap and, accordingly, the optical characteristics of the light signals passing therethrough.

  8. Experimental and numerical characterization of a hybrid Fabry-Pérot cavity for temperature sensing.

    PubMed

    Lopez-Aldaba, Aitor; Pinto, Ana Margarida Rodrigues; Lopez-Amo, Manuel; Frazão, Orlando; Santos, José Luís; Baptista, José Manuel; Baierl, Hardy; Auguste, Jean-Louis; Jamier, Raphael; Roy, Philippe

    2015-04-07

    A hybrid Fabry-Pérot cavity sensing head based on a four-bridge microstructured fiber is characterized for temperature sensing. The characterization of this cavity is performed numerically and experimentally in the L-band. The sensing head output signal presents a linear variation with temperature changes, showing a sensitivity of 12.5 pm/°C. Moreover, this Fabry-Pérot cavity exhibits good sensitivity to polarization changes and high stability over time.

  9. Engineering-reflected phase in Fabry-Perot sensors with resonant mirrors.

    PubMed

    Gellineau, Antonio; Wong, Yu-Po; Solgaard, Olav

    2013-12-01

    Fabry-Perot cavities made with photonic crystal (PC) mirrors and other resonant structures exhibit nontraditional characteristics due to the strong wavelength dependence of their reflected phase. This Letter describes how engineering the phase of PC mirrors enables sensors that are tolerant to variations in laser center frequency and line width. Reflection spectra measurements of Fabry-Perot cavities made with PC mirrors were collected as a function of wavelength and cavity length, providing experimental verification of theory and simulations.

  10. Experimental and numerical characterization of a hybrid Fabry-Pérot cavity for temperature sensing.

    PubMed

    Lopez-Aldaba, Aitor; Pinto, Ana Margarida Rodrigues; Lopez-Amo, Manuel; Frazão, Orlando; Santos, José Luís; Baptista, José Manuel; Baierl, Hardy; Auguste, Jean-Louis; Jamier, Raphael; Roy, Philippe

    2015-01-01

    A hybrid Fabry-Pérot cavity sensing head based on a four-bridge microstructured fiber is characterized for temperature sensing. The characterization of this cavity is performed numerically and experimentally in the L-band. The sensing head output signal presents a linear variation with temperature changes, showing a sensitivity of 12.5 pm/°C. Moreover, this Fabry-Pérot cavity exhibits good sensitivity to polarization changes and high stability over time. PMID:25853404

  11. Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: a pilot study.

    PubMed

    Zanini, Sergio; Moschella, Vincenzo; Stefani, Alessandro; Peppe, Antonella; Pierantozzi, Mariangela; Galati, Salvatore; Costa, Alberto; Mazzone, Paolo; Stanzione, Paolo

    2009-09-01

    Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.

  12. Limited wrist arthrodesis versus radial osteotomy for advanced Kienböck's disease--for a fragmented lunate.

    PubMed

    Tatebe, Masahiro; Hirata, Hitoshi; Iwata, Yoshihisa; Hattori, Tatsuya; Nakamura, Ryogo

    2006-01-01

    Thirty-eight patients with advanced Kienböck's disease treated by limited wrist arthrodesis (LWA: n = 10) or radial osteotomy (RO: n = 28) for a fragmented lunate were retrospectively examined after an average of 47.9 and 68.1 months, respectively. Compared with pre-operative values, the active flexion-extension range of motion decreased by about 16.0 degrees in LWA and increased approximately 9.7 degrees in RO and the grip strength improved by approximately 7.5 kg in LWA and 8.0 kg in RO. In both groups, radiographs showed no significant progression of carpal collapse. Although LWA caused some decrease in wrist flexion-extension, both procedures are appropriate for surgical treatment of advanced Kienböck's disease. Most patients experienced a reduction in pain and were able to return to work. PMID:17080522

  13. Advanced containment methods for the treatment of Perthes disease: Salter plus varus osteotomy and triple pelvic osteotomy.

    PubMed

    Wenger, Dennis R; Pandya, Nirav K

    2011-09-01

    The goal of intervention in Legg-Calvé-Perthes disease has been to prevent femoral head deformation by containing the head within the acetabulum, using it as a mold for guiding femoral head development. With appropriate proximal femoral morphology, premature arthritis can hopefully be avoided. Both nonsurgical and surgical methods of treatment have evolved over time, from abduction casts and braces to advanced surgical containment methods, which are now the mainstay of treatment. The purpose of this study is to briefly review the evolution of surgical treatment of Legg-Calvé-Perthes disease, and to concentrate on 2 advanced surgical containment methods: combined Salter innominate osteotomy with femoral varus osteotomy and triple pelvic osteotomy.

