Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): Evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes
Williams, Ruth; Vesa, Jouni; Järvelä, Irma; McKay, Tristan; Mitchison, Hannah; Hellsten, Elina; Thompson, Andrew; Callen, David; Sutherland, Grant; Luna-Battadano, David; Stallings, Ray; Peltonen, Leena; Gardiner, Mark
The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjögren-Vogt, or Batten, disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci. PMID:8213822
Williams, Ruth E; Adams, Heather R; Blohm, Martin; Cohen-Pfeffer, Jessica L; de Los Reyes, Emily; Denecke, Jonas; Drago, Kristen; Fairhurst, Charlie; Frazier, Margie; Guelbert, Norberto; Kiss, Szilárd; Kofler, Annamaria; Lawson, John A; Lehwald, Lenora; Leung, Mary-Anne; Mikhaylova, Svetlana; Mink, Jonathan W; Nickel, Miriam; Shediac, Renée; Sims, Katherine; Specchio, Nicola; Topcu, Meral; von Löbbecke, Ina; West, Andrea; Zernikow, Boris; Schulz, Angela
CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness, and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step toward the development of consensus-based management guidelines for CLN2 disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Kohlschütter, Alfried; Schulz, Angela
CLN2 disease is an inherited metabolic storage disorder caused by the deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The disease affects mainly the brain and the retina and is characterized by progressive dysfunction of the central nervous system, leading to dementia, epilepsy, loss of motor function and blindness. The classical late infantile type begins at around three years of age with epilepsy and/or a standstill of psychomotor development, followed by a rapid loss of all abilities and death in childhood. A late onset form in a small proportion of patients starts at the age of 4 to 10 years, but also leads to severe neurological deterioration. The deficiency of TPP1 causes the lysosomal accumulation of a material called ceroid lipofuscin. The natural substrate of TPP1 is not known, nor is the connection between storage process and neurodegeneration, which is characterized by loss of neurons. Among various experimental approaches to treatment, enzyme replacement therapy (ERT) and gene therapy have developed remarkably. Enzyme delivery through the cerebrospinal fluid led to wide distribution of enzyme activity in the brain and to attenuated neuropathology and disease progression in a TPP1-deficient mouse model as well as in a natural TPP1-deficient dog model. Safety of the intrathecal delivery, pharmacokinetics, and tissue distribution of the administered enzyme studied in non-human primates were encouraging, and a phase I/II clinical trial for intraventricular ERT in CLN2 patients is ongoing. A second approach uses intracerebral injection of viral vectors containing normal coding segments of the CLN2 gene. In a CLN2 mouse model, this procedure resulted in cerebral enzyme expression, reduced brain pathology and increased survival. A small number of patients have been treated the same way using an AAV2-vector for gene transfer to the brain. Although there were no serious adverse events unequivocally attributable to the vector used, there were
Geraets, Ryan D.; Beraldi, Rosanna; Weimer, Jill M.; Pearce, David A.
The Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, result from mutations in over a dozen genes. Although, adults are susceptible, the NCLs are frequently classified as pediatric neurodegenerative diseases due to their greater pediatric prevalence. Initial clinical presentation usually consists of either seizures or retinopathy but develops to encompass both in conjunction with declining motor and cognitive function. The NCLs result in premature death due to the absence of curative therapies. Nevertheless, preclinical and clinical trials exist for various therapies. However, the genotypes of NCL animal models determine which therapeutic approaches can be assessed. Mutations of the CLN2 gene encoding a soluble lysosomal enzyme, tripeptidyl peptidase 1 (TPP1), cause late infantile NCL/CLN2 disease. The genotype of the original mouse model of CLN2 disease, Cln2-/-, excludes mutation guided therapies like antisense oligonucleotides and nonsense suppression. Therefore, the purpose of this study was to develop a model of CLN2 disease that allows for the assessment of all therapeutic approaches. Nonsense mutations in CLN2 disease are frequent, the most common being CLN2R208X. Thus, we created a mouse model that carries a mutation equivalent to the human p.R208X mutation. Molecular assessment of Cln2R207X/R207X tissues determined significant reduction in Cln2 transcript abundance and TPP1 enzyme activity. This reduction leads to the development of neurological impairment (e.g. tremors) and neuropathology (e.g. astrocytosis). Collectively, these assessments indicate that the Cln2R207X/R207X mouse is a valid CLN2 disease model which can be used for the preclinical evaluation of all therapeutic approaches including mutation guided therapies. PMID:28464005
Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas
Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.
Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S
CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system. PMID:28079862
Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S
CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.Gene Therapy advance online publication, 2 February 2017; doi:10.1038/gt.2017.4.
... tripeptidyl peptidase 1. This enzyme is found in cell structures called lysosomes , which digest and recycle different types of molecules. Tripeptidyl peptidase 1 breaks down protein fragments, known as ... accumulations occur in cells throughout the body; however, nerve cells seem to ...
Galvis, D A; Nakazato, Y; Wells, T R; Landing, B H
Eighty-eight specimens of esophagus, small intestine, or colon from 45 patients, predominantly infants and children, with 30 different genetic diseases were analyzed by a microdissection technique for the following abnormalities of the Auerbach (myenteric) plexus: (1) abnormality of the pattern of the nervous network of the plexus, (2) abnormal fraction of neural tissue in the plane of the plexus, (3) abnormal size or appearance of the cytoplasm of the neurons of the plexus, and (4) abnormal number of neurons in the ganglia of the plexus. Seven of 8 specimens of esophagus from patients with neuronal storage diseases (infantile Niemann-Pick disease, Jansky-Bielschowsky disease, etc.) showed an increased fraction of neural tissue in the plane of the plexus, whereas 2 of 3 patients with Cockayne syndrome showed a reduced fraction, with abnormally slender interganglionic fibers. The fraction of neural tissue in the plane of the plexus was also abnormal at one or more levels in patients with adrenoleukodystrophy, ataxia telangiectasia, Krabbe disease, and juvenile metachromatic leukodystrophy. Abnormality of neuron size and cytology was seen in several neuronal lipidoses, including Jansky-Bielschowsky and Sandhoff diseases and juvenile GM2 gangliosidosis, with the most striking neuronal enlargement noted in infantile Niemann-Pick disease. Abnormalities of plexus mass or pattern, as well as those of neuronal cytoplasm and neuron number, offer improved insight into possible mechanisms producing gastrointestinal tract dysfunction (swallowing difficulty, gastroesophageal reflux, constipation, etc) in patients with genetic disorders.
Quilis, Inma; Igual, Juan Carlos
Cln1 and Cln2 are very similar but not identical cyclins. In this work, we tried to describe the molecular basis of the functional distinction between Cln1 and Cln2. We constructed chimeric cyclins containing different fragments of Cln1 and Cln2 and performed several functional analysis that make it possible to distinguish between Cln1 or Cln2. We identified that region between amino acids 225 and 299 of Cln2 is not only necessary but also sufficient to confer Cln2 specific functionality compared with Cln1. We also studied Cln1 and Cln2 subcellular localization identifying additional differences between them. Both cyclins are distributed between the nucleus and the cytoplasm, but Cln1 shows stronger nuclear accumulation. Nuclear import of both cyclins is mediated by the classical nuclear import pathway and by sequences in the N-terminal end of the proteins. For Cln2, but not for Cln1, a nuclear export mechanism mediated by karyopherin Msn5 has been identified. Strikingly, Cln2 export depends on a Msn5-dependent NES between amino acids 225 and 299. In fact, the introduction of this region confers to Cln1 an export mechanism dependent on Msn5; importantly, this causes the gain of Cln2-specific cytosolic functions and the impairment of nuclear function. In short, a region from Cln2 controlling an Msn5-dependent nuclear export mechanism confers a specific functionality to Cln2 compared with Cln1. PMID:22889732
Cross, F R; Hoek, M; McKinney, J D; Tinkelenberg, A H
Expression of the Saccharomyces cerevisiae CLN1 and CLN2 genes is cell cycle regulated, and the genes may be controlled by positive feedback. It has been proposed that positive feedback operates via Cln/Cdc28 activation of the Swi4/Swi6 transcription factor, leading to CLN1 and CLN2 transcription due to Swi4 binding to specific sites (SCBs) in the CLN1 and CLN2 promoters. To test this proposal, we have examined the effects of deletion either of the potential SCBs in the CLN2 promoter or of the SWI4 gene on CLN2 transcriptional control. Deletion of a restriction fragment containing the identified SCBs from the promoter does not prevent cell cycle regulation of CLN2 expression, although expression is lowered at all cell cycle positions. A promoter containing a 5.5-kb plasmid insertion or an independent 2.5-kb insertion at the point of deletion of the SCB-containing restriction fragment also exhibits cell cycle regulation, so involvement of unidentified upstream SCBs is unlikely. Neither Swi4 nor the related Mbp1 transcription factor is required for cell cycle regulation of the intact CLN2 promoter. In contrast, Swi4 (but not Mbp1) is required for correct cell cycle regulation of the insertion/deletion promoter lacking SCB sites. We have extended previous genetic evidence for involvement of Swi4 in some aspect of CLN2 function: a mutant hunt for CLN2 positive regulatory factors yielded only swi4 mutations at saturation. Swi4 may bind to nonconsensus sequences in the CLN2 promoter (possibly in addition to consensus sites), or it may act indirectly to regulate CLN2 expression. Images PMID:8007977
Quilis, Inma; Igual, J Carlos
The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1 and Cln2 in order to further investigate the possible differences between them. Both cyclins show the same half-life but, while Cln2 degradation depends on ubiquitin ligases SCF(G)(rr1) and SCF(C)(dc4), Cln1 is affected only by SCF(G)(rr1). Degradation analysis of chimeric cyclins, constructed by combining fragments from Cln1 and Cln2, identifies the N-terminal sequence of the proteins as responsible of the cyclin degradation pattern. In particular, the N-terminal region of Cln2 is required to mediate degradation by SCF(C)(dc4). This region is involved in nuclear import of Cln1 and Cln2, which suggests that differences in degradation may be due to differences in localization. Moreover, a comparison of the cyclins that differ only in the presence of the Cln2 nuclear export signal indicates a greater instability of exported cyclins, thus reinforcing the idea that cyclin stability is influenced by their localization.
Salama, S R; Hendricks, K B; Thorner, J
The 545-residue Cln2 protein, like the other G1 cyclins of Saccharomyces cerevisiae, is a very unstable protein. This instability is thought to play a critical role in regulating cell cycle progression. The carboxyl-terminal domains of Cln2 and the other G1 cyclins contain sequences rich in Pro, Glu (and Asp), Ser, and Thr (so-called PEST motifs) that have been postulated to make up the signals that are responsible for the rapid degradation of these and other unstable proteins. To test this hypothesis, the carboxyl-terminal 178 residues of Cln2 were fused to the C terminus of a reporter enzyme, a truncated form of human thymidine kinase (hTK delta 40). The resulting chimeric protein (hTK delta 40-Cln2) retained thymidine kinase activity but was markedly less stable than hTK, hTK delta 40, or an hTK-beta-galactosidase fusion protein, as judged by enzyme assay, immunoblotting with anti-hTK antibodies, pulse-chase analysis of the radiolabeled polypeptides, and ability to support the growth of a thymidylate auxotroph (cdc21 mutant) on thymidine-containing medium. Thus, the presence of the Cln2 PEST domain was sufficient to destabilize a heterologous protein. Furthermore, the half-life of hTK delta 40-Cln2 was similar to that of authentic Cln2, and the rate of degradation of neither protein was detectably enhanced by treatments known to cause G1 arrest, including exposure of MATa haploids to alpha-factor mating pheromone and shifting cdc28ts and cdc34ts mutants to the restrictive temperature. These results suggest that the major signals responsible for Cln2 instability are confined to its C-terminal third. Because hTK delta 40-Cln2 and Cln2 were expressed from heterologous promoters yet their half-lives both in asynchronous cultures and when arrested at various cell cycle stages were always similar, the Cln2 PEST domain contains a signal for rapid protein turnover that is constitutively active and operative throughout the cell cycle. Removal of the 37 codons that encode
Sondhi, D; Peterson, D A; Giannaris, E L; Sanders, C T; Mendez, B S; De, B; Rostkowski, A B; Blanchard, B; Bjugstad, K; Sladek, J R; Redmond, D E; Leopold, P L; Kaminsky, S M; Hackett, N R; Crystal, R G
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal, autosomal recessive disease resulting from mutations in the CLN2 gene with consequent deficiency in its product tripeptidyl peptidase I (TPP-I). In the central nervous system (CNS), the deficiency of TPP-I results in the accumulation of proteins in lysosomes leading to a loss of neurons causing progressive neurological decline, and death by ages 10-12 years. To establish the feasibility of treating the CNS manifestations of LINCL by gene transfer, an adeno-associated virus 2 (AAV2) vector encoding the human CLN2 cDNA (AAV2CUhCLN2) was assessed for its ability to establish therapeutic levels of TPP-I in the brain. In vitro studies demonstrated that AAV2CUhCLN2 expressed CLN2 and produced biologically active TPP-I protein of which a fraction was secreted as the pro-TPP-I precursor and was taken up by nontransduced cells (ie, cross-correction). Following AAV2-mediated CLN2 delivery to the rat striatum, enzymatically active TPP-I protein was detected. By immunohistochemistry TPP-I protein was detected in striatal neurons (encompassing nearly half of the target structure) for up to 18 months. At the longer time points following striatal administration, TPP-I-positive cell bodies were also observed in the substantia nigra, frontal cerebral cortex and thalamus of the injected hemisphere, and the frontal cerebral cortex of the noninjected hemisphere. These areas of the brain contain neurons that extend axons into the striatum, suggesting that CNS circuitry may aid the distribution of the gene product. To assess the feasibility of human CNS delivery, a total of 3.6 x 10(11) particle units of AAV2CUhCLN2 was administered to the CNS of African green monkeys in 12 distributed doses. Assessment at 5 and 13 weeks demonstrated widespread detection of TPP-I in neurons, but not glial cells, at all regions of injection. The distribution of TPP-I-positive cells was similar between the two time points at all injection
Autefage, Hélène; Albinet, Virginie; Garcia, Virginie; Berges, Hortense; Nicolau, Marie-Laure; Therville, Nicole; Altié, Marie-Françoise; Caillaud, Catherine; Levade, Thierry; Andrieu-Abadie, Nathalie
Apoptosis is a highly organized, energy-dependent program by which multicellular organisms eliminate damaged, superfluous, and potentially harmful cells. Although caspases are the most prominent group of proteases involved in the apoptotic process, the role of lysosomes has only recently been unmasked. This study investigated the role of the lysosomal serine protease CLN2 in apoptosis. We report that cells isolated from patients affected with late infantile neuronal ceroid lipofuscinosis (LINCL) having a deficient activity of CLN2 are resistant to the toxic effect of death ligands such as tumor necrosis factor (TNF), CD95 ligand, or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not to receptor-independent stress agents. CLN2-deficient cells exhibited a defect in TNF-induced Bid cleavage, release of cytochrome c, and caspase-9 and -3 activation. Moreover, extracts from CLN2-overexpressing cells or a CLN2 recombinant protein were able to catalyze the in vitro cleavage of Bid. Noteworthy, correction of the lysosomal enzyme defect of LINCL fibroblasts using a medium enriched in CLN2 protein enabled restoration of TNF-induced Bid and caspase-3 processing and toxicity. Conversely, transfection of CLN2-corrected cells with small interfering RNA targeting Bid abrogated TNF-induced cell death. Altogether, our study demonstrates that genetic deletion of the lysosomal serine protease CLN2 and the subsequent loss of its catalytic function confer resistance to TNF in non-neuronal somatic cells, indicating that CLN2 plays a yet unsuspected role in TNF-induced cell death. PMID:19246452
Autefage, Hélène; Albinet, Virginie; Garcia, Virginie; Berges, Hortense; Nicolau, Marie-Laure; Therville, Nicole; Altié, Marie-Françoise; Caillaud, Catherine; Levade, Thierry; Andrieu-Abadie, Nathalie
Apoptosis is a highly organized, energy-dependent program by which multicellular organisms eliminate damaged, superfluous, and potentially harmful cells. Although caspases are the most prominent group of proteases involved in the apoptotic process, the role of lysosomes has only recently been unmasked. This study investigated the role of the lysosomal serine protease CLN2 in apoptosis. We report that cells isolated from patients affected with late infantile neuronal ceroid lipofuscinosis (LINCL) having a deficient activity of CLN2 are resistant to the toxic effect of death ligands such as tumor necrosis factor (TNF), CD95 ligand, or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not to receptor-independent stress agents. CLN2-deficient cells exhibited a defect in TNF-induced Bid cleavage, release of cytochrome c, and caspase-9 and -3 activation. Moreover, extracts from CLN2-overexpressing cells or a CLN2 recombinant protein were able to catalyze the in vitro cleavage of Bid. Noteworthy, correction of the lysosomal enzyme defect of LINCL fibroblasts using a medium enriched in CLN2 protein enabled restoration of TNF-induced Bid and caspase-3 processing and toxicity. Conversely, transfection of CLN2-corrected cells with small interfering RNA targeting Bid abrogated TNF-induced cell death. Altogether, our study demonstrates that genetic deletion of the lysosomal serine protease CLN2 and the subsequent loss of its catalytic function confer resistance to TNF in non-neuronal somatic cells, indicating that CLN2 plays a yet unsuspected role in TNF-induced cell death.
Kohan, Romina; Noelia Carabelos, María; Xin, Winnie; Sims, Katherine; Guelbert, Norberto; Adriana Cismondi, Inés; Pons, Patricia; Alonso, Graciela Irene; Troncoso, Mónica; Witting, Scarlet; Pearce, David A.; de Kremer, Raquel Dodelson; Oller-Ramírez, Ana María; de Halac, Inés Noher
Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n=11, null TPP1 activity in leukocytes; (II) n=8, residual TPP1 activity of 0.60–15.85 nmol/h/mg (nr 110–476); (III) n=6, activity not measured in leukocytes. Curvilinear bodies (CB) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887-10A>G (intron 7), and to a lesser extent at c.89+5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at nonconserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity. PMID:23266810
Leza, M A; Elion, E A
In the absence of a successful mating, pheromone-arrested Saccharomyces cerevisiae cells reenter the mitotic cycle through a recovery process that involves downregulation of the mating mitogen-activated protein kinase (MAPK) cascade. We have isolated a novel gene, POG1, whose promotion of recovery parallels that of the MAPK phosphatase Msg5. POG1 confers alpha-factor resistance when overexpressed and enhances alpha-factor sensitivity when deleted in the background of an msg5 mutant. Overexpression of POG1 inhibits alpha-factor-induced G1 arrest and transcriptional repression of the CLN1 and CLN2 genes. The block in transcriptional repression occurs at SCB/MCB promoter elements by a mechanism that requires Bck1 but not Cln3. Genetic tests strongly argue that POG1 promotes recovery through upregulation of the CLN2 gene and that the resulting Cln2 protein promotes recovery primarily through an effect on Ste20, an activator of the mating MAPK cascade. A pog1 cln3 double mutant displays synthetic mutant phenotypes shared by cell-wall integrity and actin cytoskeleton mutants, with no synthetic defect in the expression of CLN1 or CLN2. These and other results suggest that POG1 may regulate additional genes during vegetative growth and recovery. PMID:9927449
Leman, Adam R; Polochock, Susan; Mole, Sara E; Pearce, David A; Rothberg, Paul G
The neuronal ceroid lipofuscinoses (NCLs) are a family of autosomal recessive lysosomal storage diseases characterized by progressive epilepsy, dementia and visual loss. The juvenile form of the disease (onset age 4-8 years with visual loss) is usually caused by mutations in the CLN3 gene, but some cases have been shown to be due to specific mutations in the CLN1 or CLN2 genes, which are usually associated with NCL with onset in infancy or late infancy, respectively. The CLN1 mutations T75P and R151X, and the CLN2 mutations R208X and IVS5-1G>C, are found in many NCL patients with a juvenile presentation that is not due to CLN3 mutation. We have developed and validated a set of assays for these mutations using PCR followed by differential melting of a fluorescently labeled oligo probe, on a Roche LightCycler platform. The nucleobase quenching phenomenon was used to detect probe hybridization. The tests were validated using alternate assays: PCR followed by allele specific restriction enzyme digestion for the CLN1 mutations, and PCR followed by sequencing for the CLN2 mutations. The homogeneous PCR method gave 100% concordance of results with the alternate methods. This new assay, combined with a test for the common 1 kbp deletion in the CLN3 gene, provides a set of DNA-based assays suitable for detection of the most common mutations causing NCL with onset in the juvenile age range.
Awano, Tomoyuki; Katz, Martin L; O'Brien, Dennis P; Sohar, Istvan; Lobel, Peter; Coates, Joan R; Khan, Shahnawaz; Johnson, Gayle C; Giger, Urs; Johnson, Gary S
The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases characterized by progressive neuropathy and the accumulation of autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in a 9-month-old male Dachshund with vomiting, mental dullness, and loss of previously learned commands and rapidly progressed to include disorientation, ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months of age. Neurons throughout the CNS contained autofluorescent storage granules that stained with periodic acid-Schiff and Luxol fast blue stains. Electron microscopy revealed that the storage granule contents consisted of curvilinear-appearing material characteristic of human late infantile NCL caused by CLN2 mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame shift with a premature stop codon. Brain tissue from the affected dog lacked detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas the specific activities of 15 other lysosomal enzymes were higher than those in the brains of three control dogs. The affected Dachshund was homozygous for the mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A DNA assay that detects the mutant allele will help Dachshund breeders avoid producing affected puppies in future generations. Furthermore, this Dachshund NCL may prove to be a useful model for studying the pathogenesis of neurodegeneration in human late infantile NCL and for evaluating novel therapeutic interventions for this disease.
Chihara, H.; Nakamura, N.
This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H13ClN2O3S (Subst. No. 1266)
Chihara, H.; Nakamura, N.
This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H13ClN2O3S (Subst. No. 1265)
Oguz, Cihan; Palmisano, Alida; Laomettachit, Teeraphan; Watson, Layne T.; Baumann, William T.; Tyson, John J.
In this study, we focus on a recent stochastic budding yeast cell cycle model. First, we estimate the model parameters using extensive data sets: phenotypes of 110 genetic strains, single cell statistics of wild type and cln3 strains. Optimization of stochastic model parameters is achieved by an automated algorithm we recently used for a deterministic cell cycle model. Next, in order to test the predictive ability of the stochastic model, we focus on a recent experimental study in which forced periodic expression of CLN2 cyclin (driven by MET3 promoter in cln3 background) has been used to synchronize budding yeast cell colonies. We demonstrate that the model correctly predicts the experimentally observed synchronization levels and cell cycle statistics of mother and daughter cells under various experimental conditions (numerical data that is not enforced in parameter optimization), in addition to correctly predicting the qualitative changes in size control due to forced CLN2 expression. Our model also generates a novel prediction: under frequent CLN2 expression pulses, G1 phase duration is bimodal among small-born cells. These cells originate from daughters with extended budded periods due to size control during the budded period. This novel prediction and the experimental trends captured by the model illustrate the interplay between cell cycle dynamics, synchronization of cell colonies, and size control in budding yeast. PMID:24816736
Bhaduri, Samyabrata; Valk, Ervin; Winters, Matthew J.; Gruessner, Brian; Loog, Mart; Pryciak, Peter M.
Summary Background Eukaryotic cell division is driven by cyclin-dependent kinases (CDKs). Distinct cyclin-CDK complexes are specialized to drive different cell cycle events, though the molecular foundations for these specializations are only partly understood. In budding yeast, the decision to begin a new cell cycle is regulated by three G1 cyclins (Cln1–Cln3). Recent studies revealed that some CDK substrates contain a novel docking motif that is specifically recognized by Cln1 and Cln2, and not by Cln3 or later S- or M-phase cyclins, but the responsible cyclin interface was unknown. Results Here, to explore the role of this new docking mechanism in the cell cycle, we first show that it is conserved in a distinct cyclin subtype (Ccn1). Then, we exploit phylogenetic variation to identify cyclin mutations that disrupt docking. These mutations disrupt binding to multiple substrates as well as the ability to use docking sites to promote efficient, multi-site phosphorylation of substrates in vitro. In cells where the Cln2 docking function is blocked, we observed reductions in the polarized morphogenesis of daughter buds and reduced ability to fully phosphorylate the G1/S transcriptional repressor Whi5. Furthermore, disruption of Cln2 docking perturbs the coordination between cell size and division, such that the G1/S transition is delayed. Conclusions The findings point to a novel substrate interaction interface on cyclins, with patterns of conservation and divergence that relate to functional distinctions among cyclin subtypes. Furthermore, this docking function helps ensure full phosphorylation of substrates with multiple phosphorylation sites, and this contributes to punctual cell cycle entry. PMID:25619768
Kim, D.; Worster, T.; Boustany, R.M.
