Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease

PubMed Central

Karumuthil-Melethil, Subha; Kalburgi, Sahana Nagabhushan; Thompson, Patrick; Tropak, Michael; Kaytor, Michael D.; Keimel, John G.; Mark, Brian L.; Mahuran, Don; Walia, Jagdeep S.; Gray, Steven J.

2016-01-01

GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 ganglioside (GM2) in neuronal tissue. Two of these are due to the deficiency of the heterodimeric (α–β), “A” isoenzyme of lysosomal β-hexosaminidase (HexA). Mutations in the α-subunit (encoded by HEXA) lead to Tay-Sachs disease (TSD), whereas mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). The third form results from a deficiency of the GM2 activator protein (GM2AP), a substrate-specific cofactor for HexA. In their infantile, acute forms, these diseases rapidly progress with mental and psychomotor deterioration resulting in death by approximately 4 years of age. After gene transfer that overexpresses one of the deficient subunits, the amount of HexA heterodimer formed would empirically be limited by the availability of the other endogenous Hex subunit. The present study used a new variant of the human HexA α-subunit, μ, incorporating critical sequences from the β-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP– GM2 complex. We report the design of a compact adeno-associated viral (AAV) genome using a synthetic promoter–intron combination to allow self-complementary (sc) packaging of the HEXM gene. Also, a previously published capsid mutant, AAV9.47, was used to deliver the gene to brain and spinal cord while having restricted biodistribution to the liver. The novel capsid and cassette design combination was characterized in vivo in TSD mice for its ability to efficiently transduce cells in the central nervous system when delivered intravenously in both adult and neonatal mice. This study demonstrates that the modified HexM is capable of degrading long-standing GM2 storage in mice, and it further demonstrates the potential of this novel scAAV vector design to facilitate widespread distribution of the HEXM gene or potentially other similar-sized genes to the

Sandhoff Disease

MedlinePlus

... Coordinating Committees CounterACT Rigor & Transparency Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene ... virus-delivered gene therapy seen in an animal model of Tay-Sachs and Sandhoff diseases for use ...

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

ClinicalTrials.gov

2018-03-15

Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

A double mutation in exon 6 of the [beta]-hexosaminidase [alpha] subunit in a patient with the B1 variant of Tay-Sachs disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ainsworth, P.J.; Coulter-Mackie, M.B.

1992-10-01

The B1 variant form of Tay-Sachs disease is enzymologically unique in that the causative mutation(s) appear to affect the active site in the [alpha] subunit of [beta]-hexosaminidase A without altering its ability to associate with the [beta] subunit. Most previously reported B1 variant mutations were found in exon 5 within codon 178. The coding sequence of the [alpha] subunit gene of a patient with the B1 variant form was examined with a combination of reverse transcription of mRNA to cDNA, PCR, and dideoxy sequencing. A double mutation in exon 6 has been identified: a G[sub 574][yields]C transversion causing a val[submore » 192][yields]leu change and a G[sub 598][yields] A transition resulting in a val[sub 200][yields]met alteration. The amplified cDNAs were otherwise normal throughout their sequence. The 574 and 598 alterations have been confirmed by amplification directly from genomic DNA from the patient and her mother. Transient-expression studies of the two exon 6 mutations (singly or together) in COS-1 cells show that the G[sub 574][yields]C change is sufficient to cause the loss of enzyme activity. The biochemical phenotype of the 574 alteration in transfection studies is consistent with that expected for a B1 variant mutation. As such, this mutation differs from previously reported B1 variant mutations, all of which occur in exon 5. 31 refs., 2 figs., 2 tabs.« less

The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported.

PubMed

Maegawa, Gustavo H B; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T R

2006-11-01

Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal beta-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, beta-hexosaminidase enzyme activity, and mutation analysis was collected. In our cohort of patients, the mean (+/-SD) age of onset of symptoms was 5.3 +/- 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 +/- 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 +/- 5.5 years. The mean age of onset of speech problems was 7.0 +/- 5.6 years, with a mean time of progression to anarthria of 5.6 +/- 5.3 years. Muscle wasting (10.6 +/- 7.4 years), proximal weakness (11.1 +/- 7.7 years), and incontinence of sphincters (14.6 +/- 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence of R178H and R

Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.

PubMed

Frisch, Amos; Colombo, Roberto; Michaelovsky, Elena; Karpati, Mazal; Goldman, Boleslaw; Peleg, Leah

2004-03-01

The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To investigate the genetic history of this mutation in the AJ population, a conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15 homozygotes and 40 heterozygotes for the TSD mutation), suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the insertion was found to be 40+/-12 generations (95% confidence interval: 30-50 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 8th-9th century. This corresponds with the demographic expansion of AJs in central Europe, following the founding of the Ashkenaz settlement in the early Middle Ages. The results are consistent with the geographic distribution of the main TSD mutation, 1278insTATC being more common in central Europe, and with the coalescent times of mutations causing two other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence of a determinant positive selection (heterozygote advantage) over the mutation is provided by a comparison between the estimated age of 1278insTATC and the probability of the current AJ frequency of the mutant allele as a function of its age, calculated by use of a branching-process model. Therefore, the founder effect in a rapidly expanding population arising from a bottleneck provides a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in AJ individuals.

The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

PubMed Central

Maegawa, Gustavo H. B.; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T. R.

2010-01-01

OBJECTIVE Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. METHODS A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, β-hexosaminidase enzyme activity, and mutation analysis was collected. RESULTS In our cohort of patients, the mean (±SD) age of onset of symptoms was 5.3 ± 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 ± 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 ± 5.5 years. The mean age of onset of speech problems was 7.0 ± 5.6 years, with a mean time of progression to anarthria of 5.6 ± 5.3 years. Muscle wasting (10.6 ± 7.4 years), proximal weakness (11.1 ± 7.7 years), and incontinence of sphincters (14.6 ± 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence

GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.

PubMed

Sheth, Jayesh; Datar, Chaitanya; Mistri, Mehul; Bhavsar, Riddhi; Sheth, Frenny; Shah, Krati

2016-07-11

GM2 gangliosidosis-AB variants a rare autosomal recessive neurodegenerative disorder occurring due to deficiency of GM2 activator protein resulting from the mutation in GM2A gene. Only seven mutations in nine cases have been reported from different population except India. Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. Horizontal nystagmus and cherry red spot was detected during ophthalmic examination. MRI of brain revealed putaminal hyperintensity and thalamic hypointensity with some unmyelinated white matter in T2/T1 weighted images. Initially he was suspected having Tay-Sachs disease and finally diagnosed as GM2 gangliosidosis, AB variant due to truncated protein caused by nonsense mutation c.472 G > T (p.E158X) in GM2Agene. Children with phenotypic presentation as GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) and normal enzyme activity of β-hexosaminidase-A and -B in leucocytes need to be investigated for GM2 activator protein deficiency.

Genetics Home Reference: Tay-Sachs disease

MedlinePlus

... NIH Resources (4 links) GeneEd National Human Genome Research Institute National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet National Institute of Neurological ...

A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

PubMed

Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

2009-01-02

Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.

Tay-Sachs disease preconception screening in Australia: self-knowledge of being an Ashkenazi Jew predicts carrier state better than does ancestral origin, although there is an increased risk for c.1421 + 1G > C mutation in individuals with South African heritage.

PubMed

Lew, Raelia; Burnett, Leslie; Proos, Anné

2011-12-01

The Australasian Community Genetics Program provided a preconception screening for Tay-Sachs disease (TSD) to 4,105 Jewish high school students in Sydney and Melbourne over the 12-year period 1995-2007. By correlating the frequencies of mutant HEXA, MIM *606869 (gene map locus 15q23-q24) alleles with subjects' nominated ethnicity (Ashkenazi/Sephardi/Mixed) and grandparental birthplaces, we established that Ashkenazi ethnicity is a better predictor of TSD carrier status than grandparental ancestral origins. Screening self-identified Ashkenazi subjects detected 95% of TSD carriers (carrier frequency 1:25). Having mixed Ashkenazi and non-Ashkenazi heritage reduced the carrier frequency (1:97). South African heritage conveyed a fourfold risk of c.1421 + 1G > C mutation compared with other AJ subjects (odds ratio (OR), 4.19; 95% confidence interval (CI), 1.83-9.62, p = 0.001), but this was the only specific case of ancestral origin improving diagnostic sensitivity over that based on determining Ashkenazi ethnicity. Carriers of c.1278insTATC mutations were more likely to have heritage from Western Europe (OR, 1.65 (95% CI, 1.04-2.60), p = 0.032) and South Eastern Europe (OR, 1.77 (95% CI, 1.14-2.73), p = 0.010). However, heritage from specific European countries investigated did not significantly alter the overall odds of TSD carrier status.

GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed.

PubMed

Smith, Nicholas J; Winstone, Anne Marie; Stellitano, Lesley; Cox, Timothy M; Verity, Christopher M

2012-02-01

To report the demographic, phenotypic, and time-to-diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK-based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay-Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile-onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile-onset Tay-Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile-onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile- and juvenile-onset disease respectively. GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high-risk ethnic groups. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

GM2 gangliosidosis in British Jacob sheep.

PubMed

Wessels, M E; Holmes, J P; Jeffrey, M; Jackson, M; Mackintosh, A; Kolodny, E H; Zeng, B J; Wang, C B; Scholes, S F E

2014-01-01

GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis.

PubMed

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-06-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

PubMed Central

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-01-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

Stem Cell Transplant for Inborn Errors of Metabolism

ClinicalTrials.gov

2017-12-03

Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

Tay-Sachs and Sandhoff Diseases

MedlinePlus

... birth and infant mortality. Solving premature birth Featured articles Accomplishments and lessons learned since the establishment of ... The impact of premature birth on society Featured articles How long should you wait before getting pregnant ...

Learning about Tay-Sachs Disease

MedlinePlus

... New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About ... Genome Exhibition Talking Glossary: English Talking Glossary: Español Issues ... Contacts Media Resources NHGRI-Related News Journal Articles ...

NN′-Diacetylchitobiase activity in Tay–Sachs disease and Sandhoff's disease (Short Communication)

PubMed Central

Stirling, John L.

1974-01-01

In Tay–Sachs disease and Sandhoff's disease respectively, one of the N-acetyl-β-hexosaminidases (form A) or both (forms A and B) are absent, but glycosaminoglycans containing N-acetylhexosamines are not accumulated. The presence of NN′-diacetylchitobiase in livers from patients with these diseases raises the possibility that this new enzyme is involved in the metabolism of glycosaminoglycans rather than the enzymes previously described. PMID:4455225

Hypotonia

MedlinePlus

... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ...

SAChES: Scalable Adaptive Chain-Ensemble Sampling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swiler, Laura Painton; Ray, Jaideep; Ebeida, Mohamed Salah

We present the development of a parallel Markov Chain Monte Carlo (MCMC) method called SAChES, Scalable Adaptive Chain-Ensemble Sampling. This capability is targed to Bayesian calibration of com- putationally expensive simulation models. SAChES involves a hybrid of two methods: Differential Evo- lution Monte Carlo followed by Adaptive Metropolis. Both methods involve parallel chains. Differential evolution allows one to explore high-dimensional parameter spaces using loosely coupled (i.e., largely asynchronous) chains. Loose coupling allows the use of large chain ensembles, with far more chains than the number of parameters to explore. This reduces per-chain sampling burden, enables high-dimensional inversions and the usemore » of computationally expensive forward models. The large number of chains can also ameliorate the impact of silent-errors, which may affect only a few chains. The chain ensemble can also be sampled to provide an initial condition when an aberrant chain is re-spawned. Adaptive Metropolis takes the best points from the differential evolution and efficiently hones in on the poste- rior density. The multitude of chains in SAChES is leveraged to (1) enable efficient exploration of the parameter space; and (2) ensure robustness to silent errors which may be unavoidable in extreme-scale computational platforms of the future. This report outlines SAChES, describes four papers that are the result of the project, and discusses some additional results.« less

Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

ClinicalTrials.gov

2017-11-15

Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

Therapeutic evaluation of GM2 gangliosidoses by ELISA using anti-GM2 ganglioside antibodies.

PubMed

Tsuji, Daisuke; Higashine, Yukari; Matsuoka, Kazuhiko; Sakuraba, Hitoshi; Itoh, Kohji

2007-03-01

GM2 gangliosidoses, including Tay-Sachs disease, Sandhoff disease and the AB variant, comprise deficiencies of beta-hexosaminidase isozymes and GM2 ganglioside activator protein associated with accumulation of GM2 ganglioside (GM2) in lysosomes and neurosomatic clinical manifestations. A simple assay system for intracellular quantification of GM2 is required to evaluate the therapeutic effects on GM2-gangliosidoses. We newly established a cell-ELISA system involving anti-GM2 monoclonal antibodies for measuring GM2 storage in fibroblasts from Tay-Sachs and Sandhoff disease patients. We succeeded in detecting the corrective effect of enzyme replacement on elimination of GM2 in the cells with this ELISA system. This simple and sensitive system should be useful as additional diagnosis tool as well as therapeutic evaluation of GM2 gangliosidoses.

[Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

PubMed

Tsuji, Daisuke

2013-01-01

Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice.

Tay's syndrome: MRI.

PubMed

Porto, L; Weis, R; Schulz, C; Reichel, P; Lanfermann, H; Zanella, F E

2000-11-01

Tay's syndrome is a trichothiodystrophy associated with congenital ichthyosis. We report the findings on MRI and spectroscopy in a young girl with sparse, short, ruffled hair, dry skin and delayed milestones. T2-weighted images showed prominent diffuse confluent increase in signal symmetrically in all the supratentorial white matter. These findings are similar to those in a previously described case, and consistent with dysmyelination. Spectroscopy showed increased myoinositol and decreased choline.

Lysosomal storage diseases

PubMed Central

Ferreira, Carlos R.; Gahl, William A.

2016-01-01

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458

75 FR 14379 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG (RRD) Models Tay 620-15, Tay 650-15...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

...: Following a review of operational data of the Tay 651-54 engine, it has been found that the actual stress... found that the actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3... actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3, 6, 7 and 12...

An economic evaluation of a genetic screening program for Tay-Sachs disease.

PubMed Central

Nelson, W B; Swint, J M; Caskey, C T

1978-01-01

The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives. PMID:418675

An economic evaluation of a genetic screening program for Tay-Sachs disease.

PubMed

Nelson, W B; Swint, J M; Caskey, C T

1978-03-01

The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives.

An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).

PubMed

Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

2011-01-01

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were

Longitudinal Study of Neurodegenerative Disorders

ClinicalTrials.gov

2018-01-31

MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

Establishment of the Fox Chase Network Breast Cancer Risk Registry

DTIC Science & Technology

1996-10-01

Neurofibromatosis, type I h) Non-insulin dependent diabetes i) Turner Syndrome j) Tay Sachs Disease k) Marfan Syndrome 1) Cancer (tricky!) 2. Human chromosomes are...gastrointestinal and genitourinary cancers (4). Altogether, over 12 genetic-cancer syndromes have been localized to a specific gene (5). Some families suffer...component of the rare help test the best ways to Risk Registry._5, cases of breast cancer tions are likely to result Li-Fraumeni syndrome , only and up to

Gangliosidoses.

PubMed

Patterson, Marc C

2013-01-01

The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. Copyright © 2013 Elsevier B.V. All rights reserved.

Animal models of GM2 gangliosidosis: utility and limitations.

PubMed

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.

Proper Conformal Killing Vectors in Kantowski-Sachs Metric

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Farhan, Muhammad

2018-04-01

This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

Genetic Counseling in Mental Retardation.

ERIC Educational Resources Information Center

Bowen, Peter

The task of the genetic counselor who identifies genetic causes of mental retardation and assists families to understand risk of recurrence is described. Considered are chromosomal genetic disorders such as Down's syndrome, inherited disorders such as Tay-Sachs disease, identification by testing the amniotic fluid cells (amniocentresis) in time…

75 FR 24825 - Airworthiness Directives; Rolls-Royce Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... for corrosion attack are required. The action specified by this European Aviation Safety Agency (EASA... Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay 651-54 Turbofan Engines AGENCY: Federal Aviation...-pressure turbine disks stage 2 and stage 3. The corrosion is considered to be caused by the environment in...

Judaism, genetic screening and genetic therapy.

PubMed

Rosner, F

1998-01-01

Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

Compulsory DNA Sampling of Service Members for Inclusion in the DOD DNA Registry: Remains Identification With a Risk

DTIC Science & Technology

1996-04-01

for Tay-Sachs disease, cystic fibrosis, Huntingtons disease, Duchenne muscular dystrophy , 26alcoholism, and susceptibility to certain types of cancer...and an increased risk of infection and injury to muscle , nerves, and blood vessels was sufficiently compelling to outweigh the state’s interest in...them into electrical impulses. These surgically implanted devices could produce electronic impulses to induce paralyzed muscles to contract and

Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

PubMed Central

Kingsmore, Stephen

2012-01-01

Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

PubMed

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J; Samulski, R Jude; Wakarchuk, Warren; Mark, Brian L; Mahuran, Don J

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

In Cellulo Examination of a Beta-Alpha Hybrid Construct of Beta-Hexosaminidase A Subunits, Reported to Interact with the GM2 Activator Protein and Hydrolyze GM2 Ganglioside

PubMed Central

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J.; Samulski, R. Jude; Wakarchuk, Warren; Mark, Brian L.; Mahuran, Don J.

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

PubMed

Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

2011-03-01

Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

PubMed

Levin, M

1999-01-01

Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

Constant mean curvature slicings of Kantowski-Sachs spacetimes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinzle, J. Mark

2011-04-15

We investigate existence, uniqueness, and the asymptotic properties of constant mean curvature (CMC) slicings in vacuum Kantowski-Sachs spacetimes with positive cosmological constant. Since these spacetimes violate the strong energy condition, most of the general theorems on CMC slicings do not apply. Although there are in fact Kantowski-Sachs spacetimes with a unique CMC foliation or CMC time function, we prove that there also exist Kantowski-Sachs spacetimes with an arbitrary number of (families of) CMC slicings. The properties of these slicings are analyzed in some detail.

Julius Sachs (1868): The father of plant physiology.

PubMed

Kutschera, Ulrich; Niklas, Karl J

2018-05-17

The year 2018 marks the 150th anniversary of the first publication of Julius von Sachs' (1832-1897) Lehrbuch der Botanik (Textbook of Botany), which provided a comprehensive summary of what was then known about the plant sciences. Three years earlier, in 1865, Sachs produced the equally impressive Handbuch der Experimental-Physiologie der Pflanzen (Handbook of Experimental Plant Physiology), which summarized the state of knowledge in all aspects of the discipline known today as plant physiology. Both of these books provided numerous insights based on Sachs' seminal experiments. By virtue of a reliance on detailed empirical observation and the rigorous application of chemical and physical principles, it is fair to say that the publication of these two monumental works marked the beginning of what can be called "modern-day" plant science. Moreover, Sachs' Lehrbuch der Botanik prefigured the ascendance of plant molecular biology and the systems biology of photoautotrophic organisms. Regrettably, many of the insights of this great scientist have been forgotten by the generations who followed. It is only fitting, therefore, that the anniversary of the publication of the Lehrbuch der Botanik and the career of "the father of plant physiology" should be honored and reviewed, particularly because Sachs established the physiology of green organisms as an integral branch of botany and incorporated a Darwinian perspective into plant biology. Here we highlight key insights, with particular emphasis on Sachs' detailed discussion of sexual reproduction at the cellular level and his endorsement of Darwinian evolution. © 2018 Botanical Society of America.

Classification of Kantowski-Sachs metric via conformal Ricci collineations

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Khan, Fawad; Bokhari, Ashfaque H.; Akhtar, Sumaira Saleem

In this paper, we present a classification of the Kantowski-Sachs spacetime metric according to its conformal Ricci collineations (CRCs). Solving the CRC equations, it is shown that the Kantowski-Sachs metric admits 15-dimensional Lie algebra of CRCs when its Ricci tensor is non-degenerate and an infinite dimensional group of CRCs when the Ricci tensor is degenerate. Some examples of Kantowski-Sachs metric admitting nontrivial CRCs are presented and their physical interpretation is provided.

Natural History of Infantile GM2 Gangliosidosis

PubMed Central

Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.

2011-01-01

OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. PMID:22025593

Tectonic Evolution of Jabal Tays Ophiolite Complex, Eastern Arabian Shield, Saudi Arabia

NASA Astrophysics Data System (ADS)

AlHumidan, Saad; Kassem, Osama; Almutairi, Majed; Al-Faifi, Hussain; Kahal, Ali

2017-04-01

Microstructural analysis is important for investigation of tectonic evaluation of Jable Tays area. Furthermore, the Jable Tays ophiolite complex is effected by Al Amar -Idsas fault. The nature of the Al Amar-Idsas fault is a part of the Eastern Arabian Shield, which was subjected to multiple interpretations. Through fieldwork investigation, microscopic examination, and microstructural analysis, we aim to understand the evolution and tectonic setting of the Jable Tays area. Finite-strain data displays that the Abt schist, the metavolcanics and the metagranites are highly to moderately deformed. The axial ratios in the XZ section range from 1.40 to 2.20. The long axes of the finite-strain ellipsoids trend NW- SE and W-E in the Jable Tays area while, their short axes are subvertical to subhorizontal foliations. The strain magnitude does not increase towards the tectonic contacts between the Abt schist and metavolcano-sedimentary. While majority of the obtained data indicate a dominant oblate with minor prolate strain symmetries in the Abt schist, metavolcano-sedimentary and metagranites. The strain data also indicate flattening with some constriction. We assume that the Abt schist and the metavolcano-sedimentry rocks have similar deformation behavior. The finite strain in the studied rocks accumulated during the metamorphism that effected by thrusting activity. Based on these results, we finally concluded that the contact between Abt schist and metavolcano-sedimentary rocks were formed during the progressive thrusting under brittle to semi-ductile deformation conditions by simple shear that also involved a component of vertical shortening, causing subhorizontal foliation in Jable Tays area.

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.

PubMed

Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

2016-01-01

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

PubMed Central

Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

2016-01-01

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

Julius Sachs (1832–1897) and the Unity of Life

PubMed Central

Kutschera, Ulrich; Baluška, František

2015-01-01

In 1865, the German botanist Julius Sachs published a seminal monograph entitled Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) and hence became the founder of a new scientific discipline that originated 150 y ago. Here, we outline the significance of the achievements of Sachs. In addition, we document, with reference to his Vorlesungen über Pflanzen-Physiologie (Lectures on the Physiology of Plants, 1882), that Sachs was one of the first experimentalists who proposed the functional unity of all organisms alive today (humans, animals, plants and other “vegetable” organisms, such as algae, cyanophyceae, fungi, myxomycetes, and bacteria). PMID:26359706

Fingerprinting of bed sediment in the Tay Estuary, Scotland: an environmental magnetism approach

NASA Astrophysics Data System (ADS)

Jenkins, Pierre A.; Duck, Rob W.; Rowan, John S.; Walden, John

Sediment fingerprinting is commonly used for sediment provenance studies in lakes, rivers and reservoirs and on hillslopes and floodplains. This investigation explores the mixing of terrestrial and marine-derived sediment in the Tay Estuary, Scotland, using mineral magnetic attributes for fingerprinting. Samples representative of the estuary sediments and of four sources (end-members) were subjected to a suite of magnetic susceptibility and remanence measurements. Sediment samples from the beds of the Rivers Tay and Earn represented fluvial inputs while samples from the Angus and Fife coasts represented marine input. Multivariate discriminant and factor analysis showed that the sources could be separated on the basis of six magnetic parameters in a simple multivariate unmixing model to identify source contributions to estuarine bed sediments. Multi-domain magnetite signatures, characteristic of unweathered bedrock, dominate the magnetic measurements. Overall contributions of 3% from the River Earn, 17% from the River Tay, 29% from the Angus coast and 51% from the Fife coast source end-members, demonstrated the present-day regime of marine sediment derivation in the Tay Estuary. However, this conceals considerable spatial variability both along-estuary and in terms of sub-environments, with small-scale variations in sediment provenance reflecting local morphology, particularly areas of channel convergence.

GM1 and GM2 gangliosides: recent developments.

PubMed

Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

2014-03-01

GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction.

17 CFR 249.619 - Form TA-Y2K, information required of transfer agents pursuant to section 17 of the Securities...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form TA-Y2K, information... Certain Exchange Members, Brokers, and Dealers § 249.619 Form TA-Y2K, information required of transfer... affecting Form TA-Y2K, see the List of CFR Sections Affected, which appears in the Finding Aids section of...

CO2 Storage Potential of the Eocene Tay Sandstone, Central North Sea, UK

NASA Astrophysics Data System (ADS)

Gent, Christopher; Williams, John

2017-04-01

Carbon Capture and Storage (CCS) is crucial for low-carbon industry, climate mitigation and a sustainable energy future. The offshore capacity of the UK is substantial and has been estimated at 78 Gt of CO2 in saline aquifers and hydrocarbon fields. The early-mid Eocene Tay Sandstone Member of the Central North Sea (CNS) is a submarine-fan system and potential storage reservoir with a theoretical capacity of 123 Mt of CO2. The Tay Sandstone comprises of 4 sequences, amalgamating into a fan complex 125km long and 40 km at a minimum of 1500 m depth striking NW-SE, hosting several hydrocarbon fields including Gannett A, B, D and Pict. In order to better understand the storage potential and characteristics, the Tay Sandstone over Quadrant 21 has been interpreted using log correlation and 3D seismic. Understanding the internal and external geometry of the sandstone as well as the lateral extent of the unit is essential when considering CO2 vertical and horizontal fluid flow pathways and storage security. 3D seismic mapping of a clear mounded feature has revealed the youngest sequence of the Tay complex; a homogenous sand-rich channel 12 km long, 1.5 km wide and on average 100 m thick. The sandstone has porosity >35%, permeability >5 D and a net to gross of 0.8, giving a total pore volume of 927x106 m3. The remaining three sequences are a series of stacked channels and interbedded mudstones which are more quiescent on the seismic, however, well logs indicate each subsequent sequence reduce in net to gross with age as mud has a greater influence in the early fan system. Nevertheless, the sandstone properties remain relatively consistent and are far more laterally extensive than the youngest sequence. The Tay Sandstone spatially overlaps several other potential storage sites including the older Tertiary sandstones of the Cromarty, Forties and Mey Members and deeper Jurassic reservoirs. This favours the Tay Sandstone to be considered in a secondary or multiple stacked

78 FR 26407 - Goldman Sachs Trust II, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-06

... Sachs Trust II, et al.; Notice of Application April 29, 2013. AGENCY: Securities and Exchange Commission... would grant relief from certain disclosure requirements. APPLICANTS: Goldman Sachs Trust II (the ``Trust...'', each of GSAM and GSAMI an ``Adviser'' and collectively, ``Advisers,'' and together with the Trust...

Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

PubMed

Oddoux, C; Guillen-Navarro, E; Ditivoli, C; Dicave, E; Cilio, M R; Clayton, C M; Nelson, H; Sarafoglou, K; McCain, N; Peretz, H; Seligsohn, U; Luzzatto, L; Nafa, K; Nardi, M; Karpatkin, M; Aksentijevich, I; Kastner, D; Axelrod, F; Ostrer, H

1999-12-01

The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried the connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin.

[Physician satire and patient scorn in Hans Sachs' old Nürnberg and the physicians].

PubMed

Sauerbeck, K O

1993-01-01

Among the best poems of Hans Sachs quite a few describe patient-physician relationships in 16th century Nuremberg. These poems offer a vivid impression of the technical aspects as well as of the social context of medical treatment at the time. Hans Sachs ridiculed the doctors and their patients, implying that everybody attempted to cheat the other side, and he provides evidence of a great influence of charlatans on the country population. The poems of Hans Sachs are extraordinary pieces or art; their aesthetics, though, appear unusual to us today. Medical satire is part of all European cultures, and has been written throughout medical history. Most motives of later satires focussing on physicians may be traced to Hans Sachs' poetry.

Basic versus applied research: Julius Sachs (1832-1897) and the experimental physiology of plants.

PubMed

Kutschera, Ulrich

2015-01-01

The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This "plant-microbe-view" of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845-1920), so that the term "Sachs-Pfeffer-Principle of Experimental Plant Research" appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria).

75 FR 44031 - Goldman, Sachs & Co., et al.; Notice of Application and Temporary Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... International (``GSAMI''), Goldman Sachs Hedge Fund Strategies LLC (``GSHFS''), Commonwealth Annuity and Life... marketing materials used in connection with residential mortgage-related securities offerings by Goldman... marketing materials, (iv) where Goldman Sachs is the lead underwriter of an offering of residential mortgage...

GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.

PubMed

Kaya, Namik; Al-Owain, Mohammad; Abudheim, Nada; Al-Zahrani, Jawaher; Colak, Dilek; Al-Sayed, Moeen; Milanlioglu, Aysel; Ozand, Pinar T; Alkuraya, Fowzan S

2011-06-01

The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. Copyright © 2011 Wiley-Liss, Inc.

Basic versus applied research: Julius Sachs (1832–1897) and the experimental physiology of plants

PubMed Central

Kutschera, Ulrich

2015-01-01

The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This “plant-microbe-view” of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845–1920), so that the term “Sachs-Pfeffer-Principle of Experimental Plant Research” appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria). PMID:26146794

Posterior shoulder dislocation with a reverse Hill-Sachs lesion treated with frozen femoral head bone allograft combined with osteochondral autograft transfer.

PubMed

Mastrokalos, Dimitrios S; Panagopoulos, Georgios N; Galanopoulos, Ioannis P; Papagelopoulos, Panayiotis J

2017-10-01

Management of a posterior shoulder dislocation with an associated reverse Hill-Sachs lesion is challenging, both diagnostically and therapeutically. Diagnosis is frequently delayed or missed, whereas the resulting humeral head defect is often larger and more difficult to salvage than in anterior shoulder dislocations. This report presents the case of a 29-year-old male with a recurrent posterior shoulder dislocation associated with a large reverse Hill-Sachs defect, treated with bone augmentation of the lesion with a combination of fresh femoral head allograft and a locally harvested humeral head autograft transfer, with a successful outcome. Level of evidence V.

Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

PubMed

Olkhovych, N V; Gorovenko, N G

2016-01-01

The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may

The white matter of the human cerebrum: Part I The occipital lobe by Heinrich Sachs

PubMed Central

Forkel, Stephanie J.; Mahmood, Sajedha; Vergani, Francesco; Catani, Marco

2015-01-01

This is the first complete translation of Heinrich Sachs' outstanding white matter atlas dedicated to the occipital lobe. This work is accompanied by a prologue by Prof Carl Wernicke who for many years was Sachs' mentor in Breslau and enthusiastically supported his work. PMID:25527430

Kantowski-Sachs Einstein-æther perfect fluid models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latta, Joey; Leon, Genly; Paliathanasis, Andronikos, E-mail: lattaj@mathstat.dal.ca, E-mail: genly.leon@pucv.cl, E-mail: anpaliat@phys.uoa.gr

We investigate Kantowski-Sachs models in Einstein-æ ther theory with a perfect fluid source using the singularity analysis to prove the integrability of the field equations and dynamical system tools to study the evolution. We find an inflationary source at early times, and an inflationary sink at late times, for a wide region in the parameter space. The results by A.A. Coley, G. Leon, P. Sandin and J. Latta ( JCAP 12 (2015) 010), are then re-obtained as particular cases. Additionally, we select other values for the non-GR parameters which are consistent with current constraints, getting a very rich phenomenology. Inmore » particular, we find solutions with infinite shear, zero curvature, and infinite matter energy density in comparison with the Hubble scalar. We also have stiff-like future attractors, anisotropic late-time attractors, or both, in some special cases. Such results are developed analytically, and then verified by numerics. Finally, the physical interpretation of the new critical points is discussed.« less

Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions Using Homologous Osteochondral Allograft.

PubMed

Alkaduhimi, Hassanin; van den Bekerom, Michel P J; van Deurzen, Derek F P

2017-06-01

Posterior shoulder dislocations are accompanied by high forces and can result in an anteromedial humeral head impression fracture called a reverse Hill-Sachs lesion. This reverse Hill-Sachs lesion can result in serious complications including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis, persistent joint stiffness, and loss of shoulder function. Treatment is challenging and depends on the amount of bone loss. Several techniques have been reported to describe the surgical treatment of lesions larger than 20%. However, there is still limited evidence with regard to the optimal procedure. Favorable results have been reported by performing segmental reconstruction of the reverse Hill-Sachs lesion with bone allograft. Although the procedure of segmental reconstruction has been used in several studies, its technique has not yet been well described in detail. In this report we propose a step-by-step description of the technique how to perform a segmental reconstruction of a reverse Hill-Sachs defect.

GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease.

PubMed

Sanders, Douglas N; Zeng, Rong; Wenger, David A; Johnson, Gary S; Johnson, Gayle C; Decker, Jared E; Katz, Martin L; Platt, Simon R; O'Brien, Dennis P

2013-01-01

GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of G(M2) gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins. Copyright © 2012 Elsevier Inc. All rights reserved.

Calculating the Sachs-Wolfe Effect from Solutions of Null Geodesics in Perturbed FRW Spacetime

NASA Astrophysics Data System (ADS)

Arroyo-Cárdenas, C. A.; Muñoz-Cuartas, J. C.

2017-07-01

In the upcoming precision era in cosmology, fine grained effects will be measured accurately. In particular, the late integrated Sachs-Wolfe (ISW) effect measurements will be improved to levels of unprecedented precision. The ISW consists on temperature fluctuations in the CMB due to gravitational redshift induced by the evolving potential well of large scale structure in the Universe. Currently there is large controversy related to the actual observability of the ISW effect. In principle, it is expected that, as an effect of the late accelerated expansion of the universe motivated by the current amount of dark energy, large scale structures may evolve rapidly, inducing an observable signature in the CMB photons in the way of a ISW anisotropy in the CMB. Tension arises since using galaxy redshift surveys some works report a temperature fluctuations with amplitude smaller than predicted by the Lambda-CDM. We argue that these discrepancies may be originated in the approximation that one has to make to get the classic Sachs-Wolfe effect. In this work, we compare the classic Sachs-Wolfe approximation with an exact solution to the propagation of photons in a dynamical background. We solve numerically the null geodesics on a perturbed FRW spacetime in the Newtonian gauge. From null geodesics, temperature fluctuations in the CMB due to the evolving potential has been calculated. Since solving geodesics accounts for more terms than solving the Sachs-Wolfe (approximated) integral, our results are more accurate. We have been able to substract the background cosmological redshift with the information provided by null geodesics, which allows to get an estimate of the integrated Sachs-Wolfe effect contribution to the temperature of the CMB.

Diagnosing Lysosomal Storage Disorders: The GM2 Gangliosidoses.

PubMed

Hall, Patricia; Minnich, Sara; Teigen, Claire; Raymond, Kimiyo

2014-10-01

The GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by defective β-hexosaminidase. There are three clinical conditions in this group: Tay-Sachs disease (TSD), Sandhoff disease (SD), and hexosaminidase activator deficiency. The three conditions are clinically indistinguishable. TSD and SD have been identified with infantile, juvenile, and adult onset forms. The activator deficiency is only known to present with infantile onset. Diagnosis of TSD and SD is based on decreased hexosaminidase activity and a change in the percentage of activity between isoforms. There are no biochemical tests currently available for activator deficiency. This unit provides a detailed procedure for identifying TSD and SD in affected individuals and carriers from leukocyte samples, the most robust sample type available. Copyright © 2014 John Wiley & Sons, Inc.

Sachs equations for light bundles in a cold plasma

NASA Astrophysics Data System (ADS)

Schulze-Koops, Karen; Perlick, Volker; Schwarz, Dominik J.

2017-11-01

We study the propagation of light bundles in non-empty spacetime, as most of the Universe is filled by baryonic matter in the form of a (dilute) plasma. Here we restrict to the case of a cold (i.e. pressureless) and non-magnetised plasma. Then the influence of the medium on the light rays is encoded in the spacetime dependent plasma frequency. Our result for a general spacetime generalises the Sachs equations to the case of a cold plasma Universe. We find that the reciprocity law (Etherington theorem), the relation that connects area distance with luminosity distance, is modified. Einstein’s field equation is not used, i.e. our results apply independently of whether or not the plasma is self-gravitating. As an example, our findings are applied to a homogeneous plasma in a Robertson-Walker spacetime. We find small modifications of the cosmological redshift of frequencies and of the Hubble law.

Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection

PubMed Central

Risch, Neil; Tang, Hua; Katzenstein, Howard; Ekstein, Josef

2003-01-01

The presence of four lysosomal storage diseases (LSDs) at increased frequency in the Ashkenazi Jewish population has suggested to many the operation of natural selection (carrier advantage) as the driving force. We compare LSDs and nonlysosomal storage diseases (NLSDs) in terms of the number of mutations, allele-frequency distributions, and estimated coalescence dates of mutations. We also provide new data on the European geographic distribution, in the Ashkenazi population, of seven LSD and seven NLSD mutations. No differences in any of the distributions were observed between LSDs and NLSDs. Furthermore, no regular pattern of geographic distribution was observed for LSD versus NLSD mutations—with some being more common in central Europe and others being more common in eastern Europe, within each group. The most striking disparate pattern was the geographic distribution of the two primary Tay-Sachs disease mutations, with the first being more common in central Europe (and likely older) and the second being exclusive to eastern Europe (primarily Lithuania and Russia) (and likely much younger). The latter demonstrates a pattern similar to two other recently arisen Lithuanian mutations, those for torsion dystonia and familial hypercholesterolemia. These observations provide compelling support for random genetic drift (chance founder effects, one ∼11 centuries ago that affected all Ashkenazim and another ∼5 centuries ago that affected Lithuanians), rather than selection, as the primary determinant of disease mutations in the Ashkenazi population. PMID:12612865

CMB anisotropies at all orders: the non-linear Sachs-Wolfe formula

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roldan, Omar, E-mail: oaroldan@if.ufrj.br

2017-08-01

We obtain the non-linear generalization of the Sachs-Wolfe + integrated Sachs-Wolfe (ISW) formula describing the CMB temperature anisotropies. Our formula is valid at all orders in perturbation theory, is also valid in all gauges and includes scalar, vector and tensor modes. A direct consequence of our results is that the maps of the logarithmic temperature anisotropies are much cleaner than the usual CMB maps, because they automatically remove many secondary anisotropies. This can for instance, facilitate the search for primordial non-Gaussianity in future works. It also disentangles the non-linear ISW from other effects. Finally, we provide a method which canmore » iteratively be used to obtain the lensing solution at the desired order.« less

The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

PubMed Central

Gan-Or, Ziv; Ozelius, Laurie J.; Bar-Shira, Anat; Saunders-Pullman, Rachel; Mirelman, Anat; Kornreich, Ruth; Gana-Weisz, Mali; Raymond, Deborah; Rozenkrantz, Liron; Deik, Andres; Gurevich, Tanya; Gross, Susan J.; Schreiber-Agus, Nicole; Giladi, Nir; Bressman, Susan B.