  14. [Adequacy of clinical interventions in patients with advanced and complex disease. Proposal of a decision making algorithm].

    PubMed

    Ameneiros-Lago, E; Carballada-Rico, C; Garrido-Sanjuán, J A; García Martínez, A

    2015-01-01

    Decision making in the patient with chronic advanced disease is especially complex. Health professionals are obliged to prevent avoidable suffering and not to add any more damage to that of the disease itself. The adequacy of the clinical interventions consists of only offering those diagnostic and therapeutic procedures appropriate to the clinical situation of the patient and to perform only those allowed by the patient or representative. In this article, the use of an algorithm is proposed that should serve to help health professionals in this decision making process.

  15. Fabry-Pérot interferometer utilized for displacement measurement in a large measuring range.

    PubMed

    Wang, Yung-Cheng; Shyu, Lih-Horng; Chang, Chung-Ping

    2010-09-01

    The optical configuration of a Fabry-Pérot interferometer is uncomplicated. This has already been applied in different measurement systems. For the displacement measurement with the Fabry-Pérot interferometer, the result is significantly influenced by the tilt angles of the measurement mirror in the interferometer. Hence, only for the rather small measuring range, the Fabry-Pérot interferometer is available. The goal of this investigation is to enhance the measuring range of Fabry-Pérot interferometer by compensating the tilt angles. To verify the measuring characteristic of the self-developed Fabry-Pérot interferometer, some comparison measurements with a reference standard have been performed. The maximum deviation of comparison experiments is less than 0.3 μm in the traveling range of 30 mm. The experimental results show that the Fabry-Pérot interferometer is highly stable, insensitive to environment effects, and can meet the measuring requirement of the submicrometer order.

  16. Translating Genomic Advances to Physical Therapist Practice: A Closer Look at the Nature and Nurture of Common Diseases.

    PubMed

    Curtis, Catherine L; Goldberg, Allon; Kleim, Jeffrey A; Wolf, Steven L

    2016-04-01

    The Human Genome Project and the International HapMap Project have yielded new understanding of the influence of the human genome on health and disease, advancing health care in significant ways. In personalized medicine, genetic factors are used to identify disease risk and tailor preventive and therapeutic regimens. Insight into the genetic bases of cellular processes is revealing the causes of disease and effects of exercise. Many diseases known to have a major lifestyle contribution are highly influenced by common genetic variants. Genetic variants are associated with increased risk for common diseases such as cardiovascular disease and osteoarthritis. Exercise response also is influenced by genetic factors. Knowledge of genetic factors can help clinicians better understand interindividual differences in disease presentation, pain experience, and exercise response. Family health history is an important genetic tool and encourages clinicians to consider the wider client-family unit. Clinicians in this new era need to be prepared to guide patients and their families on a variety of genomics-related concerns, including genetic testing and other ethical, legal, or social issues. Thus, it is essential that clinicians reconsider the role of genetics in the preservation of wellness and risk for disease to identify ways to best optimize fitness, health, or recovery. Clinicians with knowledge of the influence of genetic variants on health and disease will be uniquely positioned to institute individualized lifestyle interventions, thereby fulfilling roles in prevention and wellness. This article describes how discoveries in genomics are rapidly evolving the understanding of health and disease by highlighting 2 conditions: cardiovascular disease and osteoarthritis. Genetic factors related to exercise effects also are considered. PMID:26637647

  17. Translating Genomic Advances to Physical Therapist Practice: A Closer Look at the Nature and Nurture of Common Diseases.

    PubMed

    Curtis, Catherine L; Goldberg, Allon; Kleim, Jeffrey A; Wolf, Steven L

    2016-04-01

    The Human Genome Project and the International HapMap Project have yielded new understanding of the influence of the human genome on health and disease, advancing health care in significant ways. In personalized medicine, genetic factors are used to identify disease risk and tailor preventive and therapeutic regimens. Insight into the genetic bases of cellular processes is revealing the causes of disease and effects of exercise. Many diseases known to have a major lifestyle contribution are highly influenced by common genetic variants. Genetic variants are associated with increased risk for common diseases such as cardiovascular disease and osteoarthritis. Exercise response also is influenced by genetic factors. Knowledge of genetic factors can help clinicians better understand interindividual differences in disease presentation, pain experience, and exercise response. Family health history is an important genetic tool and encourages clinicians to consider the wider client-family unit. Clinicians in this new era need to be prepared to guide patients and their families on a variety of genomics-related concerns, including genetic testing and other ethical, legal, or social issues. Thus, it is essential that clinicians reconsider the role of genetics in the preservation of wellness and risk for disease to identify ways to best optimize fitness, health, or recovery. Clinicians with knowledge of the influence of genetic variants on health and disease will be uniquely positioned to institute individualized lifestyle interventions, thereby fulfilling roles in prevention and wellness. This article describes how discoveries in genomics are rapidly evolving the understanding of health and disease by highlighting 2 conditions: cardiovascular disease and osteoarthritis. Genetic factors related to exercise effects also are considered.