The neuronal lipofuscinoses (NCLs) are a group of disorders characterized by cognitive decline, blindness, seizures, and death. Pathologically, it is characterized by accumulation of lipofuscin deposits, generally in easily identifiable `curvilinear bodies`. It is inherited as an autosomal recessive disorder, with the exception of the adult onset form, which may be inherited as an autosomal dominant trait. The loci for the juvenile (CLN3), infantile (CLN1), and very recently, Finnish late-infantile (CLN5) NCLs have been mapped by genetic linkage analysis to chromosome 16p, 1p, and 13q, respectively. The classical late-infantile (LNCL) defect (CLN2) has not yet been mapped. Previous analysis with tightly linked markers excluded CLN2 from the CLN1 and CLN3 regions. We have initiated a genome-wide screen for CLN2, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 U.S. families and 11 Costa Rican families. Simulation studies have shown that we can detect linkage using a subset of 6 LNCL families, a 10 cM sieve, and a lod score criterion of 0.50 for follow-up. A linked region spanned by two markers has over a 95% chance of generating such a lod score, while an unlinked marker has less than a 5% chance of doing so. Follow-up will consist of genotyping the additional families and two additional markers in this region. To date, we have completed typing with 65 markers on chromosomes 1, 2, 9, 13, 16, 18, 19, 20, 21, and 22. The results of this analysis formally exclude about 25% of the human genome as the location of CLN2, including the region of chromosome 13 where CLN5 has been mapped. Updated results will be presented.
Wagler, Jörg; Brendler, Erica; Heine, Thomas; Zhechkov, Lyuben
The reaction of 1-methyl-3-trimethylsilylimidazoline-2-thione with hexachlorodisilane proceeds toward substitution of four of the disilane Cl atoms during the formation of disilicon complexes with two neighboring hexacoordinate Si atoms. The N,S-bidentate methimazolide moieties adopt a buttressing role, thus forming paddlewheel-shaped complexes of the type ClSi(μ-mt)4 SiCl (mt=methimazolyl). Most interestingly, three isomers (i.e., with (ClN4 )SiSi(S4 Cl), (ClN3 S)SiSi(S3 NCl), and (ClN2 S2 )SiSi(S2 N2 Cl) skeletons as so-called (4,0), (3,1), and cis-(2,2) paddlewheels) were detected in solution by using (29) Si NMR spectroscopic analysis. Two of these isomers could be isolated as crystalline solids, thus allowing their molecular structures to be analyzed by using X-ray diffraction studies. In accord with time-dependent NMR spectroscopy, computational analyses proved the cis-(2,2) isomer with a (ClN2 S2 )SiSi(S2 N2 Cl) skeleton to be the most stable. The compounds presented herein are the first examples of crystallographically evidenced disilicon complexes with two SiSi-bonded octahedrally coordinated Si atoms and representatives of the still scarcely explored class of Si coordination compounds with sulfur donor atoms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Micsenyi, Matthew C; Sikora, Jakub; Stephney, Gloria; Dobrenis, Kostantin; Walkley, Steven U
Protein aggregates are a common pathological feature of neurodegenerative diseases and several lysosomal diseases, but it is currently unclear what aggregates represent for pathogenesis. Here we report the accumulation of intraneuronal aggregates containing the macroautophagy adapter proteins p62 and NBR1 in the neurodegenerative lysosomal disease late-infantile neuronal ceroid lipofuscinosis (CLN2 disease). CLN2 disease is caused by a deficiency in the lysosomal enzyme tripeptidyl peptidase I, which results in aberrant lysosomal storage of catabolites, including the subunit c of mitochondrial ATP synthase (SCMAS). In an effort to define the role of aggregates in CLN2, we evaluated p62 and NBR1 accumulation in the CNS of Cln2(-/-) mice. Although increases in p62 and NBR1 often suggest compromised degradative mechanisms, we found normal ubiquitin-proteasome system function and only modest inefficiency in macroautophagy late in disease. Importantly, we identified that SCMAS colocalizes with p62 in extra-lysosomal aggregates in Cln2(-/-) neurons in vivo. This finding is consistent with SCMAS being released from lysosomes, an event known as lysosomal membrane permeability (LMP). We predicted that LMP and storage release from lysosomes results in the sequestration of this material as cytosolic aggregates by p62 and NBR1. Notably, LMP induction in primary neuronal cultures generates p62-positive aggregates and promotes p62 localization to lysosomal membranes, supporting our in vivo findings. We conclude that LMP is a previously unrecognized pathogenic event in CLN2 disease that stimulates cytosolic aggregate formation. Furthermore, we offer a novel role for p62 in response to LMP that may be relevant for other diseases exhibiting p62 accumulation.
... GRODSs) are the characteristic storage body at the electron microscope level. Does it have any alternative name? CLN1 ... CVB) are the characteristic storage body at the electron microscope level. Does it have any alternative name? CLN2 ...
Hart, Y.M.; Andermann, E.; Mitchison, H.M.
The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while the gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.
Specchio, Nicola; Bellusci, Marcello; Pietrafusa, Nicola; Trivisano, Marina; de Palma, Luca; Vigevano, Federico
This study aimed to identify early clinical, magnetic resonance imaging (MRI), and electroencephalographic (EEG) characteristics of neuronal ceroid lipofuscinosis type 2 (CLN2) disease to enable early diagnosis, thus providing the key to early treatment, and optimized care and outcomes. Retrospective clinical chart review of a series of patients diagnosed with CLN2 disease from 2005 to 2015 at a single center in Italy. Clinical, MRI, and EEG findings were reviewed. A total of 14 patients were included. For the whole group, median (range) age at disease onset was 3.0 (2.0-3.8) years. Epilepsy was the most commonly reported presenting symptom (in 50% [seven of 14] of patients), occurring at the age of 3.2 (2.6-3.8) years. First seizure was myoclonic in 36% (five of 14) of patients, followed by generalized tonic-clonic in 29% (4 of 14), atonic in 22% (three of 14), and focal with motor signs in 14% (two of 14). All patients walked independently at the age of 12.0 (11.0-18.0) months, but delayed speech or regression of acquired verbal skills was present in 100% of patients at 3 years. EEGs revealed a photoparoxysmal response (PPR) on intermittent photic stimulation in 93% (13 of 14) of patients. PPR was present from the first EEG, which was performed at 3.6 (3.1-4.0) years, in 43% (six of 14) of patients; it was documented at low (1-3 Hz) stimulation frequencies in 69% (nine of 13) and took the form of a flash-per-flash response in 69% (nine of 13). First brain MRI at the age of 3.8 (3.0-5.1) years revealed cerebellar atrophy in 100% (14 of 14) of patients and alteration of the periventricular white matter signal in the posterior hemispheric region in 79% (11 of 14). Early photosensitivity (typically PPR at low stimulation frequencies of 1-3 Hz) is a hallmark of CLN2 disease. This diagnosis should be considered in a child presenting with any type of seizure, and particularly if it is accompanied by delayed speech and/or ataxia or MRI abnormalities (posterior white
Thomas E. Hinds
Although many diseases attack aspen, relatively few kill or seriously injure living trees. The common leaf diseases, in general, are widely distributed throughout the range of aspen, whereas there are subtle differences in distribution between the important decay fungi, and apparently entirely different areas of distribution of major cankercausing organisms. However,...
Faller, Kiterie M E; Bras, Jose; Sharpe, Samuel J; Anderson, Glenn W; Darwent, Lee; Kun-Rodrigues, Celia; Alroy, Joseph; Penderis, Jacques; Mole, Sara E; Gutierrez-Quintana, Rodrigo; Guerreiro, Rita J
Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole-genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease.
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Infectious diseases kill more people worldwide than any other single cause. Infectious diseases are caused by germs. Germs are tiny living ... live NIH: National Institute of Allergy and Infectious Diseases
Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...
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Columnaris disease is caused by the Gram-negative bacterium, Flavobacterium columnare. The disease was first described in 1917-1919 in the United States and the bacterium was not successfully isolated and grown in the laboratory until 1944. Columnaris disease continues to be a prevalent disease of...
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In general, the development of civilization is viewed as a positive step for the well-being of the human species, leading to an increased duration and quality of life. The accelerated progress of civilization (mainly industrialization, urbanization and nutrition) has lead to new possibilities for adverse effects on human health. In former high civilization--like old Egypt, Greece, Roman, Chinese, Indian, Maya civilizations--the "modem civilization diseases" were unknown. Modem science through improved sanitation, vaccination and antibiotics as well as improved social and economical conditions, has eliminated the threat of death from most infectious diseases. In the years after World War II the social, economic and health conditions changed. Most deaths have resulted from heart disease, stroke, cancer and other diseases as a result of an inappropriate relationship of people with their environment and changed lifestyle. Lifestyle diseases are different from other diseases because they are potentially preventable and can be lowered with changes in diet, lifestyle and environment.
AlGhamdi, Fares E.; Al-Khatib, Talal A.; Marzouki, Hani Z.; AlGarni, Mohammed A
Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non-Asian patient with a similar clinicopathologic presentation. PMID:26905356
... if your child has any symptoms of Canavan disease. Prevention Genetic counseling is recommended for people who want to have children and have a family history of Canavan disease. Counseling should be considered if both parents are ...
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Raynaud's disease is a rare disorder of the blood vessels, usually in the fingers and toes. It causes the ... secondary Raynaud's, which is caused by injuries, other diseases, or certain medicines. People in colder climates are ...
Gaucher disease is a rare, inherited disorder. It is a type of lipid metabolism disorder. If you have it, ... It usually starts in childhood or adolescence. Gaucher disease has no cure. Treatment options for types 1 ...
... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...
Chagas disease is caused by a parasite. It is common in Latin America but not in the United States. ... nose, the bite wound or a cut. The disease can also spread through contaminated food, a blood ...
Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...
Meniere's disease is a disorder of the inner ear. It can cause severe dizziness, a roaring sound in your ... together over several days. Some people with Meniere's disease have "drop attacks" during which the dizziness is ...
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Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...
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Fifth disease is a viral infection caused by parvovirus B19. The virus only infects humans; it's not the same parvovirus that dogs and cats can get. Fifth disease mostly affects children. Symptoms can include a low ...
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... with other NIH Institutes, supports the Lysosomal Disease Network, a network of centers that addresses some of the major ... with other NIH Institutes, supports the Lysosomal Disease Network, a network of centers that addresses some of ...
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... examining the genetic origins of Menkes disease and studying the effectiveness of early copper injections and gene-replacement therapies for treating the disease. Research also includes work on a universal newborn screening test for newborns. ...
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Schessel, David A.
Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…
Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described.
Capriotti, Teri; Terzakis, Kristina
Parkinson disease (PD) is a progressive neurodegenerative disease that affects one million people in the United States. This article reviews the etiology and pathophysiology of PD, risk factors, clinical manifestations, diagnostic criteria, and treatment of this common disease. Implications for home care clinicians are included.
Short history of Kawasaki disease, clinical features (principal symptoms and other significant symptoms or findings), diagnosis, cardiovascular involvement, epidemiology. Pathological features (lesion of vessels and lesion of organs exclusive of vessels), comparison between infantile periarteritis nodosa (IPN)/Kawasaki disease and classic periarteritis nodosa (CPN), etiology, treatment and management of Kawasaki disease are described. PMID:25792773
... washing also helps protect you from most infectious diseases. Symptoms Each infectious disease has its own specific signs and symptoms. General ... person who passes the germ may have no symptoms of the disease, but may simply be a carrier. Animal to ...
Schessel, David A.
Meniere's disease is characterized by unpredictable spells of severe vertigo and fluctuations in hearing and tinnitus. This article discusses the incidence of Meniere's disease, the present status of our understanding of this disease, controversies in its diagnosis, and the multiple therapeutic modalities recruited in its treatment. (Contains…
Taylor, George C.
This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…
... disease is caused by a bacterium known as legionella. You can't catch legionnaires' disease from person-to-person contact. Instead, most people ... with weakened immune systems are particularly susceptible to legionnaires' disease. The legionella bacterium also causes Pontiac fever, a milder illness ...
Taylor, George C.
This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…
Geschwind, Michael D.
Purpose of Review This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Recent Findings Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Summary Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and
McKintosh, Edward; Tabrizi, Sarah J; Collinge, John
Prion diseases are incurable neurodegenerative conditions affecting both animals and humans. They may be sporadic, infectious, or inherited in origin. Human prion diseases include Creutzfeldt-Jakob desease (CJD), Gerstmann-Straussler-Scheinker disease, kuru, and fatal familial insomnia. The appearance of variant CJD, and the demonstration that is caused by strains indistinguishable from bovine spongiform encephalopathy (BSE) in cattle, has led to the threat of a major epidemic of human prion disease in the UK and other countries where widespread dietary exposure to bovine prions has occurred. This article reviews the history and epidemiology of these diseases, and then focuses on important areas of current research in human prion disorders.
Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar
Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered. PMID:23633816
Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar
Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered.
Murray, Thomas S; Shapiro, Eugene D
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies, and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in most patients after treatment with appropriate antimicrobials for 2 to 4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with only nonspecific symptoms such as fatigue or arthralgia without objective signs of infection.
Murray, Thomas S.; Shapiro, Eugene D.
Synopsis Lyme disease, caused by spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. The clinical presentation varies depending on the stage of the illness: early disease includes erthyma migrans, early disseminated disease includes multiple erythema migrans, meningitis, cranial nerve palsies and carditis; late disease is primarily arthritis. The symptoms and signs of infection resolve in the vast majority of patients after appropriate treatment with antimicrobials for from 2-4 weeks. Serologic testing should be used judiciously as it often results in misdiagnosis when performed on blood from patients with a low prior probability of disease and those with non-specific symptoms such as fatigue or arthralgia without signs of infection. PMID:20513553
Pierson, Duane L.
This is a collection of viewgraphs on the Johnson Space Center's work on infectious disease. It addresses their major concern over outbreaks of infectious disease that could jeopardize the health, safety and/or performance of crew members engaged in long duration space missions. The Antarctic environment is seen as an analogous location on Earth and a good place to carry out such infectious disease studies and methods for proposed studies as suggested.
Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test-the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible.
Gaucher disease is the commonest lysosomal storage disease seen in India and worldwide. It should be considered in any child or adult with an unexplained splenohepatomegaly and cytopenia which are seen in the three types of Gaucher disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the neuronopathic forms. Type 2 is a more severe neuronopathic form leading to mortality by 2 years of age. Definitive diagnosis is made by a blood test–the glucocerebrosidase assay. There is no role for histological examination of the bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for mutations are useful for confirming diagnosis, screening family members and prognosticating the disease. A splenectomy should not be performed except for palliation or when there is no response to enzyme replacement treatment or no possibility of getting any definitive treatment. Splenectomy may worsen skeletal and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has completely revolutionized the prognosis and is now the standard of care for patients with this disease. Best results are seen in type 1 disease with good resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2 disease. Monitoring of patients on ERT involves evaluation of growth, blood counts, liver and spleen size and biomarkers such as chitotriosidase which reflect the disease burden. Therapy with ERT is very expensive and though patients in India have so far got the drug through a charitable access programme, there is a need for the government to facilitate access to treatment for this potentially curable disease. Bone marrow transplantation is an inferior option but may be considered when access to expensive ERT is not possible. PMID:25755533
Huntington's disease (HD) is the most common inherited neurodegenerative disease and is characterized by uncontrolled excessive motor movements and cognitive and emotional deficits. The mutation responsible for HD leads to an abnormally long polyglutamine (polyQ) expansion in the huntingtin (Htt) protein, which confers one or more toxic functions to mutant Htt leading to neurodegeneration. The polyQ expansion makes Htt prone to aggregate and accumulate, and manipulations that mitigate protein misfolding or facilitate the clearance of misfolded proteins tend to slow disease progression in HD models. This article will focus on HD and the evidence that it is a conformational disease. PMID:21441583
The outlook for patients with Hodgkin's disease has improved dramatically over the past 20 years. The question is no longer whether cure is possible, but rather, how can cure be best achieved. With better understanding of the biology of Hodgkin's disease and with continued evolution of treatment approaches, the goal of curing all patients with Hodgkin's disease is clearly within reach. This article provides a summary of current concepts in the biology and management of Hodgkin's disease. Staging, treatment options, and complications of therapy are discussed.
... low sperm count or infertility. Still others develop non-insulin-dependent diabetes mellitus. Kennedy's disease is an x-linked recessive ... low sperm count or infertility. Still others develop non-insulin-dependent diabetes mellitus. Kennedy's disease is an x-linked recessive ...
... after a few weeks or months and causes no long-term damage to the joints. Autoinflammatory disease. A disease that results when the immune system mistakenly attacks the body’s own tissues. Biologics. A class of drugs, also known as biologic response modifiers, ...
... high or too low, you may have an endocrine disease or disorder. Endocrine diseases and disorders also occur if your body does not respond to hormones the way it is supposed to. Featured Topics Adrenal Insufficiency ... Topics Research Discoveries & News Children with Cushing ...
Cardiovascular disease (CVD), particularly CHD (coronary heart disease) and stroke, remain the leading causes of death of women in America and most developed countries. In recent years the rate of CVD has declined in men but not in women. This is contributed to by an under-recognition of women’s C...
Pradhan, D J; Ikins, P M
Aspiration disease, a term used to define both an acute and chronic form of a disease entity, is described. Etiological factors, pathophysiology and therapy are discussed with emphasis on aspiration of gastric juice. A brief mention of a small clinical experience is included.
Stephan, F; Haber, R
Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease.
Bertoldi, I; Cantarini, L; Filippou, G; Frediani, B
Paget's disease of bone is the most common metabolic bone disease after osteoporosis and affects 2-4% of adults over 55 years of age. Its etiology is only partly understood and includes both genetic and environmental factors. The disease may be asymptomatic and can be uncovered incidentally on x-ray or in biochemical tests performed for another condition. It can also manifest itself with bone pain, deformity, fracture or other complications. Paget's disease is diagnosed by x-rays and in general has very typical radiological features, but occasionally the clinical picture may be unusual and a differential diagnosis of sclerotic or lytic metastases needs to be considered. Plasma total alkaline phosphatase activity is the most clinically useful indicator of disease activity. It is elevated in most untreated patients, but may be within the normal range in patients with monostotic or limited disease. Bisphosphonate therapy is indicated for patients with symptoms and should also be considered in patients with disease sites that suggest a risk of complications, such as long bones, vertebrae or base of the skull. Orthopedic surgery in Paget's disease patients includes almost exclusively the correction of fractures and arthroplasty.
F. I. McCracken
The canker stain disease, one of several fungi that cause cankers of sycamore, can cause serious loss of sycamores in natural stands, plantations, and urban areas. As many as 35 percent of the trees in some stands may be diseased. Affected trees develop thin crowns, twig dieback, small leaves and epicormic branches. The narrow, elongate, bark covered, flat, spiraling...
... or 203–744–0100 Fax: 203–798–2291 Internet: www.rarediseases.org Office of Rare Diseases Research ... Fax: 301–480–9655 Email: email@example.com Internet: www.rarediseases.info.nih.gov 7 Whipple Disease ...
Prion diseases comprise a set of rare fatal neurological diseases found in humans and other mammals. A prion is a protein capable of converting a normal cellular protein (PrPC) into a prion and thereby propagating an infection. A prion and PrPC differ solely in their conformation. There are differen...
... Women - particularly African-American, Hispanic-American, and Native-American women - have a higher risk for some autoimmune diseases. There are more than 80 types of autoimmune diseases, and some have similar symptoms. This makes it hard for your health care provider to know if ...
... Gum Disease and Other Diseases Gum Disease and Diabetes Gum Disease and Heart Disease Gum Disease and Other Systemic ... Gum Disease and Other Diseases Gum Disease and Diabetes Gum Disease and Heart Disease Gum Disease and Other Systemic ...
... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...
... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...
Rizk, Tamer M.; Ariganjoye, Rafiu O.; Alsaeed, Gihad I.
We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with regular follow up with multiple subspecialties. PMID:26166597
Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria
Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
Playfer, J. R.
Parkinson's disease is a common disabling disease of old age. The diagnosis of idiopathic Parkinson's disease is based on clinical signs and has poor sensitivity, with about 25% of patients confidently diagnosed as having the disease actually having other conditions such as multi-system atrophy and other parkinsonism-plus syndromes. Benign essential tremor and arteriosclerotic pseudo-parkinsonism can easily be confused with Parkinson's disease. The cause of Parkinson's disease remains unknown. Speculative research highlights the role of oxidative stress and free radical mediated damage to dopaminergic cells. Parkinson's disease is the one neurodegenerative disorder in which drugs have been demonstrated to be of value. There is now a wide variety of drugs and formulations available, including anticholinergics, amantidine, L-dopa, dopamine agonists including apomorphine, selegiline and soon to be available catechol-O-methyltransferase inhibitors. Disabling side-effects of treatment, fluctuations, dyskinesias and psychiatric problems require strategic use of the drugs available. There is an increasing potential for neurosurgical intervention. PMID:9196696
Boggio, Paula; Luna, Paula Carolina; Abad, María Eugenia; Larralde, Margarita
Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.
Aruna, Chintaginjala; Ramamurthy, D. V. S. B.; Neelima, T.; Bandaru, Haritha
Keratosis lichenoides chronica also known as Nekam's disease is a rare mucocutaneous disorder, characterized clinically by asymptomatic violaceous keratotic papules arranged in linear, reticular, or plaque form usually on the trunk and extremities and histologically by interface dermatitis. The disease is considered rare with only 128 cases being reported in the literature till date and very few from India. We report a case of a 40-year-old man who presented with constellation of features of lichen planus, seborrheic dermatitis, and apthous ulcers, which upon workup was found to be Nekam's disease. PMID:27990390
Hunter, D. J.; Fairfield, G.
The disease management approach to patient care seeks to coordinate resources across the healthcare delivery system. The growing interest in evidence based medicine and outcomes, and a commitment to integrated care across the primary, secondary, and community care sectors, all contribute to making disease management an attractive idea. A combination of patient education, provider use of practice guidelines, appropriate consultation, and supplies of drugs and ancillary services all come together in the disease management process. But its effectiveness is largely untested, so evaluation is essential. PMID:9233330
Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon
Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination showed only mild lymphocytic infiltration, and failed to reveal evidence of any microorganism. The polymerase chain reaction for Borrelia burgdorferi was negative in her serum. PMID:28392653
Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon; Kim, Kyu Han
Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination showed only mild lymphocytic infiltration, and failed to reveal evidence of any microorganism. The polymerase chain reaction for Borrelia burgdorferi was negative in her serum.
Schucany, William G.; Opatowsky, Michael J.
Kummell disease, or avascular necrosis of a vertebral body, presents as vertebral osteonecrosis typically affecting a thoracic vertebra with compression deformity, intravertebral vacuum cleft, and exaggerated kyphosis weeks to months after a minor traumatic injury. This rare disease is increasing in prevalence secondary to an aging population and the associated rise in osteoporosis. Treatment with vertebroplasty or surgical decompression and fusion is often required. We present a classic case of Kummell disease to illustrate the salient features of the condition, with associated imaging findings on computed tomography and magnetic resonance imaging. PMID:23814399
... Lesch-Nyhan Syndrome Information Page Leukodystrophy Information Page Lipid Storage Diseases Information Page Lipoid Proteinosis Information Page ... Career Awards Fellowships Summer Internships Diversity & Re-Entry Supplements Pre-Application Considerations Apply for Funding New Investigators ...
... after a disaster . Global emergence of multidrug-resistant Candida auris Fungal Outbreaks Fungal Diseases Types of Fungal ... Treatment & Outcomes Health Professionals Statistics More Resources Candidiasis Candida infections of the mouth, throat, and esophagus Vaginal ...
... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...
... good flexibility while your child is growing. The stretching exercises pictured in the treatment section can lower ... your child has already recovered from Sever's disease, stretching and putting ice on the heel after activity ...
... autoimmune thyroid disease. This includes radiation from the atomic bomb in Japan, the nuclear accident at Chernobyl, ... symptoms as normal pregnancy , such as fatigue and weight gain. Yet untreated underactive thyroid during pregnancy may ...