2013-01-01

Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD). Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex. Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9–22.8, p < 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions: The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development. PMID:23535491

Cloning and sequence analysis of a cDNA encoding the alpha-subunit of mouse beta-N-acetylhexosaminidase and comparison with the human enzyme.

PubMed Central

Beccari, T; Hoade, J; Orlacchio, A; Stirling, J L

1992-01-01

cDNAs encoding the mouse beta-N-acetylhexosaminidase alpha-subunit were isolated from a mouse testis library. The longest of these (1.7 kb) was sequenced and showed 83% similarity with the human alpha-subunit cDNA sequence. The 5' end of the coding sequence was obtained from a genomic DNA clone. Alignment of the human and mouse sequences showed that all three putative N-glycosylation sites are conserved, but that the mouse alpha-subunit has an additional site towards the C-terminus. All eight cysteines in the human sequence are conserved in the mouse. There are an additional two cysteines in the mouse alpha-subunit signal peptide. All amino acids affected in Tay-Sachs-disease mutations are conserved in the mouse. Images Fig. 1. PMID:1379046

Sachs' free data in real connection variables

NASA Astrophysics Data System (ADS)

De Paoli, Elena; Speziale, Simone

2017-11-01

We discuss the Hamiltonian dynamics of general relativity with real connection variables on a null foliation, and use the Newman-Penrose formalism to shed light on the geometric meaning of the various constraints. We identify the equivalent of Sachs' constraint-free initial data as projections of connection components related to null rotations, i.e. the translational part of the ISO(2) group stabilising the internal null direction soldered to the hypersurface. A pair of second-class constraints reduces these connection components to the shear of a null geodesic congruence, thus establishing equivalence with the second-order formalism, which we show in details at the level of symplectic potentials. A special feature of the first-order formulation is that Sachs' propagating equations for the shear, away from the initial hypersurface, are turned into tertiary constraints; their role is to preserve the relation between connection and shear under retarded time evolution. The conversion of wave-like propagating equations into constraints is possible thanks to an algebraic Bianchi identity; the same one that allows one to describe the radiative data at future null infinity in terms of a shear of a (non-geodesic) asymptotic null vector field in the physical spacetime. Finally, we compute the modification to the spin coefficients and the null congruence in the presence of torsion.

Simultaneous quantification of GM1 and GM2 gangliosides by isotope dilution tandem mass spectrometry.

PubMed

Gu, Jianghong; Tifft, Cynthia J; Soldin, Steven J

2008-04-01

Gangliosides (GGs) are considered as diagnostic biomarkers and therapeutic targets and agents. The goal of this study was to develop a tandem mass spectrometry (MS/MS) method for the simultaneous measurement of both GM1 and GM2 gangliosides in human cerebrospinal fluid (CSF) samples in order to be able to determine their concentrations in patients with Tay-Sachs and Sandhoff disease and assess whether drugs or transplantation affect their concentrations. An API-4000 tandem mass spectrometer equipped with TurboIonSpray source and Shimadzu HPLC system was employed to perform the analysis using isotope dilution with deuterium labeled internal standards. To a 1.5 mL conical plastic Eppendorf centrifuge tube, 40 microL of human CSF sample was added and mixed with 400 microL of internal standard solution for deproteinization. After centrifugation, 100 microL of supernatant was injected onto a C-18 column. After a 2.5 min wash, the switching valve was activated and the analytes were eluted from the column with a water/methanol gradient into the MS/MS system. Quantification by multiple reaction-monitoring (MRM) analysis was performed in the negative mode. The within-day coefficients of variation were <3% for GM1 and <2% for GM2 and the between-day coefficients of variation were <5% for both GM1 and GM2 at all concentrations tested. Accuracy ranged between 98% and 102% for both analytes. Good linearity was also obtained within the concentration range of 10-200 ng/mL (6.5-129.3 nmol/L) for GM1 and 5-100 ng/mL (3.6-72.3 nmol/L) for GM2 (r> or =0.995). A new simple, accurate, and fast isotope dilution tandem mass spectrometry method was developed for the simultaneous quantification of GM1 and GM2 gangliosides in a small amount of human CSF. Concentrations were measured in "normal" CSF and in CSF from patients with Tay-Sachs disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petroulakis, E.; Cao, Z.; Salo, T.

Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affectedmore » brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.« less

Stigmatization of carrier status: social implications of heterozygote genetic screening programs.

PubMed Central

Kenen, R H; Schmidt, R M

1978-01-01

Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585

78 FR 24447 - Goldman Sachs Trust, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30471; 812-14075] Goldman Sachs Trust, et al.; Notice of Application April 19, 2013. AGENCY: Securities and Exchange Commission..., or cause more than 10% of the acquired company's voting stock to be owned by investment companies and...

Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory of gravitation

NASA Astrophysics Data System (ADS)

Pawar, D. D.; Shahare, S. P.; Dagwal, V. J.

2018-02-01

Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory for perfect fluid has been investigated. The general solution of field equations in Brans-Dicke theory for the combined scalar and tensor field are obtained by using power law relation. Also, some physical and geometrical parameters are obtained and discussed.

Current practices of commercial cryobanks in screening prospective donors for genetic disease and reproductive risk.

PubMed

Conrad, E A; Fine, B; Hecht, B R; Pergament, E

1996-01-01

To determine how the screening practices of commercial semen banks vary from published guidelines, which factors influence cryobanks to exclude prospective semen donors for genetic reasons, and the current role of clinical geneticists/genetic counselors in evaluating prospective semen donors. The genetic screening of prospective donors by commercial semen banks was evaluated using written questionnaires completed by bank directors. Responses were analyzed to determine exclusion criteria, adherence to published guidelines, and contribution of genetic professionals. Semen banks were selected on the basis of membership in the American Association of Tissue Banks and commercial use of semen for artificial insemination by donor. Semen bank practices as reported by commercial semen bank directors. Of 37 eligible banks, 16 responded. All screen prospective donors by medical/family history and physical examination, 94% have upper age limits; 63% examine for minor physical defects; 56% routinely karyotype; 81% screen men of ethnic groups at risk for Tay Sachs disease, sickle cell disease and thalassemia; 19% screen all donors; 25% screen all donors for cystic fibrosis and 50% only screen if family history positive. Donor rejection was based on three criteria: mode of inheritance of familial disorder, severity of disease, and availability of carrier/confirmatory testing of donor genotype. Ten of 16 banks have no genetic professional on staff. Commercial semen banks primarily rely on family history as the major exclusion criterion in genetic screening of donors. Considerable differences exist among semen bank practices in accordance with guidelines published by national agencies. Genetic professionals have a minimal effect overall on evaluation of semen donors.

The Kantowski-Sachs Quantum Model with Stiff Matter Fluid

NASA Astrophysics Data System (ADS)

Alvarenga, F. G.; Fracalossi, R.; Freitas, R. C.; Gonçalves, S. V. B.

2018-05-01

In this paper, we study the quantum cosmological Kantowski-Sachs model and we solve the Wheeler-DeWitt equation in minisuperspace to obtain the wave function of the corresponding universe. The perfect fluid is described by Schutz's canonical formalism, which allows to attribute dynamical degrees of freedom to matter. The time is introduced phenomenologically using the fluid's degrees of freedom. In particular, we adopt a stiff matter fluid. The viability of this model is analyzed and discussed.

Black Hole Entropy from Bondi-Metzner-Sachs Symmetry at the Horizon.

PubMed

Carlip, S

2018-03-09

Near the horizon, the obvious symmetries of a black hole spacetime-the horizon-preserving diffeomorphisms-are enhanced to a larger symmetry group with a three-dimensional Bondi-Metzner-Sachs algebra. Using dimensional reduction and covariant phase space techniques, I investigate this augmented symmetry and show that it is strong enough to determine the black hole entropy in any dimension.

Application of DNA Machineries for the Barcode Patterned Detection of Genes or Proteins.

PubMed

Zhou, Zhixin; Luo, Guofeng; Wulf, Verena; Willner, Itamar

2018-06-05

The study introduces an analytical platform for the detection of genes or aptamer-ligand complexes by nucleic acid barcode patterns generated by DNA machineries. The DNA machineries consist of nucleic acid scaffolds that include specific recognition sites for the different genes or aptamer-ligand analytes. The binding of the analytes to the scaffolds initiate, in the presence of the nucleotide mixture, a cyclic polymerization/nicking machinery that yields displaced strands of variable lengths. The electrophoretic separation of the resulting strands provides barcode patterns for the specific detection of the different analytes. Mixtures of DNA machineries that yield, upon sensing of different genes (or aptamer ligands), one-, two-, or three-band barcode patterns are described. The combination of nucleic acid scaffolds acting, in the presence of polymerase/nicking enzyme and nucleotide mixture, as DNA machineries, that generate multiband barcode patterns provide an analytical platform for the detection of an individual gene out of many possible genes. The diversity of genes (or other analytes) that can be analyzed by the DNA machineries and the barcode patterned imaging is given by the Pascal's triangle. As a proof-of-concept, the detection of one of six genes, that is, TP53, Werner syndrome, Tay-Sachs normal gene, BRCA1, Tay-Sachs mutant gene, and cystic fibrosis disorder gene by six two-band barcode patterns is demonstrated. The advantages and limitations of the detection of analytes by polymerase/nicking DNA machineries that yield barcode patterns as imaging readout signals are discussed.

The effect of a combined glenoid and Hill-Sachs defect on glenohumeral stability: a biomechanical cadaveric study using 3-dimensional modeling of 142 patients.

PubMed

Arciero, Robert A; Parrino, Anthony; Bernhardson, Andrew S; Diaz-Doran, Vilmaris; Obopilwe, Elifho; Cote, Mark P; Golijanin, Petr; Mazzocca, Augustus D; Provencher, Matthew T

2015-06-01

Bone loss in anterior glenohumeral instability occurs on both the glenoid and the humerus; however, existing biomechanical studies have evaluated glenoid and humeral head defects in isolation. Thus, little is known about the combined effect of these bony lesions in a clinically relevant model on glenohumeral stability. The purpose of this study was to determine the biomechanical efficacy of a Bankart repair in the setting of bipolar (glenoid and humeral head) bone defects determined via computer-generated 3-dimensional (3D) modeling of 142 patients with recurrent anterior shoulder instability. The null hypothesis was that adding a bipolar bone defect will have no effect on glenohumeral stability after soft tissue Bankart repair. Controlled laboratory study. A total of 142 consecutive patients with recurrent anterior instability were analyzed with 3D computed tomography scans. Two Hill-Sachs lesions were selected on the basis of volumetric size representing the 25th percentile (0.87 cm(3); small) and 50th percentile (1.47 cm(3); medium) and printed in plastic resin with a 3D printer. A total of 21 cadaveric shoulders were evaluated on a custom shoulder-testing device permitting 6 degrees of freedom, and the force required to translate the humeral head anteriorly 10 mm at a rate of 2.0 mm/s with a compressive load of 50 N was determined at 60° of glenohumeral abduction and 60° of external rotation. All Bankart lesions were made sharply from the 2- to 6-o'clock positions for a right shoulder. Subsequent Bankart repair with transosseous tunnels using high-strength suture was performed. Hill-Sachs lesions were made in the cadaver utilizing a plastic mold from the exact replica off the 3D printer. Testing was conducted in the following sequence for each specimen: (1) intact, (2) posterior capsulotomy, (3) Bankart lesion, (4) Bankart repair, (5) Bankart lesion with 2-mm glenoid defect, (6) Bankart repair, (7) Bankart lesion with 2-mm glenoid defect and Hill-Sachs lesion

What influences participation in genetic carrier testing? Results from a discrete choice experiment.

PubMed

Hall, Jane; Fiebig, Denzil G; King, Madeleine T; Hossain, Ishrat; Louviere, Jordan J

2006-05-01

This study explores factors that influence participation in genetic testing programs and the acceptance of multiple tests. Tay Sachs and cystic fibrosis are both genetically determined recessive disorders with differing severity, treatment availability, and prevalence in different population groups. We used a discrete choice experiment with a general community and an Ashkenazi Jewish sample; data were analysed using multinomial logit with random coefficients. Although Jewish respondents were more likely to be tested, both groups seem to be making very similar tradeoffs across attributes when they make genetic testing choices.

Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

PubMed

Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

2016-02-01

The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

[The plant physiologist Julius von Sachs and the academic education of women].

PubMed

Gimmler, Hartmut

2005-01-01

The attitude of the famous plant physiologist Julius von Sachs (1832-1897) to higher education of women is described on the basis of some new documents. Generally, Sachs was in favour of academic education of women at universities, but initially wanted to exclude females from the study of medicine. However, by the example of a bright young Russian lady, who studied medicine in St. Petersburg and who worked 1871 in his laboratory in Würzburg on lower fungi for some time (presumably illegally, since the access for woman to the university was at that time officially forbidden in Würzburg), he changed his mind: 1) In contrast to many colleagues of his time he granted females similar intelligence and skills as males and stated that women had legal rights for the access to the university. 2) He favoured the general necessity of higher education (in particular in science) for women and did not see any contrast in respect to this to the role of women in the society as wives, mothers, and housewives. 3) Access to the university would stimulate the development of young women and thereby would be an improvement for our society. However, in conclusion he asked himself, whether the higher education of females should take place at special women colleges (not existing at that time in Germany) or at universities and whether girl students should preferentially become teachers at high schools for daughters of the high society. He admitted that he also felt uncomfortable because of the threatening job competition between young academic male (traditionally the majority of students in science) and female students. The liberal view of Sachs in respect to higher education of women is compared to the rather conservative view of his former student and friend Hugo Thiel.

Simple, explicitly time-dependent, and regular solutions of the linearized vacuum Einstein equations in Bondi-Sachs coordinates

NASA Astrophysics Data System (ADS)

Mädler, Thomas

2013-05-01

Perturbations of the linearized vacuum Einstein equations in the Bondi-Sachs formulation of general relativity can be derived from a single master function with spin weight two, which is related to the Weyl scalar Ψ0, and which is determined by a simple wave equation. By utilizing a standard spin representation of tensors on a sphere and two different approaches to solve the master equation, we are able to determine two simple and explicitly time-dependent solutions. Both solutions, of which one is asymptotically flat, comply with the regularity conditions at the vertex of the null cone. For the asymptotically flat solution we calculate the corresponding linearized perturbations, describing all multipoles of spin-2 waves that propagate on a Minkowskian background spacetime. We also analyze the asymptotic behavior of this solution at null infinity using a Penrose compactification and calculate the Weyl scalar Ψ4. Because of its simplicity, the asymptotically flat solution presented here is ideally suited for test bed calculations in the Bondi-Sachs formulation of numerical relativity. It may be considered as a sibling of the Bergmann-Sachs or Teukolsky-Rinne solutions, on spacelike hypersurfaces, for a metric adapted to null hypersurfaces.

Pathology of GM2 gangliosidosis in Jacob sheep.

PubMed

Porter, B F; Lewis, B C; Edwards, J F; Alroy, J; Zeng, B J; Torres, P A; Bretzlaff, K N; Kolodny, E H

2011-07-01

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model. © The Authors 2011

Identification of an active acidic residue in the catalytic site of beta-hexosaminidase.

PubMed

Tse, R; Vavougios, G; Hou, Y; Mahuran, D J

1996-06-11

Human beta-hexosaminidases A and B (EC 3.2.1.52) are dimeric lysosomal glycosidases composed of evolutionarily related alpha and/or beta subunits. Both isozymes hydrolyze terminal beta-linked GalNAc or GlcNAc residues from numerous artificial and natural substrates; however, in vivo GM2 ganglioside is a substrate for only the heterodimeric A isozyme. Thus, mutations in either gene encoding its alpha or beta subunits can result in GM2 ganglioside storage and Tay-Sachs or Sandhoff disease, respectively. All glycosyl hydrolases ae believed to have one or more acidic residues in their catalytic site. We demonstrate that incubation of hexosaminidase with a chemical modifier specific for carboxyl side chains produces a time-dependent loss of activity, and that this effect can be blocked by the inclusion of a strong competitive inhibitor in the reaction mix. We hypothesized that the catalytic acid residue(s) should be located in a region of overall homology and be invariant within the aligned deduced primary sequences of the human alpha and beta subunits, as well as hexosaminidases from other species, including bacteria. Such a region is encoded by exons 5-6 of the HEXA and HEXB genes. This region includes beta Arg211 (invariant in 15 sequences), which we have previously shown to be an active residue. This region also contains two invariant and one conserved acidic residues. A fourth acidic residue, Asp alpha 258, beta 290, in exon 7 was also investigated because of its association with the B1 variant of Tay-Sachs disease. Conservative substitutions were made at each candidate residue by in vitro mutagenesis of a beta cDNA, followed by cellular expression. Of these, only the beta Asp196Asn substitution decreased the kcat (350-910-fold) without any noticeable effect on the K(m). Mutagenesis of either beta Asp240 or beta Asp290 to Asn decreased kcat by 10- or 1.4-fold but also raised the K(m) of the enzyme 11- of 3-fold, respectively. The above results strongly suggest that

Fragments of Science: Festschrift for Mendel Sachs

NASA Astrophysics Data System (ADS)

Ram, Michael

1999-11-01

The Table of Contents for the full book PDF is as follows: * Preface * Sketches at a Symposium * For Mendel Sachs * The Constancy of an Angular Point of View * Information-Theoretic Logic and Transformation-Theoretic Logic * The Invention of the Transistor and the Realization of the Hole * Mach's Principle, Newtonian Gravitation, Absolute Space, and Einstein * The Sun, Our Variable Star * The Inconstant Sun: Symbiosis of Time Variations of Sunspots, Atmospheric Radiocarbon, Aurorae, and Tree Ring Growth * Other Worlds * Super-Classical Quantum Mechanics * A Probabilistic Approach to the Phase Problem of X-Ray Crystallography * A Nonlinear Twist on Inertia Gives Unified Electroweak Gravitation * Neutrino Oscillations * On an Incompleteness in the General-Relativistic Description of Gravitation * All Truth is One * Ideas of Physics: Correspondence between Colleagues * The Influence of the Physics and Philosophy of Einstein's Relativity on My Attitudes in Science: An Autobiography

Generalized Bondi-Sachs equations for characteristic formalism of numerical relativity

NASA Astrophysics Data System (ADS)

Cao, Zhoujian; He, Xiaokai

2013-11-01

The Cauchy formalism of numerical relativity has been successfully applied to simulate various dynamical spacetimes without any symmetry assumption. But discovering how to set a mathematically consistent and physically realistic boundary condition is still an open problem for Cauchy formalism. In addition, the numerical truncation error and finite region ambiguity affect the accuracy of gravitational wave form calculation. As to the finite region ambiguity issue, the characteristic extraction method helps much. But it does not solve all of the above issues. Besides the above problems for Cauchy formalism, the computational efficiency is another problem. Although characteristic formalism of numerical relativity suffers the difficulty from caustics in the inner near zone, it has advantages in relation to all of the issues listed above. Cauchy-characteristic matching (CCM) is a possible way to take advantage of characteristic formalism regarding these issues and treat the inner caustics at the same time. CCM has difficulty treating the gauge difference between the Cauchy part and the characteristic part. We propose generalized Bondi-Sachs equations for characteristic formalism for the Cauchy-characteristic matching end. Our proposal gives out a possible same numerical evolution scheme for both the Cauchy part and the characteristic part. And our generalized Bondi-Sachs equations have one adjustable gauge freedom which can be used to relate the gauge used in the Cauchy part. Then these equations can make the Cauchy part and the characteristic part share a consistent gauge condition. So our proposal gives a possible new starting point for Cauchy-characteristic matching.

δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders*

PubMed Central

Xu, Miao; Liu, Ke; Swaroop, Manju; Porter, Forbes D.; Sidhu, Rohini; Finkes, Sally; Ory, Daniel S.; Marugan, Juan J.; Xiao, Jingbo; Southall, Noel; Pavan, William J.; Davidson, Cristin; Walkley, Steven U.; Remaley, Alan T.; Baxa, Ulrich; Sun, Wei; McKew, John C.; Austin, Christopher P.; Zheng, Wei

2012-01-01

Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca2+ response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. PMID:23035117

Defect Characteristics of Reverse Hill-Sachs Lesions.

PubMed

Moroder, Philipp; Tauber, Mark; Scheibel, Markus; Habermeyer, Peter; Imhoff, Andreas B; Liem, Dennis; Lill, Helmut; Buchmann, Stefan; Wolke, Julia; Guevara-Alvarez, Alberto; Salmoukas, Katharina; Resch, Herbert

2016-03-01

Little scientific evidence regarding reverse Hill-Sachs lesions (RHSLs) in posterior shoulder instability exists. Recently, standardized measurement methods of the size and localization were introduced, and the biomechanical effect of the extent and position of the defects on the risk of re-engagement was determined. To analyze the characteristics and patterns of RHSLs in a large case series using standardized measurements and to interpret the results based on the newly available biomechanical findings. Case series; Level of evidence, 4. In this multicenter study, 102 cases of RHSLs in 99 patients were collected from 7 different shoulder centers between 2004 and 2013. Patient- as well as injury-specific information was gathered, and defect characteristics in terms of the size, localization, and depth index were determined on computed tomography or magnetic resonance imaging scans by means of standardized measurements. Additionally, the position (gamma angle) of the posterior defect margin as a predictor of re-engagement was analyzed. Three types of an RHSL were distinguished based on the pathogenesis and chronicity of the lesion: dislocation (D), locked dislocation (LD), and chronic locked dislocation (CLD). While the localization of the defects did not vary significantly between the subgroups (P = .072), their mean size differed signficantly (D: 32.6° ± 11.7°, LD: 49.4° ± 17.2°, CLD: 64.1° ± 20.7°; P < .001). The mean gamma angle as a predictor of re-engagement was similarly significantly different between groups (D: 83.8° ± 14.5°, LD: 96.5° ± 17.9°, CLD: 108.7° ± 18.4°; P < .001). The orientation of the posterior defect margin was consistently quite parallel to the humeral shaft axis, with a mean difference of 0.3° ± 8.1°. The distinction between the 3 different RHSL types based on the pathogenesis and chronicity of the defect helps identify defects prone to re-engagement. The gamma angle as a measurement of the position of the posterior

Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

PubMed Central

Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Stevens, Christine; Pirinen, Matti; Neale, Benjamin M.; Ganna, Andrea; Graham, Daniel; Glaser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levine, Adam P.; Schiff, Elena; Weisburd, Ben; Lek, Monkol; Bloom, Jonathan; Minikel, Eric V.; Petersen, Britt-Sabina; Beaugerie, Laurent; Seksik, Philippe; Cosnes, Jacques; Schreiber, Stefan; Bokemeyer, Bernd; Bethge, Johannes; Ahmad, Tariq; Plagnol, Vincent; Segal, Anthony W.; Targan, Stephan; Turner, Dan; Saavalainen, Paivi; Farkkila, Martti; Kontula, Kimmo; Palotie, Aarno; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Weersma, Rinse K.; Franke, Andre; Jostins, Luke; Barrett, Jeffrey C.; MacArthur, Daniel G.; Jalas, Chaim; Sokol, Harry; Xavier, Ramnik J.; Pulver, Ann; Cho, Judy H.; McGovern, Dermot P. B.; Daly, Mark J.

2018-01-01

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10–100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel

Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

PubMed

Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

2012-08-01

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.

Integrated Sachs-Wolfe effect in massive bigravity

NASA Astrophysics Data System (ADS)

Enander, Jonas; Akrami, Yashar; Mörtsell, Edvard; Renneby, Malin; Solomon, Adam R.

2015-04-01

We study the integrated Sachs-Wolfe (ISW) effect in ghost-free, massive bigravity. We focus on the infinite-branch bigravity (IBB) model which exhibits viable cosmic expansion histories and stable linear perturbations, while the cosmological constant is set to zero and the late-time accelerated expansion of the Universe is due solely to the gravitational interaction terms. The ISW contribution to the CMB auto-correlation power spectrum is predicted, as well as the cross-correlation between the CMB temperature anisotropies and large-scale structure. We use ISW amplitudes as inferred from the WMAP 9-year temperature data together with galaxy and AGN data provided by the WISE mission in order to compare the theoretical predictions to the observations. The ISW amplitudes in IBB are found to be larger than the corresponding ones in the standard Λ CDM model by roughly a factor of 1.5, but are still consistent with the observations.

GM2 Activator Deficiency Caused by a Homozygous Exon 2 Deletion in GM2A.

PubMed

Hall, Patricia L; Laine, Regina; Alexander, John J; Ankala, Arunkanth; Teot, Lisa A; Lidov, Hart G W; Anselm, Irina

2018-01-01

GM2 activator (GM2A) deficiency (OMIM 613109) is a rare lysosomal storage disorder, with onset typically in infancy or early childhood. Clinically, it is almost indistinguishable from Tay-Sachs disease (OMIM 272800) or Sandhoff disease (OMIM 268800); however, traditionally available biochemical screening tests will most likely reveal normal results. We report a 2-year-old male with initially normal development until the age of 9 months, when he presented with developmental delay and regression. Workup at that time was unrevealing; at 15 months, he had abnormal brain MRI findings and a cherry red spot on ophthalmological examination. Family history and all laboratory studies were uninformative. The combination of a cherry red spot and developmental regression was strongly suggestive of a lysosomal storage disorder. Sequence analysis of GM2A did not reveal any pathogenic variants; however, exon 2 of GM2A could not be amplified by PCR, raising suspicion for a large, homozygous deletion. Subsequent copy number analysis confirmed a homozygous deletion of exon 2 in GM2A. This is the first reported case of GM2A deficiency being caused by a whole exon deletion. We describe previously unreported electron microscopy findings in this disease, thus expanding the clinical and variant spectrum for GM2 activator deficiency. These findings demonstrate the increased degree of suspicion required for diagnosis of this rare disorder. Brief Summary: This case of GM2 activator deficiency was caused by a homozygous deletion in GM2A, demonstrating the need to include exon level copy number analysis in any workup to fully exclude this disorder.

Genetics and Therapies for GM2 Gangliosidosis.

PubMed

Cachon-Gonzalez, María Begona; Zaccariotto, Eva; Cox, Timothy Martin

2018-04-04

Tay-Sachs disease, caused by impaired β-N-acetylhexosaminidase activity, was the first GM2 gangliosidosis to be studied and one of the most severe and earliest lysosomal diseases to be described. The condition, associated with the pathological build-up of GM2 ganglioside, has acquired almost iconic status and serves as a paradigm in the study of lysosomal storage diseases. Inherited as a classical autosomal recessive disorder, this global disease of the nervous system induces developmental arrest with regression of attained milestones; neurodegeneration progresses rapidly to cause premature death in young children. There is no effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular and cellular events, from disease-causing mutations and glycosphingolipid storage to disease manifestations, remain to be fully delineated. Several therapeutic approaches has been attempted in patients, including enzymatic augmentation, bone marrow transplantation, enzyme enhancement, and substrate reduction therapy. Hitherto, none of these stratagems has materially altered the course of the disease. Authentic animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, shows great promise. This review outlines current knowledge pertaining the pathobiology as well as potential innovative treatments for the GM2 gangliosidoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

PubMed

de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

2016-10-04

Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

[Dr Mavro Sachs (1817-1888): the first lecturer of Zagreb University].

PubMed

Dugacki, Vladimir

2010-01-01

Mavro Sachs (Jánosháza, Hungary, 1817 % emdash; Rijeka, 1888.) was a Zagreb student since 1828. In 1846 he graduated in medicine from the University of Vienna and returned to Zagreb to be the city physician. In 1849, he started to teach forensic medicine at the School of Law of the Royal Academy of Sciences in Zagreb and continued teaching the same subject at the Zagreb University Faculty of Law in the capacity of docent (corresponds to lecturer in the British system). He also taught medical law at pharmaceutical studies of Zagreb University. From 1855 to 1860, he presided over the Jewish Community of Zagreb.

The effect of a Hill-Sachs defect on glenohumeral translations, in situ capsular forces, and bony contact forces.

PubMed

Sekiya, Jon K; Jolly, John; Debski, Richard E

2012-02-01

Hill-Sachs defects have been associated with failed repairs for anterior shoulder instability. However, the biomechanical consequences of these defects are not well understood because of the complicated interaction between the passive soft tissue and bony stabilizers. The creation of a 25% Hill-Sachs defect would not significantly alter the glenohumeral translations but would increase the in situ forces in the glenohumeral capsule as well as the glenohumeral bony contact forces. Controlled laboratory study. A robotic/universal force-moment sensor (UFS) testing system was used to apply joint compression (22 N) and an anterior or posterior load (44 N) to cadaveric shoulders (n = 9) with the skin and deltoid removed (intact) at 3 glenohumeral joint positions (abduction/external rotation): 0°/0°, 30°/30°, and 60°/60° (corresponds to 90°/90° of shoulder abduction/external rotation). A 25% bony defect on the posterolateral humeral head (defect) was then created in the most common position of anterior shoulder dislocation (90°/90°), and the loading protocol was repeated. A nonparametric repeated-measures Friedman test with a Wilcoxon signed-rank post hoc test was performed to compare translations, in situ forces in the capsule, and bony contact forces between each state (P < .05). At 0°/0°, anterior translation significantly increased from 15.3 ± 8.2 mm to 16.6 ± 9.0 mm (P < .05) in response to an anterior load. At 30°/30°, anterior and posterior translations, respectively, significantly increased in response to both anterior (intact: 13.6 ± 7.1 mm vs defect: 14.2 ± 7 mm; P < .05) and posterior loads (intact: 15.7 ± 5.8 mm vs defect: 17.7 ± 5.1 mm; P < .05). In situ force in the capsule during anterior loading was increased in the defect state at both 60°/60° (intact: 38.9 ± 14.4 N vs defect: 43.2 ± 15.9 N; P < .05) and 30°/30° (intact: 39.6 ± 13.8 N vs defect: 45.6 ± 9.3 N; P < .05). The medial bony contact forces were also increased in the

[Transhumeral head plasty and massive osteocartilaginous allograft transplantation for the management of large hill-sachs lesions].

PubMed

Hart, R; Okál, F; Komzák, M

2010-10-01

is essential for the choice of appropriate shoulder treatment. Up to now large lesions have mostly been managed by non-causal techniques affecting shoulder biomechanics. Transhumeral head plasty or transplantation of a massive osteochondral allograft, on the other hand, offers a causal treatment. However, these two methods have rarely been mentioned in the international literature, and usually only as case reports. Transhumeral head plasty and transplantation of a massive osteochondral allograft offer a causal therapy for the management of Hill-Sachs lesions that does not alter shoulder biomechanics. They are not associated with a higher percentage of post-operative complications. Neither technique is more demanding than non-causal procedures. Operations carried out as primary and not as "salvage" procedures restored the function of the shoulder joint to normal. After secondary surgery, occasional shoulder pain may persist as well as its restricted range of motion.

Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

PubMed Central

Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi

2016-01-01

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.

PubMed

Kitakaze, Keisuke; Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi; Itoh, Kohji

2016-05-02

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses.

The concept of wrongful life in the law.

PubMed

Kasper, A S

1983-01-01

In the history of the law the concept of wrongful life is not new, but it has become of interest recently due to changing social attitudes and advances in contraceptive and genetic technologies. This discussion tries to assess the effects of wrongful life as a legal concept on the rights of childbearing women and their offspring. An unborn child had no rights under common law, which held that a fetus in utero had no existence separate from its mother. Consequently, a child had no right of action for personal harm brought upon it by another person. On occasion early courts disagreed with this view, but the majority of courts maintained that a child had no existence as a human being during gestation. The effect that this concept of common law would have on current abortion laws would be to make it considerably easier to argue for a woman's right to choose an abortion. The notion of wrongful life initially appeared in cases of illegitimate births. In Zepeda v. Zepeda, 1963, and Williams v. State of New York, 1966, the plaintiffs maintained that the children's births and existence were wrongful because they were unintended and illegitimate. In Williams the court ruled that birth under 1 set of circumstances and not another is not a recoverable injury. These cases failed to meet the requirements of tort law, and the court rejected the notion of children finding legal recourse for being born to a poor family or being born to a less desired race or class. A series of cases followed in which recovery for physical injury or birth deformities were claimed by parents for themselves and their children. In June 1980 a California appeals court reversed the decision of a lower court, addressing the fundamental principles of wrongful life as a legal concept. In Curlender v. Bio-Science Laboratories an infant brought suit alleging that the laboratories failed to correctly inform her parents of their status as carriers of Tay-Sachs disease during the mother's pregnancy. The infant

Non-minimally coupled scalar field in Kantowski-Sachs model and symmetry analysis

NASA Astrophysics Data System (ADS)

Dutta, Sourav; Lakshmanan, Muthusamy; Chakraborty, Subenoy

2018-06-01

The paper deals with a non-minimally coupled scalar field in the background of homogeneous but anisotropic Kantowski-Sachs space-time model. The form of the coupling function of the scalar field with gravity and the potential function of the scalar field are not assumed phenomenologically, rather they are evaluated by imposing Noether symmetry to the Lagrangian of the present physical system. The physical system gets considerable mathematical simplification by a suitable transformation of the augmented variables (a , b , ϕ) →(u , v , w) and by the use of the conserved quantities due to the geometrical symmetry. Finally, cosmological solutions are evaluated and analyzed from the point of view of the present evolution of the Universe.

On the structure and applications of the Bondi-Metzner-Sachs group

NASA Astrophysics Data System (ADS)

Alessio, Francesco; Esposito, Giampiero

This work is a pedagogical review dedicated to a modern description of the Bondi-Metzner-Sachs (BMS) group. Minkowski space-time has an interesting and useful group of isometries, but, for a generic space-time, the isometry group is simply the identity and hence provides no significant informations. Yet symmetry groups have important role to play in physics; in particular, the Poincaré group describing the isometries of Minkowski space-time plays a role in the standard definitions of energy-momentum and angular-momentum. For this reason alone it would seem to be important to look for a generalization of the concept of isometry group that can apply in a useful way to suitable curved space-times. The curved space-times that will be taken into account are the ones that suitably approach, at infinity, Minkowski space-time. In particular we will focus on asymptotically flat space-times. In this work, the concept of asymptotic symmetry group of those space-times will be studied. In the first two sections we derive the asymptotic group following the classical approach which was basically developed by Bondi, van den Burg, Metzner and Sachs. This is essentially the group of transformations between coordinate systems of a certain type in asymptotically flat space-times. In the third section the conformal method and the notion of “asymptotic simplicity” are introduced, following mainly the works of Penrose. This section prepares us for another derivation of the BMS group which will involve the conformal structure, and is thus more geometrical and fundamental. In the subsequent sections we discuss the properties of the BMS group, e.g. its algebra and the possibility to obtain as its subgroup the Poincaré group, as we may expect. The paper ends with a review of the BMS invariance properties of classical gravitational scattering discovered by Strominger, that are finding application to black hole physics and quantum gravity in the literature.

Mapping the integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Manzotti, A.; Dodelson, S.

2014-12-01

On large scales, the anisotropies in the cosmic microwave background (CMB) reflect not only the primordial density field but also the energy gain when photons traverse decaying gravitational potentials of large scale structure, what is called the integrated Sachs-Wolfe (ISW) effect. Decomposing the anisotropy signal into a primordial piece and an ISW component, the main secondary effect on large scales, is more urgent than ever as cosmologists strive to understand the Universe on those scales. We present a likelihood technique for extracting the ISW signal combining measurements of the CMB, the distribution of galaxies, and maps of gravitational lensing. We test this technique with simulated data showing that we can successfully reconstruct the ISW map using all the data sets together. Then we present the ISW map obtained from a combination of real data: the NRAO VLA sky survey (NVSS) galaxy survey, temperature anisotropies, and lensing maps made by the Planck satellite. This map shows that, with the data sets used and assuming linear physics, there is no evidence, from the reconstructed ISW signal in the Cold Spot region, for an entirely ISW origin of this large scale anomaly in the CMB. However a large scale structure origin from low redshift voids outside the NVSS redshift range is still possible. Finally we show that future surveys, thanks to a better large scale lensing reconstruction will be able to improve the reconstruction signal to noise which is now mainly coming from galaxy surveys.

[The "Chapter on health preservation" in the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr by Avenzoar (1095-1162)].

PubMed

Peña, Carmen; Girón, Fernando

2010-01-01

The Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr (The Method of Preparing Medicines and Diet) was written in Arabic by Avenzoar (1095-1162). It has yet to be translated into any Western modern language, and we wish to take on this task. We begin by offering an annotated Spanish translation (with commentary) of its preliminary "Chapter on the preservation of health". The Al-mohad caliph 'Abd al-Mu'min, for whom Avenzoar served as court physician, requested the book for his personal use. The work begins with this chapter, which contains measures for preventing and curing certain diseases. This section is followed by the main body of the book. It consists of a complete list of diseases working from head to toe and including their description, symptoms and treatment. The translated chapter is an atypical and concise treatise on the subject. It is presented in a quasi-aphoristic style that appears to have been used by Avenzoar to rapidly deal with the prevention area, in order to concentrate his efforts on what is surely one of the finest and most extensive mediaeval nosographies. We make this claim because our author does not exclusively use for this purpose the so-called "non-naturals"--the usual focus of health preservation measures of the time. Rather, he makes wide use of simple medicines with preventative ends--an unusual practice. Moreover, he indiscriminately intersperses prevention elements with others that are intended to cure. In order to better understand the meaning of this text, we previously refer to the foundations of health preservation practices in the mediaeval world, to the reasons why Avenzoar wrote the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr, and to the characteristics of its translated chapter. We also examine the medical sources and contents of this chapter.

Representations of the Bondi—Metzner—Sachs group in three space—time dimensions

NASA Astrophysics Data System (ADS)

Melas, Evangelos

2017-01-01

The original Bondi-Metzner-Sachs group B is the common asymptotic symmetry group of all asymptotically at Lorentzian 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, P. J. McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here, we construct the IRS of B(2, 1), the analogue of B, in 3 space-time dimensions. The IRS are induced from ‘little groups’ which are compact. The finite ‘little groups’ are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

Conserved charges of the extended Bondi-Metzner-Sachs algebra

NASA Astrophysics Data System (ADS)

Flanagan, Éanna É.; Nichols, David A.

2017-02-01

Isolated objects in asymptotically flat spacetimes in general relativity are characterized by their conserved charges associated with the Bondi-Metzner-Sachs (BMS) group. These charges include total energy, linear momentum, intrinsic angular momentum and center-of-mass location, and, in addition, an infinite number of supermomentum charges associated with supertranslations. Recently, it has been suggested that the BMS symmetry algebra should be enlarged to include an infinite number of additional symmetries known as super-rotations. We show that the corresponding charges are finite and well defined, and can be divided into electric parity "super center-of-mass" charges and magnetic parity "superspin" charges. The supermomentum charges are associated with ordinary gravitational-wave memory, and the super center-of-mass charges are associated with total (ordinary plus null) gravitational-wave memory, in the terminology of Bieri and Garfinkle. Superspin charges are associated with the ordinary piece of spin memory. Some of these charges can give rise to black hole hair, as described by Strominger and Zhiboedov. We clarify how this hair evades the no-hair theorems.