  18. Elevated Neutrophil-to-Lymphocyte Ratio Predicts Intermediate-Term Outcomes in Patients Who Have Advanced Chronic Kidney Disease with Peripheral Artery Disease Receiving Percutaneous Transluminal Angioplasty

    PubMed Central

    Chen, I-Chih; Yu, Chao-Chin; Wu, Yi-Hsuan; Chao, Ting-Hsing

    2016-01-01

    Background Inflammation plays an important role in the pathogenesis of cardiovascular disease in patients with advanced chronic kidney disease (CKD). Neutrophil-to-lymphocyte ratio (NLR), an inflammatory biomarker, has not been evaluated in patients who have advanced CKD with peripheral artery disease (PAD) undergoing percutaneous transluminal angioplasty (PTA), especially in Taiwan. Methods We retrospectively evaluated 148 advanced CKD (creatinine clearance rate ≤ 30 mL/min/1.73 m2) identified from a prospective registry in our hospital (303 PTA cases in total). Kaplan-Meier analysis with log-rank test was used to study event-free survival, and all univariables (p value < 0.1) were put into multivariate Cox regression analysis. Results During the mean follow-up time of 8.6 ± 7.8 months, 35.1% of the cases achieved primary composite endpoint (all-cause mortality or major amputation), 25.5% underwent death from any cause, and 14.9% underwent major or minor amputation. Rutherford grade 6, either NLR or NLR ≥ 3.76, and a history of hypertension had a positively prognostic impact on the occurrence of primary composite endpoint, whereas higher albumin level (≥ 3.0 mg/dL) and technical success had a significantly protective effect. History of hypertension, either NLR or NLR ≥ 3.76, and age were associated with all-cause mortality. In addition, Rutherford 6, higher albumin level (≥ 3.0 mg/dL), technical success, NLR, and age could predict the occurrence of major amputation. Conclusions NLR, but not C-reactive protein or platelet-lymphocyte ratio, is an important prognostic predictor of all major clinical outcomes in patients with advanced CKD and PAD receiving PTA. Further studies are warranted to establish a better strategy and healthcare program in this clinical setting. PMID:27713601

  19. Advanced LIGO

    NASA Astrophysics Data System (ADS)