... Blogs Image Library News Conferences Press Releases Radio Public Service Announcements Real Stories, Real People Share Your Story Additional ... Centers for Disease Control and Prevention (CDC) #NoRegrets Public service announcement on the importance of getting vaccinated against both ...
... of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, you might ... help you to feel your best. Meditation, self-hypnosis, and guided imagery, are simple relaxation techniques that ...
... risk of Wilson's disease if your parents or siblings have the condition. Ask your doctor whether you ... in the urine. Psychological problems. These might include personality changes, depression, irritability, bipolar disorder or psychosis. Blood ...
... have surgery are fully cured and able to pass bowel movements normally. About Hirschsprung Disease Hirschsprung (HERSH- ... The condition — which prevents bowel movements (stool) to pass through the intestines due to missing nerve cells ...
... factors. A full understanding of Parkinson's risk requires integrated efforts to study both genetic and environmental factors. ... Parkinson’s disease (December 2014) Australian researcher outlines an integrated approach for studying Parkinson’s (December 2014) Research on ...
Nair, Jagdish R; Moots, Robert J
Behçet's disease (BD) is a chronic relapsing and remitting vasculitis of unknown aetiology. It has the capacity to affect almost all organ systems because of its potential to involve both arteries and veins of all sizes, resulting in significant organ-threatening morbidity and mortality. Traditionally known as the 'silk road' disease, it has a worldwide occurrence. The aetiopathological mechanisms of disease development in BD remain poorly understood, but genome wide studies show human leukocyte antigen and non-human leukocyte antigen associations. Environmental influences and genetic factors may have a role in the aetiopathogenetic mechanisms that lead to development of the disease, indicating the autoimmune and auto-inflammatory nature of BD. The evidence base for treatment is limited but new knowledge is emerging and current treatment options range from symptomatic treatment, through to non-biological and biological immunosuppressive drugs, to cover the spectrum of clinical manifestations.
... there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. × Definition Alexander disease is ... there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. View Full Definition Treatment ...
... is called hyperthyroidism . (An underactive thyroid leads to hypothyroidism .) Graves disease is the most common cause of ... radioactive iodine often will cause an underactive thyroid (hypothyroidism). Without getting the correct dosage of thyroid hormone ...
... more common in people who live in colder climates. Treatment of Raynaud's disease depends on its severity ... begins between the ages of 15 and 30. Climate. The disorder is also more common in people ...
... your menstrual period. Your thyroid helps control your menstrual cycle. Too much or too little thyroid hormone can ... Problems getting pregnant. When thyroid disease affects the menstrual cycle, it also affects ovulation. This can make it ...
... disease among people who are genetically susceptible. Pregnancy. Pregnancy or recent childbirth may increase the risk of the disorder, particularly among women who are genetically susceptible. Smoking. Cigarette smoking, which can affect the immune system, ...
... disease is a rare inherited disorder that causes copper to accumulate in your liver, brain and other ... can affect younger and older people, as well. Copper plays a key role in the development of ...
... swollen neck glands, swollen hands and feet, and red eyes, lips, and tongue. Early on, Kawasaki Disease can ... body but more severe in the diaper area. Red, bloodshot eyes without any pus, drainage, or crusting. Tender, swollen ...
... ways to prevent it. A decrease in color perception also occurs in Stargardt disease. This is because photoreceptor cells involved in color perception are concentrated in the macula. Back to top ...
... specific part of your brain. The electrodes are connected to a generator implanted in your chest near ... with Parkinson's disease to improve their walking and speech. Participating in art therapy, such as painting or ...
... can pass the gene mutation to the next generation. Genetic testing is a procedure that identifies changes ... recessive diseases are typically not seen in every generation of an affected family. The following chart shows ...
... the rest of the body. This is called malabsorption . Causes Whipple disease is caused by infection with ... and the A.D.A.M. Editorial team. Malabsorption Syndromes Read more Latest Health News Read more ...
... large bowel ( colon ). Crohn's disease may lead to deep ulcers in the intestinal tract, giving a "cobblestone" ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...
... Rigor & Transparency Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene Expression Research Reagents ... Definition Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical ...
... abuse Cigarette smoking Chronic illnesses, such as kidney failure or diabetes Long-term (chronic) lung disease, such as COPD Long-term use of a breathing machine (ventilator) Medicines that suppress the immune system, including ...
Portillo, Aránzazu; Santibáñez, Sonia; Oteo, José A
Lyme disease (LD) is a worldwide-distributed multisystemic process caused by Borrelia burgdorferi sensu lato (s.l.) and transmitted by hard ticks. In fact, it is the most common tick-borne infectious disease in the northern hemisphere. In Spain it is transmitted by Ixodes ricinus ticks and Borrelia garinii is the genoespecies of B. burgdorferi s.l. mostly involved in our area. LD is known as "the last great imitator" due to the broad clinical spectrum that may cause. Except in the case of erythema migrans (pathognomonic feature of the disease), the remaining clinical manifestations should be confirmed using microbiological tests. This review is intended to provide readers a current vision of the etiology, epidemiology, clinical manifestations, laboratory diagnosis and treatment of Lyme disease in our environment. Controversial aspects arising from the use of non-validated microbiological tests that are being used without scientific rigor are highlighted.
... away from the teeth. This is known as periodontitis (pronounced: pair-ee-oh-don-TY-tus), a more advanced form of gum disease. With periodontitis, gums become weakened and form pockets around the ...
... causing the illnesses.Lyme disease is carried by black-legged ticks (sometimes called deer ticks). These ticks are typically about the size of a sesame seed. They live only in certain areas of the ...
... the symptoms. Dopamine blockers may help reduce abnormal behaviors and movements. Drugs such as amantadine and tetrabenazine are used to try to control extra movements. Depression and suicide are common among persons with Huntington disease. It ...
... or gained weight very quickly. It's also more common in people of African heritage, kids who started ... worse and can't be traced to an injury — your doctor may consider Blount disease as a ...
Stappenbeck, Thaddeus S.; Rioux, John D.; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J.
Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.1 Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk. PMID:20729636
... with this type may live into adulthood. Symptoms Bleeding because of low platelet count is the most common symptom seen in Gaucher disease. Other symptoms may include: Bone pain and fractures Cognitive impairment (decreased thinking ability) Easy bruising Enlarged ...
Vaginal problems are some of the most common reasons women go to the doctor. They may have ... that affect the vagina include sexually transmitted diseases, vaginal cancer, and vulvar cancer. Treatment of vaginal problems ...
Kawasaki disease is an acute febrile, systemic vasculitic syndrome of an unknown etiology that primarily occurs in children younger than five years of age. The principal presentations of Kawasaki disease include fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develops in 15% to 25% of untreated children with the disease, which may later lead to myocardial infarction, sudden death, or ischemic heart disease. Treatment with intravenous gamma globulin (IVIG) is effective, but the mode of action is still unclear. The development of a diagnostic test, a more specific therapy, and ultimately the prevention of this potentially fatal illness in children are all dependent upon the continued advances in determining the etiopathogenesis of this fascinating disorder. PMID:17191303
Your endocrine system includes eight major glands throughout your body. These glands make hormones. Hormones are chemical messengers. They ... levels. In the United States, the most common endocrine disease is diabetes. There are many others. They ...
... inherited and non-inherited PD and suggesting new strategies, now at various stages of testing, to slow the course of disease. Several studies suggest environmental influences on PD. Exposure to certain ...
... there are about a million tiny structures called nephrons. They filter your blood. They remove wastes and ... to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys unable to remove ...
Huster, D; Kühn, H-J; Mössner, J; Caca, K
Wilson disease is an autosomal recessive inherited disorder of human copper metabolism that leads to neurological symptoms and hepatic damage of variable degree. The affected gene ATP7B encodes a hepatic copper transport protein, which plays a key role in human copper metabolism. Clinical symptoms are complex with neurologic symptoms such as tremor, dysarthria, psychiatric disorders etc., predominant hepatic disease or mixed forms. Copper deposition in the liver results in acute liver failure, chronic hepatitis or liver cirrhosis. Early recognition by means of clinical, biochemical or genetic examination and early initiation of therapy with chelators or zinc-salts are essential for outcome and prognosis. Liver transplantation is an alternative in cases with acute and chronic liver failure and cures the hepatic disease. Frequent monitoring of drug therapy, adverse effects, and compliance is critical for the prognosis of the disease.
... passed down through families. It affects the way bilirubin is processed by the liver, and causes the ... eat. Exams and Tests A blood test for bilirubin shows changes that occur with Gilbert disease. The ...
Cortes, J; Martínez, B; Montini, C; Barraza, P; Reyes, A
We described a case of Kawasaki's disease in a chilean girl, one year and 5 months old of age, who presented the oral characteristics, cutaneous and systemic manifestation of the condition, that is not very common for the dentist but that it is necessary to know due to the heart complications and the mortality associated with the disease, and it is necessary that the dentist recognize early this condition.
Bardelli, M; D'Arienzo, M; Veneziani, C
The authors describe the clinical appearance of Ledderhose disease and emphasize the association with Dupuytren disease. They report on a series of patients treated at the 2nd Orthopedic Unit of University of Florence and describe the operating technique used. They believe that the procedure of removal of nodules must always be performed in association with careful exeresis of normal tissue, employing total aponeurectomy only in revision surgery.
Burdge, David R.; O'Hanlon, David
Lyme borreliosis is an infectious disease caused by the tick-transmitted spirochete Borrelia burgdorferi. To date, the only known endemic focus of Lyme disease in Canada is Long Point, Ont. A national case definition for surveillance purposes, consensus statement regarding laboratory diagnosis, and treatment guidelines have recently been developed in an attempt to standardize the approach to surveillance, diagnosis, and management of Lyme borreliosis in Canada. PMID:21221399
John W. Peacock
Dutch elm disease was found in Cleveland, Ohio, in 1930, and is now in most of the contiguous 48 states. The disease is caused by a fungus that has killed millions of wild and planted elms. Losses have been the greatest in the eastern United States. The fungus attacks all elms, but our native species, American, slippery, and rock elm have little or no resistance to the...
Bates, Gillian P; Dorsey, Ray; Gusella, James F; Hayden, Michael R; Kay, Chris; Leavitt, Blair R; Nance, Martha; Ross, Christopher A; Scahill, Rachael I; Wetzel, Ronald; Wild, Edward J; Tabrizi, Sarah J
Huntington disease is devastating to patients and their families - with autosomal dominant inheritance, onset typically in the prime of adult life, progressive course, and a combination of motor, cognitive and behavioural features. The disease is caused by an expanded CAG trinucleotide repeat (of variable length) in HTT, the gene that encodes the protein huntingtin. In mutation carriers, huntingtin is produced with abnormally long polyglutamine sequences that confer toxic gains of function and predispose the protein to fragmentation, resulting in neuronal dysfunction and death. In this Primer, we review the epidemiology of Huntington disease, noting that prevalence is higher than previously thought, geographically variable and increasing. We describe the relationship between CAG repeat length and clinical phenotype, as well as the concept of genetic modifiers of the disease. We discuss normal huntingtin protein function, evidence for differential toxicity of mutant huntingtin variants, theories of huntingtin aggregation and the many different mechanisms of Huntington disease pathogenesis. We describe the genetic and clinical diagnosis of the condition, its clinical assessment and the multidisciplinary management of symptoms, given the absence of effective disease-modifying therapies. We review past and present clinical trials and therapeutic strategies under investigation, including impending trials of targeted huntingtin-lowering drugs and the progress in development of biomarkers that will support the next generation of trials. For an illustrated summary of this Primer, visit: http://go.nature.com/hPMENh.
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.
Shankar, P R; Subish, P
Convincing healthy people that they are sick and require medicines can enormously expand the market. Disease mongering can turn ordinary ailments like baldness into medical problems, consider risk factors such as hypertension and osteoporosis as diseases and frame prevalence estimates to increase potential markets. In Asia, conditions like erectile dysfunction, male pattern baldness, attention deficit hyperactivity disorder and irritable bowel syndrome, and the drugs to treat them, are widely promoted. Fairness creams and traditional medicines are also widely used. The cost of disease mongering to the individual and the community is expected to be high. Some authors have argued that medicalisation of illnesses may not be a problem and the real problem may be the lack of medicines. Doctors will play a key role in combating disease mongering. Disentanglement from the pharmaceutical industry and development of a capacity for critical analysis are required. Educating patients and empowering them to make decisions are important. Several initiatives have been undertaken to combat disease mongering. Initiatives at the level of the patient and the physician are especially important. Studies on the extent and knowledge of disease mongering among doctors and medical students, and their economic and social consequences are urgently required.
Cunha, Burke A; Burillo, Almudena; Bouza, Emilio
Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.
William, D C
This paper focuses on the growing incidence of the "new" sexually transmitted parasitic enteric diseases: amebiasis and giardiasis. Two major behavioral factors influence transmission of these diseases in the gay community: 1) oral-rectal and oral-genital sexual contact and 2) multiple sexual partners. Pathogenesis, clinical signs and symptoms and complications associated with these diseases are also discussed. Although many patients present with severe symptoms, approximately 50 percent of infected patients are asymptomatic. The diagnostic procedures include a fresh purged stool examination, nonpurged warm stool examinations, and/or cold stool specimens. The serologic tests (serum precipitin and hemagglutination) are of value only in severely symptomatic invasive disease. Different treatment regimens and their side effects are discussed. Drugs used in the treatment of the enteric diseases include diiodohydroxyquin, metronidazole, furamide, and paromomycin. Only 60 to 70 percent of patients with the disease are cured, and 30 to 40 percent of patients require multiple courses of therapy. Test-of-cure examinations, ideally consisting of one or two purged stool specimens, are necessary in follow-up management.
Poewe, Werner; Seppi, Klaus; Tanner, Caroline M; Halliday, Glenda M; Brundin, Patrik; Volkmann, Jens; Schrag, Anette-Eleonore; Lang, Anthony E
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.
... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...
Wolters, E C; Calne, D B
In Parkinson's disease there is degeneration of neurons in the substantia nigra, with consequent depletion of the neurotransmitter dopamine. The triad of tremor, rigidity and bradykinesia is the clinical hallmark. Drugs currently used for palliative therapy fall into three categories: anticholinergic agents, dopamine precursors (levodopa combined with extracerebral decarboxylase inhibitors) and artificial dopamine agonists. It has been argued, on theoretical grounds, that some drugs slow the progress of Parkinson's disease, although no firm evidence has supported this. Treatment must be individualized, and more than one type of drug can be given concurrently after a careful build-up in dosage. We review the adverse effects of various drugs and consider new developments such as slow-release preparations, selective D-1 and D-2 agonists and transplants of dopaminergic cells into the brain. The treatment of Parkinson's disease can be demanding, rewarding and sometimes frustrating, but it remains a most challenging exercise in pharmacotherapy. Images Fig. 1 Fig. 2 Fig. 3 PMID:2563667
Wagner, Pablo; Román, Javier A; Vergara, Jorge
Dupuytren disease (DD) is a connective tissue disorder that consists in fibromatosis of the palmar and digital fascia (in form of nodules or flanges) that leads to the development of flexion contractures of the palm and fingers. The little and ring finger are particularly affected. The disease can limit hand function, reducing the quality of life. The disease can have a traumatic origin and is also associated with conditions such as diabetes mellitus, alcoholism, dyslipidemia, epilepsy and AIDS, among others. However, none of these conditions can fully explain the genesis of DD. A hereditary component is described in 40% of patients and is attributed to an autosomal dominant gene of variable penetrance, probably related to collagen synthesis. However there are also spontaneous and recessive inheritance cases. The diagnosis is clinical and based on physical examination. Treatment ranges from observation or use of injectable collagenase to the surgical option in cases with significant functional limitations.
Balmes, John R.
The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in chest diseases. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in chest diseases that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Chest Diseases of the California Medical Association, and the summaries were prepared under its direction. PMID:1441468
Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis
Pryor, John; Akkus, Emre; Alter, Gary; Jordan, Gerald; Lebret, Thierry; Levine, Laurence; Mulhall, John; Perovic, Sava; Ralph, David; Stackl, Walter
Peyronie's disease is a sexual medicine condition that may adversely affect male sexual function. To provide expert opinions/recommendations concerning state-of-the-art knowledge for the pathophysiology, diagnosis and treatment of Peyronie's disease. An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a scientific and debate process. Concerning the Peyronnie's disease committee, there were 10 experts from six countries. Expert opinions/recommendations are based on grading of evidence-based medical literature, extensive internal committee discussion over 2 years, public presentation and deliberation. Peyronie's disease is characterized by an inflammatory response beneath the tunica albuginea with fibroblast proliferation forming a thickened fibrous plaque that may cause penile pain, penile curvature and erectile dysfunction. Medical treatments have been described but few prospective controlled trials have revealed significant clinical benefits. Surgical treatments (penile plication, Nesbit excision, plaque incision and grafting and penile prosthesis insertion) should be considered after Peyronie's disease has stabilized. Surgical outcome studies reveal that a stable deformity is best corrected with the least postoperative ED by a Nesbit procedure. Plaque incision and grafting should be reserved for men with good erectile function and marked penile shortening although there is a higher prevalence of postoperative ED. Implantation of a penile prosthesis is an excellent option for men with an accompanying erectile deficit. Safe and effective treatments for Peyronie
Introduction Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty. PMID:21524318
Whipple's disease is a rare infectious disorder affecting mostly middle aged men. The causative organism, Tropheryma whipplei, recently has been cultivated and phylogenetically identified as an actinomycete. The rareness of the disease despite the ubiquitous occurence of T. whipplei presumably is related to a predisposing defect in cellular immunity. The diagnosis usually can be established by small bowel biopsy, but is frequently delayed due to protean clinical manifestations. The initiation of antibiotic treatment in most cases results in clinical remission, however, a significant number of patients is refractory to antimicrobial therapy or has a relapsing course.
Talhari, Sinésio; Grossi, Maria Aparecida de Faria; Oliveira, Maria Leide W D R de; Gontijo, Bernardo; Talhari, Carolina; Penna, Gerson Oliveira
The introduction, implementation, successes and failures of multidrug therapy (MDT) in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.
Guandalini, Stefano; Setty, Mala
Research in celiac disease is unraveling new findings at a high rate, and major advances seem to occur in all areas such as genetics, environmental factor, pathophysiology, and even prospective therapeutic implications. New insight is being gained into the interplay between genetic and environmental factors causing celiac disease. In addition to the known human leukocyte antigen haplotypes, genome-wide studies have now identified additional susceptibility loci and the majority of newly discovered risk regions harbor genes controlling immune pathways. The mechanism of translocation of gliadin peptides across the intestinal barrier has been the subject of much investigation, and there is now evidence that the toxic 33-mer peptide can also be translocated transcellularly. As for the paracellular route, this appears to be enhanced by gliadin's stimulation of zonulin release. The growing role of the innate immunity is being recognized and the increased expression of some Toll-like receptors appears to delineate a new inherent defect in this branch of innate immunity. Finally, new perspectives are opening in the treatment of celiac disease based on new detoxified grains, enzymatic degradation of gluten, and prevention of its crossing the mucosal barrier. The pace of new knowledge in this 'ancient' disease is very fast, and this review outlines the principal lines of such exciting developments.
... in teens. In Blount disease, a lot of pressure is put on the growth plate at the top of the tibia. This is called the physis and it's made out of cartilage , which is weaker than ... this excess pressure prevents the bone from growing normally. Instead, the ...
... wear to record a continuous ECG, usually for 24 to 72 hours. Holter monitoring is used to detect heart rhythm ... your doctor to make sure you're properly managing your heart condition. ... making the same lifestyle changes that can improve your heart disease, such ...
Araújo, Abelardo Q-C
Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing protein but apparently lacking nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear. Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD) and its variants, Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI)] result from accumulation of abnormal isoforms of the prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal prion protein in humans (PRNP) - located on the short arm of chromosome 20 - and forms of prion disease with a familial predisposition (familial CJD, GSS, FFI). Clinically a prionopathy should be suspected in any case of a fast progressing dementia with ataxia, myoclonus, or in individuals with pathological insomnia associated with dysautonomia. Magnetic resonance imaging, identification of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases.
Kinane, Denis F; Stathopoulou, Panagiota G; Papapanou, Panos N
Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease. This pathophysiological situation persists through bouts of activity and quiescence, until the affected tooth is extracted or the microbial biofilm is therapeutically removed and the inflammation subsides. The severity of the periodontal disease depends on environmental and host risk factors, both modifiable (for example, smoking) and non-modifiable (for example, genetic susceptibility). Prevention is achieved with daily self-performed oral hygiene and professional removal of the microbial biofilm on a quarterly or bi-annual basis. New treatment modalities that are actively explored include antimicrobial therapy, host modulation therapy, laser therapy and tissue engineering for tissue repair and regeneration.
... 3, or late disseminated, Lyme disease can cause long-term joint inflammation (Lyme arthritis) and heart rhythm problems. Brain and nervous system problems are also possible, and may include: Decreased concentration Memory disorders Nerve damage Numbness Pain Paralysis of the face ...
Fabry disease results from deficient activity of the enzyme α-galactosidase A and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The main neurological presentations of Fabry disease patients are painful neuropathy, hypohidrosis, and stroke. Fabry neuropathy is characterized as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. Enzyme replacement therapy (ERT) has been shown to have some positive effects on the reduction of neuropathic pain, the improvement of detection threshold for thermal sensation, and sweat function. On the contrary, the effect of ERT on the central nervous system has not been established. Early initiation of ERT before irreversible organ failure is extremely important, and alternative therapeutic approaches are currently being explored. Heterozygotes suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. As well as being carriers, heterozygotes also display symptoms of Fabry disease, and should be carefully monitored and given adequate therapy.
The sunflower disease chapter is part of the Sunflower Oilseeds Monograph, which will be a new publication in the AOCS Oilseeds Monograph series. The monograph contains an overview and history of sunflower crop development, how the oilseed is cultivated, how the oilseed is produced, how the seed is...
Mohammadi, Ladan; Miller, Anthony; Ashurst, John V.
Marijuana smoke can cause thermal injury, and since legalization and increased use of marijuana in our society, differentiating, diagnosing, and managing this condition have become mandatory. A case of a 28-year-old male with Quincke's disease secondary to marijuana inhalation is presented. PMID:28217604
Al-Amri, Ali M.
Castleman and Towne described a disease presenting as a mediastinal mass resembling thymoma. It is also known as "giant lymph node hyperplasia", "lymph node hamartoma", "angiofollicular mediastinal lymph node hyperplasia", and "angiomatous lymphoid hyperplasia". The pathogenesis is unknown, but the bulk of evidence points toward faulty immune regulation, resulting in excessive B-lymphocyte and plasma-cell proliferation in lymphatic tissue. In addition to the mediastinal presentation, extrathoracic involvement in the neck, axilla, mesentery, pelvis, pancreas, adrenal gland, and retroperitoneum also have been described. There are 2 major pathologic variations of Castleman disease: (1) hyaline-vascular variant, the most frequent, characterized by small hyaline-vascular follicles and capillary proliferation; and (2) the plasma-cell variant, in which large lymphoid follicles are separated by sheets of plasma cells. The hyaline-vascular cases usually are largely asymptomatic, whereas the less common plasma-cell variant may present with fever, anemia, weight loss, and night sweats, along with polyclonal hypergamma-globulinemia. Castleman disease is a rare lymphoproliferative disorders. Few cases have been described world widely. In this article we reviewed the classification, pathogenesis, pathology, radiological features and up to date treatment with special emphasis on the role of viral stimulation, recent therapeutic modalities and the HIV-associated disease. PMID:23071471
Burns, E C; Dunger, D B; Dillon, M J
We report five children who presented with Raynaud's disease in whom we could find no clinical, haematological, or immunological evidence of a collagen disorder. Oral phenoxybenzamine proved useful for maintenance treatment in most, with infusions of prostacyclin, nitroprusside, and ketanserin during acute attacks. PMID:3160308
... Behçet’s Disease Progress and Promise Key Words The Immune System When your body is attacked – perhaps by a virus or other germs – your immune system defends you. It “sees” and kills the germs ...
When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...
... or 414–961–0533 Email: firstname.lastname@example.org Internet: www.wilsonsdisease.org National Organization for Rare Disorders ... or 203–744–0100 Fax: 203–798–2291 Internet: www.rarediseases.org Office of Rare Diseases Research ...