Synthesis and electrochemical characterization of TixTayAlzN1-δOγ for fuel cell catalyst supports

NASA Astrophysics Data System (ADS)

Wakabayashi, Ryo H.; Abruña, Héctor D.; DiSalvo, Francis J.

2017-02-01

Quinary TixTayAlzN1-δOγ of various compositions have been prepared by a co-precipitation method followed by ammonolysis. The nitride samples were examined as potential catalyst supports in polymer electrolyte membrane fuel cells. The nitride products crystallized in the rock salt (NaCl) structure over a wide range of compositions. The addition of Ta and Al was highly beneficial towards improving the chemical and electrochemical stability of TiN, without a significant loss of electrical conductivity. Platinum particles were successfully deposited on the (oxy)nitride samples, and the composite samples at some compositions were found to be comparable to Pt/carbon in their stability and catalytic activity even without optimizing the Pt deposition and dispersion processes.

The integrated Sachs-Wolfe signal from BOSS superstructures

NASA Astrophysics Data System (ADS)

Granett, B. R.; Kovács, A.; Hawken, A. J.

2015-12-01

Cosmic structures leave an imprint on the microwave background radiation through the integrated Sachs-Wolfe (ISW) effect. We construct a template map of the linear signal using the Sloan Digital Sky Survey-III Baryon Acoustic Oscillation Survey at redshift 0.43 < z < 0.65. We verify the imprint of this map on the Planck cosmic microwave background (CMB) temperature map at the 97 per cent confidence level and show consistency with the density-temperature cross-correlation measurement. Using this ISW reconstruction as a template, we investigate the presence of ISW sources and further examine the properties of the Granett-Neyrinck-Szapudi supervoid and supercluster catalogue. We characterize the three-dimensional density profiles of these structures for the first time and demonstrate that they are significant structures. Model fits demonstrate that the supervoids are elongated along the line of sight and we suggest that this special orientation may be picked out by the void-finding algorithm in photometric redshift space. We measure the mean temperature profiles in Planck maps from public void and cluster catalogues. In an attempt to maximize the stacked ISW signal, we construct a new catalogue of superstructures based upon local peaks and troughs of the gravitational potential. However, we do not find a significant correlation between these structures and the CMB temperature.

Right services to right patients at right time in right setting in Tays Eye Centre.

PubMed

Tuulonen, Anja; Kataja, Marko; Syvänen, Ulla; Miettunen, Sirpa; Uusitalo, Hannu

2016-11-01

The report describes the concepts behind procedures implemented in Tays Eye Centre to enable improved access to care and improved productivity. The strategy was developed in 2009 after hospital district decided to construct a new eye hospital which was opened in 2012. The following principles were implemented: (i) identification of high-volume patient groups: the 'big four' eye diseases accounting for 70% of patient visits and costs: age-related macular degeneration (AMD), glaucoma, retinal diseases and cataract; (ii) stratification and prioritization of patient care based on risk of permanent visual disability; (iii) standardization of services for low-risk patients; (iv) maximization of productivity; and (v) shared care. The impact of the new strategy on access to care and productivity is reported for years 2011-2015. In 2011-2015, the total number of services provided increased 46% while the work contribution increased 15%. The number of referrals increased 76% and the number of outpatient appointments increased 2.5-fold. Simultaneously, the number of delayed follow-up visits decreased to zero. Age-related macular degeneration (AMD) injections increased 1.8-fold. However, after 50% yearly increase in Age-related macular degeneration (AMD) injections, a plateau was reached in 2014 with a 3% decline in 2014-2015 with no changes in treatment indications. In the beginning of 2016, the number of injections has started to increase again (+9% compared to 2015).  The total number of surgical procedures increased 98%. The annual number of cataract surgeries increased 64% and bilateral surgeries from 11% to 39%. Revised operational concepts and new facilities together with a 15% increase in work contribution led to a 46% increase in overall productivity, improved access to care and the clearance of delayed services. Efforts continue to further refine cost-effective care and to define the appropriate levels of services. © 2016 Acta Ophthalmologica Scandinavica Foundation

Quaternions, Torsion and the Physical Vacuum: Theories of M. Sachs and G. Shipov Compared

NASA Astrophysics Data System (ADS)

Cyganski, David; Page, William S.

Of several developments of unified field theories in the spirit of Einstein's original objective of a fully geometric description of all classical fields as well as quantum mechanics, two are particularly noteworthy. The works of Mendel Sachs and Gennady Shipov stand apart as major life works comprising tens of papers, several monographs and decades of effort. Direct comparison of these theories is hampered however by differences in notation and conceptual view-point. Despite these differences, there are many parallels between the fundamental mathematical structures appearing in each. In this paper we discuss the main tenets of the two approaches and demonstrate that they both give rise to a factorization of the invariant interval of general relativity.

Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity[S

PubMed Central

Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

2015-01-01

Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

A SENSITIVE FLUORESCENCE-BASED ASSAY FOR MONITORING GM2 GANGLIOSIDE HYDROLYSIS IN LIVE PATIENT CELLS AND THEIR LYSATES

PubMed Central

Tropak, Michael B.; Bukovac, Scott W.; Rigat, Brigitte A.; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J.

2010-01-01

Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is anattractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are alsoinhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Herewe demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the β-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant β-hexosaminidase A and substrate-hydrolysis as compared to mock treated cells. PMID:19917668

A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates.

PubMed

Tropak, Michael B; Bukovac, Scott W; Rigat, Brigitte A; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J

2010-03-01

Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is an attractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are also inhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Here we demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the beta-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant beta-hexosaminidase A and substrate-hydrolysis as compared to mock-treated cells.

Carrier screening in the era of expanding genetic technology.

PubMed

Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

2016-12-01

The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, G.A.; Blitzer, M.G.; Mules, E.H.

A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the [beta]-hexosaminidase A (Hex A) [alpha]-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes. The mutation in the remaining allele was a single-base transition in the donor splice site of the [alpha]-subunit intron 9. To determine the origins of these two mutations in the Cajun population, the TSD carrier status was enzymatically determined formore » 90 members of four of the six families, and extensive pedigrees were constructed for all carriers. A single ancestral couple from France was found to be common to most of the carriers of the exon 11 insertion. Pedigree data suggest that this mutation has been in the Cajun population since its founding over 2 centuries ago and that it may be widely distributed within the population. In contrast, the intron 9 mutation apparently was introduced within the last century and probably is limited to a few Louisiana families. 29 refs., 4 figs.« less

Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.

PubMed

Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

2015-09-01

Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

The Late Integrated Sachs-Wolfe Effect and its detectability in galaxy-redshift surveys

NASA Astrophysics Data System (ADS)

Valencia-Díaz, D. R.; Muñoz-Cuartas, J. C.

2017-07-01

The late Integrated Sachs-Wolfe (ISW) effect is underwent by the Cosmic Microwave Background (CMB) photons due to the presence of the Large-Scale Structures (LSS) in an expanding Universe and can be measured through the temperature fluctuations of the CMB. In this work we use numerical simulations of structure formation to study the detectability of the ISW effect. Our method comprises the estimation of the density field through a Cloud-In-Cell mass assignment scheme. With the help of Fourier transforms we estimate the time derivative of the gravitational potential field in Fourier and in coordinate's space. Finally, this field is integrated numerically to know the ISW contribution. We study the time derivative of the potential in two approaches. First, an exact solution that makes use of the full velocity field. Second, a linear approximation related with the linear theory for the formation of LSS. We apply the method to three cosmological simulations. First, a box of 400 h-1 Mpc; second, the MultiDark1 simulation; third, the MultiDark-Plank simulation. For all cases we obtain coherent results with the expected in the literature for a ΛCDM cosmology: with the exact solution the temperature fluctuation is near the ± 30 μ K; the linear approximation shows a signal in the expected range of ± 20 μ K. This positive detection on simulations is important in order to know an expectation for the results we should obtain when working with observational data and will have important implications due to the lack of consensus about the detection of the ISW effect in previous works. Acknowledgements: This work was supported by Colciencias and Universidad de Antioquia, Convenio Beca-Pasantía Joven Investigador Convocatoria 645 de 2014.

Qualitative analysis of Kantowski-Sachs metric in a generic class of f(R) models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leon, Genly; Roque, Armando A., E-mail: genly.leon@ucv.cl, E-mail: arestrada@ucf.edu.cu

2014-05-01

In this paper we investigate, from the dynamical systems perspective, the evolution of a Kantowski-Sachs metric in a generic class of f(R) models. We present conditions (i.e., differentiability conditions, existence of minima, monotony intervals, etc.) for a free input function related to the f(R), that guarantee the asymptotic stability of well-motivated physical solutions, specially, self-accelerated solutions, allowing to describe both inflationary- and late-time acceleration stages of the cosmic evolution. We discuss which f(R) theories allows for a cosmic evolution with an acceptable matter era, in correspondence to the modern cosmological paradigm. We find a very rich behavior, and amongst othersmore » the universe can result in isotropized solutions with observables in agreement with observations, such as de Sitter, quintessence-like, or phantom solutions. Additionally, we find that a cosmological bounce and turnaround are realized in a part of the parameter-space as a consequence of the metric choice.« less

Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis.

PubMed

Tsuji, Daisuke; Akeboshi, Hiromi; Matsuoka, Kazuhiko; Yasuoka, Hiroko; Miyasaki, Eri; Kasahara, Yoshiko; Kawashima, Ikuo; Chiba, Yasunori; Jigami, Yoshifumi; Taki, Takao; Sakuraba, Hitoshi; Itoh, Kohji

2011-04-01

Novel recombinant human lysosomal β-hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay-Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency. A recombinant human HexA (Om4HexA) with a high mannose 6-phosphate (M6P)-type-N-glycan content, which was produced by a methylotrophic yeast strain, Ogataea minuta, overexpressing the OmMNN4 gene, was intracerebroventricularly (ICV) administered to Sandhoff disease model mice (Hexb⁻/⁻ mice) at different doses (0.5-2.5 mg/kg), and then the replacement and therapeutic effects were examined. The Om4HexA was widely distributed across the ependymal cell layer, dose-dependently restored the enzyme activity due to uptake via cell surface cation-independent M6P receptor (CI-M6PR) on neural cells, and reduced substrates, including GM2 ganglioside (GM2), asialo GM2 (GA2), and oligosaccharides with terminal N-acetylglucosamine residues (GlcNAc-oligosaccharides), accumulated in brain parenchyma. A significant inhibition of chemokine macrophage inflammatory protein-1 α (MIP-1α) induction was also revealed, especially in the hindbrain (< 63%). The decrease in central neural storage correlated with an improvement of motor dysfunction as well as prolongation of the lifespan. This lysosome-directed recombinant human enzyme drug derived from methylotrophic yeast has the high therapeutic potential to improve the motor dysfunction and quality of life of the lysosomal storage diseases (LSDs) patients with neurological manifestations. We emphasize the importance of neural cell surface M6P receptor as a delivery target of neural cell-directed enzyme replacement therapy (NCDERT) for neurodegenerative metabolic diseases. Copyright © 2010 American Neurological Association.

The Influence of Arthroscopic Remplissage for Engaging Hill-Sachs Lesions Combined with Bankart Repair on Redislocation and Shoulder Function Compared with Bankart Repair Alone.

PubMed

Ko, Sang-Hun; Cha, Jae-Ryong; Lee, Chae-Chil; Hwang, Il-Yeong; Choe, Chang-Gyu; Kim, Min-Seok

2016-12-01

Recurrence of glenohumeral dislocation after arthroscopic Bankart repair can be associated with a large osseous defect in the posterosuperior part of the humeral head. Our hypothesis is that remplissage is more effective to prevent recurrence of glenohumeral instability without a severe motion deficit. Engaging Hill-Sachs lesions were observed in 48 of 737 patients (6.5%). Twenty-four patients underwent arthroscopic Bankart repair combined with remplissage (group I) and the other 24 patients underwent arthroscopic Bankart repair alone (group II). Clinical outcomes were prospectively evaluated by assessing the range of motion. Complications, recurrence rates, and functional results were assessed utilizing the American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and the Korean Shoulder Score for Instability (KSSI) score. Capsulotenodesis healing after remplissage was evaluated with magnetic resonance imaging. The average ASES, Rowe, and KSSI scores were statistically significantly higher in group I than group II. The frequency of recurrence was statistically significantly higher in group II. The average loss in external rotation measured with the arm positioned at the side of the trunk was greater in group II and that in abduction was also higher in group II. Compared to single arthroscopic Bankart repair, the remplissage procedure combined with arthroscopic Bankart repair was more effective to prevent the recurrence of anterior shoulder instability without significant impact on shoulder mobility in patients who had huge Hill-Sachs lesions.

The cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Zieser, Britta; Merkel, Philipp M.

2016-06-01

We present the first calculation of the cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe (iSW) effect. Both signals are combined in a single formalism, which permits the computation of the full covariance matrix. In order to avoid the uncertainties presented by the non-linear evolution of the matter power spectrum and intrinsic alignments of galaxies, our analysis is restricted to large scales, I.e. multipoles below ℓ = 1000. We demonstrate in a Fisher analysis that this reduction compared to other studies of 3D weak lensing extending to smaller scales is compensated by the information that is gained if the additional iSW signal and in particular its cross-correlation with lensing data are considered. Given the observational standards of upcoming weak-lensing surveys like Euclid, marginal errors on cosmological parameters decrease by 10 per cent compared to a cosmic shear experiment if both types of information are combined without a cosmic wave background (CMB) prior. Once the constraining power of CMB data is added, the improvement becomes marginal.

Degeneracy between nonadiabatic dark energy models and Λ CDM : Integrated Sachs-Wolfe effect and the cross correlation of CMB with galaxy clustering data

NASA Astrophysics Data System (ADS)

Velten, Hermano; Fazolo, Raquel Emy; von Marttens, Rodrigo; Gomes, Syrios

2018-05-01

As recently pointed out in [Phys. Rev. D 96, 083502 (2017), 10.1103/PhysRevD.96.083502] the evolution of the linear matter perturbations in nonadiabatic dynamical dark energy models is almost indistinguishable (quasidegenerated) to the standard Λ CDM scenario. In this work we extend this analysis to CMB observables in particular the integrated Sachs-Wolfe effect and its cross-correlation with large scale structure. We find that this feature persists for such CMB related observable reinforcing that new probes and analysis are necessary to reveal the nonadiabatic features in the dark energy sector.

Crohns disease: a case report.

PubMed

Adi, Ashindoitiang John; Lloyd, Geoffrey J

2010-01-01

Inflammatory bowel disease (IBD) was previously regarded as a disease of the Western Countries. A number of studies showed a high incidence and prevalence of inflammatory bowel disease in United States, United Kingdom and Northern Europe, whereas it was considered uncommon in Asians population and rare in Africa. To report case of crohns disease that is rare in the tropic like Nigeria so as to create a high index of awareness that inflammatory bowel disease may be present but not correctly diagnosed

Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts.

PubMed

Kitakaze, Keisuke; Tasaki, Chikako; Tajima, Youichi; Hirokawa, Takatsugu; Tsuji, Daisuke; Sakuraba, Hitoshi; Itoh, Kohji

2016-09-01

GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA , HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses.

Addison's disease secondary to connective tissue diseases: a report of six cases.

PubMed

Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

2009-04-01

Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

78 FR 71532 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. [[Page 71533... (AD) 2007-03- 02 for all Rolls-Royce Deutschland (RRD) Tay 620-15, Tay 650-15, and Tay 651-54 turbofan..., January 29, 2007) (``AD 2007-03-02'') for certain RRD Tay 611-8 and Tay 620-15 turbofan engines with LP...

Disease severity in familial cases of IBD.

PubMed

Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

2014-03-01

Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

Diffuse Lewy body disease: clinical features in 15 cases.

PubMed Central

Byrne, E J; Lennox, G; Lowe, J; Godwin-Austen, R B

1989-01-01

Fifteen cases of diffuse Lewy body disease were diagnosed on pathological grounds during a single year in one health district. The range and frequency of clinical features contrast strikingly with previous reports. The majority of cases presented with classical levodopa-responsive Parkinson's disease either alone (6 cases) or with mild cognitive impairment (3 cases); the remaining 6 cases presented with cognitive impairment alone. In time almost all patients developed both dementia and Parkinsonism. The dementia was cortical in type, but unusual in that most (12 cases) showed day-to-day fluctuation in severity at some point in their illness. These findings suggest that diffuse Lewy body disease is not rare, and that it presents in a range of ways from dementia with subsequent Parkinsonism to Parkinson's disease with subsequent dementia. The latter mode of presentation suggests that it should be considered as a significant pathological substrate of dementia in Parkinson's disease. Images PMID:2545827

Integrated Sachs-Wolfe map reconstruction in the presence of systematic errors

NASA Astrophysics Data System (ADS)

Weaverdyck, Noah; Muir, Jessica; Huterer, Dragan

2018-02-01

The decay of gravitational potentials in the presence of dark energy leads to an additional, late-time contribution to anisotropies in the cosmic microwave background (CMB) at large angular scales. The imprint of this so-called integrated Sachs-Wolfe (ISW) effect to the CMB angular power spectrum has been detected and studied in detail, but reconstructing its spatial contributions to the CMB map, which would offer the tantalizing possibility of separating the early- from the late-time contributions to CMB temperature fluctuations, is more challenging. Here, we study the technique for reconstructing the ISW map based on information from galaxy surveys and focus in particular on how its accuracy is impacted by the presence of photometric calibration errors in input galaxy maps, which were previously found to be a dominant contaminant for ISW signal estimation. We find that both including tomographic information from a single survey and using data from multiple, complementary galaxy surveys improve the reconstruction by mitigating the impact of spurious power contributions from calibration errors. A high-fidelity reconstruction further requires one to account for the contribution of calibration errors to the observed galaxy power spectrum in the model used to construct the ISW estimator. We find that if the photometric calibration errors in galaxy surveys can be independently controlled at the level required to obtain unbiased dark energy constraints, then it is possible to reconstruct ISW maps with excellent accuracy using a combination of maps from two galaxy surveys with properties similar to Euclid and SPHEREx.

Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan.

PubMed

Herbort, Carl P; Mochizuki, Manabu

2007-01-01

To delineate the historical steps associated with the genesis of the name and the definition of Vogt-Koyanagi-Harada (VKH) disease. A bibliographical review of the major publications that were relevant to the original development of the name of the clinical entity known today as Vogt-Koyanagi-Harada disease, in the historical context of the early 20th century. Three distinct time periods can be considered to be important in terms of providing a historical perspective on VKH disease. Given that the cutaneous manifestations of VKH disease are so characteristic, these could not have been missed even before the actual clinical entity of VKH was recognized in the early 20th century. Indeed, several authors, including the Arabic doctor Mohammad-al-Ghâfiqî in the 12th century as well as Jacobi, Nettelship and Tay in the 19th century, described poliosis, neuralgias and hearing disorders. Many of these cases were probably due to sympathetic ophthalmia, but some were clearly VKH cases. The second phase is characterized by the surge of articles that appeared early in the 20th century that defined the disease more precisely. A number of these authors subsequently became associated with the disease name, the first being Alfred Vogt from Switzerland, followed by Japanese researchers. Yoshizo Koyanagi was in fact not the first Japanese author to describe the disease; this honor goes to the first Japanese Professor of Ophthalmology at the University of Tokyo, Dr. Jujiro Komoto, who published in a German language journal, Klinische Monatsblätter für Augenheilkunde in 1911. Yoshizo Koyanagi published his first report in the Nippon Ganka Gakkai Zasshi 3 years later, in 1914, but it was a much later article, one published in 1929, that definitively associated his name with the disease. In this review article, Koyanagi reported 16 cases, of which six were his own cases, that beautifully illustrate the natural course of the disease. In this same time period, Einosuke Harada, in an

Pinpointing clusters of apparently sporadic cases of Legionnaires' disease.

PubMed Central

Bhopal, R. S.; Diggle, P.; Rowlingson, B.

1992-01-01

OBJECTIVES--To test the hypothesis that many non-outbreak cases of legionnaires' disease are not sporadic and to attempt to pinpoint cases clustering in space and time. DESIGN--Descriptive study of a case series, 1978-86. SETTING--15 health boards in Scotland. PATIENTS--203 probable cases of non-outbreak, non-travel, community acquired legionnaires' disease in patients resident in Scotland. MAIN MEASURES--Date of onset of disease and postcode and health board of residence of cases. RESULTS--Space-time clustering was present and numerous groups of cases were identified, all but two being newly recognised. Nine cases occurred during three months within two postcodes in Edinburgh, and an outbreak was probably missed. In several places cases occurred in one area over a prolonged period--for example, nine cases in postcode districts G11.5 and G12.8 in Glasgow during five years (estimated mean annual incidence of community acquired, non-outbreak, non-travel legionnaires' disease of 146 per million residents v 4.8 per million for Scotland). Statistical analysis showed that the space time clustering of cases in the Glasgow and Edinburgh areas was unusual (p = 0.036, p = 0.068 respectively). CONCLUSION--Future surveillance requires greater awareness that clusters can be overlooked; case searching whenever a case is identified; collection of complete information particularly of date of onset of the disease and address or postcode; ongoing analysis for space-time clustering; and an accurate yet workable definition of sporadic cases. Other researchers should re-examine their data on apparently sporadic infection. PMID:1586784

78 FR 17079 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... Tay 620-15 and Tay 650-15 turbofan engines with a low-pressure compressor (LPC) rotor disc assembly...

Chagasic cardiomyopathy and Pompe disease: case report

PubMed Central

de Morais, Rafael OB; Chaves-Markman, Ândrea V; Miranda, Anna PP; Amorim, Ingrid G; Cavalcanti, Maria da GA de M; Markman, Manuel; Markman-Filho, Brivaldo

2018-01-01

Background: Pompe disease is a lysosomal storage disease with an autosomal recessive inheritance characterized by an insufficient activity of the acid alpha-glucosidase enzyme. The incidence varies from 1:40000 to 1:200000 live births and cardiac involvement in adults is rare. Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, in which one-third of the cases progress to the chronic form, and may lead to cardiac involvement, usually from the fifth decade of life onwards. We report a case of a patient with Chagas and Pompe diseases who had early cardiac involvement and rapid evolution to heart failure. Case report: A 43-year-old male patient with a history of ischemic stroke at 28 years with gait ataxia sequelae. A few years after the episode, he experienced gait impairment and difficulty climbing stairs, attributed to stroke. A family screening for Pompe disease was carried out years later, and thus the diagnosis was made. As for Chagas disease, the investigation was performed because the patient lives in an endemic area. The cardiovascular physical examination did not show significant changes. The electrocardiogram showed sinus rhythm with left bundle branch block and first-degree atrioventricular block; the transthoracic echocardiogram demonstrated left ventricular systolic dysfunction; the Holter monitoring showed several episodes of ventricular tachycardia. The patient is undergoing optimized treatment for heart failure and enzyme replacement therapy for Pompe disease. Conclusion: Cardiomyopathy with early onset and with rapid evolution suggests overlap of the two diseases. PMID:29755837

Case for diagnosis. Metastatic Crohn's disease*

PubMed Central

Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; de Sousa, Maria Silvia Laborne Alves

2016-01-01

Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

Periodontal disease and anemias associated with Crohn's disease. A case report.

PubMed

Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L

2012-03-01

Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.

Reproductive health and genetic testing in the Third World.

PubMed

Penchaszadeh, V B

1993-09-01

New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.

[Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases].

PubMed

Frikha, F; Marzouk, S; Frigui, M; Jallouli, M; Kechaou, M; Kaddour, N; Boudawara, T; Jlidi, R; Bahloul, Z

2008-02-01

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.

The first case of imported Borrelia miyamotoi disease concurrent with Lyme disease.

PubMed

Oda, Rentaro; Kutsuna, Satoshi; Sekikawa, Yoshiyuki; Hongo, Igen; Sato, Kozue; Ohnishi, Makoto; Kawabata, Hiroki

2017-05-01

Borrelia miyamotoi disease (BMD) is an emerging infectious disease caused by B. miyamotoi. Although BMD has been reported in the United States, Europe, and Japan, no case of imported BMD has been described in the world. Here, we report a 63-year-old American man living in Japan who presented with malaise, headache, myalgia, and arthralgia. We suspected Lyme disease because of his travel history to Minnesota and presence of erythema migrans. Serologic analysis supported our diagnosis, and doxycycline was administered for 14 days. However, we also suspected coinfection with BMD because of his fever, elevated liver function test results and his travel history. The patient was seropositive for the immunoglobulin M antibody to recombinant glycerophosphodiester phosphodiesterase, and was diagnosed with coinfection with BMD. This case suggests that BMD should be considered in febrile travelers returning from the Northeastern and Midwestern regions of the United States, and that BMD and Lyme disease coinfection should be considered to detect cases of imported BMD. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

PubMed Central

Brandt-Rauf, Sherry I.; Raveis, Victoria H.; Drummond, Nathan F.; Conte, Jill A.; Rothman, Sheila M.

2006-01-01

We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay–Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815

On the representation theory of the Bondi-Metzner-Sachs group and its variants in three space-time dimensions

NASA Astrophysics Data System (ADS)

Melas, Evangelos

2017-07-01

The original Bondi-Metzner-Sachs (BMS) group B is the common asymptotic symmetry group of all asymptotically flat Lorentzian radiating 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here we introduce the analogue B(2, 1) of the BMS group B in 3 space-time dimensions. B(2, 1) itself admits thirty-four analogues both real in all signatures and in complex space-times. In order to find the IRS of both B(2, 1) and its analogues, we need to extend Wigner-Mackey's theory of induced representations. The necessary extension is described and is reduced to the solution of three problems. These problems are solved in the case where B(2, 1) and its analogues are equipped with the Hilbert topology. The extended theory is necessary in order to construct the IRS of both B and its analogues in any number d of space-time dimensions, d ≥3 , and also in order to construct the IRS of their supersymmetric counterparts. We use the extended theory to obtain the necessary data in order to construct the IRS of B(2, 1). The main results of the representation theory are as follows: The IRS are induced from "little groups" which are compact. The finite "little groups" are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

A Lyme Disease Case Study and Individualized Healthcare Plan

ERIC Educational Resources Information Center

Cavendish, Roberta

2003-01-01

The Atlantic and Pacific coasts are the boundaries of Lyme disease with the Northeastern and Midwestern regions of the United States continuing to report the majority of cases. New reported cases of Lyme disease doubled from 1991 to 2001 according to statistics published by the Centers for Disease Control and Prevention (CDC, 2002). Within that…

[Eye and cat scratch disease: A case series].

PubMed

Deschasse, C; Bielefeld, P; Muselier, A; Bour, J B; Besancenot, J F; Garcher, C C; Bron, A M

2016-02-01

Cat scratch disease is a pleiomorphic condition, sometimes with isolated ophthalmic involvement. We report the clinical observations of seven cases with ophthalmologic manifestations of cat scratch disease. There were seven patients, with a median age of 52 years, of whom five were women and three had unilateral involvement. Six exhibited Leber's stellate neuroretinitis, an incomplete syndrome in two cases, and one associated with chorioretinal foci. One patient had isolated retinal infiltrates. The diagnosis of cat scratch disease was confirmed by Bartonella henselae serology, positive in all cases. All patients received treatment with doxycycline. Ocular complications (with optic atrophy and macular retinal pigment epithelial changes) were noted in five cases. Ocular bartonellosis is an atypical clinical form. It requires a directed ancillary work-up with serology or PCR, which has the peculiarity of being highly specific if not very sensitive. Treatment is above all preventive. Antibiotics may be initiated. Cat scratch disease must be excluded in the work-up of posterior uveitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Addison's Disease Mimicking as Acute Pancreatitis: A Case Report.

PubMed

Chaudhuri, Sayani; Rao, Karthik N; Patil, Navin; Ommurugan, Balaji; Varghese, George

2017-04-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison's disease. Adrenal insufficiency (Addison's disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison's disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis.

Integrated Sachs-Wolfe effect from the cross correlation of WMAP 3year and the NRAO VLA sky survey data: New results and constraints on dark energy

NASA Astrophysics Data System (ADS)

Pietrobon, Davide; Balbi, Amedeo; Marinucci, Domenico

2006-08-01

We cross correlate the new 3 year Wilkinson Microwave Anistropy Probe (WMAP) cosmic microwave background data with the NRAO VLA Sky Survey radio galaxy data and find further evidence of late integrated Sachs-Wolfe (ISW) effect taking place at late times in cosmic history. Our detection makes use of a novel statistical method (P. Baldi, G. Kerkyacharian, D. Marinucci, and D. Picard, math.ST/0606154 and P. Baldi, G. Kerkyacharian, D. Marinucci, D. Picard, math.ST/0606599) based on a new construction of spherical wavelets, called needlets. The null hypothesis (no ISW) is excluded at more than 99.7% confidence. When we compare the measured cross correlation with the theoretical predictions of standard, flat cosmological models with a generalized dark energy component parameterized by its density, ΩDE, equation of state w and speed of sound cs2, we find 0.3≤ΩDE≤0.8 at 95% C.L., independently of cs2 and w. If dark energy is assumed to be a cosmological constant (w=-1), the bound on density shrinks to 0.41≤ΩDE≤0.79. Models without dark energy are excluded at more than 4σ. The bounds on w depend rather strongly on the assumed value of cs2. We find that models with more negative equation of state (such as phantom models) are a worse fit to the data in the case cs2=1 than in the case cs2=0.

Kawasaki disease following Rocky Mountain spotted fever: a case report

PubMed Central

2009-01-01

Introduction Kawasaki disease is an idiopathic acute systemic vasculitis of childhood. Although it simulates the clinical features of many infectious diseases, an infectious etiology has not been established. This is the first reported case of Kawasaki disease following Rocky Mountain spotted fever. Case presentation We report the case of a 4-year-old girl who presented with fever and petechial rash. Serology confirmed Rocky Mountain spotted fever. While being treated with intravenous doxycycline, she developed swelling of her hands and feet. She had the clinical features of Kawasaki disease which resolved after therapy with intravenous immune globulin (IVIG) and aspirin. Conclusion This case report suggests that Kawasaki disease can occur concurrently or immediately after a rickettsial illness such as Rocky Mountain spotted fever, hypothesizing an antigen-driven immune response to a rickettsial antigen. PMID:19830185

The role of the case manager in a disease management program.

PubMed

Huston, Carol J

2002-01-01

Disease management programs provide new opportunities and roles for case managers to provide population-based healthcare to the chronically ill. This article identifies common components of disease management programs and examines roles assumed by case managers in disease management programs such as baseline assessment, performing economic analyses of diseases and their respective associated resource utilization, developing and/or implementing care guidelines or algorithms, educational interventions, disease management program implementation, and outcomes assessment. Areas of expertise needed to be an effective case manager in a disease management program are also identified.

The role of the case manager in a disease management program.

PubMed

Huston, C J

2001-01-01

Disease management programs provide new opportunities and roles for case managers to provide population-based healthcare to the chronically ill. This article identifies common components of disease management programs and examines roles assumed by case managers in disease management programs such as baseline assessment, performing economic analyses of diseases and their respective associated resource utilization, developing and/or implementing care guidelines or algorithms, educational interventions, disease management program implementation, and outcomes assessment. Areas of expertise needed to be an effective case manager in a disease management program are also identified.

[Juvenile Parkinson's disease and recurring prematurity. Case report].

PubMed

Ha, D-E; Legendre, G; Colau, J-C

2007-03-01

The association of Parkinson's disease and pregnancy is very rare. Some thirty cases are found in the literature. We report the case of a pregnancy in a 30-year-old patient with juvenile Parkinson's disease. During this pregnancy treated by levodopa and bromocriptine, no aggravation of the symptoms was been observed. However, the pregnancy was complicated by a premature delivery at 31 weeks of amenorrhoea.

Magnification-temperature correlation: The dark side of integrated Sachs-Wolfe measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

LoVerde, Marilena; Hui, Lam; Gaztanaga, Enrique

2007-02-15

Integrated Sachs-Wolfe (ISW) measurements, which involve cross-correlating the microwave background anisotropies with the foreground large-scale structure (e.g. traced by galaxies/quasars), have proven to be an interesting probe of dark energy. We show that magnification bias, which is the inevitable modulation of the foreground number counts by gravitational lensing, alters both the scale dependence and amplitude of the observed ISW signal. This is true especially at high redshifts because (1) the intrinsic galaxy-temperature signal diminishes greatly back in the matter-dominated era, (2) the lensing efficiency increases with redshift and (3) the number count slope generally steepens with redshift in a magnitudemore » limited sample. At z > or approx. 2, the magnification-temperature correlation dominates over the intrinsic galaxy-temperature correlation and causes the observed ISW signal to increase with redshift, despite dark energy subdominance--a result of the fact that magnification probes structures all the way from the observer to the sources. Ignoring magnification bias therefore can lead to (significantly) erroneous conclusions about dark energy. While the lensing modulation opens up an interesting high z window for ISW measurements, high redshift measurements are not expected to add much new information to low redshift ones if dark energy is indeed the cosmological constant. This is because lensing introduces significant covariance across redshifts. The most compelling reasons for pursuing high redshift ISW measurements are to look for potential surprises such as early dark energy domination or signatures of modified gravity. We conclude with a discussion of existing measurements, the highest redshift of which is at the margin of being sensitive to the magnification effect. We also develop a formalism which might be of more general interest: to predict biases in estimating parameters when certain physical effects are ignored in interpreting

Hansen’s Disease with HIV: A Case of Immune Reconstitution Disease

PubMed Central

Chow, Dominic; Okinaka, Leila; Souza, Scott; Shikuma, Cecilia; Tice, Alan

2009-01-01

Immune reconstitution inflammatory syndrome (IRIS) is an acute symptomatic expression of a latent infection during the recovery of the immune system usually as a response to antiretroviral therapy (ART). Opportunistic infections can trigger IRIS. Hansen’s disease is an infection caused by Mycobacterium leprae (M. leprae). There have been a limited number of case reports reporting the presentation of the co-infection of HIV and M. leprae. We report an unique case of IRIS in a patient co-infected with HIV and M. leprae presenting as an exacerbation of his Hansen’s Disease where the patient’s skin lesions progressed from borderline tuberculoid to lepromatous leprosy following ART administration. PMID:19385373

Enterohepatic fistula in a Crohn's disease patient: A case report.

PubMed

Van Backer, Justin T; Lee, Edward C

2017-01-01

Fistulous tracts are a hallmark of Crohn's Disease. However, solid organ to intestinal fistulas are rare with previously few case reports of colosplenic fistulas and one case report of an enterohepatic fistula. We review the available literature and present the first case report of an enterohepatic fistula in a female with Crohn's Disease to be treated operatively. The patient did well postoperatively with complete resolution of her fistula. Crohn's Disease is an inflammatory bowel disease that can present with fistulas. However, a fistula between the liver and bowel is exceedingly rare with only one previous case report. This is the first report of an enteroheptic fistula that has been managed successfully with an operation. Not all enteroenteric fistulas are apparent preoperatively. When discovered, laparoscopic enterohepatic fistula takedown is feasible for this rare disease process manifestation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

PubMed

Pan, Xuefang; De Aragão, Camila De Britto Pará; Velasco-Martin, Juan P; Priestman, David A; Wu, Harry Y; Takahashi, Kohta; Yamaguchi, Kazunori; Sturiale, Luisella; Garozzo, Domenico; Platt, Frances M; Lamarche-Vane, Nathalie; Morales, Carlos R; Miyagi, Taeko; Pshezhetsky, Alexey V

2017-08-01

Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, G M3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of G M1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of G M2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of β-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. © FASEB.

A rare case of Weil's disease with alveolar haemorrhage.

PubMed

Chakrabarti, Abhiram; Nandy, Manab; Pal, Dipankar; Mallik, Sudesna

2014-05-01

Leptospirosis, a disease of protean manifestations occurs sporadically throughout the year with a peak seasonal incidence during the rainy season mimicking other febrile viral illness. In the rare case, the disease leads to renal and hepatic involvement with hemorrhage which may be associated with multisystem organ dysfunction in form of pulmonary, cardiac and central nervous system, when it is known as Weil's disease. Rarely haemorrhagic manifestations are assosciated. Early diagnosis is important as sometimes the disease may be life threatening. Proper antibiotics results in dramatic improvement. We hereby presented a case that had clinical features of Weil's disease with cough, dyspnoea and haemoptysis. Leptospirosis was detected on ELISA testing. Patient was cured rapidly with antibiotics.

Kawasaki disease following Rocky Mountain spotted fever: a case report.

PubMed

Bal, Aswine K; Kairys, Steven W

2009-07-06

Kawasaki disease is an idiopathic acute systemic vasculitis of childhood. Although it simulates the clinical features of many infectious diseases, an infectious etiology has not been established. This is the first reported case of Kawasaki disease following Rocky Mountain spotted fever. We report the case of a 4-year-old girl who presented with fever and petechial rash. Serology confirmed Rocky Mountain spotted fever. While being treated with intravenous doxycycline, she developed swelling of her hands and feet. She had the clinical features of Kawasaki disease which resolved after therapy with intravenous immune globulin (IVIG) and aspirin. This case report suggests that Kawasaki disease can occur concurrently or immediately after a rickettsial illness such as Rocky Mountain spotted fever, hypothesizing an antigen-driven immune response to a rickettsial antigen.

Addison’s Disease Mimicking as Acute Pancreatitis: A Case Report

PubMed Central

Chaudhuri, Sayani; Rao, Karthik N; Ommurugan, Balaji; Varghese, George

2017-01-01

Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison’s disease. Adrenal insufficiency (Addison’s disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison’s disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis. PMID:28571196

Carotid body tumor imitator: An interesting case of Castleman's disease.

PubMed

Shakir, Hakeem J; Diletti, Sara M; Hart, Alexandra M; Meyers, Joshua E; Dumont, Travis M; Siddiqui, Adnan H

2015-01-01

There are very few reports in the literature of Castleman's disease affecting the carotid artery and a single previous report of a case of Castleman's disease of the neck originally mistaken as a carotid body tumor. We describe a rare case of Castleman's disease, manifesting with classic radiographic hallmarks of a carotid body tumor. The postoperative pathologic examination identified the resected mass as Castleman's lymphadenopathy. The management of this particular case is discussed, and the findings are highlighted. We present a unique case of a tumor initially and incorrectly diagnosed as a carotid body tumor. However, after comprehensive treatment with endovascular and surgical modalities and subsequent pathologic examination, the diagnosis of this rare entity was made.

Early recognition of Cushing's disease: a case study.