    LIGO Scientific Collaboration; Aasi, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V.; Affeldt, C.; Aggarwal, N.; Aguiar, O. D.; Ain, A.; Ajith, P.; Alemic, A.; Allen, B.; Amariutei, D.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J. S.; Ashton, G.; Ast, S.; Aston, S. M.; Aufmuth, P.; Aulbert, C.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballmer, S. W.; Barayoga, J. C.; Barbet, M.; Barclay, S.; Barish, B. C.; Barker, D.; Barr, B.; Barsotti, L.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Batch, J. C.; Baune, C.; Behnke, B.; Bell, A. S.; Bell, C.; Benacquista, M.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Biscans, S.; Biwer, C.; Blackburn, J. K.; Blackburn, L.; Blair, C. D.; Blair, D.; Bock, O.; Bodiya, T. P.; Bojtos, P.; Bond, C.; Bork, R.; Born, M.; Bose, Sukanta; Brady, P. R.; Braginsky, V. B.; Brau, J. E.; Bridges, D. O.; Brinkmann, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchman, S.; Buikema, A.; Buonanno, A.; Cadonati, L.; Calderón Bustillo, J.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Caride, S.; Caudill, S.; Cavaglià, M.; Cepeda, C.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chao, S.; Charlton, P.; Chen, Y.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Collette, C.; Cominsky, L.; Constancio, M., Jr.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cutler, C.; Dahl, K.; Dal Canton, T.; Damjanic, M.; Danilishin, S. L.; Danzmann, K.; Dartez, L.; Dave, I.; Daveloza, H.; Davies, G. S.; Daw, E. J.; DeBra, D.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; DeRosa, R. T.; DeSalvo, R.; Dhurandhar, S.; D´ıaz, M.; Di Palma, I.; Dojcinoski, G.; Dominguez, E.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Driggers, J. C.; Du, Z.; Dwyer, S.; Eberle, T.; Edo, T.; Edwards, M.; Edwards, M.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Essick, R.; Etzel, T.; Evans, M.; Evans, T.; Factourovich, M.; Fairhurst, S.; Fan, X.; Fang, Q.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Feldbaum, D.; Ferreira, E. C.; Fisher, R. P.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fuentes-Tapia, S.; Fulda, P.; Fyffe, M.; Gair, J. R.; Gaonkar, S.; Gehrels, N.; Gergely, L. Á.; Giaime, J. A.; Giardina, K. D.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Goßler, S.; Gräf, C.; Graff, P. B.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Grote, H.; Grunewald, S.; Guido, C. J.; Guo, X.; Gushwa, K.; Gustafson, E. K.; Gustafson, R.; Hacker, J.; Hall, E. D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harry, G. M.; Harry, I. W.; Hart, M.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Hee, S.; Heintze, M.; Heinzel, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hewitson, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hollitt, S. E.; Holt, K.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E.; Howell, E. J.; Hu, Y. M.; Huerta, E.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Islas, G.; Isler, J. C.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacobson, M.; Jang, H.; Jawahar, S.; Ji, Y.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Ju, L.; Haris, K.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Keiser, G. M.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, C.; Kim, K.; Kim, N. G.; Kim, N.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Korobko, M.; Korth, W. Z.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Krueger, C.; Kuehn, G.; Kumar, A.; Kumar, P.; Kuo, L.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Le, J.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Leong, J. R.; Levin, Y.; Levine, B.; Lewis, J.; Li, T. G. F.; Libbrecht, K.; Libson, A.; Lin, A. C.; Littenberg, T. B.; Lockerbie, N. A.; Lockett, V.; Logue, J.; Lombardi, A. L.; Lormand, M.; Lough, J.; Lubinski, M. J.; Lück, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macarthur, J.; MacDonald, T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Magee, R.; Mageswaran, M.; Maglione, C.; Mailand, K.; Mandel, I.; Mandic, V.; Mangano, V.; Mansell, G. L.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Martin, I. W.; Martin, R. M.; Martynov, D.; Marx, J. N.; Mason, K.; Massinger, T. J.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McLin, K.; McWilliams, S.; Meadors, G. D.; Meinders, M.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyers, P. M.; Miao, H.; Middleton, H.; Mikhailov, E. E.; Miller, A.; Miller, J.; Millhouse, M.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohanty, S. D.; Mohapatra, S. R. P.; Moore, B.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mossavi, K.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nash, T.; Nayak, R. K.; Necula, V.; Nedkova, K.; Newton, G.; Nguyen, T.; Nielsen, A. B.; Nissanke, S.; Nitz, A. H.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; Oram, R.; O'Reilly, B.; Ortega, W.; O'Shaughnessy, R.; Osthelder, C.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Pai, S.; Palashov, O.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Papa, M. A.; Paris, H.; Patrick, Z.; Pedraza, M.; Pekowsky, L.; Pele, A.; Penn, S.; Perreca, A.; Phelps, M.; Pierro, V.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Post, A.; Poteomkin, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S.; Prestegard, T.; Price, L. R.; Principe, M.; Privitera, S.; Prix, R.; Prokhorov, L.; Puncken, O.; Pürrer, M.; Qin, J.; Quetschke, V.; Quintero, E.; Quiroga, G.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramirez, K.; Raymond, V.; Reed, C. M.; Reid, S.; Reitze, D. H.; Reula, O.; Riles, K.; Robertson, N. A.; Robie, R.; Rollins, J. G.; Roma, V.; Romano, J. D.; Romanov, G.; Romie, J. H.; Rowan, S.; Rüdiger, A.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Saleem, M.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J. R.; Sannibale, V.; Santiago-Prieto, I.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Sawadsky, A.; Scheuer, J.; Schilling, R.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, S. M.; Sellers, D.; Sengupta, A. S.; Sergeev, A.; Serna, G.; Sevigny, A.; Shaddock, D. A.; Shahriar, M. S.; Shaltev, M.; Shao, Z.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siemens, X.; Sigg, D.; Silva, A. D.; Simakov, D.; Singer, A.; Singer, L.; Singh, R.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Son, E. J.; Sorazu, B.; Souradeep, T.; Staley, A.; Stebbins, J.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Steplewski, S.; Stevenson, S.; Stone, R.; Strain, K. A.; Strigin, S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sutton, P. J.; Szczepanczyk, M.; Szeifert, G.; Talukder, D.; Tanner, D. B.; Tápai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, R.; Tellez, G.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tomlinson, C.; Torres, C. V.; Torrie, C. I.; Traylor, G.; Tse, M.; Tshilumba, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; Vallisneri, M.; van Veggel, A. A.; Vass, S.; Vaulin, R.; Vecchio, A.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Vincent-Finley, R.; Vitale, S.; Vo, T.; Vorvick, C.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, H.; Wang, M.; Wang, X.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wilkinson, C.; Williams, L.; Williams, R.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Xie, S.; Yablon, J.; Yakushin, I.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yang, Q.; Zanolin, M.; Zhang, Fan; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhu, X. J.; Zucker, M. E.; Zuraw, S.; Zweizig, J.