Essential facts [Figure: see text] Coeliac disease is a lifelong autoimmune condition where the body reacts to eating gluten, a protein found in wheat, rye and barley. This leads to chronic inflammation of the small intestine and can result in malabsorption of nutrients.
Celiac disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 (tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the “gold standard” for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.
Lyme disease is among the most frequently diagnosed zoonotic tick-borne diseases worldwide. The number of human cases has been on the increase since the first recognition of its aetiological agent. Lyme disease is caused by spirochete bacteria belonging to the genus Borrelia, with B. burgdorferi sensu stricto (s.s.) found in the Americas, and B. afzelii and B. garinii, in addition to B. burgdorferi s.s., in Europe and Asia. Environmental factors, such as human encroachment onto habitats favourable to ticks and their hosts, reduced deforestation, increased human outdoor activities, and climatic factors favouring a wider distribution of tick vectors, have enhanced the impact of the disease on both humans and animals. Clinical manifestations in humans include, in the early phases, erythema migrans, followed several weeks later by neuro-borreliosis (meningo-radiculitis, meningitis or meningo-encephalitis), Lyme arthritis and/or Borrelia lymphocytoma. In dogs, acute signs include fever, general malaise, lameness, lymph node enlargement and polyarthritis, as well as neuro-borreliosis in the chronic form. Diagnosis is mainly serological in both humans and animals, based on either a two-tier approach (an immunoenzymatic test followed by a Western blot confirmatory test) in humans or C(6) peptide, only in dogs. Early treatment with antibiotics, such as doxycycline or amoxicillin, for three weeks usually reduces the risk of chronic disease. Tick control, including the use of tick repellents for both humans and animals, particularly dogs, is highly reliable in preventing transmission. Vaccines are not available to prevent human infection, whereas several vaccines are available to reduce transmission and the clinical manifestations of infection in dogs.
Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda
Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.
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
Minamata disease (methylmercury poisoning) was first discovered in 1956 around Minamata Bay, Kumamoto Prefecture, Japan. A second epidemic in Japan occurred in 1965 along the Agano River, Niigata Prefecture. This paper presents a brief review of Minamata disease with an emphasis on the cases found in Kumamoto Prefecture. At autopsy, the most conspicuous destructive lesion in the cerebrum was found in the anterior portions of the calcarine cortex. Less severe but similar lesions may be found in the post-central, pre-central and temporal transverse cortices. Secondary degeneration from primary lesions may be seen in cases with long survival. In the cerebellum, pathological changes occur deep in the hemisphere. The granule cell population was more affected, compared with Purkinje cells. Among peripheral nerves, sensory nerves were more affected than motor nerves. Our recent experimental studies that reveal knowledge of the pathogenesis of methylmercury poisoning will be discussed.
Tümer, Zeynep; Møller, Lisbeth B
Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar 'kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs due to mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms.
Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.
Walker, Francis O
Huntington's disease may present at any age, but most typically manifests between the ages of 35 and 45 years as a slowly progressive neurodegenerative movement disorder with cognitive and behavioral impairment. It is an autosomal-dominant disorder that has a substantial impact on family structure and dynamics in terms of providing care for affected family members and, for the offspring of an affected parent, dealing with at-risk status. Therapy that slows the progressive neuronal dysfunction or degeneration is unavailable, so pharmacotherapy is currently aimed primarily at managing behavioral and psychiatric symptoms, and, in selected cases, controlling severe chorea. Effective intervention by clinicians is possible, however, in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.
Tümer, Zeynep; Møller, Lisbeth B
Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar ‘kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs due to mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms. PMID:19888294
Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John
Morgellons disease, a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, was first described many centuries ago, but has recently been given much attention on the internet and in the mass media. The present authors present a history of Morgellons disease, in addition to which they discuss the potential benefit of using this diagnostic term as a means of building trust and rapport with patients to maximize treatment benefit. The present authors also suggest "meeting the patient halfway" and creating a therapeutic alliance when providing dermatologic treatment by taking their cutaneous symptoms seriously enough to provide both topical ointments as well as antipsychotic medications, which can be therapeutic in these patients.
Mareček, Z; Brůha, R
Wilsons disease is an autosomal recessive genetic disorder in which copper accumulates in tissues, especially in the liver and the brain. The genetic defect affects the P type ATPase gene (ATP7B). More than 500 mutations causing Wilsons disease have been described. The most common mutation in Central Europe concerns H1069Q. The symptoms of Wilsons disease include hepatic or neurological conditions. The hepatic condition is manifested as steatosis, acute or chronic hepatitis or cirrhosis. The neurological conditions are most often manifested after the age of 20 as motor disorders (tremor, speech and writing disorders), which may result in severe extrapyramidal syndrome with rigidity, dysarthria and muscle contractions. The dia-gnosis is based on clinical and laboratory assessments (neurological signs, liver lesions, low ceruloplasmin, increased free serum copper, high Cu volumes in urine, KayserFleischer ring). The dia-gnosis is confirmed by a high Cu level in liver tissue or genetic proof. Untreated Wilsons disease causes death of the patient. If treated properly the survival rate approximates to the survival rate of the common population. The treatment concerns either removal of copper from the body using chelating agents excreted into the urine (Penicillamine, Trientine) or limitation of copper absorption from the intestine and reducing the toxicity of copper (zinc, ammonium tetrathiomolybdate). In the Czech Republic, Penicillamine or zinc is used. A liver transplant is indicated in patients with fulminant hepatic failure or decompensated liver cirrhosis. In the family all siblings of the affected individual need to be screened in order to treat any asymptomatic subjects.
In recent years, it has become apparent that Tropheryma whipplei not only causes a chronic multisystemic infection which is often preceded by arthropathies for many years, well known as 'classical' Whipple's disease, but also clinically becomes manifest with localized organ affections and acute (transient) infections in children. T. whipplei is found ubiquitously in the environment and colonizes in some healthy carriers. In this review, we highlight new aspects of this enigmatic infectious disorder.
Fausto de Souza, Dominique; Micaelo, Lilian; Cuzzi, Tullia
Plantar fibromatosis, or Ledderhose disease, is a rare hyperproliferative disorder of the plantar aponeurosis. It may occur at any age with the greatest prevalence at middle age and beyond. This disorder is more common in men than woman and it is sometimes associated with other forms of fibromatosis. A 28-year-old Brazilian woman with a six-year history of painless bilateral plantar nodules is described in this article. PMID:20877526
Hu, Linden T
This issue provides a clinical overview of Lyme disease, focusing on prevention, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Scherer, John R
Celiac disease is an autoimmune disorder caused by the continued ingestion of gluten, a protein found in wheat, barley and rye, by predisposed individuals. With the development of highly sensitive serologic tests, this has become an increasingly recognized disease with prevalence as high as 1% in certain patient populations, such as Caucasian females. Almost all celiac patients carry the human leukocyte antigen DQ2/DQ8 gene. Much has recently been discovered about the role of the innate immune system in exposing genetically vulnerable patients to the pathogenic gliadin fraction of gluten. The "classical" presentation of chronic diarrhea and malabsorption is now a rarity. Due to earlier detection and increased awareness, celiac disease now presents with a myriad of "atypical" signs and symptoms such as iron-deficiency anemia and osteoporosis. Associated conditions include T-cell lymphoma, dermatitis herpetiformis, autoimmune thyroiditis and type 1 diabetes. Diagnosis requires serologic confirmation with either antiendomysial or antitransglutaminase antibodies as well as histologic confirmation from endoscopic small bowel biopsy. The only effective treatment necessitates a lifelong, continual adherence to a gluten-free diet.
After two workers at the nuclear weapons plant at Oak Ridge National Laboratory in Tennessee were diagnosed earlier this year with chronic beryllium disease (CBD), a rare and sometimes fatal scarring of the lungs, the Department of Energy ordered up a 4-year probe. Now, part of that probe has begun - tests conducted by the Oak Ridge Associated Universities' Center for Epidemiological Research measuring beryllium sensitivity in 3,000 people who've been exposed to the metal's dust since Manhattan Project managers opened the Y-12 plant at Oak Ridge in 1943. Currently, 119 Y-12 employees process beryllium, which has a number of industrial uses, including rocket heat shields and nuclear weapon and electrical components. The disease often takes 20 to 25 years to develop, and the stricken employees haven't worked with beryllium for years. There is no cure for CBD, estimated to strike 2% of people exposed to the metal. Anti-inflammatory steroids alleviate such symptoms as a dry cough, weight loss, and fatigue. Like other lung-fibrosis diseases that are linked to lung cancer, some people suspect CBD might cause some lung cancer. While difficult to diagnose, about 900 cases of CBD have been reported since a Beryllium Case Registry was established in 1952. The Department of Energy (DOE) estimates that about 10,000 DOE employees and 800,000 people in private industry have worked with beryllium.
Lebwohl, Benjamin; Sanders, David S; Green, Peter H R
Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Sleat, D E; Gin, R M; Sohar, I; Wisniewski, K; Sklower-Brooks, S; Pullarkat, R K; Palmer, D N; Lerner, T J; Boustany, R M; Uldall, P; Siakotos, A N; Donnelly, R J; Lobel, P
The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL. PMID:10330339
The history of Lyme disease, a contagious condition caused by Borrelia burgdorferi transmitted to man by ticks offers infectiologists a formidable lesson on how medicine progresses. Clinical description started in Europe at the turn of the century with Pick's description of what was then labelled chronic atrophic acrodermatitis. Fifty years later Hauser noted the affection was transmitted by ticks. Independently, Afzelius, then Lipschutz, described erythema chronicum migrans and its relationship with tick bites. Neurological involvement was also described with the skin signs. These early dermatological descriptions suddenly came into the limelight in 1975 when an epidemia of arthritis occurred in children in Lyme, Connecticut, USA. Many of the affected children had erythema chronicum migrans. Based on these observations and an epidemiological analysis of the epidemia, Steele and co-workers defined "Lyme disease" as a rheumatological disorder commonly associated with erythema chronicum migrans and sometimes with multiple organ involvement. In 1982 Borgdorfer suggested that tick bites transmitted a Spirochaeta which was later authentified as the causal agent: Borrelia burgdorferi. Immunofluorescence and ELISA tests were rapidly developed for the diagnosis of infection by this germ which is very difficult to culture. Antibiotic curative treatment was immediately available and in 1991 a consensus conference established recommendations for treatment of isolated and disseminated forms. Antibiotic prophylaxis is not necessary but rapid extraction of the tick after the bite can prevent the disease as transmission from tick to man takes several hours. And medical progress continues. Work is now being conducted on evaluating the extent of late neurological manifestations, on developing polymerase chain reaction methods to identify B. burgdorferi infection in specific organs and on developing a vaccine.
Fomegné, G; Dratwa, M; Wens, R; Mesquita, M; Van der Straaten, M; Vanden Haute, K; Fosso, C
We report one case of acute renal failure with oliguria, microscopic haematuria and normocytic anemia in a 86-year old Swedish woman. A full investigation led to the diagnosis of Goodpasture disease, an isolated form of Goodpasture syndrome. Goodpasture disease is and autoimmune disorder characterized by the development of autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen, found mainly in glomerular basement membranes (GBM). When the disease affects both the lung and the kidney, it is called Goodpasture syndrome but the pulmonary or renal involvement can be isolated or separated in years. Its pathogenesis is not well known. It occurs essentially in Caucasian subjects, preferentially from Nordic and Anglo-Saxon countries (higher prevalence of HLA DR B1-15 and B1-4 group). Are also mentioned, the exposure to hydrocarbons, rustproof, insecticides and greasy solvents. The annual incidence of Goodpasture syndrome is rare and has been estimated in Europe to be about 0.5 to 1 case per million inhabitants. The isolated renal form represents about 1/3 of the cases. The clinical presentation is characterized by rapidly progressive renal failure with oliguria or anuria and in case of lung involvement, pulmonary hemorrhage responsible of hemoptysis, sometimes massive. Renal biopsy and immunofluorescence analysis play a key role in the diagnosis. The presence of both linear deposits of IgG along the glomerular basement membrane (GBM) and circulating anti-GBM antibodies is of paramount importance. The treatment, which depends on the degree of renal involvement, is based on the association of corticosteroids, cyclophosphamide and plasma exchanges.
Uebelhart, Brigitte; Rizzoli, René
Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.
Celiac disease is an immunologically mediated enteropathy of the small intestine, characterized by lifelong intolerance to the gliadin and related prolamines from wheat and other cereals, that occurs in genetically predisposed individuals. Symptoms result from structural damage to the mucosa of the small intestine, which may cause malabsorption with positive autoantibodies in the sera. Normal mucosal architecture is restored after the use of a gluten-free diet and the normalization of the autoantibodies. Villous atrophy and high levels of autoantibodies reappear when gluten is reintroduced into the diet (gluten challenge).
Henchcliffe, Claire; Severt, W Lawrence
Parkinson's disease (PD) is an age-related, progressive, multisystem neurodegenerative disorder resulting in significant morbidity and mortality, as well as a growing social and financial burden in an aging population. The hallmark of PD is loss of dopaminergic neurons of the substantia nigra pars compacta, leading to bradykinesia, rigidity and tremor. Current pharmacological treatment is therefore centred upon dopamine replacement to alleviate symptoms. However, two major problems complicate this approach: (i) motor symptoms continue to progress, requiring increasing doses of medication, which result in both short-term adverse effects and intermediate- to long-term motor complications; (ii) dopamine replacement does little to treat non-dopaminergic motor and non-motor symptoms, which are an important source of morbidity, including dementia, sleep disturbances, depression, orthostatic hypotension, and postural instability leading to falls. It is critical, therefore, to develop a broader and more fundamental therapeutic approach to PD, and major research efforts have focused upon developing neuroprotective interventions. Despite many encouraging preclinical data suggesting the possibility of addressing the underlying pathophysiology by slowing cell loss, efforts to translate this into the clinical realm have largely proved disappointing in the past. Barriers to finding neuroprotective or disease-modifying drugs in PD include a lack of validated biomarkers of progression, which hampers clinical trial design and interpretation; difficulties separating symptomatic and neuroprotective effects of candidate neuroprotective therapies; and possibly fundamental flaws in some of the basic preclinical models and testing. However, three recent clinical trials have used a novel delayed-start design in an attempt to overcome some of these roadblocks. While not examining markers of cell loss and function, which would determine neuroprotective effects, this trial design
Goldings, E A; Jericho, J
Although initially considered a localized epidemic form of arthritis. Lyme disease is now known to have protean manifestation (skin, joint, heart, nervous system) and worldwide distribution. It is caused by infection with the spirochaete Borrelia burgdorferi and is transmitted by a variety of hard ticks and, in some localities, fleas. Antigenic variation between isolates may determine the differences in clinical expression observed between cases in North America and Europe. The reservoir in the animal kingdom is primarily in deer and mice but house pets have also been implicated. The disease is easily treated with oral antibiotics (tetracycline or penicillin) at an early stage but requires parenteral penicillin and can become refractory to medication at late stages. Prompt diagnosis assures the best outcome. Whereas the classic rash, erythema chronicum migrans, is pathognomonic, diagnosis in its absence may rest on serological tests. Bacteriological isolation is seldom successful and is lengthy (Shrestha et al, 1985). Since cloning of the DNA for several of B. burgdorferi antigens has been accomplished, utilization of hybridization techniques may allow rapid detection of the presence of the organism and confirm difficult cases in the future.
Bernscherer, G; Berényi, E; Karabélyos, C; László, A; Dávid, Z; Hollódy, K; Tóth, E Z
For the first time in literature the authors interpret the pathography of Refsum's disease, in the case of their patient, as pseudo-hypervitaminosis A. The biochemical basis of the clinical picture is a defect in the activity of phytanic-acid-alpha-hydrolase belonging to the peroxisomal system. As a consequence, phytanic acid accumulates in the serum and in the parenchymal tissues. Retinol, an alcohol with high molecular weight, is a natural ligand of nuclear RXR (retinoid-X-receptor), which plays an important role in the regulation of peroxisoma synthesis. In Refsum's disease the phytanic acid accumulated because of the enzyme defect competes with the biotransformation derivates (all-trans-retinoic acid, 9-cis-retinoic acid) of the all-trans-retinol (vitamin A) for the nuclear RX receptor binding sites, and as a very potent receptoractivator it causes the intestinal symptoms of hypervitaminosis A. The authors review the procedure of fatty-acid chromatography necessary for the establishment of the diagnosis and discuss--in addition to dietary restrictions--recent therapeutic possibilities, like plasmapheresis, cascade filtration, lipapheresis and oral batylalcohol treatment.
Tanowitz, H B; Kirchhoff, L V; Simon, D; Morris, S A; Weiss, L M; Wittner, M
Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. Images PMID:1423218
De-Paula, Vanessa J; Radanovic, Marcia; Diniz, Breno S; Forlenza, Orestes V
Alzheimer's disease (AD) is a chronic neurodegenerative disease with well-defined pathophysiological mechanisms, mostly affecting medial temporal lobe and associative neocortical structures. Neuritic plaques and neurofibrillary tangles represent the pathological hallmarks of AD, and are respectively related to the accumulation of the amyloid-beta peptide (Aβ) in brain tissues, and to cytoskeletal changes that arise from the hyperphosphorylation of microtubule-associated Tau protein in neurons. According to the amyloid hypothesis of AD, the overproduction of Aβ is a consequence of the disruption of homeostatic processes that regulate the proteolytic cleavage of the amyloid precursor protein (APP). Genetic, age-related and environmental factors contribute to a metabolic shift favoring the amyloidogenic processing of APP in detriment of the physiological, secretory pathway. Aβ peptides are generated by the successive cleavage of APP by beta-secretase (BACE-1) and gamma-secretase, which has been recently characterized as part of the presenilin complex. Among several beta-amyloid isoforms that bear subtle differences depending on the number of C-terminal amino acids, Aβ (1-42) plays a pivotal role in the pathogenesis of AD. The neurotoxic potential of the Aβ peptide results from its biochemical properties that favor aggregation into insoluble oligomers and protofibrils. These further originate fibrillary Aβ species that accumulate into senile and neuritic plaques. These processes, along with a reduction of Aβ clearance from the brain, leads to the extracellular accumulation of Aβ, and the subsequent activation of neurotoxic cascades that ultimately lead to cytoskeletal changes, neuronal dysfunction and cellular death. Intracerebral amyloidosis develops in AD patients in an age-dependent manner, but recent evidence indicate that it may be observed in some subjects as early as in the third or fourth decades of life, with increasing magnitude in late middle age
Apostolova, Liana G.
ABSTRACT Purpose of Review: This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). Recent Findings: In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Summary: Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions. PMID:27042902
Apostolova, Liana G
This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions.
Branco, N A A Castelo; Alves-Pereira, M
Vibroacoustic disease (VAD) is a whole-body, systemic pathology, characterized by the abnormal proliferation of extra-cellular matrices, and caused by excessive exposure to low frequency noise (LFN). VAD has been observed in LFN-exposed professionals, such as, aircraft technicians, commercial and military pilots and cabin crewmembers, ship machinists, restaurant workers, and disk-jockeys. VAD has also been observed in several populations exposed to environmental LFN. This report summarizes what is known to date on VAD, LFN-induced pathology, and related issues. In 1987, the first autopsy of a deceased VAD patient was performed. The extent of LFN induced damage was overwhelming, and the information obtained is, still today, guiding many of the associated and ongoing research projects. In 1992, LFN-exposed animal models began to be studied in order to gain a deeper knowledge of how tissues respond to this acoustic stressor. In both human and animal models, LFN exposure causes thickening of cardiovascular structures. Indeed, pericardial thickening with no inflammatory process, and in the absence of diastolic dysfunction, is the hallmark of VAD. Depressions, increased irritability and aggressiveness, a tendency for isolation, and decreased cognitive skills are all part of the clinical picture of VAD. LFN is a demonstrated genotoxic agent, inducing an increased frequency of sister chromatid exchanges in both human and animal models. The occurrence of malignancies among LFN-exposed humans, and of metaplastic and displastic appearances in LFN-exposed animals, clearly corroborates the mutagenic outcome of LFN exposure. The inadequacy of currently established legislation regarding noise assessments is a powerful hindrance to scientific advancement. VAD can never be fully recognized as an occupational and environmental pathology unless the agent of disease--LFN--is acknowledged and properly evaluated. The worldwide suffering of LFN-exposed individuals is staggering and it is
Roca Espiau, Mercedes
The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.
... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... L. Goldstein, MD, MMSc (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...
... disease and improve diagnosis) to effectively evaluate brain biochemistry and disease progression. Other research is expanding the ... disease and improve diagnosis) to effectively evaluate brain biochemistry and disease progression. Other research is expanding the ...
... Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that are ... Transplantation End-stage Lung Disease Adult Lung Transplantation Pediatric Lung ... Aortic Aneurysm Mitral Valve Disease Overview The mitral valve is ...
... Old Feeding Your 1- to 2-Year-Old Lyme Disease KidsHealth > For Parents > Lyme Disease A A A ... Pacific Northwest, and the northern Midwest states. About Lyme Disease Lyme disease is caused by the bacterium Borrelia ...
Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...
Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...
Muskardin, Theresa W; Peterson, Bruce A; Molitor, Jerry A
Castleman disease can occur in association with autoimmune connective tissue disease and confound the clinical picture, resulting in delayed diagnosis and suboptimal treatment. This review focuses on the intersection of Castleman disease and autoimmunity with an emphasis on shared pathology and mutually beneficial treatments. Targeting CD-20, interleukin-6, and the nuclear factor-κB pathway has shown promise in achieving long-term remission in patients with Castleman disease and associated autoimmune features. Advances in understanding of pathogenic cell types and cytokines in Castleman disease have allowed the development of targeted therapies successful in the treatment of both Castleman disease and associated autoimmune disease.
Benninger, David H
In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications.
Cross, G M
Since 1926, there have been three epizootics of ND. The latter two have been directly linked with psittacine species and Racing Pigeons. The modern poultry industry is extremely vulnerable to the effects of NDV, once it gains entry to any facet of the industry. Consequently considerable expense and effort are expended to keep the virus at bay. The main threat continues to come from psittacine species and racing pigeons. The considerable international trade in these birds, together with rapid air transport, can allow virulent NDV to gain entry to a country while exotic birds are incubating the disease. It is hoped that quarantine barriers and requirements will prevent the virus from entering a country, but smuggling continues and constitutes the biggest risk. Domestic avian pets are also vulnerable to the virus. It is hoped that new in vitro testing procedures, such as monoclonal antibody and oligonucleotide fingerprinting techniques, may be used to identify rapidly and characterize emergent virulent strains, so that appropriate measures may be taken to prevent infection of commercial poultry and domestic pets.
Belletti, Gerardo A; Savio, Verónica; Minoldo, Daniel; Caminos, Susana; Yorio, Marcelo A
A 66 years female, who was since last year under astenia, arthralgias, pimply lesions in spread plates and tests showing eritrosedimentation over 100 mm, anemi, leucocitosis with neutrofilia, policlonal hypergammaglobulinemia, slight proteinuria and IgE on 900. This patient was sporadically treated with corticoids. When made the medical consult had lost 34lb., was under anorexy, as well as dyspepsia. Hemoglobyn 6.9 gr/dl, leucocytes 20000/mm3, neutrofils at 90%, proteinogram the same as former, with hypoalbuminemia. She was taking prednisona, 16 mg/day. When examined showed depress of conscience, astenia, and dermic lesions already quoted. 4 cm nonpainful right axillary adenopaty adhered to deep planes. Medulogram with increased iron, hyperegenerative. Ganglionar biopsia: linfoid hyperplasic process linked to inmune response. Toracoabdominal tomography with adenomegalia in torax and retroperitoneo. Skin biopsia: neutrofilic vasculitis. The patient suspends the 16 mg of prednisona and fever as well as generalized adenopatias come up. After laying aside other ethiologies, and understanding as Castleman Multicentric disease, it is started to supply prednisona 1 mg/kg of weight with a clinical and biochemical fast and outstanding response. After 7 months it was progressively suspended the esteroids and 60 days later, the process fall back; for that, corticoids are restarted, with a good evolution. The illness of Castleman although it is not very frequent, it should be considered as differential diagnosis in those clinical cases that are accompanied with important general commitment, linphadenopaties and respons to steroid therapy.