PubMed

Iuliano, Sherry L; Laws, Edward R

2013-08-01

To present a case study of a 34-year-old woman with Cushing's disease and provide nurse practitioners (NPs) with the understanding of the clinical presentation needed for early recognition and treatment of the disease. A comprehensive review of published literature on Cushing's disease. Findings from history, physical examination, and diagnostic studies of a woman presenting to primary care NPs, physicians and other healthcare providers with multiple symptoms of Cushing's disease. Cushing's disease is the result of the pituitary gland producing excess amounts of adrenocorticotropic hormone (ACTH) causing the overproduction of cortisol. The disease is fairly rare and is seen mostly in women. Common chief complaints include increased facial hair, weight gain, amenorrhea, changes in the face, neck, and abdomen, with muscle wasting of the lower extremities. Untreated, diabetes mellitus and hypertension can occur and increase the patient's morbidity and mortality. Early recognition and appropriate referral can reverse the signs and symptoms over time and lead to a significantly improved quality of life. This case presented the challenges faced by NPs and physicians in diagnosing patients with Cushing's disease. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

Description of new species of Pterygorhabditis Timm, and Aspidonema (Sachs, ) Andrássy, (Nematoda: Bunonematoidea) in aquatic habitats from India.

PubMed

Tahseen, Q; Khan, R; Ahlawat, S

2016-07-01

The paper contains descriptions of two new species of the genera Pterygorhabditis Timm, 1957 and Aspidonema (Sachs, 1949) Andrássy, 1958 belonging to the families Pterygorhabditidae Goodey 1963 and Bunonematidae Micoletzky 1922, respectively. Species were procured from fixed samples, collected earlier from aquatic habitats. Pterygorhabditis punctata n. sp. is characterized by a cuticle with flattened hexagonal blocks arranged in eight longitudinal rows in both sexes; each metastegostomal plate with a minute denticle, and males with long, slender, fused spicules and nine pairs of post-cloacal, prominently setose genital papillae. Aspidonema formosa n. sp. is the first report of the genus from India. The species is characterized by the right side provided with 35-48 pairs of warts flanking a row of smooth membranous shields and surrounded by a well-developed network and an anisomorphic metastegostom without discernible armature. Species are compared with other congeners, together with the diagnoses of amended genera, and keys to the identification of species are provided.

Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice.

PubMed

Osmon, Karlaina J L; Woodley, Evan; Thompson, Patrick; Ong, Katalina; Karumuthil-Melethil, Subha; Keimel, John G; Mark, Brian L; Mahuran, Don; Gray, Steven J; Walia, Jagdeep S

2016-07-01

mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay-Sachs disease (α-subunit deficiency) and similar brain disorders.

First confirmed case of Powassan neuroinvasive disease in Rhode Island.

PubMed

Patel, Kavin M; Johnson, Jennie; Zacharioudakis, Ioannis M; Boxerman, Jerrold L; Flanigan, Timothy P; Reece, Rebecca M

2018-01-01

The Powassan Virus is the arthropod-borne vector responsible for Powassan neuroinvasive disease. The virus was first isolated in 1958 and has been responsible for approximately 100 cases of neuroinvasive disease. Rates of infection have been on the rise over the past decade with numerous states reporting their first confirmed case; New Jersey, New Hampshire and Connecticut all reported their first case within the last five years. We present here the first confirmed case of Powassan neuroinvasive disease in the nearby state of Rhode Island. A previously healthy 81-year-old female with known tick exposure presented with fever, altered sensorium, seizures and focal neurological deficits. After an extensive work-up that was largely unrevealing Powassan encephalitis was suspected. The diagnosis was confirmed with serological testing consisting of Powassan IgM enzyme-linked immunosorbent assay and Powassan plaque reduction neutralization testing. The case study provides evidence for the increasing spread of Powassan neuroinvasive disease and reinforces the importance of requesting focused testing for Powassan Virus in patients from an endemic area with a clinically compatible syndrome.

Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre

PubMed Central

Toledo, Jon B.; Arnold, Steven E.; Raible, Kevin; Brettschneider, Johannes; Xie, Sharon X.; Grossman, Murray; Monsell, Sarah E.; Kukull, Walter A.

2013-01-01

Cerebrovascular disease and vascular risk factors are associated with Alzheimer’s disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer’s Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer’s disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 ‘unremarkable brain’ cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer’s disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer’s disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in

Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

DOE PAGES

Ade, P. A. R.; Aghanim, N.; Arnaud, M.; ...

2016-09-20

Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

Planck 2015 results. XXI. The integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartolo, N.; Basak, S.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bock, J. J.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Bucher, M.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Casaponsa, B.; Catalano, A.; Challinor, A.; Chamballu, A.; Chiang, H. C.; Christensen, P. R.; Church, S.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Désert, F.-X.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dupac, X.; Efstathiou, G.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Fergusson, J.; Fernandez-Cobos, R.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Frejsel, A.; Galeotta, S.; Galli, S.; Ganga, K.; Génova-Santos, R. T.; Giard, M.; Giraud-Héraud, Y.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Leonardi, R.; Lesgourgues, J.; Levrier, F.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Ma, Y.-Z.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Marcos-Caballero, A.; Maris, M.; Martin, P. G.; Martínez-González, E.; Masi, S.; Matarrese, S.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rossetti, M.; Roudier, G.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savelainen, M.; Savini, G.; Schaefer, B. M.; Scott, D.; Seiffert, M. D.; Shellard, E. P. S.; Spencer, L. D.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sunyaev, R.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Valenziano, L.; Valiviita, J.; Van Tent, F.; Vielva, P.; Villa, F.; Wade, L. A.; Wandelt, B. D.; Wehus, I. K.; Yvon, D.; Zacchei, A.; Zonca, A.

2016-09-01

This paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and the NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that ΩΛ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by combining the

Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ade, P. A. R.; Aghanim, N.; Arnaud, M.

Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

Case for diagnosis. Riga-Fede disease.

PubMed

Calistru, Ana Maria; Lisboa, Carmen; Bettencourt, Herberto; Azevedo, Filomena

2012-01-01

Riga-Fede disease is a rare, benign disorder characterized by reactive ulceration of the oral mucosa associated with repetitive dental traumatism. It was first described in children with neurologic disorders and is very rare in adults. This case report describes the occurrence of a large ulcer of the tongue, resembling squamous cell carcinoma, in an adult with hemiparesis. The lesion cleared after neurologic recovery. This case highlights the importance of considering this disorder in the differential diagnosis of oral mucosal ulcerations.

The neuropsychiatric aspect of Addison's disease: a case report.

PubMed

Abdel-Motleb, Mohamed

2012-10-01

Chronic adrenal insufficiency, known as Addison's disease, presents with a constellation of symptoms and signs. The neuropsychiatric aspect of this condition is not fully understood and not much has been documented about it in the English literature. This article presents a case of a 41-year old male patient who presented initially with depression after a recent life stressor. After his condition escalated and therapy continued to fail, the medical team revised its diagnosis to Addison's disease. Neuropsychiatric symptoms could be the first presentation of Addison's disease, and thus should be kept in mind whenever such a case presents to the physician.

A Case of Sporadic Creutzfeldt-Jakob Disease Presenting as Conversion Disorder.

PubMed

Yegya-Raman, Nikhil; Aziz, Rehan; Schneider, Daniel; Tobia, Anthony; Leitch, Megan; Nwobi, Onyi

2017-01-01

Background . Creutzfeldt-Jakob disease is a rare disorder of the central nervous system. Its initial diagnosis may be obscured by its variable presentation. This case report illustrates the complexity of diagnosing this disease early in the clinical course, especially when the initial symptoms may be psychiatric. It offers a brief review of the literature and reinforces a role for consultation psychiatry services. Methods . PUBMED/MEDLINE was searched using the terms "Creutzfeldt-Jakob disease", "psychiatric symptoms", "conversion disorder", "somatic symptom disorder", "functional movement disorder", and "functional neurologic disorder". Case . The patient was a 64-year-old woman with no prior psychiatric history who was initially diagnosed with conversion disorder and unspecified anxiety disorder but soon thereafter was discovered to have Creutzfeldt-Jakob disease. Discussion . This case highlights the central role of psychiatric symptoms in early presentations of Creutzfeldt-Jakob disease. Still, few other cases in the literature report functional neurological symptoms as an initial sign. The consultation psychiatrist must remain alert to changing clinical symptoms, especially with uncharacteristic disease presentations.

Constraining neutrino masses with the integrated-Sachs-Wolfe-galaxy correlation function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesgourgues, Julien; Valkenburg, Wessel; Gaztanaga, Enrique

2008-03-15

Temperature anisotropies in the cosmic microwave background (CMB) are affected by the late integrated Sachs-Wolfe (lISW) effect caused by any time variation of the gravitational potential on linear scales. Dark energy is not the only source of lISW, since massive neutrinos induce a small decay of the potential on small scales during both matter and dark energy domination. In this work, we study the prospect of using the cross correlation between CMB and galaxy-density maps as a tool for constraining the neutrino mass. On the one hand massive neutrinos reduce the cross-correlation spectrum because free-streaming slows down structure formation; onmore » the other hand, they enhance it through their change in the effective linear growth. We show that in the observable range of scales and redshifts, the first effect dominates, but the second one is not negligible. We carry out an error forecast analysis by fitting some mock data inspired by the Planck satellite, Dark Energy Survey (DES) and Large Synoptic Survey Telescope (LSST). The inclusion of the cross correlation data from Planck and LSST increases the sensitivity to the neutrino mass m{sub {nu}} by 38% (and to the dark energy equation of state w by 83%) with respect to Planck alone. The correlation between Planck and DES brings a far less significant improvement. This method is not potentially as good for detecting m{sub {nu}} as the measurement of galaxy, cluster, or cosmic shear power spectra, but since it is independent and affected by different systematics, it remains potentially interesting if the total neutrino mass is of the order of 0.2 eV; if instead it is close to the lower bound from atmospheric oscillations, m{sub {nu}}{approx}0.05 eV, we do not expect the ISW-galaxy correlation to be ever sensitive to m{sub {nu}}.« less

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-02-13

To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Case-control study. Cases and controls were enrolled in Durango City, Mexico. 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Serum samples of participants were analysed for anti- T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Anti- T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti- T. gondii IgG positive cases and four of the anti- T. gondii IgG positive controls had anti- T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not

Possible association of cutaneous Rosai-Dorfman disease and chronic Crohn disease: a case series report.

PubMed

Salva, Katrin A; Stenstrom, Melissa; Breadon, Jonith Y; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S

2014-02-01

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.

Possible Association of Cutaneous Rosai-Dorfman Disease and Chronic Crohn Disease A Case Series Report

PubMed Central

Salva, Katrin A.; Stenstrom, Melissa; Breadon, Jonith Y.; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S.

2014-01-01

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P < .001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease. PMID:24305684

An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq

DTIC Science & Technology

2010-05-01

Christopher E. Curtis, MC USAt 188143 ABSTRACT Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Cases have been...MILITARY MEDICINE, 175,5:367,2010 An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq CPT Jeremy B. Fisher, SP USA *; CPT...Turkey.3-S We report an unexpected case of Lyme disease from Iraq. CASE REPORT A 28-year-old active duty Army male, on a deployment to northern Iraq

Hypnosis in the treatment of Morgellons disease: a case study.

PubMed

Gartner, Ashley M; Dolan, Sara L; Stanford, Matthew S; Elkins, Gary R

2011-04-01

Morgellons Disease is a condition involving painful skin lesions, fibrous growths protruding from the skin, and subcutaneous stinging and burning sensations, along with symptoms of anxiety, depression, fatigue, and memory and attention deficits. The etiological and physiological bases of these symptoms are unclear, making the diagnosis controversial and challenging to treat. There are currently no established treatments for Morgellons Disease. The following case example depicts treatment of a woman with Morgellons Disease using hypnotherapy. Data from this case example suggest that hypnotherapy is a promising intervention for the physical and psychological symptoms associated with Morgellons Disease.

Case definition terminology for paratuberculosis (Johne's disease).

PubMed

Whittington, R J; Begg, D J; de Silva, K; Purdie, A C; Dhand, N K; Plain, K M

2017-11-09

Paratuberculosis (Johne's disease) is an economically significant condition caused by Mycobacterium avium subsp. paratuberculosis. However, difficulties in diagnosis and classification of individual animals with the condition have hampered research and impeded efforts to halt its progressive spread in the global livestock industry. Descriptive terms applied to individual animals and herds such as exposed, infected, diseased, clinical, sub-clinical, infectious and resistant need to be defined so that they can be incorporated consistently into well-understood and reproducible case definitions. These allow for consistent classification of individuals in a population for the purposes of analysis based on accurate counts. The outputs might include the incidence of cases, frequency distributions of the number of cases by age class or more sophisticated analyses involving statistical comparisons of immune responses in vaccine development studies, or gene frequencies or expression data from cases and controls in genomic investigations. It is necessary to have agreed definitions in order to be able to make valid comparisons and meta-analyses of experiments conducted over time by a given researcher, in different laboratories, by different researchers, and in different countries. In this paper, terms are applied systematically in an hierarchical flow chart to enable classification of individual animals. We propose descriptive terms for different stages in the pathogenesis of paratuberculosis to enable their use in different types of studies and to enable an independent assessment of the extent to which accepted definitions for stages of disease have been applied consistently in any given study. This will assist in the general interpretation of data between studies, and will facilitate future meta-analyses.

Validation of the technique for absolute total electron content and differential code biases estimation

NASA Astrophysics Data System (ADS)

Mylnikova, Anna; Yasyukevich, Yury; Yasyukevich, Anna

2017-04-01

We have developed a technique for vertical total electron content (TEC) and differential code biases (DCBs) estimation using data from a single GPS/GLONASS station. The algorithm is based on TEC expansion into Taylor series in space and time (TayAbsTEC). We perform the validation of the technique using Global Ionospheric Maps (GIM) computed by Center for Orbit Determination in Europe (CODE) and Jet Propulsion Laboratory (JPL). We compared differences between absolute vertical TEC (VTEC) from GIM and VTEC evaluated by TayAbsTEC for 2009 year (solar activity minimum - sunspot number about 0), and for 2014 year (solar activity maximum - sunspot number 110). Since there is difference between VTEC from CODE and VTEC from JPL, we compare TayAbsTEC VTEC with both of them. We found that TayAbsTEC VTEC is closer to CODE VTEC than to JPL VTEC. The difference between TayAbsTEC VTEC and GIM VTEC is more noticeable for solar activity maximum (2014) than for solar activity minimum (2009) for both CODE and JPL. The distribution of VTEC differences is close to Gaussian distribution, so we conclude that results of TayAbsTEC are in the agreement with GIM VTEC. We also compared DCBs evaluated by TayAbsTEC and DCBs from GIM, computed by CODE. The TayAbsTEC DCBs are in good agreement with CODE DCBs for GPS satellites, but differ noticeable for GLONASS. We used DCBs to correct slant TEC to find out which DCBs give better results. Slant TEC correction with CODE DCBs produces negative and nonphysical TEC values. Slant TEC correction with TayAbsTEC DCBs doesn't produce such artifacts. The technique we developed is used for VTEC and DCBs calculation given only local GPS/GLONASS networks data. The evaluated VTEC data are in GIM framework which is handy when various data analyses are made.

Primary immunodeficiency disease: a model for case management of chronic diseases.

PubMed

Burton, Janet; Murphy, Elyse; Riley, Patty

2010-01-01

Patient-centered chronic care management is a new model for the management of rare chronic diseases such as primary immunodeficiency disease (PIDD). This approach emphasizes helping patients become experts on the management of their disease as informed, involved, and interactive partners in healthcare decisions with providers. Because only a few patients are affected by rare illnesses, these patients are forced to become knowledgeable about their disease and therapies and to seek treatment from a healthcare team, which includes physicians and nurse specialists who are equipped to manage the complexity of the disease and its comorbidities. Importantly, therapy for PIDD can be self-administered at home, which has encouraged the transition toward a proactive stance that is at the heart of patient-centered chronic care management. We discuss the evolution of therapy, the issues with the disease, and challenges with its management within the framework of other chronic disease management programs. Suggestions and rationale to move case management of PIDD forward are presented with the intent that sharing our experiences will improve process and better manage outcomes in this patient population. The patient-centered model for the management of PIDD is applicable to the primary care settings, where nurse case managers assist patients through education, support them and their families, and facilitate access to community resources in an approach, which has been described as "guided care." The model also applies specifically to immunology centers where patients receive treatment or instruction on its self-administration at home. Patient-centered management of PIDD, with its emphasis on full involvement of patients in their treatment, has the potential to improve compliance with treatment, and thus patient outcomes, as well as patients' quality of life. The patient-centered model expands the traditional model of chronic disease management, which relies on evidence

Reducing selection bias in case-control studies from rare disease registries.

PubMed

Cole, J Alexander; Taylor, John S; Hangartner, Thomas N; Weinreb, Neal J; Mistry, Pramod K; Khan, Aneal

2011-09-12

In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example. A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching. The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

[Legionnaire's disease in Italy: case list contribution].

PubMed

Scarlini, G; Carlino, G; Coletti, C; Parente, M; Orani, A M

1986-01-01

The authors describe two cases of Legionnaires disease brought to their attention and diagnosed through serological research utilizing two different methods: the indirect immunofluorescence and the microagglutination, in cooperation with the Higher Institute of Health. They conclude with some considerations upon the real necessity of circumscribed eziological research in all the cases of "hospitalized acute respiratory illness" and confirm the effectiveness of the treatment with macrolides in the Legionella Pneumophila infections.

Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.

PubMed

Meunier, Marine; Puechal, Xavier; Hoppé, Emmanuel; Soubrier, Martin; Dieudé, Philippe; Berthelot, Jean Marie; Caramaschi, Paola; Gottenberg, Jacques-Eric; Gossec, Laure; Morel, Jacques; Maury, Emilie; Wipff, Julien; Kahan, André; Allanore, Yannick

2013-12-01

Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.

A rare case of hidebound disease with dental implications.

PubMed

Bali, Vikram; Dabra, Sarita; Behl, Ashima Bali; Bali, Rajiv

2013-07-01

Systemic sclerosis (also called as Scleroderma or hidebound disease) is a chronic sclerotic disease of unknown etiology which causes diffuse, increased deposition of extra cellular matrix in connective tissue with vascular abnormalities, resulting in tissue hypoxia. The disease is characterized by diffuse fibrosis; degenerative changes; and vascular abnormalities in the skin (scleroderma), articular structures, and internal organs. Aesthetic and facial dysfunctions are followed by important oral and facial manifestations. Most oral manifestations begin with tongue rigidity and facial skin changes. Bone resorption of mandibular angle and widening of periodontal ligament space on periapical radiographs are important radiological findings. Other systemic changes include the involvement of internal organs, which lead to serious complications as well as disorders in the cardiac muscle and Raynaud΄s phenomenon. This is a case report of 30-year-old female patient with the classical features of this disease. This case is reported for its rarity and variable expressivity. The main aim of this article is to describe thorough presentation of the case report, various forms of scleroderma, pathogenesis, oral, extraoral, periodontal manifestations of scleroderma, and its treatment options. A brief review of the literature, focusing on dental alterations is also presented.

A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study.

PubMed

Litvinchuk, Tetiana; Tao, Yunxia; Singh, Ruchi; Vasylyeva, Tetyana L

2015-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation due to mutations in genes coding for polycystin-1 [PKD1 (85-90% of cases), on ch 16p13.3] and polycystin-2 [PKD2 (10-15% of cases), on ch 4q13-23] and PKD3 gene (gene unmapped). It is also associated with TSC2/PKD1 contiguous gene syndrome. ADPKD is usually inherited, but new mutations without a family history occur in approximately 10% of the cases. A 17-year-old boy was followed up for bilateral cystic kidney disease, hypertension, and obesity since he was 13 years old. The diagnosis was an accidental finding during abdominal CT at age 13 to rule out appendicitis. A renal ultrasonogram also demonstrated a multiple bilateral cysts. Because of parental history of bilateral renal cysts, PKD1 and PKD2, genetic testing was ordered. Results showed, PKD2 variant 1:3 bp deletion of TGT; nucleotide position: 1602-1604; codon position: 512-513; mRNA reading frame maintained. The same mutation was later identified in his father. A smaller number of patients have a defect in the PKD2 locus on chromosome 4 (resulting in PKD2 disease). There are no known published cases on this familiar genetic variant of ADPKD-2 cystic kidney disease. In this case, the disease is present unusually early in life.

Detecting At-Risk Alzheimer's Disease Cases.

PubMed

Fladby, Tormod; Pålhaugen, Lene; Selnes, Per; Waterloo, Knut; Bråthen, Geir; Hessen, Erik; Almdahl, Ina Selseth; Arntzen, Kjell-Arne; Auning, Eirik; Eliassen, Carl Fredrik; Espenes, Ragna; Grambaite, Ramune; Grøntvedt, Gøril Rolfseng; Johansen, Krisztina Kunszt; Johnsen, Stein Harald; Kalheim, Lisa Flem; Kirsebom, Bjørn-Eivind; Müller, Kai Ivar; Nakling, Arne Exner; Rongve, Arvid; Sando, Sigrid Botne; Siafarikas, Nikias; Stav, Ane Løvli; Tecelao, Sandra; Timon, Santiago; Bekkelund, Svein Ivar; Aarsland, Dag

2017-01-01

While APOEɛ4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of Aβ42 (pAβ) and APOEɛ4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or mild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pAβ and APOEɛ4 frequency compared to NC. Also, NCFD had higher APOEɛ4 frequencies without increased fraction of pAβ compared to NC, and cases recruited from memory clinics had higher fractions of pAβ and APOEɛ4 frequency than self-referred. This study shows that memory clinic referrals are pAβ enriched, whereas self-referred and NCFD cases more frequently are pAβ negative but at risk (APOEɛ4 positive), suitable for primary intervention.

A retrospective study of canine persistent nasal disease: 80 cases (1998-2003).

PubMed

Meler, Erika; Dunn, Marilyn; Lecuyer, Manon

2008-01-01

Persistent canine nasal disease is a common complaint in small animal practice; however, an etiologic diagnosis can be difficult to establish. The aim of this retrospective study was to determine the percentage of cases for which the etiology was determined in our hospital population. Medical records from 80 dogs met the criteria of inclusion in the study. Nonspecific rhinitis was identified in 23.7% of cases. Other diagnoses were neoplasia (15.0%), fungal infection (nasal aspergillosis) (8.7%), cleft palate (8.7%), periodontal disease (4.0%), parasites (1.3%), foreign body (1.3%), and primary bacterial disease (1.3%). A definitive diagnosis could not be established in 36.3% of cases. Dogs with neoplastic and mycotic diseases often presented with severe radiographic and rhinoscopic lesions. Despite a systematic approach, numerous cases went undiagnosed. The use of advanced imaging should increase our ability to obtain an etiologic diagnosis in canine nasal disease.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study.

PubMed

Städler, Nicolas; Dondelinger, Frank; Hill, Steven M; Akbani, Rehan; Lu, Yiling; Mills, Gordon B; Mukherjee, Sach

2017-09-15

Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them. This is a nontrivial clustering problem, with neither subgroups nor subgroup-specific networks known at the outset. We leverage recent ideas from high-dimensional statistics for testing and clustering in the network biology setting. The methods we describe can be applied directly to most continuous molecular measurements and networks do not need to be specified beforehand. We illustrate the ideas and methods in a case study using protein data from The Cancer Genome Atlas (TCGA). This provides evidence that patterns of interplay between signalling proteins differ significantly between cancer types. Furthermore, we show how the proposed approaches can be used to learn subtypes and the molecular networks that define them. As the Bioconductor package nethet. staedler.n@gmail.com or sach.mukherjee@dzne.de. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

A complex case of congenital cystic renal disease

PubMed Central

Cordiner, David S; Evans, Clair A; Brundler, Marie-Anne; McPhillips, Maeve; Murio, Enric; Darling, Mark; Taheri, Sepideh

2012-01-01

This case outlines the potential complexity of autosomal recessive polycystic kidney disease (ARPKD). It highlights the challenges involved in managing this condition, some of the complications faced and areas of uncertainty in the decision making process. With a paucity of published paediatric cases on this subject, this should add to the pool of information currently available. PMID:22605879

Challenges and Gaps in Understanding Substance Use Problems in Transitional Age Youth.

PubMed

Bukstein, Oscar G

2017-04-01

Transitional age youth (TAY), developing from adolescence to adulthood, exhibit the highest level of alcohol and other drug use of any other age group. Risk factors mirror those for the development of problems and disorders in adolescents. Early screening of both college students and noncollege high-risk TAY in the community is critical to early and effective intervention. Brief interventions using motivational techniques are effective for many TAY, particularly for those in early stages of problem use on college campuses. Professionals in contact with TAY should be aware of evidence-based interventions and providers for substance use disorders in the community. Copyright © 2016 Elsevier Inc. All rights reserved.

CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

PubMed

Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

2016-04-01

Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

[Headache case that responded to alendronate treatment in Paget's disease].

PubMed

Bozkurt, Dilek; Hiz, Fazilet; Çinar, Meral; Can, Meltem

2012-01-01

Paget's disease of the bone is a chronic, focal skeletal disease characterized by bone pain and deformity, pathological fractures and neurological symptoms such as headache, hearing loss and tinnitus, etc. The frequency of the disease increases in later ages. Viral and genetical factors play a role in the etiology. The majority of cases are asymptomatic. It is often diagnosed with an incidental finding on radiography or with an unexpected high serum alkaline phosphatase level. Bone fractures or neurological complications can negatively affect the quality of life. Early diagnosis and treatment are thus very important. Bisphosphonates are the most frequently used medication in the treatment. We present a case who sought medical help because of headache and was diagnosed as Paget's disease. Neurological complications and the diagnosis and treatment of Paget's disease are reviewed in the literature.

HYPNOSIS IN THE TREATMENT OF MORGELLONS DISEASE: A Case Study1

PubMed Central

Gartner, Ashley M.; Dolan, Sara L.; Stanford, Matthew S.; Elkins, Gary R.

2014-01-01

Morgellons Disease is a condition involving painful skin lesions, fibrous growths protruding from the skin, and subcutaneous stinging and burning sensations, along with symptoms of anxiety, depression, fatigue, and memory and attention deficits. The etiological and physiological bases of these symptoms are unclear, making the diagnosis controversial and challenging to treat. There are currently no established treatments for Morgellons Disease. The following case example depicts treatment of a woman with Morgellons Disease using hypnotherapy. Data from this case example suggest that hypnotherapy is a promising intervention for the physical and psychological symptoms associated with Morgellons Disease. PMID:21390982

[Etiological analysis of 264 cases with chronic kidney disease stage 2 to 5 in children].

PubMed

Miao, Qianfan; Shen, Qian; Xu, Hong; Sun, Li; Tang, Xiaoshan; Fang, Xiaoyan; Liu, Haimei; Zhai, Yihui; Bi, Yunli; Wang, Xiang; Chen, Hong

2015-09-01

To study and summarize the etiology of children patients with chronic kidney disease (CKD) stage 2 to 5 seen in Children's Hospital of Fudan University from Jan. 2004 to Dec. 2013. By complying with the NKF-K/DOQI guidelines, we collected data of 264 cases of children patients with CKD stage 2-5 from Jan. 2004 to Dec. 2013 in the medical record system of Children's Hospital of Fudan University. And we retrospectively analyzed their age and CKD stage at first diagnosis, primary diseases, complications, etc. In the collected 264 cases, 52 cases (19.7%) were diagnosed at stage 2, 67 (25.4%) at stage 3, 52 (19.7%) at stage 4 and 93 (35.2%) at stage 5. For disease causes, 116 cases (43.9%) had congenital anomalies of the kidney and urinary tract (CAKUT), 61 cases (23.1%) had glomerular disease, 15 (5.7%) had hereditary kidney disease, 14 (5.3%) had other diseases and in 58 cases (22.0%) the causes of disease were unknown. In the group with age between 0 and 3.0 and 3.1 and 6.0 years, 57.1% (24 cases) and 60.0% (30 cases) had primary disease with CAKUT. In the group with age older than 10 years, 49.2% (30 cases) had primary disease with glomerular disease and 32.0% (32 cases) with unknown causes. The major cause of CKD stage 2-5 in children in our hospital during the last ten years was CAKUT (43.9%), followed by glomerular disease (23.1%). The primary diseases of CKD were significantly different between the 2 age groups. CAKUT was more common in infants and preschool children while for adolescents, glomerular disease was the major cause.

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Factors Associated with Suicidal Thought and Help-Seeking Behaviour in Transition-Aged Youth versus Adults.

PubMed

MacKinnon, Nathalie; Colman, Ian

2016-12-01

Suicide is a leading cause of death for transition-aged youth (TAY), and yet few studies examine correlates of suicidal ideation specifically in this age demographic (age 18-24 years). The transition to adulthood is a unique context, marked by novel stressors (e.g., joining the workforce) and increased independence, which may influence risk factors for suicidal ideation. This study examined correlates of suicidal ideation in TAY and adults and contrasted profiles across age. We used 4 biannual cycles (2005, 2007, 2009, 2011) of the Canadian Community Health Survey, a population-based cross-sectional survey on health. We used logistic regression to assess the association between suicidal ideation and depression, distress, alcohol use, smoking, exercise, sedentary behaviour, chronic illness, restrictions to daily living, perceived physical and mental health, and perceived social support independently in both TAY ( n = 4427) and adults ( n = 14,452). We subsequently assessed possible interactions with age (18-24 v. 25-44 years) and sex and differences in help-seeking behaviour in a combined model. TAY exhibited higher rates of suicidal ideation than adults did ( P < 0.001). Numerous factors were associated with suicidal ideation in TAY. Notably, alcohol abstinence was associated with decreased suicidal ideation in TAY but not for adults. Moreover, when depressed, TAY were significantly less likely to have received professional mental health help than adults (odds ratio = 0.64, 95% CI, 0.43 to 0.94). Suicidal ideation is more prevalent in TAY than adults, and its consequences may be aggravated by poor treatment-seeking behaviour in at-risk (i.e. depressed) individuals. These different risk profiles substantiate the recent shift toward clinical interventions focusing on transition-aged youth, rather than traditional child (<18 years) and adult (>18 years) services.

Clinical Review of 20 Cases of Addison’s Disease in Korea

PubMed Central

Sung, Sang Kyu; Kwon, Yong Joon; Lee, Bum Woo; Kim, Doo Man; Yoo, Hyung Joon

1988-01-01

Addison’s disease is a rare disorder resulting from a chronic deficiency of adrenol cortical hormone. The clinical manifestations and data of 20 patients with Addison’s disease were reviewed. They include 14 previously reported cases, total cases in korea upto 1987, and 6 new cases at National Medical Center. 13 patients were male and 7 female. The mean age was 39 years and ranged from 16 to 61 years.Common symptoms included mucocutaneous pigmentation (95 %), general weakness (90%), nasuea and/or vomiting (80%), and weight loss (60%).Initial mean blood pressure was 96±21/63±14 mmHg and adrenal crises were found in 5 cases (25%).Laboratory data indicated hyponatremia and hyperkalemia, resulting in a decreased Na/K ratio. Serum basal cortisol and ACTH levels were 2.86±1.93 ug/dl and 482.5/269.3 pg/ml, respectively.Extra-adrenal tuberculosis was present in 14 cases (70%) as a very high incidence.These 14 cases (70%) were presumed to be due to adrenal tuberculosis, although only two cases were confirmed as such by histopathology. The other cases were likely to be non-tuberculous. Thus, tuberculosis may be-considered as a predominant cause of Addision’s disease in Korea. Other features were not unusual. But further detailed and extensive studies are necessary including more pathologically confirmed cases. PMID:3153796

Factors determining disease duration in Alzheimer's disease: a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression.

PubMed

Armstrong, R A

2014-01-01

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration.

Synchronous of breast and vulvar Paget's disease: a case report.

PubMed

Cooper, J C; Hew, K E; Audlin, K M; Im, D D; Matsuo, K

2012-01-01

Synchronous Paget's disease of breast and vulva is extremely rare and has only been reported in the literature in one other case. A 58-year-old postmenopausal woman was found to have crusting, bleeding, and discharge from left nipple, as well as vulvar pruritis at the same time. Biopsy of breast lesion demonstrated Paget's disease with an underlying foci of ductal carcinoma in-situ that required total mastectomy of left breast with sentinel node biopsy and breast reconstruction. For vulvar symptoms, the patient was initially diagnosed with dermatitis and topical ointment was prescribed. However, her symptoms persisted for the next several months, and she underwent vulvar biopsy that demonstrated Paget's disease. She underwent partial vulvectomy. Multiple episodes of recurrent vulvar Paget's disease were noted in the postoperative course that medical therapy with Imiquimod and a second partial vulvectomy was performed. Synchronous of breast and vulvar Paget's disease is presented. There was a delay in diagnosing vulvar Paget's disease in this experienced case. While coincidence of breast and vulvar Paget's disease is likely, ectopic mammary tissue in vulvar as well as secondary metastasis from a focal lesion of breast Paget's disease needs to be carefully evaluated whenever the patient complains of vulvar symptoms in the setting of breast Paget's disease.

Pylephlebitis and Crohn's disease: A rare case of septic shock.

PubMed

Scaringi, Stefano; Giudici, Francesco; Gabbani, Giacomo; Zambonin, Daniela; Morelli, Marco; Carrà, Rossella; Bechi, Paolo

2017-01-01

Troncular pylephlebitis, defined as septic thrombophlebitis of the portal vein, is usually secondary to suppurative infection from the regions drained by the portal system. Therefore, pylephlebitis can occur from the portal vein main tributaries. The occurrence of mesenteric pylephlebitis in Crohn's disease is extremely rare. We describe a case of septic shock due to mesenteric pylephlebitis in a 47 years old male affected with Crohn's disease. The patient was admitted to the emergency department after he had been complained from 3h of a peri-umbilical abdominal pain associated to fever and shivering quickly followed by a severe hypotension. His medical history included histologically confirmed ileal Crohn's disease diagnosed 4 years before and treated with mesalamine only. Computed tomography scan confirmed the mesenteric pylephlebitis diagnosis. After medical therapy with antibiotics and systemic nutrition, the patient was successfully operated to treat his ileal Crohn's disease. In our case, the quick onset of a septic shock was not due to a peritonitis complicating a Crohn's disease, but to a rare condition not needing an urgent surgical resolution. This report shows that, even in Crohn's disease, once diagnosis is performed, antibiotic therapy associated to enteral and parenteral nutrition can lead to a complete clinical remission of mesenteric pylephlebitis, mandatory to perform an elective surgery. This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn's disease patient who is not showing clinical signs of peritonitis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Minimal change disease in a patient with myasthenia gravis: A case report.

PubMed

Tsai, Jun-Li; Tsai, Shang-Feng

2016-09-01

Myasthenia gravis superimposed with proteinuria is a very rare disorder with only 39 cases reported so far. Of these cases, the most commonly associated disorder is minimal change disease. Myasthenia gravis and minimal change disease are both related to the dysfunction of T lymphocytes and hence the 2 disorders may be connected. Here we report the first case on a patient diagnosed with myasthenia gravis concurrently with the minimal change disease, and it was presented in the absence of thymoma or thymic hyperplasia. Treatment for myasthenia gravis also lowered proteinuria of minimal change disease. He ever experienced good control for myasthenia gravis and minimal change disease. However, pneumonia related septic shock occurred to him and finally he was dead. Minimal change disease is generally considered to occur subsequent to the onset of myasthenia gravis with causal association. After extensive literature review, we noted only 47.8% minimal change disease had occurred after the onset of myasthenia gravis. Minimal change disease mostly occurs in children and if diagnosed in adults, clinicians should search for a potential cause such as myasthenia gravis and other associated thymic disorders.

Comparative assessment of the prevalence of periodontal disease in subjects with and without systemic autoimmune diseases: A case-control study.

PubMed

Ramesh Kumar, S G; Aswath Narayanan, M B; Jayanthi, D

2016-01-01

Immune mechanism shares a common pathway both for systemic autoimmune diseases and periodontal diseases. Scientific exploration of literature revealed limited studies on the association between systemic autoimmune diseases and periodontal diseases in India. The aim of the study is to find whether the presence of systemic autoimmune diseases in an individual is a risk factor for the development of periodontal disease. This was a hospital-based case-control study. A sample of 253 patients with systemic autoimmune diseases, attending the Rheumatology Department of Government General Hospital, Chennai-3, and 262 patients without systemic autoimmune diseases, attending the outpatient department of the Tamil Nadu Government Dental College and Hospital, Chennai-3, constituted the case and control groups, respectively. Age, gender, and oral hygiene status matching was done. Oral hygiene status was assessed using oral hygiene index (OHI) and periodontal status was assessed using community periodontal index (CPI) and loss of attachment (LOA) index. Statistical analysis was done using SPSS version 15 (SPSS Inc, 2006, Chicago). Results showed 99.2% and 73.9% prevalence of gingivitis and periodontitis, respectively, in the case group as compared to 85.5% and 14.9%, respectively, in the control group. There is no linear relationship between OHI scores and prevalence of periodontitis (CPI and LOA scores) in the case group. Patients suffering from systemic autoimmune diseases showed more prevalence of periodontal diseases irrespective of oral hygiene scores. It is postulated that the presence of systemic autoimmune diseases may pose a risk for the development of periodontal diseases.

Prediction of Disease Case Severity Level To Determine INA CBGs Rate

NASA Astrophysics Data System (ADS)

Puspitorini, Sukma; Kusumadewi, Sri; Rosita, Linda

2017-03-01

Indonesian Case-Based Groups (INA CBGs) is case-mix payment system using software grouper application. INA CBGs consisting of four digits code where the last digits indicating the severity level of disease cases. Severity level influence by secondary diagnosis (complications and co-morbidity) related to resource intensity level. It is medical resources used to treat a hospitalized patient. Objectives of this research is developing decision support system to predict severity level of disease cases and illustrate INA CBGs rate by using data mining decision tree classification model. Primary diagnosis (DU), first secondary diagnosis (DS 1), and second secondary diagnosis (DS 2) are attributes that used as input of severity level. The training process using C4.5 algorithm and the rules will represent in the IF-THEN form. Credibility of the system analyzed through testing process and confusion matrix present the results. Outcome of this research shows that first secondary diagnosis influence significant to form severity level predicting rules from new disease cases and INA CBGs rate illustration.

Two cases of Kawasaki disease presented with acute febrile jaundice.

PubMed

Kaman, Ayşe; Aydın-Teke, Türkan; Gayretli-Aydın, Zeynep Gökçe; Öz, Fatma Nur; Metin-Akcan, Özge; Eriş, Deniz; Tanır, Gönül

2017-01-01

Kawasaki disease is an acute, systemic vasculitis of unknown etiology. Although gastrointestinal involvement does not belong to the classic diagnostic criteria; diarrhea, abdominal pain, hepatic dysfunction, hydrops of gallbladder, and acute febrile cholestatic jaundice are reported in patients with Kawasaki disease. We describe here two cases presented with fever, and acute jaundice as initial features of Kawasaki disease.