    2015-04-01

    The Advanced LIGO gravitational wave detectors are second-generation instruments designed and built for the two LIGO observatories in Hanford, WA and Livingston, LA, USA. The two instruments are identical in design, and are specialized versions of a Michelson interferometer with 4 km long arms. As in Initial LIGO, Fabry-Perot cavities are used in the arms to increase the interaction time with a gravitational wave, and power recycling is used to increase the effective laser power. Signal recycling has been added in Advanced LIGO to improve the frequency response. In the most sensitive frequency region around 100 Hz, the design strain sensitivity is a factor of 10 better than Initial LIGO. In addition, the low frequency end of the sensitivity band is moved from 40 Hz down to 10 Hz. All interferometer components have been replaced with improved technologies to achieve this sensitivity gain. Much better seismic isolation and test mass suspensions are responsible for the gains at lower frequencies. Higher laser power, larger test masses and improved mirror coatings lead to the improved sensitivity at mid and high frequencies. Data collecting runs with these new instruments are planned to begin in mid-2015.

  20. Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer on interferometric signals

    SciTech Connect

    Shyu, Lih-Horng; Chang, Chung-Ping; Wang, Yung-Cheng

    2011-06-15

    Fabry-Perot interferometer is often used for the micro-displacement, because of its common optical path structure being insensitive to the environmental disturbances. Recently, the folded Fabry-Perot interferometer has been investigated for displacement measurements in large ranges. The advantages of a folded Fabry-Perot interferometer are insensitive to the tilt angle and higher optical resolution. But the design of the optical cavity has become more and more complicated. For this reason, the intensity loss in the cavity will be an important parameter for the distribution of the interferometric intensity. To obtain a more accurate result of such interferometer utilized for displacement measurements, the intensity loss of the cavity in the fabricated folded Fabry-Perot interferometer and the modified equation of the folded Fabry-Perot interferometer will be described. According to the theoretical and experimental results, the presented model is available for the analysis of displacement measurements by a folded Fabry-Perot interferometer.

  1. Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer on interferometric signals.

    PubMed

    Shyu, Lih-Horng; Chang, Chung-Ping; Wang, Yung-Cheng

    2011-06-01

    Fabry-Perot interferometer is often used for the micro-displacement, because of its common optical path structure being insensitive to the environmental disturbances. Recently, the folded Fabry-Perot interferometer has been investigated for displacement measurements in large ranges. The advantages of a folded Fabry-Perot interferometer are insensitive to the tilt angle and higher optical resolution. But the design of the optical cavity has become more and more complicated. For this reason, the intensity loss in the cavity will be an important parameter for the distribution of the interferometric intensity. To obtain a more accurate result of such interferometer utilized for displacement measurements, the intensity loss of the cavity in the fabricated folded Fabry-Perot interferometer and the modified equation of the folded Fabry-Perot interferometer will be described. According to the theoretical and experimental results, the presented model is available for the analysis of displacement measurements by a folded Fabry-Perot interferometer.

  2. Experimental Studies of Alignment Tolerance and High Temperature Performance of A Fabry-Perot Interferometric Pressure Sensor

    NASA Astrophysics Data System (ADS)

    Padron, Ivan; Fiory, Anthony; Ravindra, Nuggehalli

    2008-03-01

    Fabry-Perot interferometry is one of the most reliable of the several optical techniques that can be utilized to facilitate the fabrication of an optical sensor. Devices based on this technique can provide high degree of sensitivity, versatility and immunity to environmental noise. The Fabry-Perot Interferometric Sensor (FPIS), to be discussed in this presentation, consists of a Fabry-Perot cavity formed between two bonded surfaces: a corrugated diaphragm with a center rigid body (or boss) which deflects under external pressure and keeps a high alignment tolerance and a glass surface with an optical fiber insert. The Fabry-Perot cavity and optical fiber have been used as the sensing element and interconnect, respectively. The Fabry-Perot cavity has been fabricated using the MEMS technology. Micromachining techniques make Fabry-Perot sensors very attractive by reducing the size and cost of the sensing element.