Siroky, Brian J.; Yin, Hong
Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease. PMID:20091054
Weidlich, Patrícia; Cimões, Renata; Pannuti, Claudio Mendes; Oppermann, Rui Vicente
Current evidence suggests that periodontal disease may be associated with systemic diseases. This paper reviewed the published data about the relationship between periodontal disease and cardiovascular diseases, adverse pregnancy outcomes, diabetes and respiratory diseases, focusing on studies conducted in the Brazilian population. Only a few studies were found in the literature focusing on Brazilians (3 concerning cardiovascular disease, 7 about pregnancy outcomes, 9 about diabetes and one regarding pneumonia). Although the majority of them observed an association between periodontitis and systemic conditions, a causal relationship still needs to be demonstrated. Further studies, particularly interventional well-designed investigations, with larger sample sizes, need to be conducted in Brazilian populations.
Vutcovici, Maria; Brassard, Paul; Bitton, Alain
Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.
McBroom, Lynn W.
Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…
Tay-Sachs disease is a rare, inherited disease. It is a type of lipid metabolism disorder. It causes too ... cells, causing mental and physical problems. . Infants with Tay-Sachs disease appear to develop normally for the first few ...
COPD; Chronic obstructive airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... can do to relieve symptoms and keep the disease from getting worse. If you smoke, now is ...
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... Lyme disease FAQ Health care providers Educational materials Data and Statistics Recommend on Facebook Tweet Share Compartir ... sixth most common Nationally Notifiable disease . Lyme Disease Data File To facilitate the public health and research ...
Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...
... in girls, and muscle weakness. Graves disease , an autoimmune disease, is the most common cause of hyperthyroidism. The ... toes thy-roy-DYE-tiss) is also an autoimmune disease and is the most common cause of hypothyroidism ...
... in girls, and muscle weakness. Graves disease , an autoimmune disease, is the most common cause of hyperthyroidism. It ... toes thy-roy-DYE-tiss) is also an autoimmune disease and is the most common cause of hypothyroidism ...
... Alcohol Consumption and Gum Health Workshop on Regeneration Periodontal Disease More Prevalent among Ethnic Minorities Dental Implants Periodontal ... and Men Gum Disease In Children Peri-implant Diseases Comprehensive ... Evaluation Periodontal Treatments and Procedures Non-Surgical Periodontal ...
... Alcohol Consumption and Gum Health Workshop on Regeneration Periodontal Disease More Prevalent among Ethnic Minorities Dental Implants Periodontal ... factors for developing peri-implant disease include previous periodontal disease diagnosis, poor plaque control, smoking , and diabetes . It ...
... types of gum disease in children. Types of periodontal diseases in children Chronic gingivitis is common in children. ... cause the teeth to become loose. Signs of periodontal disease Four basic signs will alert you to periodontal ...
... Alcohol Consumption and Gum Health Workshop on Regeneration Periodontal Disease More Prevalent among Ethnic Minorities Dental Implants Periodontal ... suggested the possibility of an additional risk factor – periodontal disease. Pregnant women who have periodontal disease may be ...
... work? How does inflammatory bowel disease interfere with digestion? Who gets inflammatory bowel disease? How is inflammatory ... top How does inflammatory bowel disease interfere with digestion? When the small intestine becomes inflamed, as in ...
... What Happens in the Operating Room? What's Mad Cow Disease? KidsHealth > For Kids > What's Mad Cow Disease? A A A You might have heard news reports about mad cow disease and wondered: What the heck is that? ...
Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads ... have you take different medicines to treat your Parkinson disease and many of the problems that may ...
... Healthy Eating Reflux and Lung Disease Reflux and Lung Disease Make an Appointment Ask a Question Find a Doctor Many people with chronic lung disease also suffer from gastroesophageal reflux (GERD). In this ...
... in Some People Who Were Treated with hGH Pregnancy & Thyroid Disease What is thyroid disease? Thyroid disease ... pituitary responds by decreasing TSH production. How does pregnancy normally affect thyroid function? Two pregnancy-related hormones— ...
Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...
Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program -- www.nkdep.nih.gov National Kidney Foundation -- www.kidney.org National ...
Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association -- www.heart.org Centers for Disease Control and Prevention -- www.cdc.gov/heartdisease
... from the NHLBI on Twitter. What Is Von Willebrand Disease? Von Willebrand disease (VWD) is a bleeding disorder. ... while hemophilia mainly affects males. Types of von Willebrand Disease The three major types of VWD are called ...
... Resources Heart Diseases & Disorders Back to Patient Resources Heart Diseases & Disorders Millions of people experience irregular heartbeats, called ... harmless and happen in healthy people free of heart disease. However, some abnormal heart rhythms can be serious ...
... Conditions Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Make an Appointment Refer ... ILD clinical trials and most effective therapies. Interstitial Lung Disease Care at National Jewish Health At National ...
... Disease How do doctors treat celiac disease? A gluten-free diet Doctors treat celiac disease with a ... absorb nutrients from food into the bloodstream normally. Gluten-free diet and dermatitis herpetiformis If you have ...
... be coronary heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ...
... Professionals Treatment & Programs Health Information Doctors ... disease (UCTD) is a systemic autoimmune disease. This means the body's natural immune system does not behave normally. Instead of ...
... Sheet National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet Researching Disease: Dr. ... Gaucher disease Orphanet: Gaucher disease-ophthalmoplegia-cardiovascular ...
Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII
Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan
Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity. Copyright © 2015 Elsevier Inc. All rights reserved.
Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša
The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.
Sanan, Akshay; Cognetti, David M
The differential diagnosis for "rare" parotid gland diseases is broad and encompasses infectious, neoplastic, autoimmune, metabolic, and iatrogenic etiologies. The body of knowledge of parotid gland diseases has grown owing to advances in imaging and pathologic analysis and molecular technology. This article reviews rare parotid diseases, discussing the respective disease's clinical presentation, diagnosis, imaging, pathogenesis, treatment, and prognosis.
Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...
Wanner, Nicola; Bechtel-Walz, Wibke
DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.
Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease in which patients experience a progressive decline in lung function, worsening exercise capacity, and frequent exacerbations. Based on clinical evidence, the progression of COPD could be modified by focus on earlier diagnosis; risk reduction through smoking cessation; symptom reduction with pharmacotherapy, improving health-related quality of life, and pulmonary rehabilitation; and decreasing complications by reducing exacerbations. Smoking cessation has been shown to slow lung function decline and reduce mortality, including deaths due to cardiovascular disease, lung cancer, and other respiratory disease (including COPD).
Kolettis, Peter N
Genetic diseases that do not primarily affect the genitourinary tract may have urologic manifestations. These urologic manifestations range from benign and malignant renal disease to infertility. Thus, the practicing urologist may be involved in the care of these patients and should have knowledge of these diseases. Continued improvements in the diagnosis and treatment of these genetic diseases will likely result in improved survival and will increase the number of patients who may develop urologic manifestations of these diseases.
Meer-Scherrer, Laurence; Chang Loa, Chien; Adelson, Martin E; Mordechai, Eli; Lobrinus, Johannes Alexander; Fallon, Brian A; Tilton, Richard C
This case report discusses a patient with co-occurring neuroborreliosis and Alzheimer's disease (AD). Although no claim is made for causality nor is there objective evidence that spirochetes are involved in AD, co-infection may exacerbate the symptoms of either neuroborreliosis or AD. Much is to be learned about the role of spirochetes in degenerative central nervous system disease.
Gouras, Gunnar K
Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoing immunotherapy clinical trials for Alzheimer disease are in progress. The background and ongoing challenges for these immunological approaches for the treatment of Alzheimer disease are discussed.
Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary hypertension? ... tissue diseases (scleroderma and lupus for example), chronic liver disease, congenital heart disease, or HIV infec- tion. ...
Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470
... can help lower their risk of future heart disease. (Following a healthy lifestyle is advised for all children, not just those who have Kawasaki disease). Children treated with immune globulin should wait 11 ...
Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...
... 3900 Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? ... and move closer to a cure. Treatments for Alzheimer's disease Currently, there is no cure for Alzheimer's. But ...
... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases A ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...
... that help with blood clotting. With bone marrow disease, there are problems with the stem cells or ... marrow makes too many white blood cells Other diseases, such as lymphoma, can spread into the bone ...
Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry the infection ... symptoms of CSD, call your doctor. Centers for Disease Control and Prevention
Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...
... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...
Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...
Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...
Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss of mental ... to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build ...
Creutzfeldt-Jakob disease (CJD) is a rare, degenerative brain disorder. Symptoms usually start around age 60. Memory problems, behavior changes, vision ... during a medical procedure Cattle can get a disease related to CJD called bovine spongiform encephalopathy (BSE) ...
... disease of diabetes, or diabetic nephropathy. How does diabetes cause kidney disease? High blood glucose , also called ... I keep my kidneys healthy if I have diabetes? The best way to slow or prevent diabetes- ...
Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...
... coronary artery disease: High levels of low-density lipoprotein cholesterol (bad cholesterol) and triglycerides in the blood. High blood pressure Diabetes Smoking Family history of coronary artery disease Obesity ...
... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ...
... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...
... Alcohol Consumption and Gum Health Workshop on Regeneration Periodontal Disease More Prevalent among Ethnic Minorities Dental Implants Periodontal ... of other health factors. Research has found that periodontal disease is higher in men (56.4 percent) than ...
... be the same one that causes vCJD in humans. Varient CJD causes less than 1% of all ... Scrapie (found in sheep) Other very rare inherited human diseases, such as Gerstmann-Straussler-Scheinker disease and ...
Cysts - kidneys; Kidney - polycystic; Autosomal dominant polycystic kidney disease; ADPKD ... Polycystic kidney disease (PKD) is passed down through families (inherited). The 2 inherited forms of PKD are autosomal dominant ...
... A Real Lifesaver Kids Talk About: Coaches Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...
... gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html Emphysema/COPD (Chronic Obstructive Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and ...
Moore, Phillip Anthony
The cornea is naturally transparent. Anything that interferes with the cornea's stromal architecture, contributes to blood vessel migration, increases corneal pigmentation, or predisposes to corneal edema, disrupts the corneas transparency and indicates corneal disease. The color, location, and shape and pattern of a corneal lesion can help in determining the underlying cause for the disease. Corneal disease is typically divided into congenital or acquired disorders. Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired corneal disease associated with nonulcerative or ulcerative keratitis is common. Primary ocular disease, such as tear film instability, adenexal disease (medial canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are associated with the majority of acquired corneal disease in cats. Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative disease in cats, such as chronic corneal epithelial defects and corneal sequestration are more common than progressive corneal ulcerations.
Seçil, Yaprak; Arıcı, Şehnaz; İncesu, Tülay Kurt; Gürgör, Nevin; Beckmann, Yeşim; Ertekin, Cumhur
To investigate electrophysiological parameters of swallowing in all stages of Alzheimer's disease. Forty Alzheimer's disease patients, 20 age-matched normal controls and 20 young normal controls were included. Dysphagia limit (DL) and sequential water swallowing (SWS) tests were performed. Cardiac rhythm, respiration and sympathetic skin responses were concomitantly recorded. Dysphagia was found in 30/40 (75%) of Alzheimer's disease patients. Mean volume at the DL test was significantly reduced (16.5±1.0mL) in the Alzheimer's disease group. Swallowing and apnea times in the SWS test were significantly prolonged in elderly controls, but even longer in Alzheimer's disease patients. Alzheimer's disease patients had electrophysiological features of dysphagia, even in the early period of disease. The cortical involvement and severity of cognitive disorder can increase swallowing problems, but subclinical signs of dysphagia may be observed even in patients with mild or moderate Alzheimer's disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
... sponsors, Larry and Terri Gury. American Behcet's Disease Association PO BOX 80576 Rochester, MI 48308 Contact Us | Website Policy | email@example.com American Behcet's Disease Association Copyright 2014
Diefenbach, Karen A; Breuer, Christopher K
Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn’s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease. PMID:16718840
Cat scratch disease is an infectious illness associated with cat scratches, bites, or exposure to cat saliva, causing chronic swelling of the lymph nodes. Cat scratch disease is possibly the most common cause of chronic ...
... developing effective enzyme replacement therapies for Gaucher and Fabry diseases. NINDS-funded scientists continue to study how lipids ... developing effective enzyme replacement therapies for Gaucher and Fabry diseases. NINDS-funded scientists continue to study how lipids ...
... treatment strategies in the future. The clustering of multiple and different autoimmune diseases is observed frequently in ... diseases are caused by a complicated interaction of multiple genes and environmental factors such as age, gender, ...
... LS. Epidemiology of beryllium sensitizations and disease in nuclear workers. Am Rev Respir Dis 1993; 148:985- ... chronic beryllium disease. In: Rossman MD, Preuss OP, Powers MB, eds. Beryllium: Biomedical and Environmental Aspects . Baltimore: ...
Piber, D; Hinkelmann, K; Gold, S M; Heesen, C; Spitzer, C; Endres, M; Otte, C
In many neurological diseases a depressive syndrome is a characteristic sign of the primary disease or is an important comorbidity. Post-stroke depression, for example, is a common and relevant complication following ischemic brain infarction. Approximately 4 out of every 10 stroke patients develop depressive disorders in the course of the disease which have a disadvantageous effect on the course and the prognosis. On the other hand depression is also a risk factor for certain neurological diseases as was recently demonstrated in a meta-analysis of prospective cohort studies which revealed a much higher stroke risk for depressive patients. Furthermore, depression plays an important role in other neurological diseases with respect to the course and quality of life, such as Parkinson's disease, multiple sclerosis and epilepsy. This article gives a review of the most important epidemiological, pathophysiological and therapeutic aspects of depressive disorders as a comorbidity of neurological diseases and as a risk factor for neurological diseases.
Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...
Resources - Parkinson disease ... The following organizations are good resources for information on Parkinson disease : The Michael J. Fox Foundation -- www.michaeljfox.org National Institute of Neurological Disorders and Stroke -- www. ...
... contact with people who are sick, also helps. Vaccination Vaccines help protect against all three serogroups (B, ... a chance you can develop meningococcal disease after vaccination. People should know the symptoms of meningococcal disease ...
... A Week of Healthy Breakfasts Shyness Gastroesophageal Reflux Disease (GERD) KidsHealth > For Teens > Gastroesophageal Reflux Disease (GERD) ... foods garlic and onions mint flavorings spicy foods tomato-based foods, like spaghetti sauce, chili, and pizza ...
... medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features on this page, ... healthy people who are at low risk for heart disease. You provider will consider your overall medical condition ...
... genetic, molecular, and cellular mechanisms that underlie inherited neurodegenerative diseases such as MJD. Other research areas include the ... genetic, molecular, and cellular mechanisms that underlie inherited neurodegenerative diseases such as MJD. Other research areas include the ...
Ridge, Perry G.; Ebbert, Mark T. W.; Kauwe, John S. K.
Alzheimer's disease is the most common form of dementia and is the only top 10 cause of death in the United States that lacks disease-altering treatments. It is a complex disorder with environmental and genetic components. There are two major types of Alzheimer's disease, early onset and the more common late onset. The genetics of early-onset Alzheimer's disease are largely understood with variants in three different genes leading to disease. In contrast, while several common alleles associated with late-onset Alzheimer's disease, including APOE, have been identified using association studies, the genetics of late-onset Alzheimer's disease are not fully understood. Here we review the known genetics of early- and late-onset Alzheimer's disease. PMID:23984328
... is an incurable, fatal brain disease that affects cattle. Different versions of the disease can affect certain ... These prohibit the use of any high-risk cattle materials in the feed of any animal. In ...
... A Week of Healthy Breakfasts Shyness Thyroid Disease Definitions KidsHealth > For Teens > Thyroid Disease Definitions A A ... or injury. Signs of inflammation can include redness, heat, pain, or swelling. metabolism: Metabolism refers to the ...
Important diseases and their management practices of lentil were reviewed. The diseases reveiwed include Ascochyta blight (Ascochyta lentis), Anthracnose (Colletotrichum truncatum), White mold (Sclerotinia sclerotiorum), rust (Uromyces viciae-fabae), Botrytis gray mold (Botrytis cinerea and B. faba...
... Z Celiac Disease Symptoms & Diagnosis Treatment & Management Coping Gluten Free Diet Guide Eosinophilic Esophagitis Inflammatory Bowel Disease ... serious condition caused by a permanent intolerance for gluten--a protein found in wheat, rye, and barley. ...
... 1930s. People in England and Australia call ALS motor neurone disease (MND). The French refer to it ... about ALS in 1869. Lou Gehrig's disease damages motor neurons in the brain and spinal cord. Motor ...
... by which organisms grow and develop. Developmental biology studies in Parkinson's disease hold potential to identify therapeutic targets and new cell replacement strategies. Diagnosis Identification or naming of a disease by ...
Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death in the United States in both men and women. CAD happens when the arteries that supply blood to ...
... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...
... About Us Overview of CDC’s work. Advancements in Sickle Cell Disease New supplement from the American Journal of Preventive Medicine describes the state of sickle cell disease related care in the United States. Read Supplement ...
... is an incurable, fatal brain disease that affects cattle. Different versions of the disease can affect certain ... These prohibit the use of any high-risk cattle materials in the feed of any animal. In ...
NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage disease - Niemann-Pick ... cannot properly break down cholesterol and other fats (lipids). This leads to too much cholesterol in the ...
Addison's disease Diagnosis Your doctor will talk to you first about your medical history and your signs and ... If your doctor thinks that you may have Addison's disease, you may undergo some of the following tests: ...
... kids and teens who have diseases of the gastrointestinal system (the esophagus, stomach, intestines, and other organs that ... Parents MORE ON THIS TOPIC Lactose Intolerance Ulcers Digestive System Irritable Bowel Syndrome Celiac Disease Hernias Contact Us ...
Misbah, S; Mapstone, N
Whipple's disease has traditionally been considered to be a rare multisystem disorder dominated by malabsorption. The recent identification of the Whipple's disease bacillus has, using polymerase chain reaction based assays, fuelled advances in the investigation, diagnosis, and management of this disease. This leader reviews the aetiology, clinical manifestations, investigation, and treatment of Whipple's disease in the light of this new information. Key Words: Tropheryma whippelii • immune system • polymerase chain reaction PMID:11064667
Kolesárova, Eva; Sirotiaková, Jana; Kozárová, Miriam
Knowledge of important morphological, functional and hemodynamic changes occurring in the kidneys during physiological pregnancy is a prerequisite for proper diagnostics and therapy of renal diseases in pregnancy. Kidney diseases may be kidney diseases complicating pregnancy in previously healthy women, or pre-existing or superposed kidney diseases. Knowledge of renal insufficiency management in pregnancy, including haemodialysis treatment and management of pregnancy in patients who have undergone transplantation, is also important.
Doggett, J Stone; Kohlhepp, Sue; Gresbrink, Robert; Metz, Paul; Gleaves, Curt; Gilbert, David
The incidence of Lyme disease in Oregon is calculated from cases reported to the Oregon State Health Division. We reviewed the exposure history of reported cases of Lyme disease and performed field surveys for infected Ixodes pacificus ticks. The incidence of Lyme disease correlated with the distribution of infected I. pacificus ticks.
... Habits for TV, Video Games, and the Internet Tay-Sachs Disease KidsHealth > For Parents > Tay-Sachs Disease Print A A A What's in this article? ... can interfere with growth. But a baby with Tay-Sachs disease is born without one of those important enzymes, ...
... Page You are here Home » Disorders » All Disorders Acid Lipase Disease Information Page Acid Lipase Disease Information Page What research is being ... research to understand lipid storage diseases such as acid lipase deficiency. Additional research studies hope to identify ...
Friend, Milton; Franson, J. Christian
Individual disease outbreaks have killed many thousands of animals on numerous occasions. Tens of thousands of migratory birds have died in single die-offs with as many as 1,000 birds succumbing in 1 day. In mammals, individual disease outbreaks have killed hundreds to thousands of animals with, for example, hemorrhagic disease in white-tailed deer, distemper in raccoon, Errington's disease in muskrat, and sylvatic plague in wild rodents. The ability to successfully combat such explosive situations is highly dependent n the readiness of field personnel to deal with them. Because many disease agents can spread though wildlife populations very fast, advance preparation is essential in preventing infected animals from spreading disease to additional species and locations. Carefully though-out disease contingency plans should be developed as practical working documents for field personnel and updated as necessary. Such well-designed plans can prove invaluable in minimizing wildlife losses and costs associated with disease control activities. Although requirements for disease control operations vary and must be tailored to each situation, all disease contingency planning involved general concepts and basic biological information. This chapter, intended as a practical guide, identifies the major activities and needs of disease control operations, and relates them to disease contingency planning.
Chronic wasting disease (CWD) is an emerging prion disease of deer, elk, and moose in North America. This fatal neurodegenerative disease was first recognized 50 years ago and its distribution was limited to the Rocky Mountains for several decades. In the past few years, CWD has been found in the ea...
Pelvic Inflammatory Disease (PID) - CDC Fact Sheet Untreated sexually transmitted diseases (STDs) can cause pelvic inflammatory disease (PID), a ... tubal blockage; •• Ectopic pregnancy (pregnancy outside the womb); •• Infertility (inability to get pregnant); •• Long-term pelvic/abdominal ...
R.E. Williams; C.G. III Shaw; P.M. Wargo; W.H. Sites
Armillaria root disease is found throughout temperate and tropical regions of the world. In the continental United States, the disease has been reported in nearly every State. Hosts include hundreds of species of trees, shrubs, vines, and forbs growing in forests, along roadsides, and in cultivated areas. The disease is caused by fungi, which live as parasites on...
Yersinia ruckeri, the causative agent of Enteric Redmouth Disease (ERM), is a disease of salmonid fish species that is endemic in areas of the world where salmonids are intensively cultured. The disease causes a chronic to acute hemorrhagic septicemia which can lead to high rates of mortality partic...
Bender, Stephen J.
This book is one in a series of contemporary topics in health science for students. The first chapter deals with the behavioral aspects of venereal disease and how the disease has been affected by our changing society. Chapter 2 discusses the magnitude of the problem, presenting various maps and charts. The history of venereal disease and the…
This speech on venereal disease education uses as its focus this quotation from George Santayana, "Those who cannot remember the past are doomed to repeat it." The author presents a brief history of venereal disease education and statistics on the present rate of venereal disease. He concludes that past research and experience indicate that…
James W. Walters
Since its discovery in the United States in 1930, Dutch elm disease has killed thousands of native elms. The three native elms, American, slippery, and rock, have little or no resistance to Dutch elm disease, but individual trees within each species vary in susceptibility to the disease. The most important of these, American elm, is scattered in upland stands but is...
... Old Feeding Your 1- to 2-Year-Old Tay-Sachs Disease KidsHealth > For Parents > Tay-Sachs Disease A A A What's in this article? Who ... can interfere with growth. But a baby with Tay-Sachs disease is born without one of those important enzymes, ...
... Emergency Room? What Happens in the Operating Room? Lyme Disease KidsHealth > For Kids > Lyme Disease A A A What's in this article? Ticks ... and summer, you might hear about something called Lyme disease. It has nothing to do with limes, but ...
Bender, Stephen J.
This book is one in a series of contemporary topics in health science for students. The first chapter deals with the behavioral aspects of venereal disease and how the disease has been affected by our changing society. Chapter 2 discusses the magnitude of the problem, presenting various maps and charts. The history of venereal disease and the…
... kidney disease if you have diabetes high blood pressure heart disease a family history of kidney failure If you have diabetes, ... checked every year. If you have high blood pressure, heart disease, or a family history of kidney failure, talk with your health ...
... United States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing ... the blood vessels that supply blood to the heart itself. This is called coronary artery disease, and ...
Frank G. Hawksworth
Diseases are a major concern to forest managers throughout the lodgepole pine type. In many areas, diseases constitute the primary management problem. As might be expected for a tree that has a distribution from Baja California, Mexico to the Yukon and from the Pacific to the Dakotas, the diseases of chief concern vary in different parts of the tree's range. For...
Bacterial diseases of plants are usually difficult to control and often require a combination of control measures to successfully manage the disease. There are often stark differences between the means available to control bacterial diseases in annual crops versus a woody tree crop, such as apple. ...
Castañeda, Santos; Nurmohamed, Michael T; González-Gay, Miguel A
Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.
Love, Seth; Miners, J Scott
Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.