[Juvenile form of Sandhoff disease: first case reported in Argentina].

PubMed

Mugnaini, Julia; Pereyra, Marcela; Dodelson de Kremer, Raquel; Gamboni, Beatriz; Argaraña, Carlos E; Oller Ramírez, Ana M

2017-10-01

Sandhoff disease is a neurodegenerative, lysosomal and autosomal recessive disease caused by mutations in the HEXB gene. Three forms are recognized: infantile, juvenile and adult. Previously, an endogamous population in Córdoba, Argentina, was identified with a high incidence of Sandhoff disease, all reported cases were of the infantile type. In this work, we describe a child with the juvenile form of Sandhoff disease, the first case reported in Argentina. The patient is a 7-year-old boy presenting with ataxia, speech disturbances and global developmental delay, symptoms starting at the age of 2 years. Diagnosis was based on the hexosaminidase deficiency. Sequencing of genomic DNA revealed compound heterozygosity for two HEXB gene mutations: c.796T>G (p.Y266D) and c.1615C>T (p.R539C), both already reported. Sociedad Argentina de Pediatría.

Factitious disease: clinical lessons from case studies at Baylor University Medical Center

PubMed Central

Savino, Adria C.; Fordtran, John S.

2006-01-01

Factitious disease is defined as the intentional production (or feigning) of disease in oneself to relieve emotional distress by assuming the role of a sick person. Although the self-induction of disease is a conscious act, the underlying motivation is usually unconscious. It has been estimated that 3% to 5% of physician-patient encounters involve factitious disease. This article presents 6 case studies from Baylor University Medical Center that highlight various clinical aspects of factitious disease. Patients with factitious diseases are extremely difficult to recognize because they do not appear different from patients with authentic causes of similar symptoms, because their psychiatric abnormalities are not appreciated, and because doctors and nurses have alowindex of suspicion. Since patients with factitious disease present a false medicalhistory, their physicians prescribe unnecessary procedures and therapies that may result in iatrogenic disease. In many cases, damage to these patients from doctors' actions exceeds the harm resulting from the patients' self-induced illness. The clues that should suggest factitious disease, the diagnostic roles of the clinician and a consulting psychiatrist, and the ethical conflicts that confront doctors taking care of such patients are discussed. To help keep factitious disease in clinical perspective, one of the case studies involves the antithesis of factitious disease, where a patient was mistakenly diagnosed as having psychogenic pain when in fact the symptoms were caused by an overlooked physical disease. Better knowledge of the clinical features of factitious disease might have prevented the disastrous outcome. PMID:17252033

Intraoral Morgellons disease or delusional parasitosis: a first case report.

PubMed

Dovigi, Allan J

2010-08-01

Morgellons disease is a new emerging disease that is still controversial and believed to be, by some practitioners, as nothing more than delusional parasitosis. The Center for Disease Control has recently launched an epidemiological investigation into this disease due to the increased number of reports. A first case is reported of an oral lesion and symptoms consistent with Morgellons disease. The nature of the characteristic fibers associated with the intraoral lesion is investigated. Research has started at a number of institutions to elucidate the nature of this emerging disease.

[Tetanus, a current disease in pediatric population: Case report].

PubMed

Cejudo-García de Alba, María Del Pilar; Valle-Leal, Jaime Guadalupe; Sánchez Beltrán, Jesús Gabriel; Vázquez-Amparano, Amado de Jesús Francisco

2017-01-01

Tetanus is an acute disease caused by a toxin produced by Clostridium tetanii. The disease can affect people of any age, and the fatality rate is high. Thanks to immunization the number of cases of the disease has decreased, although they are still present in isolation in countries with social and economic backwardness. To describe a case of a pediatric patient with generalized tetanus to reinforce the relevance of prophylaxis and early detection. 6 years old female patient, with only one dose of pentavalent vaccine, 10 days after sharps injury by wood chips, starts with fever, muscle pain and generalized contractions, Tetanus was diagnosed by clinical symptoms and history. The management was based on the latest recommendations of the World Health Organization (WHO): Penicillin-Metronidazole antibiotic regimen, tetanus toxoid and tetanus high-dose gammaglobulin. After 2 years of follow-up under physiotherapy support, slight motor sequelae were observed. Tetanus is still presented in the pediatric population, associated with lack of vaccination. It is necessary to know the disease to provide proper diagnosis and management according to international lineaments.

Visual art therapy in sporadic Creutzfeldt-Jakob disease: a case study.

PubMed

Shrestha, Rajeet; Trauger-Querry, Barbara; Loughrin, Athena; Appleby, Brian S

2016-01-01

This paper describes the diagnostic and treatment utility of visual art therapy in a case of sporadic Creutzfeldt-Jakob disease. Visual art therapy was compared longitudinally with clinical and neuroimaging data over five-month period in an autopsy-confirmed case of sporadic Creutzfeldt-Jakob disease of MM2-cortical subtype. Art therapy sessions and content were useful in ascertaining neuropsychiatric symptoms during the course of her illness. Art therapy offered a unique emotional and cognitive outlet as illness progressed. Patients and families affected by sporadic Creutzfeldt-Jakob disease may benefit from art therapy despite the rapidly progressive nature of the illness. Art therapy can also be useful for assessment of patients with sporadic Creutzfeldt-Jakob disease by healthcare professionals.

Recent US Case of Variant Creutzfeldt-Jakob Disease-Global Implications.

PubMed

Maheshwari, Atul; Fischer, Michael; Gambetti, Pierluigi; Parker, Alicia; Ram, Aarthi; Soto, Claudio; Concha-Marambio, Luis; Cohen, Yvonne; Belay, Ermias D; Maddox, Ryan A; Mead, Simon; Goodman, Clay; Kass, Joseph S; Schonberger, Lawrence B; Hussein, Haitham M

2015-05-01

Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient's exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD.

Association between bullous pemphigoid and neurologic diseases: a case-control study.

PubMed

Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

2014-11-01

In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

A retrospective study of canine persistent nasal disease: 80 cases (1998–2003)

PubMed Central

Meler, Erika; Dunn, Marilyn; Lecuyer, Manon

2008-01-01

Persistent canine nasal disease is a common complaint in small animal practice; however, an etiologic diagnosis can be difficult to establish. The aim of this retrospective study was to determine the percentage of cases for which the etiology was determined in our hospital population. Medical records from 80 dogs met the criteria of inclusion in the study. Nonspecific rhinitis was identified in 23.7% of cases. Other diagnoses were neoplasia (15.0%), fungal infection (nasal aspergillosis) (8.7%), cleft palate (8.7%), periodontal disease (4.0%), parasites (1.3%), foreign body (1.3%), and primary bacterial disease (1.3%). A definitive diagnosis could not be established in 36.3% of cases. Dogs with neoplastic and mycotic diseases often presented with severe radiographic and rhinoscopic lesions. Despite a systematic approach, numerous cases went undiagnosed. The use of advanced imaging should increase our ability to obtain an etiologic diagnosis in canine nasal disease. PMID:18320982

An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese

PubMed Central

Kuusi, Markku; Lahti, Elina; Virolainen, Anni; Hatakka, Maija; Vuento, Risto; Rantala, Leila; Vuopio-Varkila, Jaana; Seuna, Eija; Karppelin, Matti; Hakkinen, Marjaana; Takkinen, Johanna; Gindonis, Veera; Siponen, Kyosti; Huotari, Kaisa

2006-01-01

Background Streptococcus equi subspecies zooepidemicus is a rare infection in humans associated with contact with horses or consumption of unpasteurized milk products. On October 23, 2003, the National Public Health Institute was alerted that within one week three persons had been admitted to Tampere University Central Hospital (TaYS) because of S. equi subsp. zooepidemicus septicaemia. All had consumed fresh goat cheese produced in a small-scale dairy located on a farm. We conducted an investigation to determine the source and the extent of the outbreak. Methods Cases were identified from the National Infectious Disease Register. Cases were persons with S. equi subsp. zooepidemicus isolated from a normally sterile site who had illness onset 15.9-31.10.2003. All cases were telephone interviewed by using a standard questionnaire and clinical information was extracted from patient charts. Environmental and food specimens included throat swabs from two persons working in the dairy, milk from goats and raw milk tank, cheeses made of unpasteurized milk, vaginal samples of goats, and borehole well water. The isolates were characterized by ribotyping and pulsed-field gel electrophoresis (PFGE). Results Seven persons met the case definition; six had septicaemia and one had purulent arthritis. Five were women; the median age was 70 years (range 54–93). None of the cases were immunocompromized and none died. Six cases were identified in TaYS, and one in another university hospital in southern Finland. All had eaten goat cheese produced on the implicated farm. S. equi subsp. zooepidemicus was isolated from throat swabs, fresh goat cheese, milk tank, and vaginal samples of one goat. All human and environmental strains were indistinguishable by ribotyping and PFGE. Conclusion The outbreak was caused by goat cheese produced from unpasteurized milk. Outbreaks caused by S. equi subsp. zooepidemicus may not be detected if streptococcal strains are only typed to the group level. S

Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

PubMed

Florens, N; Lemoine, S; Guebre-Egziabher, F; Valour, F; Kanitakis, J; Rabeyrin, M; Juillard, L

2017-02-06

There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

Diaphragm disease of the small intestine: an interesting case report.

PubMed

Ullah, Sana; Ajab, Shereen; Rao, Rajashekhar; Raghunathan, Girish; DaCosta, Philip

2015-06-01

Diaphragm disease of small intestine usually presents with nonspecific clinical features. Radiological investigations often fail to differentiate it from small intestinal tumors and inflammatory bowel disease. It is therefore diagnosed on final histology after surgical resection. We hereby report an interesting case of a suspected small bowel tumor later diagnosed as diaphragm disease on histology. © The Author(s) 2014.

[Gestational trophoblastic diseases in cesarean scar: an analysis of 20 cases].

PubMed

Zhang, Ge'er; Pan, Zimin

2017-05-25

To analyze the clinical features, diagnosis and treatment of gestational trophoblastic diseases in cesarean scar. Clinical data of three cases of gestational trophoblastic diseases in cesarean scar diagnosed in Women's Hospital, Zhejiang University School of Medicine during December 2011 and December 2016 were collected. And literature search was performed in Wanfang data, VIP, CNKI, PubMed, ISI Web of Knowledge and EMbase database. A total of 20 cases of gestational trophoblastic diseases were included in the analysis. Clinical features were mainly abnormal vaginal bleeding after menopause, artificial abortion or medical abortion, which might be accompanied by abdominal pain. Serum β-human chorionic gonadotropin (β-hCG) levels were increased in 19 patients. The sonographic features were increase of uterine volume, honeycomb-like abnormal intrauterine echo (or described as multiple cystic dark area, multiple anechoic area and multiple liquid dark area) or heterogeneity echo conglomeration, and no clear bound with muscular layer in some cases. There were abundant blood flow signals inside or around the lesions. The ultrasonography indicated that the lesions were located in the anterior side of the uterine isthmus with the involvement of cesarean section scar. In 12 cases with lesions in cesarean scar shown by preliminary diagnosis, 9 underwent uterine artery embolization (UAE) for pretreatment; the blood loss greater than 1500 mL was observed in only one case without UAE; no patient received hysterectomy. In 8 patients whose lesions were not shown in cesarean scar, only one case received UAE pretreatment, and hysterectomy was performed in 3 cases due to blood loss greater than 1500 mL. Two cases were lost in follow-up and no death was reported in remaining 18 cases. The serum β-hCG levels returned to normal or satisfactory level during the follow-up in 17 cases with increased β-hCG levels before treatment and no recurrence was observed. The misdiagnosis rate and

Analogies between Cushing's disease and depression: a case report.

PubMed

Becker, L; Gold, P; Chrousos, G

1983-07-01

A case report is used to illustrate the difficult differential diagnostic dilemma between depression and Cushing's disease that has led to extensive scientific collaboration to test the hypothesis that both diagnoses may fall within a pathophysiological continuum. Unique to the collaborative study underway is the commitment of psychiatric clinical investigators to bring state of the art techniques for studying neurobiology in a disease traditionally viewed as medical, and of endocrinologists to address their expertise in a disease viewed primarily as psychiatric.

Cochlear Implants and Psychiatric Assessments: a Norrie Disease Case Report.

PubMed

Jacques, Denis; Dubois, Thomas; Zdanowicz, Nicolas; Gilain, Chantal; Garin, Pierre

2017-09-01

It is important to perform psychiatric assessments of adult patients who are candidates for cochlear implants both to screen them for psychiatric disorders and to assess their understanding and compliance with the procedure. Deafness is a factor of difficulty for conducting in-depth psychiatric interviews, but concomitant blindness may make it impossible. After a description of Norrie disease, a rare disease in which blindness and deafness may occur together, we propose a case report of a patient suffering from the disease and who consulted in view of a cochlear implant. Early information on cochlear implants appears to be necessary before total deafness occurs in patients suffering from Norrie disease. An inventory of digital communication tools that can be used by the patient is also highly valuable. Research should be supported for a more systematic use of psychiatric assessments prior to cochlear implants. In the special case of Norrie disease, we recommend early screening for mental retardation and related psychotic disorders and, depending on the patient's level of understanding, preventive information on the benefits and limits of cochlear implants before total deafness occurs.

Neurological features and management of Wilson disease in children: an evaluation of 12 cases.

PubMed

Bayram, Ayşe Kaçar; Gümüş, Hakan; Arslan, Duran; Özçora, Güldemet Kaya; Kumandaş, Sefer; Karacabey, Neslihan; Canpolat, Mehmet; Per, Hüseyin

2016-03-01

Wilson's disease is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The aim of this study was to present the neurologic features of Wilson's disease and to assess the clinical course of neurological findings in children receiving anti-copper treatment. Twelve children with a diagnosis of Wilson's disease and findings of central nervous system involvement who were followed up in the Department of Pediatric Neurology and Pediatric Gastroenterology of the School of Medicine at Erciyes University were enrolled in the study. The study cases consisted of five boys (42%) and seven girls (58%). The mean age at the time of diagnosis was 9.9±3.4 years (5-15 years). The mean duration of follow-up was 49.0±36.4 months (15-128 months). Neurological findings at presentation included headache in seven cases (58%), tremor in seven cases (58%), dystonia in three cases (25%), ataxia in two cases (17%), dizziness in two cases (17%), numbness in the hands and acute weakness in one case (8%) and syncope in one case (8%). Headache, dizziness, syncope, numbness in hands and acute weakness symptoms resolved completely within six months after receiving treatment. Movement disorders either decreased or remained stable in seven of the eight cases. However, one patient developed progressively worsening dystonia despite to all treatments. Wilson's disease can be manifested with signs and symptoms of central nervous system in the childhood. Wilson's disease should be considered in all children presenting with movement disorders. A complete neurological assessment should be carried out in all cases with Wilson's disease.

[An atypical case of Aujeszky's disease in a dog (author's transl)].

PubMed

Richter, J H; van der Vijver, J W; Fischer, R F; Haagsma, J; Gruijs, E; van der Luer, R J

1975-03-15

Two cases of Aujeszky's disease in a cat and a dog belonging to the same owner are reported. The two animals each were five months of age. The symptoms shown by the cat were typical of Aujeszky's disease: intense itching, salivation and the head bent to one side. The main symptoms shown by the dog consisted in salivation, ptosis of one eye, a drooping ear, the head bent to one side and ataxia. As itching was not observed in the dog and the animal had spent the first months of its life in wooded surroundings, it could also have been affected with rabies, although it had been inoculated with LEP-Flury vaccine forty days prior to importation. It is of importance to the practitioner to know that itching may be absent in dogs with Aujeszky's disease and that rabies should also be suspected in these cases. Only a laboratory diagnosis will be conclusive. Studies were negative for rabies, the virus of Aujeszky's disease being found to be present in the two cases. The source of infection probably consisted in contaminated pork offal (larynges).

Active Surveillance of Hansen's Disease (Leprosy): Importance for Case Finding among Extra-domiciliary Contacts

PubMed Central

Moura, Maria L. N.; Dupnik, Kathryn M.; Sampaio, Gabriel A. A.; Nóbrega, Priscilla F. C.; Jeronimo, Ana K.; do Nascimento-Filho, Jose M.; Miranda Dantas, Roberta L.; Queiroz, Jose W.; Barbosa, James D.; Dias, Gutemberg; Jeronimo, Selma M. B.; Souza, Marcia C. F.; Nobre, Maurício L.

2013-01-01

Hansen's disease (leprosy) remains an important health problem in Brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world's new cases detected in that year. The purpose of this study was to use home visits as a tool for surveillance of Hansen's disease in a hyperendemic area in Brazil. A total of 258 residences were visited with 719 individuals examined. Of these, 82 individuals had had a previous history of Hansen's disease, 209 were their household contacts and 428 lived in neighboring residences. Fifteen new Hansen's disease cases were confirmed, yielding a detection rate of 2.0% of people examined. There was no difference in the detection rate between household and neighbor contacts (p = 0.615). The two groups had the same background in relation to education (p = 0.510), household income (p = 0.582), and the number of people living in the residence (p = 0.188). Spatial analysis showed clustering of newly diagnosed cases and association with residential coordinates of previously diagnosed multibacillary cases. Active case finding is an important tool for Hansen's disease control in hyperendemic areas, enabling earlier diagnosis, treatment, decrease in disability from Hansen's disease and potentially less spread of Mycobacterium leprae. PMID:23516645

Pneumocystis jirovecii pneumonia in systemic autoimmune rheumatic disease: A case-control study.

PubMed

Tadros, Susan; Teichtahl, Andrew J; Ciciriello, Sabina; Wicks, Ian P

2017-06-01

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that affects the immunocompromised. Patients with systemic autoimmune rheumatic disease are increasingly recognised as an at-risk clinical population with a high mortality. This case-control study examined differences in the characteristics and peripheral blood parameters between patients with systemic autoimmune rheumatic disease who developed PJP and gender, age and disease-matched controls. Historical data collected between 2002 and 2013 at the Royal Melbourne Hospital, Australia were reviewed. Cases were defined by having a systemic autoimmune rheumatic disease and a diagnosis of PJP (either a positive toluidine blue O stain or P. jirovecii PCR, with a concurrent respiratory illness that was clinically consistent with PJP). Controls were matched for age, gender and disease in a 4:1 ratio. Peripheral blood results were retrieved from an in-house pathology database. Clinical information including glucocorticoid exposure, PJP prophylaxis, comorbidities and month of admission were retrieved from medical notes. After adjustment for corticosteroid exposure and C-reactive protein, lymphocyte count on admission (0.4 vs. 1.3; p = 0.04) and at nadir (0.2 vs. 0.8 × 10 9 /L; p = 0.05) was significantly lower in cases than in controls. Cases (n = 11) were more frequently Caucasian rather than non-Caucasian (81.8% vs. 65.9%; p = 0.04). In addition, cases more commonly presented in autumn (March to May) than in other seasons (OR = 7.3; 95% CI: 1.4-38.7; p = 0.02). These data demonstrate that patients with systemic autoimmune rheumatic disease who develop PJP have significantly greater lymphopenia than age, gender and disease-matched controls, independent of corticosteroid exposure, as well as a potential ethnicity and seasonal predilection to PJP. This may help to inform prophylactic guidelines for PJP in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

CASE REPORT : GRAVE'S DISEASE PRESENTING AS PARANOID SCHIZOPHRENIA

PubMed Central

Singh, S.K.; Hatwal, A.; Agarwal, J.K.; Bajpai, H.S.; Sharma, I.

1989-01-01

SUMMARY The case of a 37 year old male is described who initially presented as paranoid schizophrenia unresponsive to anti-psychotic drug treatment and subsequently developed features of Grave's disease. Treatment with carbimazole alone improved his psychiatric symptoms. PMID:21927380

Fox Den Disease: An Interesting Case Following Delayed Diagnosis.

PubMed

Stehr, Ryan C; Kim, Nicholas; LoGiudice, John A; Ludwig, Kirk

2015-06-01

Pyoderma fistulans sinifica, also known as fox den disease, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues. This disorder is often mistaken for other inflammatory skin disorders and treated inappropriately. The authors describe the case of a 53-year-old male who presented to the colorectal surgery service with a longstanding diagnosis of perirectal Crohn's disease. Despite aggressive immunosuppression and numerous surgical procedures, the patient continued to have unrelenting purulent drainage from the skin of his buttocks. Following wide excision of the affected skin and subcutaneous tissues by the colorectal surgeon, the plastic surgery team reconstructed the 30 cm x 55 cm wound using a combination of local flaps and skin grafts. The initial pathology report of the excised specimen confirmed the presence of nonspecific abscesses and inflammation. Upon special request by the plastic surgery team, the sample was resectioned with the specific intent of establishing a diagnosis of fox den disease. The additional slides met the criteria for an unequivocal diagnosis of fox den disease. Immunosuppression was discontinued and the patient healed his wounds without complication. Fox den disease is often overlooked because of the obscurity of the disease and the special histological sectioning needed to establish a diagnosis. In this case, the patient was unnecessarily treated with immunosuppressive drugs for more than 3 decades because of a misdiagnosis. With increased awareness of fox den disease, perhaps its pathophysiology can be better elucidated as more patients are appropriately diagnosed and treated.

Multicentric Castleman's disease in human immunodeficiency virus infection: two case reports.

PubMed

Caroline Ribeiro Sales, Amanda; Romão de Souza Junior, Valter; Iglis de Oliveira, Marta; Azevedo Braga Albuquerque, Claudia; de Barros Campelo Júnior, Evônio; Sérgio Ramos de Araújo, Paulo

2018-05-05

Castleman's Disease is a rare B-cell lymphoproliferative disease. It is mostly benign and is characterized by non-neoplastic lymph node hypertrophy, associated with infection by human herpesvirus-8 in people with the human immunodeficiency virus/acquired immunodeficiency syndrome. Although the unicentric or localized form presents as benign, the multifocal form can manifest severe systemic symptoms. We report two unusual cases of men presenting cervical enlarged lymph nodes that were believed to be infectious. The first case is a 41-year-old feoderm man who presented to the Department of Infectious Diseases of the Hospital das Clínicas in May 2015, with irregular fever history (38-39 °C), dyspnea, weight loss (8 kg/1 year), and asthenia with increased cervical lymph nodes of 1-year duration. His immunohistochemical diagnosis presented Castleman's disease in plasmacytic/diffuse form. In the second case, a 35-year-old feoderm man presented at the same hospital with multiple cervical enlarged lymph nodes and histopathological evidence of Castleman's disease associated with human herpesvirus-8. Considering the importance of differential diagnosis of lymphoid disorders, Castleman's disease is a challenging diagnosis in people living with human immunodeficiency virus/acquired immunodeficiency syndrome and can be easily misdiagnosed when lymphoid disorders are present in the human immunodeficiency virus/acquired immunodeficiency syndrome population due to nonspecific symptoms and signs.

The case-fatality rate of meningococcal disease in Catalonia, 1990-1997.

PubMed

Domínguez, Angela; Cardeñosa, Neus; Pañella, Helena; Orcau, Angels; Companys, Maria; Alseda, Miquel; Oviedo, Manuel; Carmona, Glòria; Minguell, Sofia; Salleras, Lluis

2004-01-01

The objective was to analyse the case-fatality rate (CFR) of meningococcal disease (MD) in Catalonia, Spain. A retrospective study was carried out. Clinical histories of cases of MD reported for the period 1990-1997 in Catalonia were reviewed. For all cases, the variables gender, age, clinical type, y of presentation, province, phenotype and death by meningococcal disease were collected. The association between death and the other variables was studied by bivariate and unconditional logistic regression analysis. In the 2343 cases studied there were 146 deaths (6.2%) due to meningococcal disease. The CFR was higher in females (OR: 1.5, 95%CI: 1.1-2.1), in the 20 to 49 y (OR: 2.4, 95%CI: 1.2-4.9) and > or = 50 y (OR: 5.3, 95%CI: 2.8-10.1) age groups, in cases with septicaemia (OR: 2.4, 95%CI: 1.6-3.5), in the cases produced by serogroup A (OR: 4.7, 95%CI: 1.0-23.4) and in cases occurring during 1993 (OR: 2.1, 95%CI: 1.1-4.1) or in the province of Lleida (OR: 2.9, 95%CI: 1.2-7.2). In the multivariate analysis, death was associated with the 20-49 y age group (OR: 3.9, 95%CI: 1.8-8.4), the > or = 50 y age group (OR: 7.3, 95%CI: 3.6-14.7), septicaemia (OR: 3.1; 95%CI: 2.0-4.7) and residing in the province of Lleida (OR: 3.2; 95%CI: 1.2-8.5). The CFR of meningococcal disease in Catalonia was not associated with the emergent phenotype C:2b:P1.2,5 strain, which caused an outbreak in other regions of Spain.

Neuro-Sweet disease: report of the first autopsy case.

PubMed

Kokubo, Yasumasa; Kuzuhara, Shigeki; Isoda, Kenichi; Sato, Kenji; Kawada, Norikazu; Narita, Yugo

2007-09-01

Neuro-Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro-Sweet disease are unknown. To describe post-mortem findings of the first case of neuro-Sweet disease. A 44-year-old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. The core neuropathological findings were: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro-Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA-B54 or Cw1 positive.

Neuro‐Sweet disease: report of the first autopsy case

PubMed Central

Kokubo, Yasumasa; Kuzuhara, Shigeki; Isoda, Kenichi; Sato, Kenji; Kawada, Norikazu; Narita, Yugo

2007-01-01

Background Neuro‐Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro‐Sweet disease are unknown. Objective To describe post‐mortem findings of the first case of neuro‐Sweet disease. Results A 44‐year‐old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. Conclusions The core neuropathological findings were: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro‐Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA‐B54 or Cw1 positive. PMID:17702783

Hemizygous Fabry disease associated with membranous nephropathy: A rare case report
.

PubMed

Zhou, Wenyan; Ni, Zhaohui; Zhang, Minfang

2018-05-24

Fabry disease may coexist with various glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis, etc. In this study, we report a rare case of Fabry disease associated with membranous nephropathy (MN). A 30-year-old man with nephrotic proteinuria, normal renal function, and no other extrarenal manifestations underwent a renal biopsy in February 2017. Light microscopy and immunofluorescence indicated MN (stage 1). Under an electron microscope, there were subepithelial electron-dense deposits and abundant zebra bodies in podocytes. Both the findings of low-activity α-galactosidase A (α-Gal A, GLA) and base deletion in exon 7 of the GLA gene (GLA-E07.1286_*7 del, a newly reported mutation) confirmed that this patient was simultaneously afflicted with Fabry disease. This case report is an important reminder of the role of kidney biopsy, especially electron microscopy, as an indicator of Fabry disease and its rare coexistence with MN.
.

Huntington Disease: A Case Study of Early Onset Presenting as Depression

ERIC Educational Resources Information Center

Duesterhus, Pia; Schimmelmann, Benno Graf; Wittkugel, Oliver; Schulte-Markwort, Michael

2004-01-01

Huntington disease is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia, usually with adult onset. The rare juvenile-onset Huntington disease differs from the adult phenotype. A case presenting twice, at age 10 with all the signs of a major depression and age 14 with mutism and…

Case Management of Adolescents with Chronic Disease.

ERIC Educational Resources Information Center

Lankard, Bettina A.

This training guide presents a model for optimum delivery of the primary duties, tasks, and steps required in the comprehensive case management of adolescents with chronic disease. Using a team approach to coordinated health care, the guide involves the patient and family as key members of the care team along with the physician, nurse, dietitian,…

The population ecology of infectious diseases: pertussis in Thailand as a case study.

PubMed

Blackwood, J C; Cummings, D A T; Broutin, H; Iamsirithaworn, S; Rohani, P

2012-12-01

Many of the fundamental concepts in studying infectious diseases are rooted in population ecology. We describe the importance of population ecology in exploring central issues in infectious disease research including identifying the drivers and dynamics of host-pathogen interactions and pathogen persistence, and evaluating the success of public health policies. The use of ecological concepts in infectious disease research is demonstrated with simple theoretical examples in addition to an analysis of case notification data of pertussis, a childhood respiratory disease, in Thailand as a case study. We stress that further integration of these fields will have significant impacts in infectious diseases research.

Lyme Disease Manifestations in the Foot and Ankle: A Retrospective Case Series.

PubMed

Miller, Jason R; Dunn, Karl W; Braccia, Domenick; Ciliberti, Louis J; Becker, Dina K; Hollinger, Joshua K; Brand, Shelley M

Lyme disease is the result of Borrelia burgdorferi bacterial infection after exposure from a tick bite. A pathognomonic finding in early-stage Lyme disease is an expanding, red macular ring known as erythema migrans. Lyme arthritis is a late-stage manifestation of this disease, affecting the large, weightbearing joints with intermittent pain and swelling. The existing data on Lyme disease and subsequent arthritis have reported manifestations in the lower extremity, primarily in the knee and ankle and less commonly the small joints of the foot. We present a retrospective case series of 11 cases of painful arthritis in the foot and ankle with confirmatory Lyme disease testing. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases.

PubMed

Valle, Julio; Morgado, José Mario T; Ruiz-Martín, Juan; Guardiola, Antonio; Lopes-Nogueras, Miriam; García-Vela, Almudena; Martín-Sacristán, Beatriz; Sánchez-Muñoz, Laura

2017-10-01

Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases

PubMed Central

Morgado, José Mario T; Ruiz-Martín, Juan; Guardiola, Antonio; Lopes-Nogueras, Miriam; García-Vela, Almudena; Martín-Sacristán, Beatriz; Sánchez-Muñoz, Laura

2016-01-01

Background Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. Objective The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. Methods A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. Results In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. Conclusion Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases. PMID:29026596

Bilateral panuveitis associated with Whipple disease - case report.

PubMed

Lisboa, Maria; Domingues, Isabel; Pamplona, Jaime; Barata, Pedro; Morgado, Joana; Brotas, Vítor

2014-01-01

To describe a clinical case and literature review of Whipple disease. A 65-year-old male with bilateral decreased visual acuity for 3 weeks as well as bilateral hypoacusia, vertigo, disequilibrium, headache and decreased strength in the right upper limb for 4 months. The clinical work-up revealed a bilateral panuveitis and an ischemic cerebellar stroke. The diagnosis of Whipple disease was confirmed by histopathological analysis of adenopathy. The patient was treated with cortico-antibiotic therapy with significant clinical improvement. Although rare, Whipple disease is potentially fatal if left untreated, it must be always be taken into consideration before any panuveitis of an unknown cause, even in the absence of gastrointestinal symptoms.

First case of surgical treatment of Farber's disease.

PubMed

Haraoka, G; Muraoka, M; Yoshioka, N; Wakami, S; Hayashi, I

1997-10-01

Farber's disease (Farber's lipogranulomatosis), which is inherited as an autosomal recessive trait, was first reported by Farber in 1952. We report a case of Farber's disease in a 12-year-old female. Her younger brother was affected with Farber's disease and died of it at 2 years of age. When she first presented, our patient's main clinical features were a shrill voice; subcutaneous nodules; contracture of the joints throughout the body; and granulomas of the oral cavity, the pharynx, and the upper and lower eyelids. Serial radiographs disclosed deformation of the joints throughout the body. Due to the granulomas in her oral cavity, she could take little food orally and therefore was malnourished. We performed a granulectomy under general anesthesia, and her difficulty with feeding and upper airway obstruction improved. There is no specific treatment for Farber's disease, and most patients reported have died by 2 years of age. This is the first reported patient with Farber's disease who has been surgically treated.

[Coexisting systemic lupus erythematosus and sickle cell disease: case report and literature review].

PubMed

Robazzi, Teresa Cristina M V; Alves, Crésio; Abreu, Laís; Lemos, Gabriela

2015-01-01

To report a case of coexisting systemic lupus erythematosus (SLE) and sickle cell disease (SCD) with a review of the literature on the topic. Report of case and research of the association between SLE and SCD in literature through scientific articles in health sciences databases, such as LILACS, MEDLINE/Pubmed and Scielo, until May 2012. Descriptors used: 1. Sickle cell anemia; 2. Sickle cell disease; 3. Systemic lupus erythematosus; 4. Hemoglobinopathies. The authors describe an association between SLE and SS hemoglobinopathy in an eight-year-old female patient displaying articular, hematologic and neuropsychiatric manifestations during clinical evolution. Forty-five cases of association between SLE and SCD are described in literature, mostly adult (62.2%), women (78%) and with the SS phenotype in 78% of the cases, and different clinical manifestations. Compared with our patient, articular, hematologic and neuropsychiatric manifestations were present in 76%, 36% and 27% of the cases, respectively. SLE and SCD are chronic diseases that have several clinical and laboratory findings in common, meaning difficult diagnosis and difficulty in finding the correct treatment. Although the association between these diseases is not common, it is described in literature, so it is imperative that physicians who treat such diseases be alert to this possibility. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Neurological features and management of Wilson disease in children: an evaluation of 12 cases

PubMed Central

Bayram, Ayşe Kaçar; Gümüş, Hakan; Arslan, Duran; Özçora, Güldemet Kaya; Kumandaş, Sefer; Karacabey, Neslihan; Canpolat, Mehmet; Per, Hüseyin

2016-01-01

Aim: Wilson’s disease is an autosomal recessive disorder of copper metabolism which leads to copper overload in different tissues of the body. The aim of this study was to present the neurologic features of Wilson’s disease and to assess the clinical course of neurological findings in children receiving anti-copper treatment. Material and Methods: Twelve children with a diagnosis of Wilson’s disease and findings of central nervous system involvement who were followed up in the Department of Pediatric Neurology and Pediatric Gastroenterology of the School of Medicine at Erciyes University were enrolled in the study. Results: The study cases consisted of five boys (42%) and seven girls (58%). The mean age at the time of diagnosis was 9.9±3.4 years (5–15 years). The mean duration of follow-up was 49.0±36.4 months (15–128 months). Neurological findings at presentation included headache in seven cases (58%), tremor in seven cases (58%), dystonia in three cases (25%), ataxia in two cases (17%), dizziness in two cases (17%), numbness in the hands and acute weakness in one case (8%) and syncope in one case (8%). Headache, dizziness, syncope, numbness in hands and acute weakness symptoms resolved completely within six months after receiving treatment. Movement disorders either decreased or remained stable in seven of the eight cases. However, one patient developed progressively worsening dystonia despite to all treatments. Conclusions: Wilson’s disease can be manifested with signs and symptoms of central nervous system in the childhood. Wilson’s disease should be considered in all children presenting with movement disorders. A complete neurological assessment should be carried out in all cases with Wilson’s disease. PMID:27103860

[Whipple's disease endocarditis: report of 5 cases and review of the literature].

PubMed

Aïouaz, H; Célard, M; Puget, M; Vandenesch, F; Mercusot, A; Fenollar, F; Delahaye, F; Obadia, J F; Tebib, J; Rousset, H

2005-10-01

Endocarditic lesions (infectious endocarditis) associated with Whipple's disease are exceptional. We report five cases from the cardiovascular and pneumologic hospital Louis Pradel in Lyon. We have collected all cases of Tropheryma whipplei endocarditis diagnosed between 1995 and 2004. Five men with a mean age of 53 years at time of diagnosis. The symptoms were essentially cardiovascular: murmur, embolism in 3 cases, and heart failure secondary to valvular insufficiency in 2 cases. The valvular involvement, double in 3 cases, was more often aortic. Vegetations were present in all patients and valvular destruction sometimes very important. A low grade fever was present in 4 cases, associated with weight loss in 2 cases. The only extra-cardiac symptoms were arthralgias or arthritis in all cases, considered in 3 patients as seronegative rheumatoid arthritis, B27+ spondylarthritis, and psoriasic arthritis. Their was no other clinical manifestations of Whipple's disease, particularly digestive, ocular, neurologic or adenopathy, and duodenal biopsies secondarily performed in 4 cases were non contributive. This differs from literature as an extra-cardiac location was identified in 11 out of 17 cases. The diagnosis was obtained by histology and PCR on the cardiac valves, as all the patients underwent surgery. The evolution was favourable with a prolonged antibiotic therapy. These report confirms the existence of endocarditic forms of the Whipple's disease, in which the single extra-cardiac manifestation is rheumatologic, and reminds us the usefulness of histology and PCR on the cardiac valves at the time of valvular surgery.

Hirschsprung disease and hepatoblastoma: case report of a rare association.

PubMed

Pinto, Raquel Borges; Ramos, Ana Regina Lima; Backes, Ariane Nadia; Santos, Beatriz John Dos; Provenzi, Valentina Oliveira; Carbonera, Mário Rafael; Roenick, Maria Lúcia; Santos, Pedro Paulo Albino Dos; Falhauber, Fabrizia; Souza, Meriene Viquetti de; Bassols, João Vicente; Artigalás, Osvaldo

2016-04-01

Hirschsprung disease is a developmental disorder of the enteric nervous system that is characterized by absence of ganglion cells in the distal intestine, and it occurs in approximately 1 in every 500,000 live births. Hepatoblastoma is a malignant liver neoplasm that usually occurs in children aged 6 months to 3 years, with a prevalence of 0.54 cases per 100,000. A boy diagnosed with intestinal atresia in the first week of life progressed to a diagnosis of comorbid Hirschsprung disease. Congenital cataracts and sensorineural deafness were diagnosed. A liver mass developed and was subsequently confirmed to be a hepatoblastoma, which was treated by means of surgical resection of 70% of the liver volume and neoadjuvant chemotherapy (ifosfamide, cisplatin and doxorubicin). It is known that Hirschsprung disease may be associated with syndromes predisposing towards cancer, and that hepatoblastoma may also be associated with certain congenital syndromes. However, co-occurrence of hepatoblastoma and Hirschsprung disease has not been previously described. We have reported a case of a male patient born with ileal atresia, Hirschsprung disease and bilateral congenital cataract who was later diagnosed with hepatoblastoma.

First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features

PubMed Central

Spencer, Michael D; Knight, Richard S G; Will, Robert G

2002-01-01

Objective To describe the early psychiatric and neurological features of variant Creutzfeldt-Jakob disease. Design Cohort study. Setting National surveillance system for Creutzfeldt-Jakob disease in the United Kingdom. Participants The first 100 cases of variant Creutzfeldt-Jakob disease identified in the United Kingdom. Main outcome measures The timing and nature of early psychiatric and neurological symptoms in variant Creutzfeldt-Jakob disease. Results The early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptoms, but neurological symptoms precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of disease. Common early psychiatric features include dysphoria, withdrawal, anxiety, insomnia, and loss of interest. No common early neurological features exist, but a significant proportion of patients do exhibit neurological symptoms within 4 months of clinical onset, including poor memory, pain, sensory symptoms, unsteadiness of gait, and dysarthria. Conclusions Although the diagnosis of variant Creutzfeldt-Jakob disease may be impossible in the early stages of the illness, particular combinations of psychiatric and neurological features may allow early diagnosis in an appreciable proportion of patients. What is already known on this topicThe early stages of variant Creutzfeldt-Jakob disease are dominated by psychiatric symptomatologySome patients have early neurological features that might suggest the presence of an underlying neurological disorderWhat this study addsThis study provides a comprehensive description of the evolution of psychiatric and neurological features in variant Creutzfeldt-Jakob diseaseAn appreciable proportion of patients have early neurological symptomsA high proportion of patients have a combination of psychiatric and neurological features within four months of clinical onset that suggest the diagnosis of variant Creutzfeldt-Jakob disease

[Mucha-Habermann disease and orthotopic heart transplant. Case report].