  3. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells

    PubMed Central

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  4. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells.

    PubMed

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases. PMID:27293445

  5. Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells.

    PubMed

    Li, Shujing; Wang, Xianyun; Li, Jing; Zhang, Jun; Zhang, Fan; Hu, Jie; Qi, Yixin; Yan, Baoyong; Li, Quanhai

    2016-01-01

    Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases.

  6. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

    PubMed

    Cheikh Hassan, Hicham I; Tang, Mila; Djurdjev, Ognjenka; Langsford, David; Sood, Manish M; Levin, Adeera

    2016-10-01

    The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes. PMID:27591084

  7. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

    PubMed

    Cheikh Hassan, Hicham I; Tang, Mila; Djurdjev, Ognjenka; Langsford, David; Sood, Manish M; Levin, Adeera

    2016-10-01

    The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years. Infectious episodes were classified by anatomic location and identified by positive culture, hospital admission, or use of antibiotics. Competing risk models were used to examine the time-varying risk of infection and the risk of cardiovascular ischemia, congestive heart failure, or end-stage kidney disease accounting for the competing risk of mortality. All outcomes were independently adjudicated. Of 2370 patients (mean age, 68 years; mean baseline eGFR, 28.2 mL/min/1.73m(2)), 575 patients (24.3%) had recorded infections; 378 had 1 infection episode, whereas 197 had 2 or more episodes, the most common being urinary and respiratory. An infectious episode was independently associated with an increased risk of cardiovascular ischemia (hazard ratio 1.80, 95% confidence interval 1.24-2.60), congestive heart failure (hazard ratio, 3.2; confidence interval, 2.25-4.61), end-stage kidney disease (hazard ratio, 1.58; confidence interval, 1.22-2.05) or mortality (hazard ratio, 3.39; confidence interval, 2.65-4.33). Thus, there is a high risk of infection in advanced CKD being associated with subsequent adverse outcomes.

  8. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.

    PubMed

    Ponce, Francisco A; Asaad, Wael F; Foote, Kelly D; Anderson, William S; Rees Cosgrove, G; Baltuch, Gordon H; Beasley, Kara; Reymers, Donald E; Oh, Esther S; Targum, Steven D; Smith, Gwenn S; Lyketsos, Constantine G; Lozano, Andres M

    2016-07-01

    OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with

  9. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.

    PubMed

    Ponce, Francisco A; Asaad, Wael F; Foote, Kelly D; Anderson, William S; Rees Cosgrove, G; Baltuch, Gordon H; Beasley, Kara; Reymers, Donald E; Oh, Esther S; Targum, Steven D; Smith, Gwenn S; Lyketsos, Constantine G; Lozano, Andres M

    2016-07-01

    OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with

  10. Hyperspectral remote sensing for advanced detection of early blight (Alternaria solani) disease in potato (Solanum tuberosum) plants

    NASA Astrophysics Data System (ADS)

    Atherton, Daniel

    Early detection of disease and insect infestation within crops and precise application of pesticides can help reduce potential production losses, reduce environmental risk, and reduce the cost of farming. The goal of this study was the advanced detection of early blight (Alternaria solani) in potato (Solanum tuberosum) plants using hyperspectral remote sensing data captured with a handheld spectroradiometer. Hyperspectral reflectance spectra were captured 10 times over five weeks from plants grown to the vegetative and tuber bulking growth stages. The spectra were analyzed using principal component analysis (PCA), spectral change (ratio) analysis, partial least squares (PLS), cluster analysis, and vegetative indices. PCA successfully distinguished more heavily diseased plants from healthy and minimally diseased plants using two principal components. Spectral change (ratio) analysis provided wavelengths (490-510, 640, 665-670, 690, 740-750, and 935 nm) most sensitive to early blight infection followed by ANOVA results indicating a highly significant difference (p < 0.0001) between disease rating group means. In the majority of the experiments, comparisons of diseased plants with healthy plants using Fisher's LSD revealed more heavily diseased plants were significantly different from healthy plants. PLS analysis demonstrated the feasibility of detecting early blight infected plants, finding four optimal factors for raw spectra with the predictor variation explained ranging from 93.4% to 94.6% and the response variation explained ranging from 42.7% to 64.7%. Cluster analysis successfully distinguished healthy plants from all diseased plants except for the most mildly diseased plants, showing clustering analysis was an effective method for detection of early blight. Analysis of the reflectance spectra using the simple ratio (SR) and the normalized difference vegetative index (NDVI) was effective at differentiating all diseased plants from healthy plants, except for the