Tuttolomondo, Antonino; Pecoraro, Rosaria; Simonetta, Irene; Miceli, Salvatore; Pinto, Antonio; Licata, Giuseppe
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A. FD causes glycolipids, such as globotriaosylceramide (Gb3), to accumulate in the vascular endothelium of several organs (Fig. 2), including the skin, kidneys, nervous system, and heart, thereby triggering inflammation and fibrosis. These processes generally result in organ dysfunction, which is usually the first clinical evidence of FD. Patients with classic FD have various symptoms, eg, acroparesthesias, hypohidrosis, angiokeratomas, corneal opacities, cerebrovascular lesions, cardiac disorders, andrenal dysfunction.However, evolving knowledge about the natural course of disease suggests that it is more appropriate to describe FD as a disease with a wide spectrum of heterogeneously progressive clinical phenotypes. Indeed, most female heterozygotes develop symptoms due to yet undetermined mechanisms and a high percentage of females develops vital organ involvement including the kidneys, heart and/or brain about a decade later than males. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. The principal clinical manifestations in Fabry disease consist of artery associated complications (such as cerebral disease and nephropathy), but the pathophysiology of this specific vasculopathy is unclear. Several studies
Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga
Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.
Karstad, Lars; Pridham, T. J.
A suspension of tissues from field cases of Aleutian disease was used successfully to reproduce the disease in Aleutian mink. Similarly, suspensions of diseased tissues from the experimentally infected mink were used to transmit the agent of Aleutian disease to both Aleutian mink and standard dark mink. Seitz and millipore filtrates prepared from these tissue suspensions were also infective; a suggestion that the etiologic agent is a virus. Genetic factors and hypersensitivity are discussed as possibly contributing to development of the disease. PMID:17649371
Newberg, Andrew B; Serruya, Mijail; Wintering, Nancy; Moss, Aleezé Sattar; Reibel, Diane; Monti, Daniel A
Neurodegenerative diseases pose a significant problem for the healthcare system, doctors, and patients. With an aging population, more and more individuals are developing neurodegenerative diseases and there are few treatment options at the present time. Meditation techniques present an interesting potential adjuvant treatment for patients with neurodegenerative diseases and have the advantage of being inexpensive, and easy to teach and perform. There is increasing research evidence to support the application of meditation techniques to help improve cognition and memory in patients with neurodegenerative diseases. This review discusses the current data on meditation, memory, and attention, and the potential applications of meditation techniques in patients with neurodegenerative diseases.
DuPrey, Kevin M
Lyme disease, a bacterial infection transmitted by ticks, is the most common vector-borne disease in the northern hemisphere. Athletes who train or compete in wooded environments in endemic regions are at increased risk of contracting Lyme disease. Variability in clinical presentation, masquerading symptoms, and limitations in testing may lead to misdiagnosis. Early diagnosis and treatment result in full recovery for most patients with Lyme disease; however symptoms may persist for months to years, especially when diagnosis is delayed. This article reviews the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease, with focus on the athletic population.
Ramdass, Priya; Mullick, Sahil; Farber, Harold F
In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.
Pigott, David M.; Howes, Rosalind E.; Wiebe, Antoinette; Battle, Katherine E.; Golding, Nick; Gething, Peter W.; Dowell, Scott F.; Farag, Tamer H.; Garcia, Andres J.; Kimball, Ann M.; Krause, L. Kendall; Smith, Craig H.; Brooker, Simon J.; Kyu, Hmwe H.; Vos, Theo; Murray, Christopher J. L.; Moyes, Catherine L.; Hay, Simon I.
Background Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. Methodology/Principal Findings Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. Conclusions/Significance A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited. PMID:26061527
Diepgen, Thomas L
Occupational skin diseases are the most commonly reported notifiable occupational diseases. In Germany, 23 596 out of a total of 71 263 reported occupational diseases in 2010 were classified as occupational skin diseases (BK No. 5101: "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease"). Contact dermatitis (allergic, irritant) of the hands is the most common skin disease and atopic skin diathesis is often an important co-factor. The number of work-related skin diseases is many times higher than the number of notified occupational dermatoses. This CME article explains the legal framework of occupational diseases, the tasks and obligations of the legal statutory work insurance. Typical allergens and irritants of high risk professions are also presented as are the important steps from diagnosis to compensation. Early prevention of occupational skin diseases is very important to avoid severe chronic hand eczema. Therefore the "dermatologist's report" is crucial. Other occupational dermatoses (outside of BK 5101) are briefly mentioned. In recent years the number of notifications of occupational skin cancer due to occupational UV-irradiation has increased. According to recent epidemiological findings, there is a significant and consistent positive association between occupational UV-irradiation and squamous cell carcinoma. Therefore, an important criterion for a new occupational disease is fulfilled. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.
Pigott, David M; Howes, Rosalind E; Wiebe, Antoinette; Battle, Katherine E; Golding, Nick; Gething, Peter W; Dowell, Scott F; Farag, Tamer H; Garcia, Andres J; Kimball, Ann M; Krause, L Kendall; Smith, Craig H; Brooker, Simon J; Kyu, Hmwe H; Vos, Theo; Murray, Christopher J L; Moyes, Catherine L; Hay, Simon I
Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited.
Gastrointestinal disease is often overlooked or simply forgotten as a cause of osteoporosis. Yet, the consequences of osteoporotic fractures can be devastating. Although the bulk of the published experience regarding osteoporosis is derived from the postmenopausal population, this review will focus on gastrointestinal disorders implicated in osteoporosis, with an emphasis on inflammatory bowel disease and celiac disease. The unique aspects of gastrointestinal diseases associated with osteoporosis include early onset of disease (and, therefore, prolonged exposure to risk factors for developing osteoporosis, particularly with inflammatory bowel disease and celiac disease), malabsorption, and maldigestion of nutrients necessary for bone health and maintenance (eg, calcium, vitamin D), as well as the impact of glucocorticoids. These factors, when added to smoking, a sedentary lifestyle, hypogonadism, and a family history of osteoporosis, accumulate into an imposing package of predictors for osteoporotic fracture. This paper will review the identification and treatment strategies for patients with gastrointestinal disorders and osteoporosis. PMID:20978554
Gayed, M; Gordon, C
Pregnancy is an issue that should be discussed with all patients with rheumatic diseases who are in the reproductive age group. Infertility is rarely due to the disease but can be associated with cyclophosphamide therapy. Most rheumatic diseases that are well controlled prior to pregnancy do not deteriorate in pregnancy, providing that the patient continues with appropriate disease-modifying therapy. Some patients with inflammatory arthritis go in to remission during pregnancy. Patients with renal involvement may be at increased risk of disease flare. This needs to be distinguished from pre-eclampsia. Intrauterine growth restriction is more likely in patients with active systemic disease, hypertension, a history of thrombosis and renal involvement. Premature delivery may need to be planned to reduce the risks of stillbirth and can be associated with a variety of neonatal complications. Post-partum flare is common in all the rheumatic diseases.
Vanhauwaert, Roeland; Verstreken, Patrik
Parkinson's disease is an incurable neurodegenerative disease. Most cases of the disease are of sporadic origin, but about 10% of the cases are familial. The genes thus far identified in Parkinson's disease are well conserved. Drosophila is ideally suited to study the molecular neuronal cell biology of these genes and the pathogenic mutations in Parkinson's disease. Flies reproduce quickly, and their elaborate genetic tools in combination with their small size allow researchers to analyze identified cells and neurons in large numbers of animals. Furthermore, fruit flies recapitulate many of the cellular and molecular defects also seen in patients, and these defects often result in clear locomotor and behavioral phenotypes, facilitating genetic modifier screens. Hence, Drosophila has played a prominent role in Parkinson's disease research and has provided invaluable insight into the molecular mechanisms of this disease.
van Gils, T; de Boer, N K H; Bouma, G
Coeliac disease is a chronic autoimmune enteropathy, which is caused by exposure to dietary gluten in genetically pre-disposed individuals. -Approximately 0.5-1% of the Dutch population has coeliac disease, diag-nosed at both younger and older age. Treatment consists of a strict gluten-free diet. Symptoms can be diverse, including dental and oral manifestations. These dental and oral manifestations are often seen in patients with coeliac disease, although most of them are nonspecific. This is not the case for the symmetric enamel defects described by Aine and colleagues, which are very specific for coeliac disease. Early diagnosing of coeliac disease is important to prevent complications by (vitamin) deficiencies or rare (pre) malignant forms of coeliac disease. There seems to be a role for dentists in early diagnosing of coeliac disease.
Parkinson's disease is associated with an increased risk of falls. The risk is greatest in patients with advanced disease. Because Parkinson's disease usually occurs late in life, the risk factors related to the neurological impairments add to those associated with aging. The incidence of fractures is high in patients with Parkinson's disease, with femoral neck fractures in older women being particularly common. Risk factors for fractures include a low body mass index, limited exposure to sunlight, an inadequate vitamin D intake with low 25-OH vitamin D levels, and bone loss. Several studies found decreased bone mineral density values at the femoral neck and lumbar spine in patients with Parkinson's disease. Although this decrease is ascribable in part to factors unrelated with Parkinson's disease, such as older age and female gender, Parkinson's disease itself also plays a role, most notably in patients with severe neurological impairments (Hoehn and Yahr stages III and IV).
Autoimmune thyroid disease (ATD) is a multifactorial, genetic disease. It is the sequelae of the impaired immunoregulation, tolerance and poor recognition of one's own proteins, oligopolysaccharides and polypeptides, due to development of somatic lymphocyte mutations. It is manifested by different clinical and morphological entities, inter-related by etiopathogenetic association, i.e., all of them are caused by disorder of immune system regulation. Chronic autoimmune thyroidism (Thyreoiditis lymphocytaria Hashimoto, HT), as well as immunogenic hyperthyroidism (Morbus Graves Basedow, MGB) are frequently associated with autoimmune diseases of other organs, such as: chronic insufficiency of salivary glands (Sy Sjögren), autoimmune hemolytic anemia, megalocytic pernicious anemia, thrombocytopenia, Rheumatoid arthritis, Diabetes mellitus (more often type 2, but also type 1), Morbus Addison, Coeliakia, and other autoimmune diseases such as systemic diseases of connecting tissue (Lupus erythematosus-SLE, Sclerodermia, Vasculitis superficialis). The incidence of autoimmune diseases has been at increase in all age groups of our population. The prevalence of organ-specific and organ-nonspecific antibodies increases with the age. Antigenicity of thyroid epithelial cell may be triggered by different chemical and biological agents (repeated viral infections), repeated stress, and in individuals with genetic propensity. Unrecognized ATD progressively leads to hypothyroidism with hyperlipidemia, blood vessel changes, osteoporosis, deformities, invalidity which substantially reduces the quality of life of patient and requires medical attention and expensive treatment on what account it is medically and socio-economically significant. Multiple diagnostic procedures contribute to faster recognition of this condition. The goal of the primary health care physician (given that preclinical phase of ATD and other associated diseases have different duration) and other specialists is to
Bohacek, Johannes; Mansuy, Isabelle M
Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID:22781843
Rieu, I; Boirie, Y; Morio, B; Derost, P; Ulla, M; Marques, A; Debilly, B; Bannier, S; Durif, F
Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.
Chang, Shannon; Malter, Lisa; Hudesman, David
The optimal method for monitoring quiescent disease in patients with Crohn’s disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD. PMID:26523100
Gomes, Aldrin V.
The proteasome is a large, multiple subunit complex that is capable of degrading most intracellular proteins. Polymorphisms in proteasome subunits are associated with cardiovascular diseases, diabetes, neurological diseases, and cancer. One polymorphism in the proteasome gene PSMA6 (−8C/G) is associated with three different diseases: type 2 diabetes, myocardial infarction, and coronary artery disease. One type of proteasome, the immunoproteasome, which contains inducible catalytic subunits, is adapted to generate peptides for antigen presentation. It has recently been shown that mutations and polymorphisms in the immunoproteasome catalytic subunit PSMB8 are associated with several inflammatory and autoinflammatory diseases including Nakajo-Nishimura syndrome, CANDLE syndrome, and intestinal M. tuberculosis infection. This comprehensive review describes the disease-related polymorphisms in proteasome genes associated with human diseases and the physiological modulation of proteasome function by these polymorphisms. Given the large number of subunits and the central importance of the proteasome in human physiology as well as the fast pace of detection of proteasome polymorphisms associated with human diseases, it is likely that other polymorphisms in proteasome genes associated with diseases will be detected in the near future. While disease-associated polymorphisms are now readily discovered, the challenge will be to use this genetic information for clinical benefit. PMID:24490108
DeVries, Avery; Vercelli, Donata
Purpose of review Allergic diseases are among the most prevalent chronic diseases of childhood, affecting more than 7 million children in the United States. Epidemiological evidence supports the idea that the inception of allergic diseases is typically before the pre-school years, even when chronic symptoms do not emerge until adulthood. The role of epigenetic mechanisms (particularly DNA methylation) in allergic disease is under active investigation because these mechanisms are known to be at the interface among gene regulation, environmental stimuli and developmental processes, all of which are essential for the pathogenesis for asthma and allergy. This article specifically reviews genome-wide DNA methylation studies in allergic disease. Recent findings Differential DNA methylation at specific regions appears to be associated with concurrent allergic disease. A few studies have identified methylation signatures predictive of disease. Summary DNA methylation signatures have been shown be associated with several allergic disease phenotypes, typically concurrently with disease. The few that have been found to precede diagnosis are especially interesting because they highlight an early trajectory to disease. PMID:26418323
Lundin, Knut E A; Sollid, Ludvig M
To summarize the recent advances in coeliac disease. Details of the polygenic nature of coeliac disease with the human leukocyte antigen (HLA) locus as the dominating genetic element have been uncovered. The existence of a large number of non-HLA coeliac disease genes, only partly shared by each individual patient, suggests the genetic heterogeneity of the disease. The critical role for HLA-DQ-restricted CD4 T cells recognizing antigenic gluten peptides is further substantiated. Involvement of CD8 T cells has received new attention. Other components of wheat than gluten, in particular the amylase trypsin inhibitors, may also play a role. The disease is becoming more prevalent. New guidelines state that coeliac disease diagnosis in children can be made on the basis of clinical signs, serology and genetics without the need of biopsy. The clinical entity 'noncoeliac gluten sensitivity' has received much attention, but diagnostic and pathophysiological definitions are still elusive. The risk for mortality and morbidity in coeliac disease is less than previously thought. Our understanding of the basic and clinical aspects of coeliac disease increases. Coeliac disease stands out as a major health problem of almost global occurrence. Case finding, distinguishing coeliac disease from other gluten-sensitive conditions, better care and balanced use of resources are the current challenges.
Soliman, Neveen A
Rare kidney diseases are a unique subset of renal disorders that are often termed 'orphan' as a result of a multitude of reasons: the small number of patients with the consequent lack of well-defined natural history and course of many of these diseases, limited awareness among the medical community, and finally the significant cost of developing novel therapeutics which makes many of these diseases unattractive targets for the pharmaceutical industry. Nevertheless, in the last decade the study and clinical management of rare kidney disease patients has been the focus of many investigative efforts. In recent years we have witnessed an enormous expansion in our knowledge of the genetic nature of a number of rare kidney diseases. Moreover, the investigation of the role of genetic disruption aiming at elucidating the pathogenesis of different and complex renal diseases has helped not only in understanding the disease states, but has also given us fundamental insights into a number of kidney developmental and physiological functions. This article will give an overview of orphan renal diseases with particular emphasis on monogenic kidney diseases. It will also focus on the classification of these diseases while highlighting a prominent example in each category.
Celiac disease develops from an autoimmune response to specific dietary grains that contain gluten. Diagnosis can be made based on the classical presentation of diarrhea, fatty stools, and abdominal bloating and cramping, as well as the presence of specific serum antibodies. In addition, gluten ingestion has increasingly been found to be associated with other conditions not usually correlated with gluten intolerance. The subsequent diversity of the clinical presentation in these cases can complicate decision-making and delay treatment initiation in conditions such as ataxia, headaches, arthritis, neuropathy, type 1 diabetes mellitus, and others. This review explores the etiology and pathology of celiac disease, presents support for the relationship between gluten and other diseases, and provides effective screening and treatment protocols.
Cuende, José I; Pérez de Diego, Ignacio J; Godoy, Diego
More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.
De Winter, Gunnar
In this paper, I will argue that ageing can be construed as disease. First, the concept of disease is discussed, where the distinction is made between two lines of thought, an objectivist and a subjectivist one. After determining the disease conception to be used throughout the argument, it is proposed that senescence could be seen as disease. Three common counterarguments are discussed, none of which appears strong enough to effectively counter the advocated view. In the third section, two potential implications of the view advocated here will be briefly touched upon. These are the quest for a cure or treatment for ageing and the general attitude towards the elderly. It is concluded that, utilizing an objective disease concept, ageing could be seen as a disease. None of the considered counterarguments packs enough of a punch to discard this. The implications are complex and intertwined, but need not be negative.
Brady, Carla W
There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.
Rucker, R.R.; Bernier, A.F.; Whipple, W.J.; Burrows, R.E.
The blueback salmon fingerlings (Oncorhynchus nerka) at the U.S. Fish-Cultural Station at Winthrop, Washington, underwent an infection that was caused by a very short, Gram-positive, nonmotile, rod-shaped bacterium. A further description is impossible at this time, as the organism has not been grown satisfactorily for proper identification. The disease was characterized by white, raised areas of dead tissue mainly in the kidney: for this reason it is referred to as kidney disease. Belding and Merrill (1935) described a disease among the brook, brown, and rainbow trout at a State hatchery in Massachusetts which, from the description, might be the same as kidney disease. J.H. Wales of the California Division of Fish and Game described (unpublished manuscript, 1941) a disease in hatchery trout in California which seems to be identical to kidney disease.
de Villemeur, Thierry Billette
Prion diseases are rare in children. Three types are known: kuru, variant Creutzfeldt-Jakob disease (CJD), and iatrogenic CJD. All three affect children and young adults, and are transmitted by infectious contamination. Kuru was the result of ritual funeral practices similar to cannibalism; variant CJD affects young people who have eaten meat from cows with mad cow disease (mostly in the UK); and iatrogenic CJD is secondary to graft of human tissues performed in the 1980s (dura mater, pituitary extracted growth hormone). The disease appears after 4-30 years of incubation. The initial symptomatology is frequently neurological (cerebellar ataxia, oculomotor disturbance, peripheral nerve pain, pyramidal syndrome) followed by dementia. There is no biological test available that can give a definite diagnosis of prion disease apart from neuropathology, although prion accumulation in vCJD can be demonstrated in pharyngeal tonsil by immunohistochemical techniques. This devastating disease results inevitably in death. No specific treatment is available.
Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo
Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.
von Altrock, A; Höltig, D
Skin alterations can be caused by both environmental conditions and diseases of the organism. Some diseases may only manifest in the skin while others represent signs of a generalized infection. Regarding their origin, skin diseases can be divided into congenital, infectious, and nutritional disorders, and those resulting from housing scarcities. Additionally, there are skin diseases with unknown causes. Skin diseases in a swine herd can result in economic losses through decreased feed efficiency and growth rate and increased mortality. The knowledge of causes and symptoms as well as the selection of appropriate further laboratory investigations provide a valid diagnosis and enable a quick and effective therapy. This description of several skin diseases should provide a background.
Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life.
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... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...
Despotović, Nebojsa; Zdravković, Mihajlo
Multiple arterial disease is presented by coexistence of ischaemic heart disease, carotid disease and peripheral obliterate arterial disease. Atherosclerosis is the main factor for onset of the disease. Among 150 patients with clinical manifestations of obliterate disease of at least two aforementioned arterial systems, we examined by many noninvasive and invasive procedures the existence and degree of obliterate arterial disease of coronary, carotid and peripheral arteries of the lower extremities. The results revealed the statistically significant correlation among: ischaemic heart disease and carotid disease (r = 0.939; p < 0.01); ischaemic heart disease and peripheral arterial disease (r = 0.834; p < 0.05); ischaemic heart disease, peripheral arterial disease and carotid disease (r = 0.986; p < 0.01). The results pointed out that whenever clinical manifestations of obliterate disease of peripheral arteries are present, there is also need for routine examination of existent coronary artery disease.
Cohn, Leah A
Feline respiratory disease complex (FRDC) refers to the characteristic acute presentation of a contagious respiratory or ocular disease caused by one or multiple pathogens. Environmental and host factors impact the transmission, clinical presentation, preventive strategy, and treatment of affected cats. The FRDC is especially problematic in settings where large numbers of cats cohabit, including animal shelters, catteries, and semi-feral colonies. Although elimination of FRDC is an unrealistic goal, improved understanding can lead to strategies to minimize disease impact.
Märker-Hermann, E; Bauer, H; Gromnica-Ihle, E
Rheumatic diseases can influence the reproduction, the course of pregnancy and the development of the fetus. The inflammatory rheumatic disease itself can be modulated in its activity in terms of amelioration or exacerbation of the rheumatic symptoms. The associations between rheumatic diseases and pregnancy will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug therapy during pregnancy and the breast feeding period has to be adapted critically.
In common rheumatologic diseases skin findings are an important diagnostic clue for astute clinicians. Skin manifestations can help identify systemic disease or may require therapy uniquely targeted at the cutaneous problem. This article discusses 3 common rheumatologic conditions seen in adults by dermatologists: cutaneous lupus, dermatomyositis, and morphea. The focus is on the cutaneous findings and clinical presentation. Some approaches to treatment are explored. Clues to help identify systemic disease are also highlighted.
Hernández-Albújar, S; García-Tobaruela, A; Torres Rodríguez, E; Pacheco Cuadros, R; Vázquez Rodríguez, J J
In this article we review the concept and terminology of prions, their replication and some current hypothesis on the nature of these infectious agents causing neurodegenerative diseases. This revision also summarizes the etiopathogenic, epidemiological, clinical and neuropathological features of the prion diseases or human transmissible spongiform encephalopathies, and some methods for their early diagnosis. Finally, we discuss the possible link between the bovine spongiform encephalopathy and the new cases of Creutzfeldt-Jakob disease identified in the United Kingdom.
Firmin-Lefebvre, D; Misery, L
Because andrology is relatively undeveloped in France, the dermatologist is often the doctor first consulted for diseases of the nipple in men. All dermatological diseases can in fact occur at this site. There are some specific nipple diseases such as gynaecomastia, congenital abnormalities, hyperplasia, benign tumours and breast cancer. All clinical examinations and laboratory examinations should focus on diagnosis of this type of cancer and its elimination.
AD-AL6S 614 PHARNACOLOSY OF PERIODOINTAL DISEASE (U) UNIVERSITY OF vi1 HEALTH SCIENCES/CHICAGO NEDICAL SCHOOL DEPT OF PHRNACOLOGY S F HOFF 23 JUN 86...Capital Region Bethesda, MD 20814-5044 RE: Annual Letter Report ONC Contract #N00014-84-K-0562 "Pharmacology of Periodontal Disease " Dear Capt. Hancock...Periodontal Disease " ist Steven F. Hoff, Ph.D. (Principal Investigator) A. ’Progress Report: We are attempting to dentifyrntibacterial and anti
Lyme disease is a tick-borne illness that is wide-spread in North America, especially in the northeastern and northcentral United States. This disease could negatively influence efforts to conserve natural populations in two ways: (1) the disease could directly affect wild animal health; and (2) tick control efforts could adversely affect natural populations and communities. Lyme disease affects several domestic animals, but symptoms have been reported in only a few wild species. Direct effects of Lyme disease on wild animal populations have not been reported, but the disease should be considered as a possible cause in cases of unexplained population declines in endemic areas. Methods available to manage ticks and Lyme disease include human self-protection techniques, manipulation of habitats and hosts species populations, biological control, and pesticide applications. The diversity of available techniques allows selection of approaches to minimize environmental effects by (1) emphasizing personal protection techniques, (2) carefully targeting management efforts to maximize efficiency, and (3) integrating environmentally benign techniques to improve management while avoiding broad-scale environmentally destructive approaches. The environmental effects of Lyme disease depend, to a large extent, on the methods chosen to minimize human exposure to infected ticks. Conservation biologists can help design tick management programs that effectively lower the incidence of human Lyme disease while simultaneously minimizing negative effects on natural populations.
Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.
It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360
Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela
Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.
Kala, Zdeněk; Marek, Filip; Válek, Vlastimil A; Bartušek, Daniel
Surgery of Crohns disease is an important part of the general treatment algorithm. The role of surgery is changing with the development of conservative procedures. The recent years have seen the return to early treatment of patients with Crohns disease. Given the character of the disease and its intestinal symptoms, a specific approach to these patients is necessary, especially regarding the correct choice of surgery. The paper focuses on the luminal damage of the small and large intestine including complications of the disease. We describe the individual indications for a surgical solution, including the choice of anastomosis or multiple / repeated surgeries.