PubMed

Zetina-Tun, Hugo; de la Cerda-Belmont, Gustavo Armando; Lezama-Urtecho, Carlos Alberto; Careaga-Reyna, Guillermo

2013-01-01

Mucha-Habermann disease is a cutaneous clinical manifestation of unknown etiology that frequently appears in young patients. The aim was to present Mucha-Habermann disease that occurred in an old man who had a heart transplant. a 62 year-old male, heart transplant recipient, who four years after that transplantation procedure presented with papular lesions in neck, thoracic members of which extended to all body surfaces and that evolved vesicles and pustular lesions. A skin biopsy was performed and Mucha-Habermann disease was diagnosed. The patient was treated with steroids and antimicrobial therapy with favorable response. After two years there are no skin lesions. Mucha-Habermann disease is a low frequency disease and it requires skin biopsy to confirm diagnose. This is an uncommon case due to the age and kind of patient.

Celiac Disease and Concomitant Conditions: A Case-based Review.

PubMed

Lodhi, Muhammad Uzair; Stammann, Tracy; Kuzel, Aaron R; Syed, Intekhab Askari; Ishtiaq, Rizwan; Rahim, Mustafa

2018-02-02

Celiac disease is a chronic autoimmune disease with genetic predisposition, triggered by the ingestion of gluten. It has a wide range of clinical manifestations ranging from asymptomatic forms to classic presentation of malabsorption with diarrhea and abdominal cramps. Celiac disease can also present with several other concomitant disorders (at the time of diagnosis or during the course of celiac disease) such as: type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, thyroid disorders, nutritional deficiencies, and gram-negative sepsis. We present a 57-year-old female with past medical history of rheumatoid arthritis, who presented to the emergency department with a complaint of chronic diarrhea, complicated by gram-negative sepsis. The family history of the patient was significant for celiac disease, type 1 diabetes, and rheumatoid arthritis. The patient was closely monitored and treated appropriately. In this case-based review, we explore different associated conditions of celiac disease in the literature, as well as the patient's risk of developing malignancy.

Sudden unexpected death from natural diseases: Fifteen years' experience with 484 cases in Seychelles.

PubMed

Zhao, Peng; Wang, Ji-Gang; Gao, Peng; Li, Xia; Brewer, Rubell

2016-01-01

The aim of this study is to identify and subclassify sudden natural death (sudden death from natural diseases) cases in Seychelles. A total of 484 sudden natural death cases with autopsy at the Clinical Pathology Laboratory, Victoria Hospital, Seychelles between 1997 through 2012 were retrospectively reviewed. Among them, 363 cases (75%) were male and 121 (25%) were female. The most frequent sudden deaths were attributed to cardiovascular diseases (78.5%), and then followed by infectious diseases (9.9%), and gastrointestinal diseases (9.1%). This is the largest population-based study on sudden natural deaths in Seychelles. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Clinical manifestations of reported Lyme disease cases in Ontario, Canada: 2005–2014

PubMed Central

Nelder, Mark P.; Russell, Curtis; Li, Ye; Badiani, Tina; Sander, Beate; Sider, Douglas; Patel, Samir N.

2018-01-01

Lyme disease (LD) is the most common vector-borne disease in Ontario, Canada. We describe the epidemiology and clinical manifestations of LD in Ontario and examine trends in the incidence of non-disseminated and disseminated LD. LD surveillance data from the integrated Public Health Information System (iPHIS) from 2005–2014 were mapped to symptoms according to syndrome groups (erythema migrans (EM), flu-like, cardiac, neurologic or arthritic) and disease stages (early localized, early disseminated or late disseminated). During the study period, 1,230 cases due to Borrelia burgdoferi were reported in Ontario with annual incidence rates ranging from 0.32 (2006) to 2.16 (2013) cases per 100,000 population. Seventy percent of cases had EM and the proportion of cases with EM increased over time. Other clinical manifestations included flu-like (75%), arthritic (42%), neurologic (41%) and cardiac (6%) symptoms. Early localized disease (n = 415) manifested with EM (87%) and flu-like (57%) symptoms; early disseminated disease (n = 216) manifested with neurologic (94%), cardiac (10%) and EM (63%) symptoms; and late disseminated disease (n = 475) manifested with EM (62%), neurologic (55%), cardiac (9%), and arthritic symptoms (i.e., arthralgia (93%) and arthritis (7%)). Early localized and early disseminated cases (88% each) occurred primarily from May through September, compared to late disseminated cases (81%). The proportion of cases reported to public health within 30 days of illness onset increased during the study period, while the proportion of cases reported within 1–3 months and >3 months decreased. Geographical variations characterized by higher incidence of early localized disease and earlier public health notification (within 30 days of illness onset) occurred in regions with established or recently established LD risk areas, while later public health notification (>3 months after illness onset) was reported more frequently in regions with recently established

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma

A case-association cluster detection and visualisation tool with an application to Legionnaires’ disease

PubMed Central

Sansom, P; Copley, V R; Naik, F C; Leach, S; Hall, I M

2013-01-01

Statistical methods used in spatio-temporal surveillance of disease are able to identify abnormal clusters of cases but typically do not provide a measure of the degree of association between one case and another. Such a measure would facilitate the assignment of cases to common groups and be useful in outbreak investigations of diseases that potentially share the same source. This paper presents a model-based approach, which on the basis of available location data, provides a measure of the strength of association between cases in space and time and which is used to designate and visualise the most likely groupings of cases. The method was developed as a prospective surveillance tool to signal potential outbreaks, but it may also be used to explore groupings of cases in outbreak investigations. We demonstrate the method by using a historical case series of Legionnaires’ disease amongst residents of England and Wales. PMID:23483594

Public policies and reproductive technology: a feminist critique.

PubMed

Mccormack, T

1991-01-01

Reproductive technology comprises abortion, contraception, amniocentesis (more than 40 genetic disorders can be diagnosed), chorionic villus sampling, genetic screening (to reduce the risk of chromosomal defects such as Down syndrome, sickle cell anemia, Tay-Sachs disease, and cystic fibrosis), in vitro fertilization, artificial insemination by spouse or donor, the development of sperm banks, storage of frozen sperm (cryopreservation), the development of artificial wombs, techniques for predetermining the sex of a fetus, and nursery environments to maintain a fetus removed from the womb in the 1st trimester. In recent years, the demand for these services has increased because of higher infertility and the drop in the number of babies available for adoption. Surrogacy is especially controversial: it has become a symbol of the dehumanization of modern life and the exploitation of women. The feminist perspective discloses how patriarchal values about the subordinate status of women, about the nature of motherhood, infertility, and the family are both implicit and explicit in prevailing thinking about reproduction. The new technology offers women who wish to remain unmarried the opportunity to have a family, and it enables lesbian women to bear children. The research literature favors a Eurocentric nuclear family without any awareness that in Canada, and in the Western world, new forms of family life have been evolving as couples marry, divorce, and remarry. There is no awareness either that in other cultures this Eurocentric nuclear model is dysfunctional. Because of the rigid notion of the 2-parent nuclear family, the 3rd parties who are involved in either surrogate relationships or artificial insemination are deprecated. The feminist literature is more critical of the nuclear family, but it has been sometimes inconsistent on the relevant issues.

Expression of the GM2 activator protein in mouse testis.

PubMed

Li, Yu-Teh; Li, Su-Chen; Chen, I-Li

2017-12-01

The GM2-activator protein (GM2-AP), revealed by Li et al. in 1973 in human liver, was initially identified as a protein cofactor that stimulated β-hexosaminidase A to hydrolyze N-acetylgalactosamine from GM2 ganglioside. This cofactor was found to be missing in human variant AB Tay-Sachs disease. Over the years, the GM2-AP has also been shown to be involved in kidney vesicular transport, lipid presentation by CD1 molecule to T-cells, and interaction of human sperm with zona pellucida. Since the expression of the GM2-AP via mRNA detection in mouse tissues was found to be the highest in testis, we became interested in the localization of the GM2-AP at cellular level in mouse testis during spermatogenesis. Using immunohistochemical analysis and electron microscopy, we found that the GM2-AP was predominantly localized in the basal cytoplasm and the attenuated processes of Sertoli cells. The stained structure appeared to be lysosomes. The most interesting finding was the association of the GM2-AP with the acrosomal apparatus in early spermatids. A modest to intense staining was observed in some acrosomal granules and acrosomal caps. The GM2-AP seemed to disappear from acrosomal caps in the later stage of spermatids, in which the nucleus became elongated and condensed. These results suggest that the GM2-AP may be involved in the normal functions of Sertoli cells and play important roles during the development of acrosomal caps in the early spermatids. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A Novel Mechanism for Desulfation of Mucin: Identification and Cloning of a Mucin-Desulfating Glycosidase (Sulfoglycosidase) from Prevotella Strain RS2

PubMed Central

Rho, Jung-hyun; Wright, Damian P.; Christie, David L.; Clinch, Keith; Furneaux, Richard H.; Roberton, Anthony M.

2005-01-01

A novel enzyme which may be important in mucin degradation has been discovered in the mucin-utilizing anaerobe Prevotella strain RS2. This enzyme cleaves terminal 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sulfate (6-SO3-GlcNAc) residues from sulfomucin and from the model substrate 4-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sodium sulfate. The existence of this mucin-desulfating glycosidase (sulfoglycosidase) suggests an alternative mechanism by which this bacterium may desulfate sulfomucins, by glycosidic removal of a sulfated sugar from mucin oligosaccharide chains. Previously, mucin desulfation was thought to take place by the action of a specific desulfating enzyme, which then allowed glycosidases to remove desulfated sugar. Sulfate removal from sulfomucins is thought to be a rate-limiting step in mucin degradation by bacteria in the regions of the digestive tract with a significant bacterial flora. The sulfoglycosidase was induced by growth of the Prevotella strain on mucin and was purified 284-fold from periplasmic extracts. Tryptic digestion and sequencing of peptides from the 100-kDa protein enabled the sulfoglycosidase gene to be cloned and sequenced. Active recombinant enzyme was made in an Escherichia coli expression system. The sulfoglycosidase shows sequence similarity to hexosaminidases. The only other enzyme that has been shown to remove 6-SO3-GlcNAc from glycoside substrates is the human lysosomal enzyme β-N-acetylhexosaminidase A, point mutations in which cause the inheritable, lysosomal storage disorder Tay-Sachs disease. The human enzyme removes GlcNAc from glycoside substrates also, in contrast to the Prevotella enzyme, which acts on a nonsulfated substrate at a rate that is only 1% of the rate observed with a sulfated substrate. PMID:15716424

Completed suicide in an autopsy-confirmed case of early onset Alzheimer's disease.

PubMed

Hartzell, Jennifer Wiener; Geary, Richard; Gyure, Kymberly; Chivukula, Venkata Ravi; Haut, Marc W

2018-04-01

We report a case of a 57-year-old male with clinically diagnosed and autopsy-confirmed early onset Alzheimer's disease who completed suicide by gunshot wound to the chest. This case has several unique aspects that have not been discussed in previous case reports of completed suicide in Alzheimer's disease. In particular, our patient's death was highly planned with successful compensation for his cognitive deficits. After all firearms had been removed from the home as a safety precaution, he obtained a new weapon, hid it and left himself cues to find and use it. The case is discussed in the context of literature differentiating the neural circuitry propagating impulsive versus planned suicidal acts.

Conn syndrome and Crohn disease in a pediatric case: an interesting parallel.

PubMed

Rodriguez, Manuel A; Alkhoury, Fuad; Malvezzi, Leopoldo; Diaz, Alejandro

2013-01-01

Conn syndrome is characterized by surreptitious secretion of aldosterone in which patients are found to have hypertension, hypokalemia, and metabolic alkalosis. Although rare, the most common presentation in the pediatric population is bilateral hyperplasia of the adrenal glands as opposed to an adenoma. Crohn disease is part of the spectrum of inflammatory bowel disease, which manifests in children as flare-ups of bloody diarrhea and abdominal pain. The association of concurrent Conn syndrome and Crohn disease has been previously presented in two cases in adults. This is the first pediatric case to be reported in the literature.

Chronicle of a death foretold: a case of catastrophic vascular Behcet's disease.

PubMed

Planer, David; Leibowitz, David; Elitzur, Yair; Korach, Amit; Hiller, Nurith; Chajek-Shaul, Tova

2007-03-01

A 20-year-old man with Behcet's disease characterized by recurrent arterial aneurysms presented with a new aortic root aneurysm. This patient previously had aneurysms of the coronary arteries and vein, as well as ruptured renal artery aneurysm. Chronic maintenance immunosuppressive therapy was recommended due to the catastrophic nature of the disease, which the patient refused to take. The patient died shortly after admission. This case demonstrates the unique catastrophic natural history of vascular Behcet's disease with recurrent life-threatening arterial events, and this case stresses the therapeutic dilemma of maintenance immunosuppressive therapy in selected patients.

Early bronchopulmonary involvement in Crohn disease: a case report

PubMed Central

Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

2001-01-01

Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

Animal models of GM2 gangliosidosis: utility and limitations

PubMed Central

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

Cases of Lyme disease reported in a military community.

PubMed

Underwood, P K; Armour, V M

1993-02-01

Lyme disease, a growing public health problem in the United States, is also an increasing threat in Europe. Cases identified in a military community in West Germany are presented and problems of diagnosis and treatment discussed.

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Recognition and treatment of Alzheimer's disease: a case-based review.

PubMed

Marseille, Dana M; Silverman, Daniel H S

2006-01-01

Early recognition and treatment initiation are pivotal in managing Alzheimer's disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and should include treatment initiation with cholinesterase inhibitors (ChEIs) to improve cognition, management of comorbid conditions, and treat behavioral symptoms. Caregiver compliance is integral to AD treatment success. The purpose of this report is to present two real case studies of "suspected" AD or related dementia and stress the significance of early and accurate diagnosis in disease management. In case 1, a caregiver reports gradual but progressive loss of memory, and the patient himself complains of memory impairment. Neuroimaging analysis confirms "typical " AD. In case 2, initiation of ChEI therapy is followed by substantial clinical improvement in the face of a complex medical picture, and neuroimaging revealing more neurodegenerative changes than could be accounted for by "pure" AD.

Bilateral Adventitial Cystic Disease of the Popliteal Artery: A Case Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ortiz M, William R.; Lopera, Jorge E., E-mail: Jorge.lopera@utsouthwestern.edu; Gimenez, Carlos R.

2006-04-15

Adventitial cystic disease (ACD) of the popliteal artery is an uncommon vascular condition of unknown etiology. In the present case report, we describe a case of bilateral ACD of the popliteal artery in a 58-year-old male. To the best of our knowledge, this is the first case of bilateral ACD of the popliteal artery reported in the literature.

Mammary and extramammary Paget's disease: an immunohistochemical study of 83 cases.

PubMed

Liegl, B; Leibl, S; Gogg-Kamerer, M; Tessaro, B; Horn, L-C; Moinfar, F

2007-03-01

Mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) are rare neoplasms. The aim of this study was, by the use of immunohistochemistry, to derive further information about the cell(s) of origin, find a diagnostically useful immunohistochemical panel and investigate candidates for possible targeted therapy. Sixty MPD and 23 EMPD cases were studied using antibodies to cytokeratin (CK) 34betaE12, CK8/18, CK7, CK5/6, CK20, gross cyctic disease fluid protein (GCDFP)-15, MUC1-8, epidermal growth factor receptor (EGFR) (HER1), HER3 and HER4. In all MPD cases CK7 and MUC1 were positive. CK8/18 was positive in 59/60 cases. GCDFP-15, MUC2, MUC3, MUC4, MUC7, MUC8 were positive in 29/60, 3/60, 35/47, 4/40, 3/43 and 2/45 cases, respectively. In all EMPD cases CK8/18 and CK7 were positive. MUC1, GCDFP-15, MUC5AC, MUC3, MUC8 and CK20 were positive in 22/23, 19/23, 8/19, 3/19, 1/19 and 3/23 cases, respectively. With the remaining antibodies no immunoreactivity was observed. MUC1 and low-molecular-weight CKs in conjunction with immunonegativity for high-molecular-weight CKs are the most diagnostically useful markers. MPD is caused by the epidermotropic spread of underlying tumour cells, whereas EMPD probably arises from intraepithelial cells of sweat gland origin. Targeted therapy with antibodies against EGFR (HER1), HER3 or HER4 is unlikely to prove of clinical value.

A retrospective study of diseases in Ambystoma mexicanum: a report of 97 cases

PubMed Central

TAKAMI, Yoshinori; UNE, Yumi

2017-01-01

Ambystoma mexicanum kept as pets are affected by a variety of diseases. However, no reports regarding the incidence of specific diseases are available. This study aimed to identify the diseases that occur frequently in this species by surveying the incidence of conditions in pet A. mexicanum specimens brought to a veterinary hospital. The sample comprised 97 pet A. mexicanum individuals brought to the authors’ hospital during the 82-month period, i.e., from January 2008 to October 2014. In total, 116 diseases were identified. The most common disease was hydrocoelom (32 cases; 27.5% of all cases). Elucidating the pathogenesis of hydrocoelom, which has a high prevalence rate, is vital to maintaining the long-term health of A. mexicanum pets. PMID:28529268

A retrospective study of diseases in Ambystoma mexicanum: a report of 97 cases.

PubMed

Takami, Yoshinori; Une, Yumi

2017-06-16

Ambystoma mexicanum kept as pets are affected by a variety of diseases. However, no reports regarding the incidence of specific diseases are available. This study aimed to identify the diseases that occur frequently in this species by surveying the incidence of conditions in pet A. mexicanum specimens brought to a veterinary hospital. The sample comprised 97 pet A. mexicanum individuals brought to the authors' hospital during the 82-month period, i.e., from January 2008 to October 2014. In total, 116 diseases were identified. The most common disease was hydrocoelom (32 cases; 27.5% of all cases). Elucidating the pathogenesis of hydrocoelom, which has a high prevalence rate, is vital to maintaining the long-term health of A. mexicanum pets.

Updated tomographic analysis of the integrated Sachs-Wolfe effect and implications for dark energy

NASA Astrophysics Data System (ADS)

Stölzner, Benjamin; Cuoco, Alessandro; Lesgourgues, Julien; Bilicki, Maciej

2018-03-01

We derive updated constraints on the integrated Sachs-Wolfe (ISW) effect through cross-correlation of the cosmic microwave background with galaxy surveys. We improve with respect to similar previous analyses in several ways. First, we use the most recent versions of extragalactic object catalogs, SDSS DR12 photometric redshift (photo-z ) and 2MASS Photo-z data sets, as well as those employed earlier for ISW, SDSS QSO photo-z and NVSS samples. Second, we use for the first time the WISE × SuperCOSMOS catalog, which allows us to perform an all-sky analysis of the ISW up to z ˜0.4 . Third, thanks to the use of photo-z s , we separate each data set into different redshift bins, deriving the cross-correlation in each bin. This last step leads to a significant improvement in sensitivity. We remove cross-correlation between catalogs using masks which mutually exclude common regions of the sky. We use two methods to quantify the significance of the ISW effect. In the first one, we fix the cosmological model, derive linear galaxy biases of the catalogs, and then evaluate the significance of the ISW using a single parameter. In the second approach we perform a global fit of the ISW and of the galaxy biases varying the cosmological model. We find significances of the ISW in the range 4.7 - 5.0 σ thus reaching, for the first time in such an analysis, the threshold of 5 σ . Without the redshift tomography we find a significance of ˜4.0 σ , which shows the importance of the binning method. Finally we use the ISW data to infer constraints on the dark energy redshift evolution and equation of state. We find that the redshift range covered by the catalogs is still not optimal to derive strong constraints, although this goal will be likely reached using future datasets such as from Euclid, LSST, and SKA.

[Myasthenia gravis, Graves-Basedow disease and other autoimmune diseases in patient with diabetes type 1 - APS-3 case report, therapeutic complications].

PubMed

Klenczar, Karolina; Deja, Grażyna; Kalina-Faska, Barbara; Jarosz-Chobot, Przemysława

2017-01-01

Diabetes type 1(T1D) is the most frequent form of diabetes in children and young people, which essence is autoimmune destruction of pancreatic B cells islet. Co-occurrence of other autoimmune diseases is observed in children with T1D, the most often are: Hashimoto disease or coeliac disease. We report the case of the patient, who presents coincidence of T1D with other rare autoimmune diseases such as: Graves - Basedow disease, myasthenia gravis, vitiligo and IgA deficiency. All mentioned diseases significantly complicated both endocrine and diabetic treatment of our patient and they negatively contributed her quality of life. The clinical picture of the case allows to recognize one of the autoimmune polyendocrine syndromes: APS-3 and is associated with still high risk of developing another autoimmune disease. © Polish Society for Pediatric Endocrinology and Diabetology.

A Case of Neuro-Behcet’s Disease Presenting with Central Neurogenic Hyperventilation

PubMed Central

Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.

2016-01-01

Patient: Female, 46 Final Diagnosis: Central hyperventilation Symptoms: Hyperventilation Medication: — Clinical Procedure: None Specialty: Neurology Objective: Unusual clinical course Background: Behcet’s disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet’s disease is an autoimmune vasculitis. Neurological involvement, so called “Neuro-Behcet’s disease”, occurs in 10–20% of patients, usually from a meningoencephalitis or venous thrombosis. Case Report: We report the case of a 46-year-old patient with Neuro-Behcet’s disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. Conclusions: To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet’s disease. PMID:26965646

Noninfectious interstitial lung disease during infliximab therapy: Case report and literature review

PubMed Central

Caccaro, Roberta; Savarino, Edoardo; D’Incà, Renata; Sturniolo, Giacomo Carlo

2013-01-01

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5th infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy. PMID:23983443

Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases

PubMed Central

Movsesyan, Nina; Platt, Frances M.

2017-01-01

In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters. PMID:29119141

Case management and adherence to an online disease management system.

PubMed

Robertson, Lucy; Smith, Michael; Tannenbaum, Dennis

2005-01-01

Non-adherence to treatment presents a significant obstacle to achieving favourable health outcomes. We have studied consumers' adherence to an online disease management system for depression, called Recovery Road. Recovery Road was implemented on a pilot basis for mental health care in Western Australia. Recovery Road was available for use by consumers and clinicians to augment usual treatment. One hundred and thirty consumers who had been diagnosed with major depression were enrolled. Consumers who used Recovery Road (n = 98) were provided with education, progress monitoring, e-consultation, e-diary and online evidenced-based therapy. Consumers received either standard, automated adherence reminders by email (n = 69), or case management, which included personalized email and telephone follow-up in response to non-adherence (n = 29). After the first eight sessions, the adherence was 84% in the case management group and 55% in the automatic reminders group. The results suggest that case management increases adherence to online disease management systems.

A Case of Neuro-Behcet's Disease Presenting with Central Neurogenic Hyperventilation.

PubMed

Alkhachroum, Ayham M; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; DeGeorgia, Michael A

2016-03-11

Behcet's disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet's disease is an autoimmune vasculitis. Neurological involvement, so called "Neuro-Behcet's disease", occurs in 10-20% of patients, usually from a meningoencephalitis or venous thrombosis. We report the case of a 46-year-old patient with Neuro-Behcet's disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet's disease.

A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam.

PubMed

Poyarkov, Nikolay A; Kropachev, Ivan I; Gogoleva, Svetlana S; Orlov, Nikolai L

2018-04-20

A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8-26.4 mm); (7) head longer than wide; ED/SVL ratio 13%-15%; ESL/SVL ratio 16%-20%; (8) small tympanum (TD/EL ratio 50%-60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2-2¼ II 1½-2¾ III 2-3¼ IV 3-1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3-5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma auratum sp. nov. to

Whipple's disease. Report of five cases with different clinical features.

PubMed

Ferrari, M de L; Vilela, E G; Faria, L C; Couto, C A; Salgado, C J; Leite, V R; Brasileiro Filho, G; Bambirra, E A; Mendes, C M; Carvalho, S de C; de Oliveira, C A; da Cunha, A S

2001-01-01

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

An Unusual Presentation of Addison's Disease-A Case Report.

PubMed

Choudhary, Sandeep; Alam, Anwer; Dewan, Vivek; Yadav, Dinesh; Dubey, N K

2011-07-01

Addison's disease is most commonly due to autoimmune adrenalitis and tuberculosis and refers to primary hypoadrenalism caused by a total or near total destruction or dysfunction of both adrenal cortices. Usual manifestations involve chronic fatigue, muscle weakness, loss of appetite, nausea, vomiting, diarrhea, hypotension and hyperpigmentation of skin. We herein report a case of primary adrenal insufficiency presenting with fever and seizures in an 11-yr-old boy. His symptoms resolved after starting specific therapy. This kind of presentation of Addison's disease is rather unusual.

Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.

PubMed

Gay, Estelle; Bornallet, Géraldine; Gaucherand, Pascal; Doret, Muriel

2015-11-01

To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Development and validation of an administrative case definition for inflammatory bowel diseases

PubMed Central

Rezaie, Ali; Quan, Hude; Fedorak, Richard N; Panaccione, Remo; Hilsden, Robert J

2012-01-01

BACKGROUND: A population-based database of inflammatory bowel disease (IBD) patients is invaluable to explore and monitor the epidemiology and outcome of the disease. In this context, an accurate and validated population-based case definition for IBD becomes critical for researchers and health care providers. METHODS: IBD and non-IBD individuals were identified through an endoscopy database in a western Canadian health region (Calgary Health Region, Calgary, Alberta). Subsequently, using a novel algorithm, a series of case definitions were developed to capture IBD cases in the administrative databases. In the second stage of the study, the criteria were validated in the Capital Health Region (Edmonton, Alberta). RESULTS: A total of 150 IBD case definitions were developed using 1399 IBD patients and 15,439 controls in the development phase. In the validation phase, 318,382 endoscopic procedures were searched and 5201 IBD patients were identified. After consideration of sensitivity, specificity and temporal stability of each validated case definition, a diagnosis of IBD was assigned to individuals who experienced at least two hospitalizations or had four physician claims, or two medical contacts in the Ambulatory Care Classification System database with an IBD diagnostic code within a two-year period (specificity 99.8%; sensitivity 83.4%; positive predictive value 97.4%; negative predictive value 98.5%). An alternative case definition was developed for regions without access to the Ambulatory Care Classification System database. A novel scoring system was developed that detected Crohn disease and ulcerative colitis patients with a specificity of >99% and a sensitivity of 99.1% and 86.3%, respectively. CONCLUSION: Through a robust methodology, a reproducible set of criteria to capture IBD patients through administrative databases was developed. The methodology may be used to develop similar administrative definitions for chronic diseases. PMID:23061064

Infections as a risk factor for Parkinson's disease: a case-control study.

PubMed

Vlajinac, Hristina; Dzoljic, Eleonora; Maksimovic, Jadranka; Marinkovic, Jelena; Sipetic, Sandra; Kostic, Vladimir

2013-05-01

The etiology of Parkinson's disease (PD) is unknown. The aim of the study was to test the hypothesis that some infectious diseases are related to the occurrence of PD. The case-control study, conducted in Belgrade during the period 2001-2005, comprised 110 subjects diagnosed for the first time as PD cases, and 220 controls chosen among patients with degenerative joint disease and some diseases of the digestive tract. According to logistic regression analysis, PD was significantly related to mumps [odds ratio adjusted on occupation and family history of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95% CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66) and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89). Tuberculosis, measles and chicken pox were not associated with PD. Other infectious diseases we asked for were not reported (12 diseases), or were too rare (four diseases) to be analysed. The results obtained are in line with the suggestion that some infectious diseases may play a role in the development of PD.

Leptospira Exposure and Patients with Liver Diseases: A Case-Control Seroprevalence Study

PubMed Central

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Ramos-Nevárez, Agar; Margarita Cerrillo-Soto, Sandra; Alberto Guido-Arreola, Carlos

2016-01-01

The seroepidemiology of Leptospira infection in patients suffering from liver disease has been poorly studied. Information about risk factors associated with infection in liver disease patients may help in the optimal planning of preventive measures. We sought to determine the association of Leptospira IgG seroprevalence and patients with liver diseases, and to determine the characteristics of the patients with Leptospira exposure. We performed a case-control study of 75 patients suffering from liver diseases and 150 age- and gender-matched control subjects. Diagnoses of liver disease included liver cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver abscess. Sera of participants were analyzed for the presence of anti- Leptospira IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150 control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age- and gender-matched case control study about Leptospira seroprevalence in patients with liver diseases. Results indicate that Leptospira infection is associated with chronic and acute liver diseases. Results warrants for additional studies on the role of Leptospira exposure in chronic liver disease. PMID:27493589

Diverticular disease and the risk of colon cancer - a population-based case-control study.

PubMed

Granlund, J; Svensson, T; Granath, F; Hjern, F; Ekbom, A; Blomqvist, P; Schmidt, P T

2011-09-01

Colon cancer and diverticular disease are most common in the Western world and their incidences tend to increase with advancing age. The association between the diseases remains unclear. To analyse the risk of colon cancer after hospitalisation for diverticular disease. Nationwide case-control study. A total of 41,037 patients with colon cancer during 1992-2006, identified from the Swedish Cancer Register were included. Each case was matched with two control subjects. From the Swedish Inpatient Register, cases and control subjects hospitalised for diverticular disease were identified. Odds ratios (OR) and confidence intervals for receiving a diagnosis of colon cancer after hospital discharge for diverticular disease were calculated. Colon cancer mortality was compared between patients with or without diverticular disease. Within 6months after an admission due to diverticular disease, OR of having a colon cancer diagnosis were up to 31.49 (19.00-52.21). After 12 months, there was no increased risk. The number of discharges for diverticular disease did not affect the risk. Colon cancer mortality did not differ between patients with and without diverticular disease. Diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality. The increased risk of colon cancer within the first 12months after diagnosing diverticular disease is most likely due to surveillance and misclassification. Examination of the colon should be recommended after a primary episode of symptomatic diverticular disease. © 2011 Blackwell Publishing Ltd.

[Eosinophilic pustular folliculitis and Ofuji disease. A case report].

PubMed

Rotoli, M; Carlesimo, F; Cavalieri, S

1995-10-01

We describe the case of a young man of Calabrian origin, who came to our observation for the appearance of erythematous pustular, intensely itching, lesions on the arms, trunk and, in a less extent, on the face. The blood count revealed a differential cell count of 16.8% eosinophils. Serum IgE levels were elevated (1000 IU/ml), and T cell subsets showed an increase in CD8+ and a decrease in CD4+ with an inversion of CD4+/CD8+ ratio (= 0.78). The result of the following investigations were either normal or negative: anti-(ds)DNA antibody, anti-nuclear antibody, anti-smooth muscle antibody, anti-striated muscle antibody, serological tests for viral, bacterial, fungal and parasitic diseases and cultural examination of the material from lesion. Histopathological examination of a biopsy specimen from the left arm showed the presence of abundant perivascular inflammatory infiltrate in the dermis and inflammatory infiltrate, with numerous eosinophils, around sebaceous glands. Taken together, all these data suggest the diagnosis of eosinophilic pustular folliculitis, a dermatosis of unknown etiology, with a histopathological picture identical to Ofuji's disease. Eosinophilic pustular folliculitis can be associated with HIV infection or haematological diseases (as non-Hodgkin lymphomas, myeloma, etc.); it was also reported in adult immunocompetent healthy individuals and in children. On the basis of our findings, we propose that this case should be classified as an idiopathic form, as we were not able to demonstrate any associated disease.

Viral meningitis admitted to an infectious diseases hospital: a retrospective case series.

PubMed

Vâţă, A; Luca, Cătălina M; Duca, Elena; Irina, Teodorescu; Manciuc, Carmen; Vâţă, Luminita G; Dorobăţ, Carmen

2013-01-01

Given its epidemic potential and development of severe forms of disease, viral meningitis (VM) is a serious public health problem. to characterize the main clinical, epidemiologic features, the etiology and treatment of VM cases admitted to the Iasi Infectious Diseases Hospital, in 2012. We retrospectively analyzed the medical records of the patients admitted for viral meningitis at the Iasi "St. Parascheva" Infectious Diseases Hospital in the interval January 1- December 31, 2012 (98 cases). The etiologic diagnosis was made by determining the IgM/IgG antibodies against Coxsackie virus and/or West Nile virus in blood/CSF. There was a fourfold increase in the number of cases as compared to the average for the years 2009-2011. Most cases (73.5%) were children aged 1 to 14 years. 61.8% of patients were males, 51.7% from urban areas. The most common symptom was headache (85.7%), followed by fever (77.6%), and vomiting (66.3%). Neck stiffness was absent in 28.6% cases. In43.5% of the 39 patients serologically investigated a Coxsackie virus infection was confirmed and 1/20 was positive for West Nile virus; three varicella-zoster virus infections and one mumps infection were diagnosed clinically. 68.3% of the patients received first-line antibiotic treatment. The illness mainly affected children, fever and neck stiffness being sometimes absent. The etiology was known in 22.4% of cases; enter viruses being the most frequent causative agent. Most patients received antibiotic therapy. The course was favorable in all cases.

Four Cases of Parkinson Disease Diagnosed During the Postpartum Period.

PubMed

Maltête, David; Grangeon, Lou; Le Goff, Floriane; Ozel, Gulden; Fetter, Damien; Ahtoy, Patrick; Temgoua, Olivier; Rouillé, Audrey; Lefaucheur, Romain

2017-07-01

There is little experience with the effect of pregnancy on Parkinson disease because the number of women with Parkinson disease who are of childbearing age is small. We report four cases beginning during the postpartum period and discuss the potential contribution of different factors that may influence the occurrence of Parkinson disease in this time period. Four women aged 29-35 years developed arm tremor, shoulder pain, dizziness, or decreased dexterity of the hand in the first few days or months after childbirth. They were initially diagnosed with postpartum depression or psychogenic parkinsonism. Finally, dopamine transporter imaging confirmed the diagnosis of young-onset Parkinson disease. Early-onset Parkinson disease may present in postpartum women. In women with atypical motor symptoms in addition to depression, this diagnosis should be considered.

A combined case of macroprolactinoma, growth hormone excess and Graves' disease.

PubMed

Hussein, Z; Tress, B; Colman, P G

2005-06-01

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

[Assessment of an algorithm to identify paediatric-onset celiac disease cases through administrative healthcare databases].

PubMed

Pitter, Gisella; Gnavi, Roberto; Romor, Pierantonio; Zanotti, Renzo; Simonato, Lorenzo; Canova, Cristina

2017-01-01

to assess the role of four administrative healthcare databases (pathology reports, copayment exemptions, hospital discharge records, gluten-free food prescriptions) for the identification of possible paediatric cases of celiac disease. population-based observational study with record linkage of administrative healthcare databases. SETTING AND PARTICIPANT S: children born alive in the Friuli Venezia Giulia Region (Northern Italy) to resident mothers in the years 1989-2012, identified using the regional Medical Birth Register. we defined possible celiac disease as having at least one of the following, from 2002 onward: 1. a pathology report of intestinal villous atrophy; 2. a copayment exemption for celiac disease; 3. a hospital discharge record with ICD-9-CM code of celiac disease; 4. a gluten-free food prescription. We evaluated the proportion of subjects identified by each archive and by combinations of archives, and examined the temporal relationship of the different sources in cases identified by more than one source. RESULT S: out of 962 possible cases of celiac disease, 660 (68.6%) had a pathology report, 714 (74.2%) a copayment exemption, 667 (69.3%) a hospital discharge record, and 636 (66.1%) a gluten-free food prescription. The four sources coexisted in 42.2% of subjects, whereas 30.2% were identified by two or three sources and 27.6% by a single source (16.9% by pathology reports, 4.2% by hospital discharge records, 3.9% by copayment exemptions, and 2.6% by gluten-free food prescriptions). Excluding pathology reports, 70.6% of cases were identified by at least two sources. A definition based on copayment exemptions and discharge records traced 80.5% of the 962 possible cases of celiac disease; whereas a definition based on copayment exemptions, discharge records, and gluten-free food prescriptions traced 83.1% of those cases. The temporal relationship of the different sources was compatible with the typical diagnostic pathway of subjects with celiac

Chronic behavior disturbance and neurocognitive deficits in neuro-Behcet's disease: a case study.

PubMed

Fisher, Caroline A; Sewell, Katherine; Baker, Amy

2016-06-01

Behcet's disease is a vasculitis and multisystem inflammatory syndrome. Neurological abnormalities occur in a subset of patients. This report presents a case of neuro-Behcet's disease characterized by an initial onset of behavior changes prior to diagnosis, which evolved into a chronic behavioral syndrome. Neuroimaging investigations revealed progressive periventricular white matter and brainstem atrophy and lesions in the basal ganglia and deep white matter tracts, while neuropsychological investigations revealed reductions in information processing, executive functioning, and memory. The case indicates that behavior changes may be the first symptoms to emerge in Behcet's, before other defining features of the disease.

78 FR 17075 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) Tay 611-8 turbofan engines. This AD requires inspection... (RRD) Tay 611-8 turbofan engines, serial numbers 16245, 16256, 16417, 16418, 16584, 16585, 16639, 16640...

Multifocal oral melanoacanthoma associated with Addison's disease and hyperthyroidism: a case report.

PubMed

Dantas, Thinali Sousa; Nascimento, Isabelly Vidal do; Verde, Maria Elisa Quezado Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu; Mota, Mário Rogério Lima

2017-01-01

Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison's disease and concomitant Graves' disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison's disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison's disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma.

Autoimmune diseases in a Nigerian woman--a case report.

PubMed

Talabi, O A; Owolabi, M O; Osotimehin, B O

2003-12-01

Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.

An oral ulceration associated with Morgellons disease: a case report.

PubMed

Grosskopf, Courtney; Desai, Bhavik; Stoopler, Eric T

2011-08-01

Morgellons disease is a psycho-dermatologic condition in which patients report fibers or filaments "growing" out of their skin. This case report highlights an oral ulceration in a young woman associated with Morgellons disease, a condition that has not been previously described in the dental literature. An increasing number of individuals are self-reporting this condition and oral health care providers must be familiar with this disorder. Copyright © 2011 Mosby, Inc. All rights reserved.

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report.