  11. A novel fiber optic Fabry-Perot structure with a micrometric diameter tip

    NASA Astrophysics Data System (ADS)

    Wang, Xingwei; Xu, Juncheng; Wang, Zhuang; Cooper, Kristie L.; Wang, Anbo

    2006-08-01

    This paper presents a novel fiber optic Fabry-Perot (FP) structure with a micrometric diameter tip. The fabrication of micro scale probes has become essential in intracellular surgery, in cell sensing, manipulation, and injection. It is of great importance in many fields, such as genetics, pathology, criminology, pharmacogenetics, and food safety. With such a tiny protrusion, the sensor can be inserted into micron size cells, say, for DNA analysis. With the FP cavity inside the fiber, the change of optical path difference (OPD) caused by the environment can be demodulated. In addition, the structure is intrinsically capable of temperature compensation. What's more, it is simple, cost-efficient, and compact. Last but not the least, the structure shows promise for nanometric protrusion. Once this goal is achieved, the sensor can be inserted into most cells. The sensor could pave the way for faster, more accurate medical diagnostic tests for countless conditions and may ultimately save lives by allowing earlier disease detection and intervention.

  12. The APOE locus advances disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Crawford, F.; Bennett, C.; Osborne, A.

    1994-09-01

    An association has been observed in several independent data sets between late onset Alzheimer`s disease (AD) and the APOE locus on chromosomes 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and nonstringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease-free survival suggested that APOE genotype contributes a small fraction of the total variance, indicating that the APOE locus is a poor predictor of disease-free survival time within late onset families. We suggest that the APOE locus enhances the rate of progression of the disease in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause this disease.

  13. Cracking the nodule worm code advances knowledge of parasite biology and biotechnology to tackle major diseases of livestock.

    PubMed

    Tyagi, Rahul; Joachim, Anja; Ruttkowski, Bärbel; Rosa, Bruce A; Martin, John C; Hallsworth-Pepin, Kymberlie; Zhang, Xu; Ozersky, Philip; Wilson, Richard K; Ranganathan, Shoba; Sternberg, Paul W; Gasser, Robin B; Mitreva, Makedonka

    2015-11-01

    Many infectious diseases caused by eukaryotic pathogens have a devastating, long-term impact on animal health and welfare. Hundreds of millions of animals are affected by parasitic nematodes of the order Strongylida. Unlocking the molecular biology of representatives of this order, and understanding nematode-host interactions, drug resistance and disease using advanced technologies could lead to entirely new ways of controlling the diseases that they cause. Oesophagostomum dentatum (nodule worm; superfamily Strongyloidea) is an economically important strongylid nematode parasite of swine worldwide. The present article reports recent advances made in biology and animal biotechnology through the draft genome and developmental transcriptome of O. dentatum, in order to support biological research of this and related parasitic nematodes as well as the search for new and improved interventions. This first genome of any member of the Strongyloidea is 443 Mb in size and predicted to encode 25,291 protein-coding genes. Here, we review the dynamics of transcription throughout the life cycle of O. dentatum, describe double-stranded RNA interference (RNAi) machinery and infer molecules involved in development and reproduction, and in inducing or modulating immune responses or disease. The secretome predicted for O. dentatum is particularly rich in peptidases linked to interactions with host tissues and/or feeding activity, and a diverse array of molecules likely involved in immune responses. This research progress provides an important resource for future comparative genomic and molecular biological investigations as well as for biotechnological research toward new anthelmintics, vaccines and diagnostic tests.

  14. Swift: A Widefield Imaging Fabry Perot for Sofia

    NASA Technical Reports Server (NTRS)

    Stacey, Gordon J.