The treatment of inflammatory rheumatic diseases, such as rheumatoid arthritis, spondylitis ankylosans and systemic lupus erythematosus, is improving continuously. This has lead to an increasing number of young patients with a wish to have children. Greater insight into the course of rheumatic diseases during pregnancy and post partum has enabled optimized support for women with rheumatic diseases wishing to have children. To ensure a favorable outcome, pregnancy should be started during a period of disease stability and should be monitored closely. A careful assessment of possible risks and the justified use of antirheumatic drugs before, during and after pregnancy are key issues for success.
Kawasaki, Tomisaku; Naoe, Shiro
We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material.
Administration Connect with Wilson Disease Association Send Email Physician Contacts List of Physicians and Institutions in Your Area View Contacts Support Contacts Individuals who can offer Support ...
Densmore, Christine L; Green, David Earl
The development and refinement of amphibian medicine comprise an ongoing science that reflects the unique life history of these animals and our growing knowledge of amphibian diseases. Amphibians are notoriously fastidious in terms of captive care requirements, and the majority of diseases of amphibians maintained in captivity will relate directly or indirectly to husbandry and management. Investigators have described many infectious and noninfectious diseases that occur among various species of captive and wild amphibians, and there is considerable overlap in the diseases of captive versus free-ranging populations. In this article, some of the more commonly reported infectious and noninfectious diseases as well as their etiological agents and causative factors are reviewed. Some of the more common amphibian diseases with bacterial etiologies include bacterial dermatosepticemia or "red leg syndrome," flavobacteriosis, mycobacteriosis, and chlamydiosis. The most common viral diseases of amphibians are caused by the ranaviruses, which have an impact on many species of anurans and caudates. Mycotic and mycotic-like organisms cause a number of diseases among amphibians, including chytridiomycosis, zygomycoses, chromomycoses, saprolegniasis, and ichthyophoniasis. Protozoan parasites of amphibians include a variety of amoeba, ciliates, flagellates, and sporozoans Common metazoan parasites include various myxozoans, helminths (particularly trematodes and nematodes), and arthropods. Commonly encountered noninfectious disease etiologies for amphibians include neoplasia, absolute or specific nutritional deficiencies or overloads, chemical toxicities, and inadequate husbandry or environmental management.
... Prognosis Clinical Trials Organizations Publications Definition Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor ...
Rees, David C; Williams, Thomas N; Gladwin, Mark T
Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease.
Hodes, Richard J; Sierra, Felipe; Austad, Steven N; Epel, Elissa; Neigh, Gretchen N; Erlandson, Kristine M; Schafer, Marissa J; LeBrasseur, Nathan K; Wiley, Christopher; Campisi, Judith; Sehl, Mary E; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S; Halter, Jeffrey B; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A; Barzilai, Nir; Hurria, Arti; Hunt, Peter W
It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. © 2016 New York Academy of Sciences.
Vann, Kiara T; Xiong, Zhi-Gang
Neurodegenerative diseases are devastating conditions that lead to progressive degeneration of neurons. Neurodegeneration may result in ataxia, dementia, and muscle atrophies, etc. Despite enormous research efforts that have been made, there is lack of effective therapeutic interventions for most of these diseases. Optogenetics is a recently developed novel technique that combines optics and genetics to modulate the activity of specific neurons. Optogenetics has been implemented in various studies including neuropsychiatric disorders and neurodegenerative diseases. This review focuses on the recent advance in using this technique for the studies of common neurodegenerative diseases. PMID:27186317
Acosta, Lealani Mae Y
Although humans have long valued creativity, the generation of such innovation is still incompletely understood. Looking at the healthy brain, researchers have localized certain parts for a basic understanding of these mechanisms. By researching the brain affected by neurological disease, scientists have observed unique manifestations of creativity, such as in frontotemporal lobar degeneration, Alzheimer's disease, Parkinson's disease and parkinsonian spectrum disorders, and stroke, which help clarify these creative underpinnings. Incorporating both healthy and disease models of cerebral functioning, neurological and neuroscientific research from recent years has built on established theories and expanded current knowledge.
Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan
Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.
Shaffer, Eldon A
Gallstone disease is common: >700,000 cholecystectomies and costs of approximately 6.5 billion dollars annually in the U.S. The burden of disease is epidemic in American Indians (60-70%); a corresponding decrease occurs in Hispanics of mixed Indian origin. Ten to fifteen per cent of white adults in developed countries harbour gallstones. Frequency is further reduced in Black Americans, East Asia and sub-Saharan Africa. In developed countries, cholesterol gallstones predominate; 15% are black pigment. East Asians develop brown pigment stones in bile ducts, associated with biliary infection or parasites, or in intrahepatic ducts (hepatolithiasis). Certain risk factors for gallstones are immutable: female gender, increasing age and ethnicity/family (genetic traits). Others are modifiable: obesity, the metabolic syndrome, rapid weight loss, certain diseases (cirrhosis, Crohn's disease) and gallbladder stasis (from spinal cord injury or drugs like somatostatin). The only established dietary risk is a high caloric intake. Protective factors include diets containing fibre, vegetable protein, nuts, calcium, vitamin C, coffee and alcohol, plus physical activity.
Nanhoe-Mahabier, Wandana; de Laat, Karlijn F; Visser, Jasper E; Zijlmans, Jan; de Leeuw, Frank-Erik; Bloem, Bastiaan R
Optimal management of chronic diseases not only requires tackling of the primary disease processes, but also necessitates timely recognition and treatment of comorbid conditions. In this article, we illustrate this two-pronged approach for two common age-related disorders: Parkinson disease (PD) and cerebrovascular disease (CVD). We first discuss the pathophysiological mechanisms that could provide a link between PD and CVD. Patients with PD have a series of risk factors that could promote development of CVD, but also have several protective factors. We then review the available clinical, radiological and neuropathological evidence to support an association between these two conditions. We conclude by discussing the potential implications for clinical practice, highlighting how comorbid CVD could alter the clinical presentation of PD and reviewing the possibilities for prevention and secondary prophylaxis. Additional research will be needed to fully evaluate the prevalence and clinical relevance of comorbid CVD in PD. Pending further evidence, we recommend that cerebral neuroimaging should be considered if patients with initially uncomplicated PD develop-either acutely or chronically-prominent and/or treatment-resistant gait impairment, postural instability, depression, cognitive decline, or urinary incontinence. Finding comorbid CVD in such patients could have prognostic implications, and could necessitate treatment to arrest further progression of CVD.
Rastogi, Anjay; Linden, Ariel; Nissenson, Allen R
Chronic kidney disease (CKD) is a growing health problem of epidemic proportions both in the United States and worldwide. The care of CKD patients, before and after starting dialysis, remains highly fragmented resulting in suboptimal clinical outcomes and high costs, creating a high burden of disease on patients and the health care system. Disease management (DM) is an approach to coordinating care for this complex population of patients that has the promise of improving outcomes and constraining costs. For CKD patients not yet on dialysis, the major goals of a DM program are (1) early identification of CKD patients and therapy to slow the progression of CKD, (2) identification and management of the complications of CKD per se, (3) identification and management of the complications of comorbid conditions, and (4) smooth transition to renal replacement therapy. For those CKD patients on dialysis, focused attention on avoidable hospitalizations is a key to a successful DM program. Multidisciplinary collaboration among physicians (nephrologist, primary care physician, cardiologist, endocrinologist, vascular surgeons, and transplant physicians) and participating caregivers (nurse, pharmacist, social worker, and dietician) is critical as well. There are several potential barriers to the successful implementation of a CKD/end-stage renal disease DM program, including lack of awareness of the disease state among patients and health care providers, late identification and referrals to a nephrologist, complex fragmented care delivered by multiple providers in many different sites of care, and reimbursement that does not align incentives for all involved. Recent experience suggests that these barriers can be overcome, with DM becoming a promising approach for improving outcomes for this vulnerable population.
Jensen, Mark; Cox, Alexander P; Chaudhry, Naveed; Ng, Marcus; Sule, Donat; Duncan, William; Ray, Patrick; Weinstock-Guttman, Bianca; Smith, Barry; Ruttenberg, Alan; Szigeti, Kinga; Diehl, Alexander D
We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer's disease, multiple sclerosis, and stroke. ND is implemented in OWL 2 and currently has more than 450 terms that refer to and describe various aspects of neurological diseases. ND directly imports the development version of OGMS, which uses BFO 2. Term development in ND has primarily extended the OGMS terms 'disease', 'diagnosis', 'disease course', and 'disorder'. We have imported and utilize over 700 classes from related ontology efforts including the Foundational Model of Anatomy, Ontology for Biomedical Investigations, and Protein Ontology. ND terms are annotated with ontology metadata such as a label (term name), term editors, textual definition, definition source, curation status, and alternative terms (synonyms). Many terms have logical definitions in addition to these annotations. Current development has focused on the establishment of the upper-level structure of the ND hierarchy, as well as on the representation of Alzheimer's disease, multiple sclerosis, and stroke. The ontology is available as a version-controlled file at http://code.google.com/p/neurological-disease-ontology along with a discussion list and an issue tracker. ND seeks to provide a formal foundation for the representation of clinical and research data
Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.
CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered
... Ping Lu Validation of cis-Tau as a Therapeutic Target for Alzheimer's Disease 2014 Tsuneya Ikezu Exosome Pathway as a ... 2010 Marco Prado The Prion Protein as a Therapeutic Target in Alzheimer's Disease 2007 Michael Vitek Novel Therapeutic Reduces Abeta ...
Clinical presentation of Wilson disease can vary widely; therefore diagnosis is not always straightforward. Wilson disease is not just a disease of children and young adults, but may present at any age. The key features of Wilson disease are liver disease and cirrhosis, neuropsychiatric disturbances, Kayser-Fleischer rings, and acute episodes of hemolysis, often in association with acute liver failure. Diagnosis is particularly difficult in children and in adults presenting with active liver disease. None of the available laboratory tests is perfect and may not be specific for Wilson disease. A detailed neurologic examination is required for all cases. Neuroimaging and electrophysiologic methods are helpful. To overcome the diagnostic challenge, several clinical signs (Kayser-Fleischer rings, neurologic symptoms) and laboratory features (copper in serum, urine, liver; serum ceruloplasmin; genetic testing) are scored 0 (absent) to 2 (present) and the Leipzig score is calculated. If the score is ≥4, the diagnosis of Wilson disease is very likely. For asymptomatic siblings of index patients, mutation analysis is the most reliable approach. © 2017 Elsevier B.V. All rights reserved.
Keeling, Richard P.
Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…
Corn viruses are important disease agents worldwide that can be difficult to identify and diagnose. Previously undescribed viruses of corn also emerge periodically and their distributions and importance changes over time. The Compendium of Corn Diseases is a valuable tool for pre-diagnosis of diseas...
Lee, Noel M; Brady, Carla W
Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy. PMID:19248187
David R. Houston; James T. O' Brien
Beech bark disease causes significant mortality and defect in American beech, Fagus grandifolia (Ehrh.). The disease results when bark, attacked and altered by the beech scale, Cryptococcus fagisuga Lind., is invaded and killed by fungi, primarily Nectria coccinea var. faginata Lohman, Watson, and Ayers, and sometimes N. galligena Bres.
... Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, and the majority are not severe. Celiac disease, however, is a serious condition caused by a permanent intolerance for gluten--a protein found in wheat, rye, and barley. ...
Prakoura, Niki; Chatziantoniou, Christos
Chronic kidney disease is an incurable to date pathology, with renal replacement therapy through dialysis or transplantation being the only available option for end-stage patients. A deeper understanding of the molecular mechanisms governing the progression of kidney diseases will permit the identification of unknown mediators and potential novel markers or targets of therapy which promise more efficient diagnostic and therapeutic applications. Over the last years, periostin was established by several studies as a novel key player in the progression of renal disease. Periostin is de novo expressed focally by the injured kidney cells during the development of renal disease. In diverse cohorts of renal disease patients, the expression levels of periostin in the kidney and urine were highly correlated with the stage of the pathology and the decline of renal function. Subsequent studies in animal models demonstrated that periostin is centrally involved in mediating renal inflammation and fibrosis, contributing to the deterioration of renal structure and function. Genetic or pharmaco-genetic inhibition of periostin in animal models of renal disease was efficient in arresting the progression of the pathology. This review will summarize the recent advances on periostin in the field of kidney diseases and will discuss its utility of as a novel target of therapy for chronic kidney disease.
Dashti, Maseumeh; Chitsaz, Ahmad
Hallervorden-Spatz disease (HSD) is a rare disorder characterized by progressive extrapyramidal dysfunction and dementia. Hallervorden and Spatz first described the disease, in 1922 as a form of familial brain degeneration characterized by iron deposition in the brain. Here we present four HSD cases with different clinical pictures. PMID:25317409
Mukherjee, Pranab K; Sendid, Boualem; Hoarau, Gautier; Colombel, Jean-Frédéric; Poulain, Daniel; Ghannoum, Mahmoud A
New insights gained through the use of state-of-the-art technologies, including next-generation sequencing, are starting to reveal that the association between the gastrointestinal tract and the resident mycobiota (fungal community) is complex and multifaceted, in which fungi are active participants influencing health and disease. Characterizing the human mycobiome (the fungi and their genome) in healthy individuals showed that the gastrointestinal tract contains 66 fungal genera and 184 fungal species, with Candida as the dominant fungal genera. Although fungi have been associated with a number of gastrointestinal diseases, characterization of the mycobiome has mainly been focused on patients with IBD and graft-versus-host disease. In this Review, we summarize the findings from studies investigating the relationship between the gut mycobiota and gastrointestinal diseases, which indicate that fungi contribute to the aggravation of the inflammatory response, leading to increased disease severity. A model explaining the mechanisms underlying the role of the mycobiota in gastrointestinal diseases is also presented. Our understanding of the contribution of the mycobiota to health and disease is still in its infancy and leaves a number of questions to be addressed. Answering these questions might lead to novel approaches to prevent and/or manage acute as well as chronic gastrointestinal disease.
Szczepanek-Parulska, Ewelina; Hernik, Aleksandra; Ruchała, Marek
Anemia is a frequent, although often underestimated, clinical condition accompanying thyroid diseases. In spite of the fact that anemia and thyroid dysfunction often occur simultaneously, the causative relationship between these two disorders remains ambiguous. Thyroid hormones stimulate erythrocytes precursors proliferation directly, as well as via erythropoietin production enhancement, whereas iron-deficient anemia negatively influences thyroid hormonal status. Thus, different forms of anemia might emerge in the course of thyroid dysfunction. In fact, normocytic anemia is most common, while macrocytic or microcytic anemia occur less frequently. Anemia in hypothyroidism might result from bone marrow depression, decreased erythropoietin production, comorbid diseases, or concomitant iron, vitamin B12 or folate deficiency. Altered iron metabolism and oxidative stress may contribute to anemia in hyperthyroidism. The risk of anemia in autoimmune thyroid disease (AITD) may be posed by pernicious anemia and atrophic gastritis, celiac disease, autoimmune hemolytic syndrome, or rheumatic disorders. The simultaneous occurrence of anemia and thyroid disease, as well as their close relation, make the diseases an important clinical problem. The aim of the study is to provide a comprehensive review summarizing data on the prevalence, potential mechanisms, and therapy of anemia in the course of thyroid diseases from the clinical and pathogenetic perspective. Thyroid dysfunction and autoimmune thyroid disease should be considered in differential diagnosis of treatment-resistant or refractory anemia, as well as in case of increased red blood cell distribution width (RDW). Of note is that the presence of AITD itself, independently from thyroid hormonal status, might affect hemoglobin level.
Nakhoul, Hani; Ke, Jiangwei; Zhou, Xiang; Liao, Wenjuan; Zeng, Shelya X; Lu, Hua
Ribosomopathies are diseases caused by alterations in the structure or function of ribosomal components. Progress in our understanding of the role of the ribosome in translational and transcriptional regulation has clarified the mechanisms of the ribosomopathies and the relationship between ribosomal dysfunction and other diseases, especially cancer. This review aims to discuss these topics with updated information. PMID:25512719
Keeling, Richard P.
Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…
Diny, Nicola L; Rose, Noel R; Čiháková, Daniela
Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.
Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela
Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445
... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ...
Naik, Haley B.; Cowen, Edward W.
SYNOPSIS The inflammatory pustular dermatoses constitute a spectrum of non-infectious conditions ranging from localized involvement to generalized disease with associated acute systemic inflammation and multi-organ involvement. Despite the variability in extent and severity of cutaneous presentation, each of these diseases is characterized by non-infectious neutrophilic intra-epidermal microabscesses. Many share systemic findings including fever, elevated inflammatory markers, inflammatory bowel disease and/or osteoarticular involvement, suggesting potential common pathogenic links (Figure 1). The recent discoveries of several genes responsible for heritable pustular diseases have revealed a distinct link between pustular skin disease and regulation of innate immunity. These genetic advances have led to a deeper exploration of common pathways in pustular skin disease and offer the potential for a new era of biologic therapy which targets these shared pathways. This chapter provides a new categorization of inflammatory pustular dermatoses in the context of recent genetic and biologic insights. We will discuss recently-described monogenic diseases with pustular phenotypes, including deficiency of IL-1 receptor antagonist (DIRA), deficiency of the IL-36 receptor antagonist (DITRA), CARD14-associated pustular psoriasis (CAMPS), and pyogenic arthritis, pyoderma gangrenosum, acne (PAPA). We will then discuss how these new genetic advancements may inform how we view previously described pustular diseases, including pustular psoriasis and its clinical variants, with a focus on historical classification by clinical phenotype. PMID:23827244
Mummy Berry is the most important disease of blueberry worldwide. It has not been as severe in the southeastern U.S. on rabbiteye blueberry has it is in other areas on highbush blueberry. However, it has caused severe losses on some farms in some years. This poster gives the symptoms, disease cyc...
Suggests that doctors may one day be able to identify healthy people who will develop Alzheimer's disease. Discusses recent studies in which characteristics of a person's writing early in life appear to predict the disease, and brain scans can highlight changes that may precede dementia. (CCM)
Bechtel, Kendra; Geschwind, Michael D
This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind et al., 2010a; Paterson et al., 2012b), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care. Copyright © 2013 Elsevier Ltd. All rights reserved.
Extensive public-private partnerships, including the National Institutes of Health (NIH) and the rare diseases community, which is seeing a renewed industry interest in smaller niche markets, have resulted in an increase of interventions for rare diseases. Significant collaborative efforts are required among the pharmaceutical industry, foundations, patient-advocacy groups, academic and government investigators and funding programs, regulatory scientists, and reimbursement agencies to meet the unmet diagnostic and treatment needs for approximately 25 million people in the United States with 7,000 rare diseases. The expanding role and outreach activities of patient-advocacy groups have increased public awareness. In the United States, a rare disease is defined as a disorder or condition with a prevalence of < 200,000 people. In 2011, the NIH provided > $3.5 billion for rare diseases research, including $750 million for orphan product development activities, nearly 11.4% of the NIH research budget. Several research institutes and centers of the NIH, including the National Center for Advancing Translational Sciences, have initiated varied translational research efforts to address the absence of preclinical and clinical data required for regulatory review purposes. Clinicians can expect to see significant increases in requests from patients and their families to participate in patient registries and natural history or observational studies to gather specific information from a larger pool of patients on the progression of the disease or response to treatments. An expanding emphasis on rare diseases provides hope for the millions of patients with rare diseases. PMID:23880676
Bokor, Julie; Joseph, Drew; Darwiche, Houda
One of the crosscutting concepts in science is cause and effect. A disease model can provide understanding of cause and effect, as teachers scaffold student thinking from molecular changes in the DNA to visible traits in the organism. The project described in this article uses Pompe disease, a rare recessive disorder, as a model of cause and…
Barabas, Gabor, Ed.
This special edition explores the serious genetic disorder, Lesch-Nyhan Disease (LND), which is characterized by severe dystonia, spasticity, speech impairment, renal disease, varying degrees of cognitive deficit, and, especially, compulsive self-injury. The information provided is based on experience at the Matheny School and Hospital (New…
Bechtel, Kendra; Geschwind, Michael D.
This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind, Kuo et al. 2010; Paterson, Torres-Chae et al. 2012), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care. PMID:23906487
Fayssoil, A; Nardi, O
Myotonic dystrophy type 1 (Steinert disease) is an autosomal dominant disease characterized by myotonia and multiorgan damage. This latter is the most frequent of the adult-onset muscular dystrophies. Heart involvement is often associated, including cardiomyopathies, atrioventricular block, atrial and ventricular arrhythmias.
Pompe's disease (glycogen storage disease type II) is a lysosomal storage disorder resulting from a deficiency in alpha 1, 4 glucosidase. Prognosis is poor because of heart involvement. Treatment in adult form relies on supportive therapy. Enzyme replacement therapy with recombinant human alpha glucosidase remains a hope for patients.
Bokor, Julie; Joseph, Drew; Darwiche, Houda
One of the crosscutting concepts in science is cause and effect. A disease model can provide understanding of cause and effect, as teachers scaffold student thinking from molecular changes in the DNA to visible traits in the organism. The project described in this article uses Pompe disease, a rare recessive disorder, as a model of cause and…
Jenkins, C. David
Reviews epidemiological studies of cardiovascular diseases especially coronary heart disease (CHD), to document their major public health importance, changes in mortality during this century, and international comparisons of trends. Finds major risk factors for CHD are determined in large part by psychosocial and behavioral mechanisms. Asserts…
Leaf blights and spots caused by fungi are some of the most destructive diseases of corn in the US and around the world. Correct identification of the disease is very important in determining the best means of control. For example, gray leaf spot of maize can be caused by one of at least two species...
Knowledge of the nutritional physiology of nickel (Ni) is relatively meager. Accumulating evidence indicates that attention to management of Ni nutrition may potentially benefit yield, quality, disease resistance, and disease control of certain crop species, most notably those transporting ureido-ni...
Magel, G D; Mendoza, N; Digiorgio, C M; Haitz, K A; Lapolla, W J; Tyring, S K
Vaccines have been a cornerstone in medicine and public health since their inception in the 18th century by Edward Jenner. Today, greater than 20 vaccines are used worldwide for the prevention of both viral and bacterial diseases. This article will review the vaccines used for the following dermatological diseases: smallpox, measles, mumps, rubella, chickenpox, shingles, and human papillomavirus.
Del-Río Camacho, G; Leal Orozco, A; Camino López, M; Pérez-Tejerizo, G; Lara Capellán, J I
A 14-year-old boy manifested acute abdominal pain, vomiting, high temperature and diarrhea. He also underwent increasing hyponatremia and hyperkalemia after appendectomy. Further testing confirmed Addison disease. The serum adrenal antibody test was positive, and other autoimmune diseases were excluded.
Carratalà, Jordi; Alcamí, José; Cordero, Elisa; Miró, José M; Ramos, José Manuel
There has been a significant increase in research activity into infectious diseases in Spain in the last few years. The Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) currently has ten study groups, with the cooperation of infectious diseases specialists and microbiologists from different centres, with significant research activity. The program of Redes Temáticas de Investigación Cooperativa en Salud (Special Topics Cooperative Health Research Networks) is an appropriate framework for the strategic coordination of research groups from the Spanish autonomous communities. The Spanish Network for Research in Infectious Diseases (REIPI) and the Network for Research in AIDS (RIS) integrate investigators in Infectious Diseases from multiple groups, which continuously perform important research projects. Research using different experimental models in infectious diseases, in numerous institutions, is an important activity in our country. The analysis of the recent scientific production in Infectious Diseases shows that Spain has a good position in the context of the European Union. The research activity in Infectious Diseases carried out in our country is a great opportunity for the training of specialists in this area of knowledge.
Wadhawan, Manav; Anand, Anil C.
Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895
Strecker, Karl; Schwarz, Johannes
Parkinson's disease (PD) is the second most common neurodegenerative disease. The prevalence is increasing with age and averages approximately 0.3% in the entire population. The clinical picture is dominated by the cardinal motor symptoms such as tremor at rest, bradykinesia, muscular rigidity, stooped posture and postural instability. Psychiatric comorbidity is common, comprising dementia, depression, anxiety and psychosis. Although many drugs have been developed and introduced into the market to provide symptomatic treatment, there is still no cure for PD and not even solid evidence for disease-modifying strategies. In addition, motor complications in advanced stages of the disease, side effects of the dopaminergic therapy, and non-motor symptoms remain huge challenges during long-term therapy. Thus, new therapeutic agents are desperately needed. Here, we describe current therapies and possible future developments that we hope will contribute to sustaining quality of life in patients suffering from Parkinson's disease for many years.