PubMed

Tumminello, Richard; Glaspey, Lindsey; Bhamidipati, Anita; Sheehan, Patrick; Patel, Sundip

2017-12-01

Disseminated Lyme disease can be difficult to diagnose, as it begins with nonspecific signs and symptoms, which, if not treated correctly, can lead to atrioventricular conduction blocks and meningitis. In addition, the diagnosis can be further complicated by potentially false-positive test results. We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the difficulty in early diagnosis of disseminated Lyme disease and how a potentially false-positive laboratory test can lead to the complications of Borrelia meningitis and Lyme carditis in untreated young healthy patients. Emergency physicians need to consider Lyme disease in patients with nonspecific signs and symptoms, especially if they have been outdoors for prolonged periods of time in Lyme-endemic areas. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe panuveitis in neuro-Behçet's disease in Malaysia: a case series.

PubMed

Othman, Khairuddin; Liza-Sharmini, Ahmad Tajudin; Ibrahim, Mohtar; Tharakan, John; Yanai, Ryoji; Zunaina, Embong

2017-01-01

Behçet's disease (BD) is a multisystemic disease that is very rare in Malaysia. About 5% of patients develop central nervous system involvement, termed neuro-Behçet's. Neuro-Behçet's is one of the most serious causes of long-term morbidity and mortality. We report two cases of neuro-Behçet's associated with uveitis (ocular BD) highlighting the clinical presentation, diagnostic measurement, and therapeutic management of these cases.

78 FR 35574 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for all Rolls-Royce Deutschland Ltd & Co KG (RRD) model Tay 650-15 turbofan engines... Compliance We estimate that this proposed AD affects 52 Tay turbofan engines installed on airplanes of U.S...

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

PubMed

Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Using prediction markets of market scoring rule to forecast infectious diseases: a case study in Taiwan.

PubMed

Tung, Chen-yuan; Chou, Tzu-chuan; Lin, Jih-wen

2015-08-11

The Taiwan CDC relied on the historical average number of disease cases or rate (AVG) to depict the trend of epidemic diseases in Taiwan. By comparing the historical average data with prediction markets, we show that the latter have a better prediction capability than the former. Given the volatility of the infectious diseases in Taiwan, historical average is unlikely to be an effective prediction mechanism. We designed and built the Epidemic Prediction Markets (EPM) system based upon the trading mechanism of market scoring rule. By using this system, we aggregated dispersed information from various medical professionals to predict influenza, enterovirus, and dengue fever in Taiwan. EPM was more accurate in 701 out of 1,085 prediction events than the traditional baseline of historical average and the winning ratio of EPM versus AVG was 64.6 % for the target week. For the absolute prediction error of five diseases indicators of three infectious diseases, EPM was more accurate for the target week than AVG except for dengue fever confirmed cases. The winning ratios of EPM versus AVG for the confirmed cases of severe complicated influenza case, the rate of enterovirus infection, and the rate of influenza-like illness in the target week were 69.6 %, 83.9 and 76.0 %, respectively; instead, for the prediction of the confirmed cases of dengue fever and the confirmed cases of severe complicated enterovirus infection, the winning ratios of EPM were all below 50 %. Except confirmed cases of dengue fever, EPM provided accurate, continuous and real-time predictions of four indicators of three infectious diseases for the target week in Taiwan and outperformed the historical average data of infectious diseases.

Melorheostosis – Case Report of Rare Disease

PubMed Central

Kumar, Rakesh; Sankhala, S.S.; Bijarnia, Isha

2014-01-01

Introduction: Melorheostosis(synonyms: candle bone disease, melting wax syndrome, Leri disease) is a rare chronic bone disorder, first described in 1922 by Leri and Joanny. Men and women are equally affected, and no hereditary features have been discovered. Onset is insidious, and most common symptom is pain. Most common part of bone is diaphysis of the long bone of lower limb rarely the axial skeleton. Classical radiological appearance of ’flowing hyperosteosis’ resembling hardened wax that has dripped down the side of a candle. Case Report: A 35 years old woman presented with left leg pain with mild swelling and limitation of knee movement. On examination non tender bony heard swelling, hyperpigmented and restriction of knee movement present. Plain radiographs showed extensive, dense, undulating or irregular cortical hyperostosis, resembling candle wax, extending along the length of bone. Pamidronate as well asanalgesic were given to the patient. Physiotherepy started for the deformity. Conclusion: Routine laboratory findings usually are normal. The exact cause remain unclear. There is no definite treatment available for this disease. Only symptomatic treatment improve the condition of the patients, more fruitful result obtain with pamidronate and physiotherapy. PMID:27298954

Thalidomide induces mucosal healing in Crohn's disease: case report.

PubMed

Leite, Márcio Rios; Santos, Sandra Sousa; Lyra, André Castro; Mota, Jaciane; Santana, Genoile Oliveira

2011-12-07

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defined by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximab after three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto disease-including some interesting cases.

PubMed

Seong, Gil Myeong; Kim, Jo-Heon; Lim, Gil Chai; Kim, Jinseok

2012-10-01

Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited disease characterized by tender regional lymphadenopathy with fever. KFD remains a poorly defined disease, and no clear diagnostic criteria are available. Here, we assess the clinical, laboratory, and histopathologic findings of KFD cases and report two unusual cases. Forty KFD patients that underwent lymph node (LN) biopsy and diagnosed by immunohistochemical staining, from January 2003 to November 2010, were enrolled in this retrospective study. The patients had a mean age of 29.3 years, and 29 (72.5 %) were women. Affected LNs were mainly located unilaterally in the cervical area. Mean LN size was 15.3 mm. Twenty-eight (70 %) patients had LN tenderness, and 25 (62.5 %) patients had fever. Leukopenia was observed in 18 of 35 evaluable patients. C-reactive protein and erythrocyte sedimentation rate were elevated in most patients. Anti-nuclear antibody was positive in four of 19 evaluable patients, but all had been diagnosed with concurrent systemic lupus erythematosus. Histologically, the 40 cases were classified into three types, that is, as proliferative (37.5 %), necrotizing (55.0 %), or xanthomatous (7.5 %). Interesting cases: Case 1 was a 35-year-old female with KFD and uveitis, retinal vasculitis, and superior sagittal sinus thrombosis. Case 2 was a 47-year-old male with KFD and bone marrow involvement and presented with severe bicytopenia. Although KFD is an uncommon self-limited benign disorder, it must be included in the differential diagnosis of lymphadenopathy with fever and cytopenia. It is important that the clinical features of KFD be understood to reach a correct diagnosis.

Pyoderma gangrenosum in a patient with chronic granulomatous disease: A case report.

PubMed

Nanoudis, Sideris; Tsona, Afroditi; Tsachouridou, Olga; Morfesis, Petros; Loli, Georgia; Georgiou, Adamantini; Zebekakis, Pantelis; Metallidis, Symeon

2017-08-01

The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic granulomatous disease (CGD) is uncommon and few cases have been reported worldwide. PG is a rare, chronic, ulcerative, neutrophilic skin disease of unknown etiology that requires immunosuppressive treatment. CGD belongs to Primary Immune Deficiencies in which the main defect lies in an inability of the phagocytic cells to generate superoxide making patients susceptible to serious, potentially life-threatening bacterial and fungal infections. In this manuscript, we present a case of ulcerative pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic granulomatous disease during hospitalization for resistant pulmonary tuberculosis complicated with Aspergillus infection. Second-line therapy with dapsone and intravenous immunoglobulin was initially administered but eventually corticosteroids were added to treatment because of disease progression and further ulceration. Patient's ulcers were gradually healed with no side effects. Corticosteroids could be used under close monitoring for the treatment of PG in a patient with CGD, despite the increased risk for infections.

(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

PubMed Central

Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH. PMID:22916194

(S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.

PubMed

Zhang, Hao; Yu, Huan; Wang, Xia; Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

Ruptured posterior ethmoidal artery aneurysm and Moyamoya disease in an adult patient. Case report.

PubMed

Mélot, A; Chazot, J-V; Troude, L; De la Rosa, S; Brunel, H; Roche, P-H

2016-06-01

The association between Moyamoya disease and intracranial aneurysms is well described. In our case, we describe a unique aneurismal location and its management. We report the case of a 74-year-old woman affected by a Moyamoya disease who displayed a frontal lobe hematoma. The origin of the bleeding came from the rupture of a posterior ethmoidal artery aneurysm that was treated surgically with favourable outcome. This case of a ruptured posterior ethmoidal artery aneurysm in a Moyamoya patient illustrates the polymorphism of the vascular complications encountered in this disease. It stresses the need to obtain information from an angiographic investigation in order to select the best therapeutic option and to reduce procedural complications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Forensic Analysis of 6 Cases of Sudden Death due to Hyperthyroid Heart Disease].

PubMed

Zhang, M Z; Li, B X; Zhao, R; Guan, D W; Zhang, G H; Wu, X; Zhu, B L; Li, R B

2017-10-01

To analyse the cases of sudden death due to hyperthyroid heart disease, and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases. Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine, China Medical University. The general information （gender and age）, clinical manifestations, medical history, anatomical and histopathological findings, biochemical parameters and cause of death were analysed retrospectively. Most of the 6 patients had definite history of hyperthyroidism, and they all showed certain degrees of symptoms of cardiovascular disease; had obvious incentive factors of death; histopathological examination of thyroid conformed to the performances of diffuse toxic goiter; with increase of cardiac weight, dilatation of cardiac chambers, myocardial hypertrophy and focal necrosis; postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease. The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy, histopathological examination, postmortem toxicology tests. The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary. Copyright© by the Editorial Department of Journal of Forensic Medicine

[Field investigation of occupational disease diagnosis in Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an analysis of 136 cases].

PubMed

Fan, C Y; Li, X D; Wen, W; Wang, Y Y; Zhang, Y; Lang, L

2016-04-20

To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3). The samples of suspected occupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational

Swallowing endoscopy findings in Huntington's disease: a case report.

PubMed

Alves, Thaís Coelho; Cola, Paula Cristina; Santos, Rarissa Rúbia Dallaqua Dos; Motonaga, Suely Mayumi; Silva, Roberta Gonçalves da

2016-01-01

Huntington's disease (HD) is a degenerative genetic disorder with autosomal-dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study.

What is the probability of successive cases of Legionnaires' disease occurring in European hotels?

PubMed

Ricketts, K D; Slaymaker, E; Verlander, N Q; Joseph, C A

2006-04-01

Public health officials will normally take action at accommodation sites following an association with a cluster of cases of Legionnaires' disease. This paper seeks to determine the likelihood of such a cluster occurring at a site once it has been associated with a single case of the disease, and therefore whether more should be done at sites following individual cases. Information for UK residents reported to the EWGLINET system between 1993 and 2000 was included in a dataset. The size and country of hotel visited by the cases were divided into six country groups (France, Italy, Spain, Turkey, other Europe and other World), and eight size groups (<20 rooms, 20-49, 50-99, 100-199, 200-299, 300-399, 400-499, 500+). The data were investigated using Cox proportional hazards regression to model the probability of at least one further case following the first. The dataset comprised 793 cases that had stayed at 605 sites in 51 countries between 1993 and the end of 2000. This included 605 cases that were the first case associated with a site, and 188 subsequent cases. Following the first case, 16.6% of sites were associated with at least one subsequent case during the period under study. The probability of a subsequent case occurring within 6 months of the first varied by country and size group, with some combinations returning a probability >30%; the probability of a subsequent case occurring within 2 years of the first reached over 50% in some instances. There may be support for early intervention at some accommodation sites following a first case of Legionnaires' disease, in specific country and size groups.

Legionnaire's Disease and Acute Renal Failure: A Case Report and Literature Review

PubMed Central

Boucree, Michael C.

1988-01-01

A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad. PMID:3074172

Legionnaire's disease and acute renal failure: a case report and literature review.

PubMed

Boucree, M C

1988-10-01

A case report is presented of a young man admitted to a general hospital with leukocytosis, elevated temperature, right lower lobe infiltrate, and confusion. A diagnosis of rhabdomyolysis, acute renal failure, and Legionnaire's disease was made. The patient subsequently had a respiratory arrest and died on the 29th hospital day. This triad is currently an enigma in the field of internal medicine. The diagnosis of each entity is elusive, and in many cases must be made by the astute clinician. Diagnostic features along with early intervention measures and their expected outcomes are discussed. Recognition of the interrelationship of these diseases, risk factors, and vague clinical presentations might allow further prospective intervention methods and diagnostic procedures to be undertaken to avoid the fatal consequences seen in this disease triad.

Gingival overgrowth in Pompe disease: a case report.

PubMed

de Gijt, J Pieter; van Capelle, Carine I; Oosterhuis, J Wolter; van der Ploeg, Ans T; van der Wal, Karel G H

2011-08-01

Pompe disease, or glycogen storage disease type 2, is a rare inheritable metabolic disease caused by a deficiency of the lysosomal enzyme acid α-glucosidase. Patients with the classic infantile form of Pompe disease present with symptoms during the first 3 months after birth, and most will die within their first year. Recently, enzyme replacement therapy (ERT) with recombinant human α-glucosidase became commercially available for Pompe disease. This is a case report of an 8-year-old girl with the infantile form of Pompe disease who is one of the longest survivors through ERT. The patient was tetraplegic when she started ERT. At age 3 years, she developed massive gingival overgrowth and could not close her mouth, prompting a reduction of the gingival overgrowth surgically. We expected that massive accumulation of glycogen would explain the gingival overgrowth. However, histopathology of the gingiva tissue showed marked glycogen accumulation in smooth muscle cells of the arteries, but the glycogen content in fibroblasts did not exceed that of control individuals. Further, there was an increase of immature collagen in the connective tissue, and signs of a mild chronic inflammation. We concluded that glycogen storage is not a direct causative factor of gingival overgrowth in our patient. Chronic inflammation, dryness of the gingiva, or even the minimal glycogen accumulation in the fibroblasts may have played a role. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

77 FR 74123 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... proposing this AD to prevent failure of the LPC rotor disc assembly, uncontained engine failure, and damage...

A case of cat-scratch disease with unusual ophthalmic manifestations.

PubMed

Ghazi, Nicola G; Sams, Waler A

2012-01-01

We report a case of cat-scratch disease with unusual posterior segment manifestations. A 12-year-old healthy male presented with three weeks history of decreased visual acuity in the right eye. A significant history of cat exposure and elevated Bartonella titers were present. A large white-gray vascularized mass extending off the optic disk, an early stellate maculopathy, a plaque of choroiditis, an inferior serous retinal detachment involving the macula were present in the right eye. Sector papillitis and a focal area of chorioretinitis along the superotemporal arcade with associated retinal artery to vein anastomosis were present in the left eye. Bilateral optic nerve head involvement including peripapillary angiomatosis, retinal-retinal anastomosis and plaque choroiditis as ocular complications of cat-scratch disease have not been previously described to our knowledge and make this case noteworthy.

The edematous toddler: a case of pediatric Ménétrier disease.

PubMed

Blackstone, Mercedes M; Mittal, Manoj K

2008-10-01

Ménétrier disease is a protein-losing gastroenteropathy, characterized clinically by nonspecific gastrointestinal symptoms and generalized edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. Distinct from its adult counterpart, Ménétrier disease of childhood usually remits spontaneously and has a very good prognosis. We present a case report of Ménétrier disease in an edematous toddler and a brief review.

Recurrent intracranial Rosai-Dorfman disease: Management of a challenging case.

PubMed

Das, Sudeep; Biswas, Ahitagni; Roy, Soumyajit; Sable, Mukund N; Singh, Daljit; Jana, Manisha; Sharma, Mehar Chand; Julka, Pramod Kumar

2017-01-01

Rosai-Dorfman disease (RDD) is a rare, idiopathic, benign histioproliferative disorder. Extranodal involvement is seen in around 25-40% of patients. Central nervous system manifestation of RDD is uncommon and suprasellar location of the lesion is a distinct rarity. Surgery is the cornerstone of management of intracranial RDD. However, tumor recurrence or regrowth is a potential problem. Hence, low dose conformal radiotherapy (RT) should be considered in patients undergoing sub-total resection or having unresectable recurrent disease. Though cranial RT usually leads to satisfactory improvement of symptoms and long-term disease stabilization or regression, in few patients there may be an eventual progression of disease for which systemic chemotherapy may be considered. We have highlighted the salient features of this enigmatic disease by citing a case of a 50-year-old male patient with suprasellar RDD treated by maximal safe surgery and deferred radiation therapy on progression.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses

PubMed Central

2014-01-01

Background Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history. PMID:25103857

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

PubMed

Biagi, Federico; Marchese, Alessandra; Ferretti, Francesca; Ciccocioppo, Rachele; Schiepatti, Annalisa; Volta, Umberto; Caio, Giacomo; Ciacci, Carolina; Zingone, Fabiana; D'Odorico, Anna; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Gasbarrini, Antonio; Piscaglia, Anna Chiara; Andrealli, Alida; Astegiano, Marco; Segato, Sergio; Neri, Matteo; Meggio, Alberto; de Pretis, Giovanni; De Vitis, Italo; Gobbi, Paolo; Corazza, Gino Roberto

2014-08-07

Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

[Rosai-Dorfman's disease: a propos of an interesting case study].

PubMed

Córdova Ramos, Gustavo; Machin González, Victoriano; Benítez Tang, Som My

2008-01-01

We present a case with involvement of both nostrils by the Rosai-Dorfman's disease. Physical examination revealed tumorous lesions totally occupying the right nostril and partially the left one. The presence of proliferation of histiocytes was proved by the histological test, several of them full of non-disintegrated lymphoid nuclei, i.e. emperipolesis, the basic histological characteristic in Rosai-Dorfman's disease. The patient underwent surgical treatment with a combined approach by means of lateral rhinotomy and endoscopic nasal resection using a microdebrider.

A Case Report of Cushing's Disease Presenting as Hair Loss

PubMed Central

Lefkowitz, Emily G.; Cossman, Jack P.; Fournier, John B.

2017-01-01

Cushing's syndrome is a rare endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids. Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing's disease. Most of the signs and symptoms are nonspecific and common in the general population, making a diagnosis often challenging. However, several dermatological manifestations, such as fragile skin, easy bruising, and reddish purple striae, are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology is associated with substantial morbidity, including increased cardiovascular disease and mortality, it is important to make an early diagnosis. Unfortunately, median delays of 2 years to diagnosis have been reported. We report a case of a woman who had multiple dermatological findings, including facial plethora, easy bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting androgen excess. Of interest, our patient presented with a chief complaint of hair loss, a common complaint in the general population that occurs with a greater frequency in patients with Cushing's disease and is attributed to androgenetic alopecia, but it is rarely the presenting symptom. PMID:28413388

A Case Report of Cushing's Disease Presenting as Hair Loss.

PubMed

Lefkowitz, Emily G; Cossman, Jack P; Fournier, John B

2017-01-01

Cushing's syndrome is a rare endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids. Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing's disease. Most of the signs and symptoms are nonspecific and common in the general population, making a diagnosis often challenging. However, several dermatological manifestations, such as fragile skin, easy bruising, and reddish purple striae, are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology is associated with substantial morbidity, including increased cardiovascular disease and mortality, it is important to make an early diagnosis. Unfortunately, median delays of 2 years to diagnosis have been reported. We report a case of a woman who had multiple dermatological findings, including facial plethora, easy bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting androgen excess. Of interest, our patient presented with a chief complaint of hair loss, a common complaint in the general population that occurs with a greater frequency in patients with Cushing's disease and is attributed to androgenetic alopecia, but it is rarely the presenting symptom.

A case of Parkinson's disease following dystonia.

PubMed

Yasuda, Chiharu; Takei, Takanobu; Uozumi, Takenori; Toyota, Tomoko; Yuhi, Tomoaki; Adachi, Hiroaki

2016-09-29

Parkinsonism and dystonia are both disorders of the extrapyramidal motor system, and some patients exhibit a complex of the two symptoms. Although several reports have referred to the coexistence of these disorders as parkinsonian disorders with dystonia, in the majority of cases, dystonia appeared after parkinsonism. DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other types of parkinsonism such as dementia with Lewy bodies. This case report describes a 67-year old woman diagnosed with axial dystonia without parkinsonism 6 years previously, which had worsened despite treatment with Botulinum toxin injections, and hindered the patient's gait. The patient visited the hospital because of gait disturbances and DAT-scan showed a levodopa transducer decrease in the putamen. A few weeks later, she was re-admitted to hospital and exhibited Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this was a rare case of parkinsonian disorders with dystonia, characterized by the development of PD after dystonia. DAT-scan may be helpful for the diagnosis of patients with parkinsonian disorders with dystonia.

Fine-Tuning in a Design Experiment

ERIC Educational Resources Information Center

Ho, Foo Him; Toh, Pee Choon; Toh, Tin Lam

2013-01-01

Quek, Tay, Toh, Leong, and Dindyal (2011) proposed that a design-theory-practice troika should always be considered for a designed package to be acceptable to the research users who, in this case, are teachers and schools. This paper describes the fine-tuning to the MProSE problem-solving design made by the teachers in the school after first round…

Diagnostic challenges of early Lyme disease: Lessons from a community case series

PubMed Central

2009-01-01

Background Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown. Methods A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments. Results The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease. Conclusion For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations. PMID:19486523

Diverticular disease of the colon presenting as pyometra: a case report.

PubMed

Pankaja, Susmita; Rrukaj, Astrit; Bathula, Uma

2014-05-04

Pyometra can be caused by various etiologies. We present a rare case of diverticular disease of the colon presenting as pyometra. This type of presentation can be challenging even for an astute clinician. A 74-year-old Caucasian woman with a history of pyometra was referred to our gynecology clinic as an urgent case. She was obese, diabetic and hypertensive. Due to the patient profile and the clinical presentation, clinicians were misled toward a diagnosis of possible endometrial cancer. After further investigations, she was found to have colouterine fistula secondary to a diverticular abscess of the sigmoid colon. Persistent vaginal discharge due to pyometra can be caused by diverticular disease of the colon. Clinicians should be aware of this important differential diagnosis.

Intermittent maple syrup urine disease: two case reports.

PubMed

Axler, Olof; Holmquist, Peter

2014-02-01

The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain α-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or viral gastroenteritis triggers catabolism of muscle protein. Intermittent MSUD should be suspected in cases of common infections with a clinically atypical course, especially in children displaying ataxia or marked drowsiness.

Hydatid disease in childhood: revisited report of an interesting case.

PubMed

Jairajpuri, Zeeba Shamim; Jetley, Sujata; Hassan, Md Jaseem; Hussain, Musharraf

2012-10-01

Hydatid disease is a zoonosis caused by the tapeworm of Echinococcus spp. The disease is widely endemic in many sheep and cattle rearing locales. However, hydatidosis does not remain restricted to endemic geographical locales anymore but rather is a global health concern. It is a major public health burden causing significant morbidity and mortality. Echinococcus granulosus involvement in children has a different pattern than adults. Children of all age groups are susceptible and localization of the disease in the lungs is more commonly seen. Multiple liver cysts in the paediatric age group is relatively uncommon. We report an interesting case of multiple liver cysts in a 5-year old boy which was diagnosed as hydatid cysts on histopathological examination.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

[Coexistence of Addison-Biermer's disease with autoimmune thyroiditis - case report].

PubMed

Lacka, Katarzyna; Maciejewski, Adam; Florczak-Wyspiańska, Jolanta

2013-01-01

Addison-Biermer's anaemia is an autoimmune disease and the most common cause of vitamin B12 deficiency. Hashimoto disease is the most common type of the thyroiditis and also has autoimmunological origin. Frequent coexistence of both mentioned entities has been observed. In the paper we report a case of a woman, who was diagnosed with pernicious anaemia (PA) with predominant neurological symptoms and concomitant autoimmune thyroiditis. Many efforts have been made in order to explain frequent coexistence of mentioned diseases. Both genetic (mainly HLA region genes) and environmental (mostly bacterial infections) factors are considered. The aim of the study (was to emphasize significance of diagnosing thyroid gland diseases among PA patients. It is also important to remember that neurological symptoms are frequent in the course of PA and may precede other complaints. However it should not prevent the right diagnosis.

[Fulminant Wilson's disease in Costa Rica. Clinico-pathological study of 7 cases].

PubMed

Herra, S A; Hevia, F J; Vargas, M; Schosinsky, K

1990-01-01

In the last eighteen years, from 1972 to 1989, around 150 cases of Wilson's disease have been diagnosed in Costa Rica (6/100.000 inhabitants). In the San Juan de Dios Hospital, 120 cases have been studied during this period, seven of whom died with a picture of acute hepatic insufficiency, hemolytic anemia, encephalopathy, intestinal bleeding and renal insufficiency. In four of the cases, postmortem histopathologic studies were done with high resolution microscopy, which revealed extensive submassive necrosis of the liver, with severe cholestatic, lytic and acidophilic necrosis with nodular, irregular regeneration and specially microvacuolar steatosis, different from that observed in other forms of fulminant hepatitis. With the clinical, laboratory and histopathologic findings, we concluded that fulminant Wilson's disease is a well-defined pathological clinical entity of fatal evolution with no response to therapy, including early treatment with penicillamine and steroids.

[Erdheim-Chester disease, an incredible simulator. Cases reports and review of literature].

PubMed

Rascón-Ramírez, Fernando J; Avecillas-Chasín, Josué M; Rodríguez-Boto, Gregorio; Subhi-Issa, Issa; Salazar A, Osman A; Sallabanda D, Kita

Erdheim-Chester disease is a non-Langerhans histiocytosis. Until 2014 at least 550 cases have been reported. According to European Rare Disease Organization and National Organization for Rare Disorders it is a rare disease. The most common symptom is bone pain in the lower extremities and it usually appears between the 5th and 7th decades of life. The diagnostic is based on immunohistochemical results: S100(+/-), CD68(+), and CD1a(-), the latter 2 are mandatory. The best treatment nowadays is alpha-interferon or pegylated alpha-2. The overall survival is 96% at one year and 68% at 5 years. Central nervous system involvement is associated with a worse outcome. Two cases are presentedwith central nervous system lesions in the absence of lesions in other organs on their onset. Very few cases have been reported with this kind of presentation. We also noted that these patients had recurrences or new lesions at 8 months. A follow-up is proposed with brain MRI and thoraco-abdominal PET every 3-4 months. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Analysis of case reports submitted to the European Annals of Otorhinolaryngology Head & Neck Diseases.

PubMed

Laccourreye, O; Bonfils, P; Denoyelle, F; Garrel, R; Jankowski, R; Karkas, A; Makeieff, M; Righini, C; Vincent, C; Martin, C

2016-06-01

To assess flaws, rejection rate and reasons for rejection of case reports submitted for publication in the European Annals of Otorhinolaryngology Head & Neck Diseases. A prospective analysis of flaws noted in reviewing 118 case reports from 29 countries consecutively submitted to the European Annals of Otorhinolaryngology Head & Neck Diseases during the period Sept. 1, 2014 to Sept. 30, 2015. The most frequent flaws, noted in 74.5% of cases, were: lack of originality (more than 15 such cases previously reported in the medical literature) and lack of new data contributing to the medical literature. Overall, 5% of the cases were accepted for publication, 7% were not resubmitted by the authors, and 88% were rejected. On univariate analysis, none of the variables under analysis correlated with acceptance or rejection of the submitted case. Editorial decision time varied from 1 to 7months (median, 1 month). In 16.3% of the 104 cases of rejection (17/104), the editors suggested resubmission in the section "Letter to the Editor" or "What is your diagnosis?"; 15 of the 17 reports were resubmitted, and 10 (66.6%) were ultimately accepted for publication. The editorial committee of the European Annals of Otorhinolaryngology Head & Neck Diseases hope that the present data and review of the literature will provide authors with a framework to avoid major errors leading to rejection and will speed publication of the case reports they submit to our columns in the near future. Copyright © 2016. Published by Elsevier Masson SAS.

Familial benign chronic neutropenia associated with periodontal disease. A case report.

PubMed

Deasy, M J; Vogel, R I; Macedo-Sobrinho, B; Gertzman, G; Simon, B

1980-04-01

A rare case report of periodontal disease associated with familial benign chronic neutropenia is presented. The medical, dental and family histories as well as clinical and histologic observations are described and discussed.

[Histological features of celiac disease in south Tunisia: a study of 114 pediatric cases].

PubMed

Kallel, Rim; Krichen-Makni, Saloua; Ellouze, Sameh; Châari, Chiraz; Charfi, Slim; Sellami, Ahmed; Tahri, Mohamed-Nabil; Hachicha, Mongia; Sellami-Boudawara, Tahya

2009-04-01

To report the histological features of celiac disease in a paediatric population originating from south Tunisia. A retrospective study of a series of duodenal biopsies from 114 children with celiac disease diagnosed over a period of 6 years (from January 1999 to December 2004). The diagnosis was confirmed by histological results, serological studies and clinical response to gluten free diet. The average age of patients was of 6.2 years (range 6 months-15 years). Sex ratio was 0.71. Symptoms were dominated by chronic diarrhea (48%), weight loss (50%) and anemia (20.1%). Histological findings showed an intraepithelial lymphocytosis (Marsh type 1) in 12.2% of cases, type 2 was present in 1.7% of cases and type 3 (villous atrophy) in 86% of cases. A treatment with a gluten-free diet was indicated for all patients, only the cases who haven't presented a clinical amelioration (11 cases) have beneficed a control biopsie; a villous atrophy was persistent in 80% of this patients. Histological features in duodenal biopsies for the diagnosis and the follow-up of patients with coeliac disease. This allows an appropriate treatment and prevents further complications.

Investigation into High Barmah Forest Virus Disease Case Numbers Reported in the Northern Territory, Australia in 2012-2013.

PubMed

Kurucz, Nina; Markey, Peter; Draper, Anthony; Melville, Lorna; Weir, Richard; Davis, Steven; Warchot, Allan; Boyd, Rowena; Stokeld, Danielle

2016-02-01

Between October 2012 and October 2013, unprecedented high numbers of Barmah Forest virus (BFV) disease cases were reported in the Northern Territory (NT). An investigation was launched by the NT Department of Health in cooperation with the Department of Primary Industry and Fisheries and the Department of Land Resource Management to investigate possible causes for this phenomenon. The investigation included virus isolations from mosquitoes collected in Darwin urban areas, BFV antibody testing in peri-urban small mammals and a human BFV disease case series investigation of recent cases. No BFV was isolated from the 4641 mosquitoes tested, none of the mammals tested positive for BFV antibodies, and the high BFV disease case numbers did not correlate with the relatively low mosquito vector numbers trapped in 2012-2013. It was estimated that up to 89% of the 79 human cases investigated did not have an acute arboviral illness and therefore had tested falsely positive. An Alere PanBio BFV immunoglobulin M enzyme-linked immunosorbent assay test kit is generally used to test for BFV, with the BFV disease case definition based on immunoglobulin M positives only. Other jurisdictions in Australia also reported high numbers of BFV disease cases, with the majority of the cases suspected to be false positives. Therefore, current testing methods need to be revised to reflect the true numbers of BFV disease cases occurring in Australia and to provide correct diagnoses for patients.

The Case for Chronic Disease Management for Addiction

PubMed Central

Saitz, Richard; Larson, Mary Jo; LaBelle, Colleen; Richardson, Jessica; Samet, Jeffrey H.

2009-01-01

Chronic disease (care) management (CDM) is a patient-centered model of care that involves longitudinal care delivery; integrated, and coordinated primary medical and specialty care; patient and clinician education; explicit evidence-based care plans; and expert care availability. The model, incorporating mental health and specialty addiction care, holds promise for improving care for patients with substance dependence who often receive no care or fragmented ineffective care. We describe a CDM model for substance dependence and discuss a conceptual framework, the extensive current evidence for component elements, and a promising strategy to reorganize primary and specialty health care to facilitate access for people with substance dependence. The CDM model goes beyond integrated case management by a professional, colocation of services, and integrated medical and addiction care—elements that individually can improve outcomes. Supporting evidence is presented that: 1) substance dependence is a chronic disease requiring longitudinal care, although most patients with addictions receive no treatment (eg, detoxification only) or short-term interventions, and 2) for other chronic diseases requiring longitudinal care (eg, diabetes, congestive heart failure), CDM has been proven effective. PMID:19809579

Self-limited coeliac-like enteropathy: a series of 18 cases highlighting another coeliac disease mimic.

PubMed

Brown, Ian S; Bettington, Andrew; Bettington, Mark; Rosty, Christophe

2016-01-01

To describe the clinical and pathological features of a series of patients with biopsy findings of a coeliac disease-like enteropathy in the setting of an acute illness. Eighteen cases of an abrupt-onset, self-limited illness with coeliac-like enteropathy (SLCE) were collected prospectively. Medication reaction, immune disorder, food allergy and parasitic infection were excluded. Coeliac disease was excluded by the transient nature of the illness and absence of tissue transglutaminase (TTG) elevation (nine of nine) or human leucocyte antigen (HLA)-DQ2/DQ8 haplotype (eight of nine). Clinical symptoms were recorded and histopathological findings in all gastrointestinal sites were quantified. Findings in the duodenum were compared to a coeliac disease control group. In 12 cases the clinical diagnosis was infective enteritis, probably viral in type. In six cases, a definite diagnosis was not established. Histological differences from coeliac disease included intra-epithelial neutrophil infiltration (P < 0.001), fewer intra-epithelial lymphocytes (P = 0.038) and uniform or crypt predominant intra-epithelial lymphocytosis in SCLE. One case displayed pan-gastrointestinal tract lymphocytosis. All resolved within 6 months. Histopathologists need to be aware that a coeliac disease-like enteropathy may occur in the setting of an acute gastrointestinal illness and resolve without sequelae. © 2015 John Wiley & Sons Ltd.

Hepatocellular carcinoma in patients with autoimmune liver diseases: two case reports and literature review.

PubMed

Meza-Junco, Judith; Montaño-Loza, Aldo J; Martínez-Benitez, Braulio; Kimura-Hayama, Eric

2007-01-01

Hepatocellular carcinoma has been reported as a rare complication of autoimmune liver diseases. We describe herein two patients with this neoplasia associated with autoimmune hepatitis and primary biliary cirrhosis, and we also review the literature. The first case corresponds to a 49-year-old woman presented for evaluation of right upper abdominal pain. She had been diagnosed with autoimmune hepatitis 4 years before. Alpha-fetoprotein was markedly elevated and an abdominal MRI showed a 10 cm x 9.0 cm mass. She received transarterial chemoembolization, and currently the disease has progressed to the lungs and bones, and she is on supportive care. The second case corresponds to a 68-year-old woman presented for evaluation of a liver mass found in a screening ultrasound. She had been diagnosed with primary biliary cirrhosis 5 years previously. At admission alpha-fetoprotein was 1000 ng/mL and an abdominal MRI revealed a 4 cm x 3 cm liver tumor. She was treated with percutaneous radiofrequency ablation getting complete response, and currently she has no evidence of neoplastic disease. These two patients constitute the only cases of hepatocellular carcinoma associated to autoimmune liver diseases that have been attended in our Institute. These cases highlight that hepatocellular carcinoma secondary to autoimmune hepatitis and primary biliary cirrhosis, although rare, can occur in the absence of coexistent viral hepatitis, or excessive alcohol consumption. The utility of screening for hepatocellular carcinoma in autoimmune liver diseases is still not defined.

Rare case of Takayasu's arteritis associated with Crohn's disease.

PubMed

Kusunoki, Ryusaku; Ishihara, Shunji; Sato, Mariko; Sumita, Yoshiko; Mishima, Yoshiyuki; Okada, Mayumi; Tada, Yasumasa; Oka, Akihiko; Fukuba, Nobuhiko; Oshima, Naoki; Moriyama, Ichiro; Yuki, Takafumi; Sato, Shuichi; Amano, Yuji; Murakawa, Yohko; Kinoshita, Yoshikazu

2011-01-01

Takayasu's arteritis (TA) and Crohn's disease (CD) are chronic inflammatory diseases of uncertain etiology. Although co-existence of these rare diseases is estimated to occur in 1 in 10 billion individuals, a theoretically unexpected association has been reported in several patients and it is suggested that those associations may have been more than an unusual coincidence. Herein, we report a case of TA associated with clinically inactive CD. A Japanese woman was diagnosed with colonic CD at the age of 15, developed aortic valve regurgitation at 19, and then presented with general fatigue, low grade fever, and painful sensations in her left arm at 25. She was diagnosed with TA based on computed tomography scanning and magnetic resonance angiography findings, and treatments with prednisolone and cyclosporine were started. Thereafter, valve replacement and right coronary artery bypass graft surgery were performed. The possible pathophysiological mechanism responsible for concurrent existence of TA and CD may be associated with immune disorders. Early diagnosis of vascular lesions for patients with inflammatory bowel disease is highly encouraged.

Rethinking the Poverty-disease Nexus: the Case of HIV/AIDS in South Africa.

PubMed

Pienaar, Kiran

2017-09-01

While it is well-established that poverty and disease are intimately connected, the nature of this connection and the role of poverty in disease causation remains contested in scientific and social studies of disease. Using the case of HIV/AIDS in South Africa and drawing on a theoretically grounded analysis, this paper reconceptualises disease and poverty as ontologically entangled. In the context of the South African HIV epidemic, this rethinking of the poverty-disease dynamic enables an account of how social forces such as poverty become embodied in the very substance of disease to produce ontologies of HIV/AIDS unique to South Africa.

The Sachs report: investing in health for economic development--or increasing the size of the crumbs from the rich man's table? Part II.

PubMed

Katz, Alison

2005-01-01

The Commission on Macroeconomics and Health report (Sachs report of 2001) has been heralded as inspiring and groundbreaking and is being adopted as the blueprint for global health policymaking. This article argues that the report is deeply conservative and unoriginal. It encourages medico-technical solutions to public health problems; it ignores macroeconomic determinants and other root causes of both poor health and poverty; it reverses public health logic and history; it is based on a set of flawed assumptions; it reflects one particular economic perspective to the exclusion of all others; and it recommends greater amounts of charity while preserving the status quo of a deeply unjust and irrational international economic order. Wishful thinking and ideology are presented as established facts to legitimize globalization, and health is conceived primarily as an input to productivity rather than as a human right. The benefits that would result from simple, macroeconomic measures directed toward social justice and the meeting of basic needs are incomparably greater than those that would result from following CMH recommendations in terms of sustainable improvements in both health and economic well-being. The ultimate source of poor health status and miserable living conditions is the extreme concentration of power, nationally and internationally, in the hands of the few.

A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam

PubMed Central

Poyarkov, Nikolay A.; Kropachev, Ivan I.; Gogoleva, Svetlana S.; Orlov, Nikolai L.

2018-01-01

A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8–26.4 mm); (7) head longer than wide; ED/SVL ratio 13%–15%; ESL/SVL ratio 16%–20%; (8) small tympanum (TD/EL ratio 50%–60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2–2¼ II 1½–2¾ III 2–3¼ IV 3–1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3–5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma

Vocal symptoms in Parkinson disease treated with levodopa. A case report.