    1999-01-01

    Contract was to pursue feasibility studies of the SOFIA Widefield Imaging Fabry-Perot (SWIFT). SWIFT was proposed as a two color 18 to 40 microns imaging Fabry-Perot that utilized two Rockwell/Boeing 256 x 256 pixel Si:Sb BIBs as detective devices. The colors were to be split between 26 and 30 microns using a MgO dichroic. The resolution achieving devices were to be a pair of cryogenic fully tunable scanning Fabry-Perot interferometers (FPIs), two in each band. For high resolving powers, a third, fixed FPI is inserted into the beam. The FPI mirrors were to be made of free standing metal mesh. We also proposed to look into a long wavelength (40 to 210 microns) band during the feasibility study period. We produced a proposal to USRA, submitted in July 1997 that substantially refined our ideas. We decided the long wavelength science was compelling, so the baseline wavelength coverage for SWIFT was widened to 17 to 205 microns. Under typical operations, we proposed to simultaneously image in two bands: 22 to 38 microns, and 50 to 205 microns. The bands were to be split by a cold CaF2 dichroic. The short wavelength (SW) band was to employ a 256 x 256 pixel Boeing/Rockwell Si:Sb BIB array, and the long wavelength (LW) band was to employ a Goddard 6 x 32 (upgradable to 32 x 32) element array of monolithic silicon "pop-up" bolometers as detective devices. The two color capability doubled the data taking efficiency, and ensured "perfect" registration between the images obtained in each band. For the SW band, the beam was to be fully sampled (0.7" pixels, 1.4 in. beam) at 17 microns, and over sampled at longer wavelengths. Even so, SWIFT has a very large (3 ft x 3 ft) field of view. To match the SW and LW fields of view (initially in one dimension only, but in 2-dimensions with 32 x 32 upgrade), SWIFT was to under sample at 63 microns (5.6 in pixels, 5.2 in beam) resulting in a 0.56 x 3 in (upgrade to 3 in x 3 in) field of view. Each band has both Lo-Res (R triple bond

  15. New Targeted Treatment May Slow Disease in Patients with Advanced GIST

    Cancer.gov

    A new oral drug, regorafenib (Stivarga®), may delay the progression of advanced gastrointestinal stromal tumors (GIST) that are resistant to treatment, according to results from an international clinical trial published November 22, 2012, in The Lancet.

  16. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase

    PubMed Central

    Warnock, David G.; Bichet, Daniel G.; Holida, Myrl; Goker-Alpan, Ozlem; Nicholls, Kathy; Thomas, Mark; Eyskens, Francois; Shankar, Suma; Adera, Mathews; Sitaraman, Sheela; Khanna, Richie; Flanagan, John J.; Wustman, Brandon A.; Barth, Jay; Barlow, Carrolee; Valenzano, Kenneth J.; Lockhart, David J.; Boudes, Pol; Johnson, Franklin K.

    2015-01-01

    Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified. Trial Registration ClinicalTrials.gov NCT01196871 PMID:26252393

  17. Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies.

    PubMed

    Barkhuizen, Melinda; Anderson, David G; Grobler, Anne F

    2016-02-01

    GBA mutations are to date the most common genetic risk factor for Parkinson's disease. The GBA gene encodes the lysomal hydrolase glucocerebrosidase. Whilst bi-allelic GBA mutations cause Gaucher disease, both mono- and bi-allelic mutations confer risk for Parkinson's disease. Clinically, Parkinson's disease patients with GBA mutations resemble idiopathic Parkinson's disease patients. However, these patients have a modest reduction in age-of-onset of disease and a greater incidence of cognitive decline. In some cases, GBA mutations are also responsible for familial Parkinson's disease. The accumulation of α-synuclein into Lewy bodies is the central neuropathological hallmark of Parkinson's disease. Pathologic GBA mutations reduce enzymatic function. A reduction in glucocerebrosidase function increases α-synuclein levels and propagation, which in turn inhibits glucocerebrosidase in a feed-forward cascade. This cascade is central to the neuropathology of GBA-associated Parkinson's disease. The lysosomal integral membrane protein type-2 is necessary for normal glucocerebrosidase function. Glucocerebrosidase dysfunction also increases in the accumulation of β-amyloid and amyloid-precursor protein, oxidative stress, neuronal susceptibility to metal ions, microglial and immune activation. These factors contribute to neuronal death. The Mendelian Parkinson's disease genes, Parkin and ATP13A2, intersect with glucocerebrosidase. These factors sketch a complex circuit of GBA-associated neuropathology. To clinically interfere with this circuit, central glucocerebrosidase function must be improved. Strategies based on reducing breakdown of mutant glucocerebrosidase and increasing the fraction that reaches the lysosome has shown promise. Breakdown can be reduced by interfering with the ability of heat-shock proteins to recognize mutant glucocerebrosidase. This underlies the therapeutic efficacy of certain pharmacological chaperones and histone deacetylase inhibitors. These

  18. Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus.

    PubMed

    Boronat, Mauro; García-Cantón, César; Quevedo, Virginia; Lorenzo, Dionisio L; López-Ríos, Laura; Batista, Fátima; Riaño, Marta; Saavedra, Pedro; Checa, María D

    2014-03-01

    Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.