Flores-Terry, M Á; García-Arpa, M; Llamas-Velasco, M; Mendoza-Chaparro, C; Ramos-Rodríguez, C
Darier disease is an autosomal-dominant inherited condition caused by mutation of a gene, which produces a protein involved in calcium channel regulation. The disease has a variety of manifestations and lacks consistent genotype-phenotype correlations. Acral hemorrhagic Darier disease causes macules, papules, vesicles and/or hemorrhagic blisters on the extremities. Other classic signs of the disease may be present in the same patient or relatives. Histopathology reveals dyskeratosis and suprabasal acantholysis with hemorrhagic lacunae. We report 3 new cases of this type of Darier disease triggered by injuries. Response to retinoid therapy was good. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Converse, K.A.; Green, D.E.; Majumdar, S.K.; Huffman, J.E.; Brenner, F.J.; Panah, A.I.
Few diseases are reported in salamanders. Two notable exceptions are infections by Ranavirus and Ichthyophonus. Except for mortality events associated with ranaviruses in tiger salamanders (Ambystoma tigrinum) and spotted salamanders (A. maculatum), dieoffs of salamanders are rarely detected or reported. Diseases presented in this chapter are those encountered in free-living salamanders of the United States and Canada. A few additional diseases that are occasionally seen in captive and zoo animals have been reviewed by Green (2001). This chapter on Diseases of Salamanders will address five common infectious diseases of free-living larval and adult salamanders: Ranavirus (iridovims) infection, chytrid fungal infection, ichthyophoniasis, Clinostomum metacercaria, chiggers. Many helminthic parasites infect salamanders, but with few exceptions, these infections are unlikely to cause illness (morbidity) or death (mortality). Readers are referred to parasitology texts for a review of protozoan, helminthic and ectoparasitic organisms of amphibians (Flynn, 1973; Poynton and Whitaker, 2001).
Increasing epidemiological evidence suggests that maternal nutrition and environmental exposure early in development play an important role in susceptibility to disease in later life. In addition, these disease outcomes seem to pass through subsequent generations. Epigenetic modifications provide a potential link between the nutrition status during critical periods in development and changes in gene expression that may lead to disease phenotypes. An increasing body of evidence from experimental animal studies supports the role of epigenetics in disease susceptibility during critical developmental periods, including periconceptional period, gestation, and early postnatal period. The rapid improvements in genetic and epigenetic technologies will allow comprehensive investigations of the relevance of these epigenetic phenomena in human diseases. PMID:24527414
John, Seby; Hajj-Ali, Rula A
Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics.
Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis
Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485
Altashina, M V; Troshina, E A; Sviridenko, N Yu; Latkina, N V
Thyvrotoxicosis is a clinical syndrome related to the negative influence of excess thyroid hormones. Its main cause in young and mid-aged patients is Graves' disease. Therapy with thyrostatic medications are most frequently used in this country as the primary method for the treatment of this disease. The experience of both Russian and foreign authors indicate that 70% of Graves' disease cases require radical treatment. Special caution is needed in the choice of therapies for young women planning pregnancy. Graves'disease developing prior to pregnancy is a contraindication for it because of high risk of its interruption and complications. Such women should be recommended careful contraception. A 27-year-old patient with Graves' disease is described who planned pregnancy and received conservative therapy for an unnecessary, long time. Therapy of thyrotoxicosis during pregnancy and after it is described.
Diseases of echinoderms are poorly documented. Most reports concern biotic diseases caused by animal agents. While parasites on echinoderms have been described in increasing numbers of papers for more than one century, the host-parasite relationship and the effects of parasitism on echinoderm life-cycles were rarely considered. The parasitic fauna differs markedly according to the echinoderm group concerned, depending on various factors such as feeding-habits or symbiogenesis. Microorganismic diseases undoubtedly occur in echinoderms but they were not investigated until recently. Microorganisms have frequently been assumed to act as agents causing mass mortalities. As for stress-caused diseases, the only — and very preliminary — data available concern almost exclusively those induced by pollution. Since echinoderms are major components of benthic ecosystems, echinoderm diseases may be expected to exert prominent ecological effects.
Diseases of the endocrine system can be classified according to the prevalence into two categories: very frequent endocrinopathies, which affect a population of several millions in Germany and include diabetes mellitus, endemic goiter, osteoporosis and obesity. On the other hand there are a large number of rare endocrine diseases which share the paradox of other rare diseases: they are also often falsely suspected in patients who are not affected but at the same time there are sometimes long delays in diagnosis in those who do have the disease. In cases of adrenal insufficiency, absolute glucocorticoid deficiency can progress to an adrenal crisis which is fatal if not treated. Patients with de Quervain thyroiditis often suffer from prolonged episodes of fever with tender, diffuse goiter and neck pain. Pheochromocytomas should be recognized early in the course of disease because of life-threatening cardiovascular complications. This article highlights the essential characteristics in order to increase awareness.
Nyhan, William L
The first description of Lesch-Nyhan disease was in 1964; the first two patients were seen in 1963. The disease has caught the imagination of a variety of clinicians and scientists. The clinical picture is striking, combining spasticity, involuntary movements, and cognitive retardation with self-injurious behavior and the manifestations of gout. Biochemically, the overproduction of uric acid--the end product of purine metabolism--was, when measured, the largest ever seen. The disease is now well understood on a molecular basis. Enzyme analysis and mutational analysis have made available a full range of genetic testing, including diagnosis, carrier detection, and prenatal diagnosis. Therapy with allopurinol has been effective for those manifestations the disease shares with gout. Treatment for the neurological and behavioral features of the disease remains elusive.
Coune, Philippe G; Schneider, Bernard L; Aebischer, Patrick
With the recent development of effective gene delivery systems, gene therapy for the central nervous system is finding novel applications. Here, we review existing viral vectors and discuss gene therapy strategies that have been proposed for Parkinson's disease. To date, most of the clinical trials were based on viral vectors to deliver therapeutic transgenes to neurons within the basal ganglia. Initial trials used genes to relieve the major motor symptoms caused by nigrostriatal degeneration. Although these new genetic approaches still need to prove more effective than existing symptomatic treatments, there is a need for disease-modifying strategies. The investigation of the genetic factors implicated in Parkinson's disease is providing precious insights in disease pathology that, combined with innovative gene delivery systems, will hopefully offer novel opportunities for gene therapy interventions to slow down, or even halt disease progression.
Watanabe, Masashi; Hatakeyama, Shigetsugu
Ubiquitination is one of the posttranslational modifications that regulates a number of intracellular events including signal transduction, protein quality control, transcription, cell cycle, apoptosis and development. The ubiquitin system functions as a garbage machine to degrade target proteins and as a regulator for several signalling pathways. Biochemical reaction of ubiquitination requires several enzymes including E1, E2 and E3, and E3 ubiquitin ligases play roles as receptors for recognizing target proteins. Most of the tripartite motif (TRIM) proteins are E3 ubiquitin ligases. Recent studies have shown that some TRIM proteins function as important regulators for a variety of diseases including cancer, inflammatory diseases, infectious diseases, neuropsychiatric disorders, chromosomal abnormalities and developmental diseases. In this review, we summarize the involvement of TRIM proteins in the aetiology of various diseases.
Wood, Joanne M; Black, Alex A
As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits.
Yuen, Noah K; Ananthakrishnan, Shubha; Campbell, Michael J
Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1.73 m2). Since the 1990s, improving medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs has expanded the treatment options for patients with rHPT, but some patients still require a parathyroidectomy to mitigate the sequelae of this challenging disease. PMID:27479950
Puri, Basant K; Monro, Jean A; Julu, Peter O O; Kingston, Michele C; Shah, Mussadiq
Neurological involvement in Lyme disease has been reported to include meningitis, cranial neuropathy and radiculoneuritis. While it is known that in some cases of asceptic meningitis patients may develop hyperosmia, the association between hyperosmia and Lyme disease has not previously been studied. Objective To carry out the first systematic study to ascertain whether hyperosmia is also a feature of Lyme disease. Method A questionnaire regarding abnormal sensory sensitivity in respect of the sense of smell was administered to 16 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex and body mass. None of the 34 subjects was suffering from migraine. Eight (50%) of the Lyme patients and none (0%) of the controls suffered from hyperosmia (p=0.0007). Conclusion This first systematic controlled study showed that Lyme disease is associated with hyperosmia.
Annus, Ádám; Csáti, Anett; Vécsei, László
The transmissible spongiform encephalopathies, which include Creutzfeldt-Jakob disease, are fatal neurodegenerative disorders caused by the pathological accumulation of abnormal prion protein. The diagnosis of Creutzfeldt-Jakob disease is complex. The electroencephalogram, magnetic resonance imaging, lumbar puncture and genetic testing findings can help in the differential diagnosis of rapidly progressive dementia. There has recently been considerable debate as to whether proteins involved in the development of neurodegenerative diseases should be regarded as prions or only share prion-like mechanisms. Two recent reports described the detection of abnormal prion protein in the nasal mucosa and urine of patients with Creutzfeldt-Jakob disease. These findings raise major health concerns regarding the transmissibility of human prion diseases. We set out to address this neurological hot topic and to draw conclusions on the basis of what is known in the literature thus far.
Shaman, J. L.
Dynamic models of infectious disease systems abound and are used to study the epidemiological characteristics of disease outbreaks, the ecological mechanisms affecting transmission, and the suitability of various control and intervention strategies. The dynamics of disease transmission are non-linear and consequently difficult to forecast. Here, we describe combined model-inference frameworks developed for the prediction of infectious diseases. We show that accurate and reliable predictions of seasonal influenza outbreaks can be made using a mathematical model representing population-level influenza transmission dynamics that has been recursively optimized using ensemble data assimilation techniques and real-time estimates of influenza incidence. Operational real-time forecasts of influenza and other infectious diseases have been and are currently being generated.
Heneka, Michael T; Carson, Monica J; El Khoury, Joseph; Landreth, Gary E; Brosseron, Frederic; Feinstein, Douglas L; Jacobs, Andreas H; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M; Herrup, Karl; Frautschy, Sally A; Finsen, Bente; Brown, Guy C; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C; Town, Terrence; Morgan, Dave; Shinohara, Mari L; Perry, V Hugh; Holmes, Clive; Bazan, Nicolas G; Brooks, David J; Hunot, Stéphane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A; Breitner, John C; Cole, Greg M; Golenbock, Douglas T; Kummer, Markus P
Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
Garnier-Lengliné, Hélène; Cerf-Bensussan, Nadine; Ruemmele, Frank M
Celiac disease is an autoimmune enteropathy, triggered by ingestion of gluten in genetically predisposed individuals. Since the use of anti-transglutaminase and anti-endomysium antibodies in the early 1990s, two main groups of clinical presentation can be identified: patients with a symptomatic form of the disease, and patients with a pauci (a)-symptomatic form detected during the work-up of another autoimmune disease or due to a family history of celiac disease. The prevalence of both forms of the disease is currently estimated between 1/100 and 1/400. Classical form of the disease is characterized by occurrence of diarrhoea, failure to thrive, and abdominal bloating in young infants in the months following gluten introduction. Serological tests show high level of anti-transglutaminase and anti-endomysium antibodies. Until recently, the diagnosis required duodenal biopsies that show villous atrophy. HLA genotype can help for diagnosis: the absence of the HLA-DQ2 or DQ8 alleles has a high negative predictive value. European guidelines recently proposed to reconsider the need for systematic endoscopy in typical symptomatic forms with high level of anti-transglutaminase and positive anti-endomysium. These recommendations are being assessed now. Currently, the gluten-free diet remains the only effective treatment for celiac disease. Children with celiac disease have to exclude from their diet all products containing wheat, barley and rye. Gluten-free diet causes clinical remission within a few weeks, but normalization of the small bowel mucosa and negativity of anti-transglutaminase antibodies are obtained in several months or even years. Gluten-free diet is useful to obtain clinical assessment, but also to prevent long-term complications of celiac disease, mainly osteoporosis, other autoimmune diseases, decreased fertility and cancers.
Beuter, Anne; Vasilakos, Konstantinon
Experimental evidence has shown a plethora of short-term fluctuations in patients with Parkinson's disease. We investigate these transitory events using the concept of dynamical disease. Several examples of short-term fluctuations in tremor are analyzed, and in two cases, other systemic variables (i.e., respiration and blood pressure) are examined as well. A model for tremor, based on negative feedback with delays is proposed, and the transient events are simulated. The theoretical implications of the model suggest that interactions between the central and peripheral loops, as well as interactions between the control loops and other systemic signals, can give rise to transitory events in tremor, both in the pathological and in the normal case.
Background Transcription factors in disease-relevant pathways represent potential drug targets, by impacting a distinct set of pathways that may be modulated through gene regulation. The influence of transcription factors is typically studied on a per disease basis, and no current resources provide a global overview of the relations between transcription factors and disease. Furthermore, existing pipelines for related large-scale analysis are tailored for particular sources of input data, and there is a need for generic methodology for integrating complementary sources of genomic information. Results We here present a large-scale analysis of multiple diseases versus multiple transcription factors, with a global map of over-and under-representation of 446 transcription factors in 1010 diseases. This map, referred to as the differential disease regulome, provides a first global statistical overview of the complex interrelationships between diseases, genes and controlling elements. The map is visualized using the Google map engine, due to its very large size, and provides a range of detailed information in a dynamic presentation format. The analysis is achieved through a novel methodology that performs a pairwise, genome-wide comparison on the cartesian product of two distinct sets of annotation tracks, e.g. all combinations of one disease and one TF. The methodology was also used to extend with maps using alternative data sets related to transcription and disease, as well as data sets related to Gene Ontology classification and histone modifications. We provide a web-based interface that allows users to generate other custom maps, which could be based on precisely specified subsets of transcription factors and diseases, or, in general, on any categorical genome annotation tracks as they are improved or become available. Conclusion We have created a first resource that provides a global overview of the complex relations between transcription factors and disease. As
Martinez, Daniel; Ercole, Cesar E.; Hakky, Tariq S.; Kramer, Andrew; Carrion, Rafael
Peyronie's Disease (PD) remains a challenging and clinically significant morbid condition. Since its first description by François Gigot de la Peyronie, much of the treatment for PD remains nonstandardized. PD is characterized by the formation of fibrous plaques at the level of the tunica albuginea. Clinical manifestations include morphologic changes, such as curvatures and hourglass deformities. Here, we review the common surgical techniques for the management of patients with PD. PMID:22956943
Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M
Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.
DRACUNCULIASIS (GUINEA WORM DISEASE) IS A PARASITIC disease that is limited to remote, rural villages in 13 sub-Saharan African countries that do not have access to safe drinking water. It is one the next diseases targeted for eradication by the World Health Organization. Guinea worm disease is transmitted by drinking water containing copepods (water fleas) that are infected with Dracunculiasis medinensis larvae. One year after human ingestion of infected water a female adult worm emerges, typically from a lower extremity, producing painful ulcers that can impair mobility for up to several weeks. This disease occurs annually when agricultural activities are at their peak. Large proportions of economically productive individuals of a village are usually affected simultaneously, resulting in decreased agricultural productivity and economic hardship. Eradication of guinea worm disease depends on prevention, as there is no effective treatment or vaccine. Since 1986, there has been a 98% reduction in guinea worm disease worldwide, achieved primarily through community-based programs. These programs have educated local populations on how to filter drinking water to remove the parasite and how to prevent those with ulcers from infecting drinking-water sources. Complete eradication will require sustained high-level political, financial and community support. PMID:14970098
Dracunculiasis (guinea worm disease) is a parasitic disease that is limited to remote, rural villages in 13 sub-Saharan African countries that do not have access to safe drinking water. It is one the next diseases targeted for eradication by the World Health Organization. Guinea worm disease is transmitted by drinking water containing copepods (water fleas) that are infected with Dracunculiasis medinensis larvae. One year after human ingestion of infected water a female adult worm emerges, typically from a lower extremity, producing painful ulcers that can impair mobility for up to several weeks. This disease occurs annually when agricultural activities are at their peak. Large proportions of economically productive individuals of a village are usually affected simultaneously, resulting in decreased agricultural productivity and economic hardship. Eradication of guinea worm disease depends on prevention, as there is no effective treatment or vaccine. Since 1986, there has been a 98% reduction in guinea worm disease worldwide, achieved primarily through community-based programs. These programs have educated local populations on how to filter drinking water to remove the parasite and how to prevent those with ulcers from infecting drinking-water sources. Complete eradication will require sustained high-level political, financial and community support.
Invernizzi, Marco; Carda, Stefano; Viscontini, Giovanni Sguazzini; Cisari, Carlo
Patients affected by Parkinson's disease are at a high risk for fractures, mainly of the hip. These fractures are caused by falls due to postural imbalance, neurological impairment and reduced bone mass. The purpose of this study was (1) to investigate the correlations and the pathophysiological mechanisms underlying bone loss in Parkinson's disease and appraise bone loss or fracture risk reduction interventions; (2) to develop a research agenda that informs the design and development of risk reduction strategies. Osteoporosis and osteopenia are very common findings in patients with Parkinson's disease, affecting up to 91% of women and 61% of men. Reduced bone mass in Parkinsonian patients seems to be caused mainly by reduced mobility through a mechanism similar to that observed in other neurological diseases. Endocrine (such as vitamin D deficiency), nutritional and iatrogenic factors also play an important role in bone mass depletion. Female gender, disease duration and severity (Hoehn and Yahr stages III and IV), old age and low body mass index are related to more severe osteoporosis. Vitamin D supplementation and bisphosphonates seem to be effective in reducing the risk of nonvertebral fractures in patients affected by Parkinson's disease. Prevention and evaluation of osteoporosis through bone mass density assessment should be considered in all patients with Parkinson's disease.
Sanz, Joaquín; Xia, Cheng-Yi; Meloni, Sandro; Moreno, Yamir
Current modeling of infectious diseases allows for the study of complex and realistic scenarios that go from the population to the individual level of description. However, most epidemic models assume that the spreading process takes place on a single level (be it a single population, a metapopulation system, or a network of contacts). In particular, interdependent contagion phenomena can be addressed only if we go beyond the scheme-one pathogen-one network. In this paper, we propose a framework that allows us to describe the spreading dynamics of two concurrent diseases. Specifically, we characterize analytically the epidemic thresholds of the two diseases for different scenarios and compute the temporal evolution characterizing the unfolding dynamics. Results show that there are regions of the parameter space in which the onset of a disease's outbreak is conditioned to the prevalence levels of the other disease. Moreover, we show, for the susceptible-infected-susceptible scheme, that under certain circumstances, finite and not vanishing epidemic thresholds are found even at the limit for scale-free networks. For the susceptible-infected-removed scenario, the phenomenology is richer and additional interdependencies show up. We also find that the secondary thresholds for the susceptible-infected-susceptible and susceptible-infected-removed models are different, which results directly from the interaction between both diseases. Our work thus solves an important problem and paves the way toward a more comprehensive description of the dynamics of interacting diseases.
Chronic disease is not a strictly defined term and includes a large number of illnesses ranging from physical to mental impairment. It is estimated that between 10% and 20% of adolescents have a chronic disease. Independence and new relations, acceptance of a new body image and sexuality, career plans and cognitive maturation are core topics in development to adulthood. Chronic disease may interfere with these developmental tasks. Most often there is no specific psychopathology, but the type of impairment, its influence on family life and functioning, age at onset, gender, and other factors will interact with psychosocial maturation. Because of the important role of the family, not only the adolescent patient him/herself, but also parents and siblings need to be included in all major decisions. As hospitalizations may be disruptive they must be planned, taking in account the patient's plans and opinions. Chronic disease may lead to death during the period of adolescence. It is believed that the concept of one's own mortality develops at age 14 to 17 years, a fact that will influence care during the terminal stage of a disease. Whatever the problems and questions raised by the family, the developmental stage of the adolescent has always to be considered when dealing with specific issues of chronic disease. Periodic reassessment of psychosocial development is therefore one of the main tasks of the primary care physician. Counselling will address not only the disease but also the developmental tasks of any teenager.
Cummings, Kristin J; Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-Long; Harley, Russell A; Roggli, Victor L; Hebisawa, Akira; Tallaksen, Robert J; Trapnell, Bruce C; Day, Gregory A; Saito, Rena; Stanton, Marcia L; Suarthana, Eva; Kreiss, Kathleen
Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.
Marizzoni, Moira; Provasi, Stefania; Cattaneo, Annamaria; Frisoni, Giovanni B
Despite the extensive research carried out in the past decades, the current pathophysiological notions of neurodegenerative disease as well as effective treatments to reduce their progression are largely unknown. Alterations of the human microbiota, the plethora of different microscopic organisms that our body hosts, have been linked to neurodegenerative disease risk, onset and progression. This review summarizes the current knowledge on the possible role of microbiota in neurodegenerative disorders and briefly discusses strategies to restore microbiota homeostasis. Preclinical evidences and human cross-sectional studies posit the gut microbiota as a key actor in the Parkinson's disease onset and progression, reporting the presence of a specific gut microbiota profile in association with the modulation of disease and symptoms. Gut microbiota alterations have been correlated with brain disease and peripheral inflammation also in Alzheimer's patients. The interaction between the microbiota and the host is promising to answer clinical questions that have so far escaped clarification with the current pathophysiological notions of health and disease. However, human longitudinal studies starting in the earlier disease phases are needed to understand the causative relation between microbiota and the hallmarks of these neurodegenerative disorders and to develop innovative treatments aimed at preventing or slowing brain damages.
Bright, John J
The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.
Selgelid, Michael J
Bioethics apparently suffers from a misdistribution of research resources analogous to the '10/90' divide in medical research. Though infectious disease should be recognized as a topic of primary importance for bioethics, the general topic of infectious disease has received relatively little attention from the discipline of bioethics in comparison with things like abortion, euthanasia, genetics, cloning, stem cell research, and so on. The fact that the historical and potential future consequences of infectious diseases are almost unrivalled is one reason that the topic of infectious disease warrants more attention from bioethicists. The 'Black Death' eliminated one third of the European population during the 14th Century; the 1989 flu killed between 20 and 100 million people; and, in the 20th Century smallpox killed perhaps three times more people than all the wars of that period. In the contemporary world, epidemics (AIDS, multi-drug resistant turberculosis, and newly emerging infectious diseases such as SARS) continue to have dramatic consequences. A second reason why the topic of infectious disease deserves further attention is that it raises difficult ethical questions of its own. While infected individuals can threaten the health of other individuals and society as a whole, for example, public health care measures such as surveillance, isolation, and quarantine can require the infringement of widely accepted basic human rights and liberties. An important and difficult ethical question asks how to strike a balance between the utilitarian aim of promoting public health, on the one hand, and libertarian aims of protecting privacy and freedom of movement, on the other, in contexts involving diseases that are--to varying degrees--contagious, deadly, or otherwise dangerous. Third, since their burden is most heavily shouldered by the poor (in developing countries), infectious diseases involve issues of justice--which should be a central concern of ethics. I conclude
Gabay, Odile; Clouse, Kathleen A
Osteoarticular diseases, such as arthritis or osteoarthritis, are multifactorial diseases with an underlying genetic etiology that are challenging to study. Genome-Wide Association studies (GWAS) have identified several genetic loci associated with these diseases. Epigenetics is a complex mechanism of chromatin and gene modulation through DNA methylation, histone deacetylation or microRNA, which might contribute to the inheritability of disease. Some of these mechanisms have been studied for decades in other diseases or as part of the aging process, where epigenetic changes seem to play an important role. With the implementation of better technological tools, such as the Illumina next generation sequencing, altered methylation of DNA has been linked to articular diseases and these mechanisms have been shown to regulate metalloprotease (MMP) expression and cartilage matrix integrity. Some miRNA have also been identified and more extensively characterized, such as delineation of the role played by miR-140 in chondrogenesis, followed by the discovery of numerous miRNA potentially involved in the epigenetic regulation of osteoarthritic disease. Histone deacetylases have long been linked to aging, particularly with respect to the Sirtuin family with Sirt1 as the major player. Because aging is the major risk factor for osteoarthritis, the involvement of Sirtuins in the etiology of osteoarthritis has been suggested and investigated. All of these fine regulations together shed new light on cartilage disease pathophysiology. We present in this short review an update of the role of these pathways in articular diseases. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.