PubMed

Schley, W S; Fenton, E; Niimi, S

1982-01-01

This is a report of a patient with unusually severe hoarseness in the absence of vocal fold pathology demonstrating Parkinson disease as one of the neurological diseases in which vocal symptoms occur. Although it is classifiably a severe, progressive, degenerative disorder, the popularity of pharmacotherapy for Parkinson disease during the past decade has resulted in improved functionality for an undetermined course of time in most patients. The classically described deterioration of speech ad voice may develop in a variant manner difficult to distinguish as disease-related, as this case report illustrates. An explanation of the hoarseness based on dyssynchronous vocal fold motion related to the disease is suggested by the acoustic methods (spectrography, waveform analysis) used in this study, and supported by strobe light laryngoscopy. This conclusion is important because of the extremely high incidences of varying degrees of hoarseness reported in recent studies of Parkinson disease.

Prenatal Diagnosis of a Case of Norrie Disease with Late Development of Bilateral Ocular Malformation.

PubMed

Wu, Li Hong; Chen, Li-Hong; Xie, Hongning; Xie, Ying-Jun

2017-06-01

We report a case of Norrie disease, diagnosed by prenatal ultrasound, confirmed by Sanger sequencing of the DNP gene from the aborted fetal cord blood and histologically. Prenatal ultrasound revealed no abnormality in either eye at 22 +1 and 31 +4 gestational weeks, but at 36 +5 gestational weeks both eyes had massive vitreous cavity opacities with complete retinal detachment. Norrie disease was initially suspected because of an older male sibling with the disease. To our knowledge, prenatal ultrasound diagnosis of Norrie disease has been previously described only one case in 1993 in a 34-week-old fetus. The normal eye development until after 31 + 4 gestational weeks provides insight into the first manifestation and then the rapid progression of the eye disease.

Coexistence of Fabry disease and IgA nephropathy: a report of two cases.

PubMed

Yin, G; Wu, Y; Zeng, C-H; Chen, H-P; Liu, Z-H

2014-12-01

Coexistence of Fabry disease and IgA nephropathy is rare. Moreover, the coexisting Fabry disease may be unrecognized due to unapparent clinical manifestations. We described two cases with coexisting Fabry disease and IgA nephropathy. The clinicopathological features of these two patients were studied. A 54-year-old male presented with proteinuria, hematuria, and hypertension, and a 33-year-old male presented with proteinuria without clinical signs or family history of Fabry disease. Both of them were diagnosed with IgA nephropathy at admission, whereas Fabry disease was not suspected. Subsequent immunofluorescent study confirmed the diagnosis of IgA nephropathy by showing positive staining for IgA and complement C3 in the mesangium. Meanwhile, light microscopy showed remarkable vacuolation of podocytes with mild mesangial expansion, which was characteristic of Fabry nephropathy. Further examination of toluidine blue-stained semi-thin sections and electron microscopy demonstrated blue bodies and myelin figures in the cytoplasm of podocytes, respectively. The diagnosis of coexisting Fabry disease was finally established based on deficient α-galactosidase A activity in both patients. This case study is an important reminder of the role of kidney biopsy as an indicator of Fabry disease and its rare coexistence with IgA nephropathy.

A population-based case-control study on statin exposure and risk of acute diverticular disease.

PubMed

Sköldberg, Filip; Svensson, Tobias; Olén, Ola; Hjern, Fredrik; Schmidt, Peter T; Ljung, Rickard

2016-01-01

A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed ≤ 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.

A case of non-lacrimal immunoglobulin G4 (IgG4)-related orbital disease with mastitis.

PubMed

Farooq, Tahir Ali; Mudhar, Hardeep; Sandramouli, S

2016-01-01

IgG4-related orbital disease is a recognised cause for orbital inflammation. As its awareness increases and diagnostic accuracy improves there will be an increased number of cases being identified. This unique case demonstrates for the first time, with histological evidence, a case of a non-lacrimal IgG4-related orbital disease with concurrent IgG4-related mastitis. We describe a 47 year old who presented with a supraorbital swelling and mass. This was initially successfully treated with oral steroids and was later excised on recurrence. Immunohistochemical and blood serum analysis confirmed IgG4-related orbital disease. On systemic enquiry she was found to have a mass of the breast, which was shown to be IgG4-related mastitis. She is currently asymptomatic with no sign of recurrence and is under long-term surveillance. This case highlights the importance of systemic work up in patients presenting with orbital foci of IgG4 disease.

Posterior segment involvement in cat-scratch disease: A case series.

PubMed

Tolou, C; Mahieu, L; Martin-Blondel, G; Ollé, P; Matonti, F; Hamid, S; Benouaich, X; Debard, A; Cassagne, M; Soler, V

2015-12-01

Cat-scratch disease (CSD) is a systemic infectious disease. The most well-known posterior segment presentation is neuroretinitis with a macular star. In this study, we present a case series emphasising the heterogeneity of the disease and the various posterior segment manifestations. A retrospective case series of consecutive patients presenting with posterior segment CSD, over a 5-year period (2010 to 2015), at two ophthalmological centres in Midi-Pyrénées. Twelve patients (17 eyes) were included, of whom 11 (92%) presented with rapidly decreasing visual acuity, with 6 of these (50%) extremely abrupt. CSD was bilateral in 5 (42% of all patients). Posterior manifestations were: 12 instances of optic nerve edema (100%), 8 of focal chorioretinitis (67%) and only 6 of the classic macular edema with macular star (25% at first examination, but 50% later). Other ophthalmological complications developed in three patients; one developed acute anterior ischemic optic neuropathy, one a retrohyaloid hemorrhage and one a branch retinal artery occlusion, all secondary to occlusive focal vasculitis adjacent to focal chorioretinitis. Classical neuroretinitis with macular star is not the only clinical presentation of CSD. Practitioners should screen for Bartonella henselae in all patients with papillitis or focal chorioretinitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis): report of a case with other autoimmune manifestations

PubMed Central

Merriman, Richard C.; Stone, Marvin J.

2007-01-01

Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited disease that mainly affects young women. Patients present with localized lymphadenopathy, fever, and leukopenia in up to half of the cases. KFD can occur in association with systemic lupus erythematosus. We present the case of a patient with KFD and systemic lupus erythematosus, as well as relapsing polychondritis. This patient had persistently low C4 complement levels, so she was evaluated for a genetic defect in complement production and was found to have two “null” C4 alleles. We believe that this may have contributed to the development of her diseases. PMID:17431451

Local disease-ecosystem-livelihood dynamics: reflections from comparative case studies in Africa.

PubMed

Leach, Melissa; Bett, Bernard; Said, M; Bukachi, Salome; Sang, Rosemary; Anderson, Neil; Machila, Noreen; Kuleszo, Joanna; Schaten, Kathryn; Dzingirai, Vupenyu; Mangwanya, Lindiwe; Ntiamoa-Baidu, Yaa; Lawson, Elaine; Amponsah-Mensah, Kofi; Moses, Lina M; Wilkinson, Annie; Grant, Donald S; Koninga, James

2017-07-19

This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people's livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform 'One Health' approaches towards managing ecosystems in ways that reduce disease risks and burdens.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

Case report of Graves’ disease manifesting with odynophagia and heartburn

PubMed Central

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-01-01

Graves’ disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves’ disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment. PMID:26730171

Case report of Graves' disease manifesting with odynophagia and heartburn.

PubMed

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-12-28

Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

Case-based lung image categorization and retrieval for interstitial lung diseases: clinical workflows.

PubMed

Depeursinge, Adrien; Vargas, Alejandro; Gaillard, Frédéric; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

2012-01-01

Clinical workflows and user interfaces of image-based computer-aided diagnosis (CAD) for interstitial lung diseases in high-resolution computed tomography are introduced and discussed. Three use cases are implemented to assist students, radiologists, and physicians in the diagnosis workup of interstitial lung diseases. In a first step, the proposed system shows a three-dimensional map of categorized lung tissue patterns with quantification of the diseases based on texture analysis of the lung parenchyma. Then, based on the proportions of abnormal and normal lung tissue as well as clinical data of the patients, retrieval of similar cases is enabled using a multimodal distance aggregating content-based image retrieval (CBIR) and text-based information search. The global system leads to a hybrid detection-CBIR-based CAD, where detection-based and CBIR-based CAD show to be complementary both on the user's side and on the algorithmic side. The proposed approach is in accordance with the classical workflow of clinicians searching for similar cases in textbooks and personal collections. The developed system enables objective and customizable inter-case similarity assessment, and the performance measures obtained with a leave-one-patient-out cross-validation (LOPO CV) are representative of a clinical usage of the system.

Boxing training for patients with Parkinson disease: a case series.

PubMed

Combs, Stephanie A; Diehl, M Dyer; Staples, William H; Conn, Lindsay; Davis, Kendra; Lewis, Nicole; Schaneman, Katie

2011-01-01

A nontraditional form of exercise recently applied for patients with Parkinson disease (PD) is boxing training. The primary purpose of this case series is to describe the effects of disease severity and duration of boxing training (short term and long term) on changes in balance, mobility, and quality of life for patients with mild or moderate to severe PD. The feasibility and safety of the boxing training program also were assessed. Six patients with idiopathic PD attended 24 to 36 boxing training sessions for 12 weeks, with the option of continuing the training for an additional 24 weeks (a seventh patient attended sessions for only 4 weeks). The 90-minute sessions included boxing drills and traditional stretching, strengthening, and endurance exercises. Outcomes were tested at the baseline and after 12, 24, and 36 weeks of boxing sessions (12-, 24-, and 36-week tests). The outcome measures were the Functional Reach Test, Berg Balance Scale, Activities-specific Balance Confidence Scale, Timed "Up & Go" Test, Six-Minute Walk Test, gait speed, cadence, stride length, step width, activities of daily living and motor examination subscales of the Unified Parkinson Disease Rating Scale, and Parkinson Disease Quality of Life Scale. Six patients completed all phases of the case series, showed improvements on at least 5 of the 12 outcome measures over the baseline at the 12-week test, and showed continued improvements at the 24- and 36-week tests. Patients with mild PD typically showed improvements earlier than those with moderate to severe PD. Despite the progressive nature of PD, the patients in this case series showed short-term and long-term improvements in balance, gait, activities of daily living, and quality of life after the boxing training program. A longer duration of training was necessary for patients with moderate to severe PD to show maximal training outcomes. The boxing training program was feasible and safe for these patients with PD.

An uncommon presentation of Kikuchi Fujimoto disease: a case report with literature review.

PubMed

Ranabhat, Sabin; Tiwari, Mamta; Kshetri, Jiwan; Maharjan, Sushna; Osti, Bidur Prasad

2015-09-26

Kikuchi-Fujimoto disease is so named because Kikuchi and Fujimoto were the first scientists to describe it in Japan in 1972. Although the disease has been reported from all over the world and more so from Asia, it is rare. To date only eight cases have been reported from Nepal. Cervical lymphadenopathy, fever and raised Erythrocyte Sedimentation Rate are usual presenting features of this disease. We describe a case which presented with thrombocytopenia and axillary lymphadenopathy in addition to the usual features. Out of the total eight cases that have been reported from Nepal so far, no patients had thrombocytopenia and only one patient had axillary lymphadenopathy. A 24-year-old Nepali female presented with a 3-week history of low-grade fever, headache, and painful, discrete, unilateral left-sided cervical and axillary lymphadenopathy. Among the multitude of tests that were carried out, Erythrocyte Sedimentation Rate was raised and there was thrombocytopenia while other tests were normal. Painful lymphadenopathy pointed to bacterial lymphadenitis while chronic low-grade fever suggested tuberculosis. A cervical lymph node was excised for histopathological examination to reach an accurate diagnosis. On the basis of pathognomonic features viz., paracortical foci composed of various types of histiocytes including crescentic type in the background of abundant apoptotic karyorrhectic debris, a diagnosis of Kikuchi-Fujimoto disease was made. On follow-up evaluation after 6 weeks, the patient had no systemic symptoms, enlarged lymph nodes had regressed in size significantly, and Erythrocyte Sedimentation Rate and platelet count had become normal. Kikuchi-Fujimoto disease should be kept in the differential diagnosis of lymphadenopathy in young patients, female or male even in tuberculosis-endemic countries and even in patients who have unusual features; for example thrombocytopenia and involvement of axillary lymph nodes in addition to cervical lymph nodes as in this

Cell Surface Expression of Biologically Active Influenza C Virus HEF Glycoprotein Expressed from cDNA

PubMed Central

Pekosz, Andrew; Lamb, Robert A.

1999-01-01

The hemagglutinin, esterase, and fusion (HEF) glycoprotein of influenza C virus possesses receptor binding, receptor destroying, and membrane fusion activities. The HEF cDNAs from influenza C/Ann Arbor/1/50 (HEF-AA) and influenza C/Taylor/1223/47 (HEF-Tay) viruses were cloned and expressed, and transport of HEF to the cell surface was monitored by susceptibility to cleavage by exogenous trypsin, indirect immunofluorescence microscopy, and flow cytometry. Previously it has been found in studies with the C/Johannesburg/1/66 strain of influenza C virus (HEF-JHB) that transport of HEF to the cell surface is severely inhibited, and it is thought that the short cytoplasmic tail, Arg-Thr-Lys, is involved in blocking HEF cell surface expression (F. Oeffner, H.-D. Klenk, and G. Herrler, J. Gen. Virol. 80:363–369, 1999). As the cytoplasmic tail amino acid sequences of HEF-AA and HEF-Tay are identical to that of HEF-JHB, the data indicate that cell surface expression of HEF-AA and HEF-Tay is not inhibited by this amino acid sequence. Furthermore, the abundant cell surface transport of HEF-AA and HEF-Tay indicates that their cell surface expression does not require coexpression of another viral protein. The HEF-AA and HEF-Tay HEF glycoproteins bound human erythrocytes, promoted membrane fusion in a low-pH and trypsin-dependent manner, and displayed esterase activity, indicating that the HEF glycoprotein alone mediates all three known functions at the cell surface. PMID:10482635

[Pathological and biochemical studies of 30 Niigata autopsy cases related to Minamata disease].

PubMed

Eto, Komyo; Takahashi, Hitoshi; Kakita, Akiyoshi; Tokunaga, Hidehiro; Yasutake, Akira; Nakano, Atsuhiro; Sawada, Masumi; Kinjo, Yoshihide

2007-01-01

To reevaluate pathologically and biochemically 30 autopsy cases related to Minamata disease (MD) in Niigata Prefecture (NP) and compare the findings with those of autopsy cases related to MD in Kumamoto Prefecture (KP). Recently, a set of pathological materials of these 30 autopsy cases has been sent from the Brain Research Institute at the University of Niigata to the National Institute for Minamata Disease (NIMD). The materials from each autopsy case were reexamined at the NIMD. There were no postnatal and fetal cases of MD in the NP autopsy materials. The contents of total mercury (T-Hg), methylmercury (Me-Hg), inorganic mercury (I-Hg) and selenium were measured in the organs of cerebrum, cerebellum, liver and kidney. The contents of T-Hg, Me-Hg and I-Hg were much higher in two cases than in controls. The pathological findings leading to the diagnosis of MD in the NP cases were essentially the same as those in KP, including the peripheral nerve lesions. In the most severely affected case of MD in NP, formation of multiple vacuoles of various sizes was observed in the cerebellar cortex, which was never encountered in the KP cases. The KP lesions were similar to that observed in an acute case of Me-Hg-treated common marmoset studied in the NIMD. The pathological features were essentially the same between the adult cases of MD in NP and KP.

Why prioritize when there isn't enough money?

PubMed

Wikler, Daniel

2003-02-26

In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs - Chairperson of the WHO Commission on Macroeconomics and Health - maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones.Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources.

Why prioritize when there isn't enough money?

PubMed Central

Wikler, Daniel

2003-01-01

In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs – Chairperson of the WHO Commission on Macroeconomics and Health – maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones. Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources. PMID:12773216

Graves' disease associated with infectious mononucleosis due to primary Epstein-Barr virus infection: report of 3 cases.

PubMed

Akahori, Hiroshi; Takeshita, Yumie; Saito, Reina; Kaneko, Shuichi; Takamura, Toshinari

2010-01-01

Although the etiology of Graves' disease is still not clear, it is generally suggested that environmental factors such as infections contribute to the development of Graves' disease. We report here three cases of Graves' disease which presented simultaneously with infectious mononucleosis due to primary EBV infection. Acute EBV infection might play an important role in the onset of Graves' disease. These three women complained of a sore throat or neck pain, resembling subacute thyroiditis. In the case of thyrotoxicosis accompanied by sore throat or neck pain, Graves' disease must be distinguished from subacute thyroiditis.

Zygomatic salivary gland diseases in the dog: three cases diagnosed by MRI.

PubMed

Boland, Laetitia; Gomes, Eymeric; Payen, Guillaume; Bouvy, Bernard; Poncet, Cyrill

2013-01-01

This article describes three original cases of zygomatic gland disease in the dog diagnosed by low-field MRI and treated by a modified lateral orbitotomy with zygomatic osteotomy. Presenting complaints included exophthalmia, protrusion of the third eyelid, and periorbital swelling without any history of trauma. Low-field MRI allowed for adequate diagnosis of zygomatic gland disease in all cases and provided detailed information about both the specific tissue characteristics of each lesion and extension into surrounding structures. MRI findings were also helpful for surgical planning and dictated the choice of a modified lateral orbitotomy without removal of the orbital ligament. Histopathologic diagnosis for each of the three dogs was a mucocele, a malignant mixed salivary tumor, and sialadenitis.

Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

PubMed

Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A

2018-02-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

Addison's Disease and Dilated Cardiomyopathy: A Case Report and Review of the Literature.

PubMed

Mozolevska, Viktoriya; Schwartz, Anna; Cheung, David; Shaikh, Bilal; Bhagirath, Kapil M; Jassal, Davinder S

2016-01-01

Addison's disease is often accompanied by a number of cardiovascular manifestations. We report the case of a 30-year-old man who presented with a new onset dilated cardiomyopathy due to Addison's disease. The clinical presentation, treatment, and outcomes of this rare hormone mediated cardiac disorder are reviewed.

Patients with glycogen storage diseases undergoing anesthesia: a case series.

PubMed

Gurrieri, Carmelina; Sprung, Juraj; Weingarten, Toby N; Warner, Mary E

2017-10-06

Glycogen storage diseases are rare genetic disorders of glycogen synthesis, degradation, or metabolism regulation. When these patients are subjected to anesthesia, perioperative complications can develop, including hypoglycemia, rhabdomyolysis, myoglobinuria, acute renal failure, and postoperative fatigue. The objective of this study was to describe the perioperative course of a cohort of patients with glycogen storage diseases. This is a retrospective review of patients with glycogen storage diseases undergoing anesthetic care at our institution from January 1, 1990, through June 30, 2015 to assess perioperative management and outcomes. We identified 30 patients with a glycogen storage disease who underwent 41 procedures under anesthesia management. Intraoperative lactic acidosis developed during 4 major surgeries (3 liver transplants, 1 myectomy), and in all cases resolved within 24 postoperative hours. Lactated Ringer solution was used frequently. Preoperative and intraoperative hypoglycemia was noted in some patients with glycogen storage disease type I, all of which responded to administration of dextrose-containing solutions. No serious postoperative complications occurred. Patients with glycogen storage disease, despite substantial comorbid conditions, tolerates the anesthetic management without major complications. Several patients who experienced self-limited metabolic acidosis were undergoing major surgical procedures, during which acidosis could be anticipated. Close monitoring and management of blood glucose levels of patients with glycogen storage disease type I is prudent.

Two Introductions of Lyme Disease into Connecticut: A Geospatial Analysis of Human Cases from 1984 to 2012.

PubMed

Xue, Ling; Scoglio, Caterina; McVey, D Scott; Boone, Rebecca; Cohnstaedt, Lee W

2015-09-01

Lyme disease has become the most prevalent vector-borne disease in the United States and results in morbidity in humans, especially children. We used historical case distributions to explain vector-borne disease introductions and subsequent geographic expansion in the absence of disease vector data. We used geographic information system analysis of publicly available Connecticut Department of Public Health case data from 1984, 1985, and 1991 to 2012 for the 169 towns in Connecticut to identify the yearly clusters of Lyme disease cases. Our analysis identified the spatial and temporal origins of two separate introductions of Lyme disease into Connecticut and identified the subsequent direction and rate of spread. We defined both epidemic clusters of cases using significant long-term spatial autocorrelation. The incidence-weighted geographic mean analysis indicates a northern trend of geographic expansion for both epidemic clusters. In eastern Connecticut, as the epidemic progressed, the yearly shift in the geographic mean (rate of epidemic expansion) decreased each year until spatial equilibrium was reached in 2007. The equilibrium indicates a transition from epidemic Lyme disease spread to stable endemic transmission, and we associate this with a reduction in incidence. In western Connecticut, the parabolic distribution of the yearly geographic mean indicates that following the establishment of Lyme disease (1988) the epidemic quickly expanded northward and established equilibrium in 2009.

Presence of voltage-gated potassium channel complex antibody in a case of genetic prion disease

PubMed Central

Jammoul, Adham; Lederman, Richard J; Tavee, Jinny; Li, Yuebing

2014-01-01

Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is a recently recognised entity which has been reported to mimic the clinical presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this neuronal surface autoantibody in patients presenting with subacute encephalopathy is therefore crucial as it may both revoke the bleak diagnosis of prion disease and allow institution of potentially life-saving immunotherapy. Tempering this optimistic view is the rare instance when a positive VGKC complex antibody titre occurs in a definite case of prion disease. We present a pathologically and genetically confirmed case of CJD with elevated serum VGKC complex antibody titres. This case highlights the importance of interpreting the result of a positive VGKC complex antibody with caution and in the context of the overall clinical manifestation. PMID:24903967

Effect of liver transplantation on brain magnetic resonance imaging pathology in Wilson disease: a case report.

PubMed

Litwin, T; Dzieżyc, K; Poniatowska, R; Członkowska, A

2013-01-01

The authors present a case report of a 28-year-old patient with hepatic, but no neurological, signs of Wilson disease, with pathological changes in both the globi pallidi and caudate found with routine brain magnetic resonance imaging (MRI). The patient was recommended for liver transplantation by hepatologists, and during the two years of observation after liver transplantation, MRI brain abnormalities due to Wilson disease completely regressed. On the basis of this case, the authors present an argument for the prognostic significance of brain MRI in Wilson disease as well as current recommendations concerning liver transplantation in Wilson disease.

[Wilson disease. A case report and review of the literature].

PubMed

Alva-Moncayo, Edith; Castro-Tarín, María; González-Serrano, Adolfo

2011-01-01

Wilson disease is a problem of cuprum metabolism, with recesive autosomic hereditary transmission and a prevalence of one in 30,000 habitants. The cuprum is deposit in a progressive and irreversible way in the liver and encephalus and it is not liberated with quelant treatment. Neurological manifestations are tremor, disartria, extrapiramidal manifestations or distonia. Ophthalmic exploration shows corneal limb with sign of Kayser-Fleischer. a 15-year-old masculine patient with previous hepatitis outbreak in two times. During the last year he presented distonia, bradicinecious, stiffness and indifference with ictericia. Ophthalmological examination reported Kayser-Fleisher rings. Magnetic resonance of brain showed high dense images in lenticular, pallidus globe and caudate nucleus suggestive of Wilson disease. Ceruloplasmin concentration, cuprum in the liver biopsy confirmed the diagnosis. the importance of the case was the hepatic initial manifestations and two years after presented with inexpressive face, and it was considered a psychiatric disease, but the neurological evaluation and the liver biopsy confirmed the diagnosis of Wilson disease.

Addison's Disease and Dilated Cardiomyopathy: A Case Report and Review of the Literature

PubMed Central

Mozolevska, Viktoriya; Schwartz, Anna; Cheung, David; Shaikh, Bilal; Bhagirath, Kapil M.

2016-01-01

Addison's disease is often accompanied by a number of cardiovascular manifestations. We report the case of a 30-year-old man who presented with a new onset dilated cardiomyopathy due to Addison's disease. The clinical presentation, treatment, and outcomes of this rare hormone mediated cardiac disorder are reviewed. PMID:28003914

Kikuchi-Fujimoto Disease Associated with Myasthenia Gravis: A Case Report

PubMed Central

Onasanya, Olukayode; Nochlin, David; Casas, Victor; Peddareddygari, Leema Reddy; Grewal, Raji P.

2010-01-01

Kikuchi-Fujimoto disease is a self-limited benign condition of unknown etiology characterized by cervical lymphadenopathy, fever, and leucopenia. An autoimmune hypothesis has been suggested and an association with systemic lupus erythematosus, Sjogren's disease, and antiphospholipid syndrome has been noted. We report a 27-year-old male who presented for evaluation of weakness and he was diagnosed with seropositive generalized myasthenia gravis and underwent a thymectomy. He was stable until five months post-thymectomy, when he developed a high fever associated with nontender cervical lymphadenopathy, chills, and night sweats. Histopathology of a cervical lymph gland biopsy was compatible with Kikuchi-Fujimoto lymphadenitis. He improved spontaneously and was asymptomatic at the followup six months later. Our case expands the association of Kikuchi-Fujimoto disease with autoimmune disorders to include myasthenia gravis. PMID:20814564

Case Report: Strawberry Disease in Farmed Chilean Rainbow Trout.

PubMed

Sandoval, Carlos; Infante, Jorge; Abad, Jessica; Ferguson, Hugh W; Paredes, Enrique; Valdebenito, Samuel; Yáñez, Alejandro J; Ilardi, Pedro; Avendaño-Herrera, Ruben

2016-03-01

Strawberry disease is a chronic, nonlethal skin condition that affects Rainbow Trout Oncorhynchus mykiss in the United States and several European countries, where it is also known as red-mark syndrome. We provide the first identification and characterization of three strawberry disease outbreaks occurring at two aquaculture farms in southern Chile. Clinically affected fish weighing an average of 400 g presented multiple bright-red, usually raised, skin lesions on the flank, ventral surface, and dorsal surface. A PCR using Rickettsia-like-organism (RLO)-specific primers was performed on nine affected fish, and all skin samples were positive for the RLO 16S ribosomal RNA sequence. All PCR results for Flavobacterium psychrophilum and other bacterial and viral pathogens were negative. Histopathological examination of the skin lesions revealed extensive dermatitis, with severe lymphocytic infiltration in advanced cases. This report is the first to describe strawberry disease in farmed Chilean Rainbow Trout. Additional studies are needed to evaluate the risk for Rainbow Trout culture; fish challenge experiments should be performed to fulfill Koch's postulates and to demonstrate that RLO is the cause of this disease. Received December 27, 2014; accepted October 23, 2015.

Cushing Disease Presenting as Primary Psychiatric Illness: A Case Report and Literature Review.

PubMed

Rasmussen, Sean A; Rosebush, Patricia I; Smyth, Harley S; Mazurek, Michael F

2015-11-01

We report the case of a woman with long-standing refractory depression and psychotic features who was eventually diagnosed with Cushing disease. After surgical treatment of a pituitary adenoma, she experienced gradual psychiatric recovery and was eventually able to discontinue all psychotropic medication. We review the psychiatric components of Cushing disease, implications of psychiatric illnesses for the treatment and prognosis of Cushing disease, and potential pathophysiological mechanisms linking glucocorticoid excess to psychiatric illness.

Madelung disease: a rare case associated with gynaecomastia and scrotal involvement.

PubMed

Nikolić, Zivorad S; Jeremić, Jelena V; Drčić, Lazar J; Rakočević, Zoran B; Tačević, Zoran D; Jeremić, Katarina V; Stojnić, Jelena D

2013-10-01

Madelung disease is rare, and characterised by accumulation of fatty non-encapsulated tissue in the head, neck, shoulders, and upper extremities. The aetiology is not completely known, but the association with alcohol intake is clear. We present a neglected case that was associated with bilateral asymmetrical gynaecomastia. To the best of our knowledge, this is a pattern of involvement not previously reported. The treatment of choice is lipectomy for severe cases and liposuction for less extensive accumulations of fat.

Rare Coexistance of Ileal Diverticulosis, Crohn’s Disease and Small Bowel Adenocarcinoma: Report of a Case

PubMed Central

SPARTALIS, ELEFTHERIOS; GARMPIS, NIKOLAOS; SPARTALIS, MICHAEL; DAMASKOS, CHRISTOS; MORIS, DEMETRIOS; ATHANASIOU, ANTONIOS; GKOLFAKIS, PARASKEVAS; KORKOLOPOULOU, PENELOPE; DIMITROULIS, DIMITRIOS; MANTAS, DIMITRIOS

2018-01-01

Background/Aim: Adenocarcinoma is one of the most common malignant tumors of the small intestine complicating Crohn’s disease. However, the coexistence of both conditions with diverticulosis of small bowel in young age makes this coincidence rare and clinical diagnosis very difficult. Case Report: We report a case of a woman admitted to our Department with acute abdominal pain and fever. The surgical and histological investigation, revealed a rare coexistence that has never been mentioned in the published medical literature. Conclusion: Ileal diverticulosis is not frequent and often asymptomatic as well as adenocarcinoma of the small bowel. In this case, those diseases along with Crohn’s disease led the patient to acute symptoms. PMID:29275319

[Bowen's disease and squamous cell carcinoma in Haber's syndrome: two cases].

PubMed

Legoupil, D; Lemasson, G; Davaine, A-C; Misery, L

2007-01-01

Haber's syndrome is a rare form of autosomal dominant genodermatosis. Clinically, it is associated with rosaceiform dermatosis of the face that begins in childhood, and profuse keratotic lesions resembling seborrheic keratoses, seen predominantly on the trunk, the tops of the limbs and the scalp. We report two cases of Bowen's disease and cutaneous epidermoid carcinoma in Haber's syndrome patients. A 67 year-old woman with Haber's syndrome and with a familial history consulted for a budding lesion on the abdomen, histological examination of which confirmed epidermoid carcinoma. A 77 year-old woman presented a clinical picture consistent with Haber's syndrome, with three infiltrated erythematosquamous abdominal lesions. Histological examination of a biopsy sample confirmed the clinical diagnosis of Bowen's disease. The patient was successfully treated with imiquimod. These two cases appear to indicate the existence of an association between Haber's syndrome and the presence of cutaneous carcinomatous lesions. We propose the hypothesis of transformation of the keratoses seen in seborrheic keratosis. These lesions may be considered as pre-cancerous. Association with skin carcinomas requires regular monitoring of these patients. The use of imiquimod to treat lesions in patients with Bowen's disease resulted in complete cure.

Occupational characteristics of cases with asbestos-related diseases in The Netherlands.

PubMed

Burdorf, Alex; Dahhan, Mohssine; Swuste, Paul

2003-08-01

To describe the occupational background of cases with an asbestos-related disease and to present overall mesothelioma risks across industries with historical exposure to asbestos. For the period 1990-2000, cases were collected from records held by two law firms. Information on jobs held, previous employers, activities performed and specific products used were obtained from patients themselves or next of kin. Branches of industry and occupations were coded and the likelihood of asbestos exposure was assessed. For each branch of industry, the overall risk of mesothelioma was calculated from the ratio of the observed number of mesothelioma cases and the cumulative population-at-risk in the period 1947-1960. In order to compare mesothelioma risks across different industries, risk ratios were calculated for the primary asbestos industry and asbestos user industries relative to all other branches of industry. In total, 710 mesotheliomas and 86 asbestosis cases were available. The average latency period was approximately 40 yr and the average duration of exposure was 22 yr. Ship building and maintenance contributed the largest number of cases (27%), followed by the construction industry (14%), the insulation industry (12%), and the navy and army, primarily related to ship building and maintenance (5%). In the insulation industry, the overall risk of mesothelioma was 5 out of 100 workers, and in the ship building industry, 1 out of 100 workers. The construction industry had an overall risk comparable with many other asbestos-using industries (7 per 10,000 workers), but due to its size claimed many mesothelioma cases. The majority of cases with asbestos-related diseases had experienced their first asbestos exposure prior to 1960. For cases with first asbestos exposure after 1960, a shift was observed from the primary asbestos industry towards asbestos-using industries, such as construction, petroleum refining, and train building and maintenance. Due to the long latency

An Ontology to Improve Transparency in Case Definition and Increase Case Finding of Infectious Intestinal Disease: Database Study in English General Practice.

PubMed

de Lusignan, Simon; Shinneman, Stacy; Yonova, Ivelina; van Vlymen, Jeremy; Elliot, Alex J; Bolton, Frederick; Smith, Gillian E; O'Brien, Sarah

2017-09-28

Infectious intestinal disease (IID) has considerable health impact; there are 2 billion cases worldwide resulting in 1 million deaths and 78.7 million disability-adjusted life years lost. Reported IID incidence rates vary and this is partly because terms such as "diarrheal disease" and "acute infectious gastroenteritis" are used interchangeably. Ontologies provide a method of transparently comparing case definitions and disease incidence rates. This study sought to show how differences in case definition in part account for variation in incidence estimates for IID and how an ontological approach provides greater transparency to IID case finding. We compared three IID case definitions: (1) Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) definition based on mapping to the Ninth International Classification of Disease (ICD-9), (2) newer ICD-10 definition, and (3) ontological case definition. We calculated incidence rates and examined the contribution of four supporting concepts related to IID: symptoms, investigations, process of care (eg, notification to public health authorities), and therapies. We created a formal ontology using ontology Web language. The ontological approach identified 5712 more cases of IID than the ICD-10 definition and 4482 more than the RCGP RSC definition from an initial cohort of 1,120,490. Weekly incidence using the ontological definition was 17.93/100,000 (95% CI 15.63-20.41), whereas for the ICD-10 definition the rate was 8.13/100,000 (95% CI 6.70-9.87), and for the RSC definition the rate was 10.24/100,000 (95% CI 8.55-12.12). Codes from the four supporting concepts were generally consistent across our three IID case definitions: 37.38% (3905/10,448) (95% CI 36.16-38.5) for the ontological definition, 38.33% (2287/5966) (95% CI 36.79-39.93) for the RSC definition, and 40.82% (1933/4736) (95% CI 39.03-42.66) for the ICD-10 definition. The proportion of laboratory results associated with a positive test

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2012 CFR

2012-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2013 CFR

2013-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2014 CFR

2014-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

Rare association of celiac disease with myasthenia gravis in a patient with other immune disorders: a case report.

PubMed

de Almeida Menezes, Marcela; Ribeiro Cabral, Vírginia Lúcia; Lorena, Sônia S; Nucci, Anamarli; Andrade Santana, Priscila; Queiroz Silva, Cecília

2016-09-01

Celiac disease is described in association with several autoimmune diseases, but rarely with myasthenia gravis. We describe the case of a 31-year-old white woman with celiac disease who presented manifestations related to a hyperactive immune system, including macroamylasemia, false-positive anti-HCV, positive antinuclear antibody, and Raynaud's phenomenon. The introduction of a gluten-free diet (GFD) resolved these features, but myasthenia gravis (MG) symptoms unexpectedly occurred on that occasion. The role of a GFD in the course of autoimmune diseases has been studied and improvement has been reported in many diseases. However, there is no consensus in the literature regarding the course of neurological disorders associated with celiac disease. In the present case, a GFD did not prevent the appearance of symptoms related to myasthenia gravis. There are few reports on the association of celiac disease with myasthenia gravis and therefore little is known about the course and time of onset of myasthenia in celiac patients. The present case increases the knowledge about this unusual autoimmune neurological disease associated with celiac disease.

Presence of voltage-gated potassium channel complex antibody in a case of genetic prion disease.

PubMed

Jammoul, Adham; Lederman, Richard J; Tavee, Jinny; Li, Yuebing

2014-06-05

Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is a recently recognised entity which has been reported to mimic the clinical presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this neuronal surface autoantibody in patients presenting with subacute encephalopathy is therefore crucial as it may both revoke the bleak diagnosis of prion disease and allow institution of potentially life-saving immunotherapy. Tempering this optimistic view is the rare instance when a positive VGKC complex antibody titre occurs in a definite case of prion disease. We present a pathologically and genetically confirmed case of CJD with elevated serum VGKC complex antibody titres. This case highlights the importance of interpreting the result of a positive VGKC complex antibody with caution and in the context of the overall clinical manifestation. 2014 BMJ Publishing Group Ltd.

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2011 CFR

2011-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2010 CFR

2010-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

PubMed

Salehi, Nooshin; Choi, Eric D; Garrison, Roger C

2017-01-16

BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.

Infectious Disease Surveillance in the 21st Century: An Integrated Web-Based Surveillance and Case Management System

PubMed Central

Haney, Gillian; Cocoros, Noelle; Cranston, Kevin; DeMaria, Alfred

2014-01-01

The Massachusetts Virtual Epidemiologic Network (MAVEN) was deployed in 2006 by the Massachusetts Department of Public Health, Bureau of Infectious Disease to serve as an integrated, Web-based disease surveillance and case management system. MAVEN replaced program-specific, siloed databases, which were inaccessible to local public health and unable to integrate electronic reporting. Disease events are automatically created without human intervention when a case or laboratory report is received and triaged in real time to state and local public health personnel. Events move through workflows for initial notification, case investigation, and case management. Initial development was completed within 12 months and recent state regulations mandate the use of MAVEN by all 351 jurisdictions. More than 300 local boards of health are using MAVEN, there are approximately one million events, and 70 laboratories report electronically. MAVEN has demonstrated responsiveness and flexibility to emerging diseases while also streamlining routine surveillance processes and improving timeliness of notifications and data completeness, although the long-term resource requirements are significant. PMID:24587547

A rare complication of CMV infection in Crohn's disease - hemophagocytic syndrome: a case report.

PubMed

Pop, Corina Silvia; Becheanu, Gabriel; Calagiu, Dorina; Jantea, Petruţa-Violeta; Rădulescu, Dragoş Mihai; Pariza, George; Mavrodin, Carmen-Iuliana; Bold, Adriana; Costache, Adrian; Nemeş, Roxana Maria

2015-01-01

We report a case of CMV (cytomegalovirus) infection in a Crohn's disease patient, resulting in severe hemophagocytic syndrome and death. A 63-year-old man with a 10-year history of ileal and colonic Crohn's disease presented with general malaise, loss of appetite and weight loss over the last month. He was in clinical remission for two years, with maintenance therapy 5-Aminosalicylic acid (5-ASA)-derived Mesalamine. The patient had no prior immunomodulators or suppressive treatment. A colonoscopy was performed and we found appearance suggestive of active Crohn's disease, confirmed by histopathological examination. A diagnosis of an exacerbation of Crohn's disease was established. Although the specific treatment was initiated, patient's general condition degraded progressively and diarrheal stools appeared, followed by an episode of massive gastrointestinal bleeding - hematochezia. We performed a new colonoscopy and the pathological examination revealed Crohn's ileocolitis with superimposed CMV infection. Despite the initiation of Ganciclovir alongside with other intensive care measures, he increasingly deteriorated and chest X-ray confirmed multilobar pneumonia. The occurrence of rapidly progressing pancytopenia and evidence for disseminated intravascular coagulopathy as well as hyperferritinemia, raised the suspicion of hemophagocytic syndrome confirmed by bone marrow aspiration. Hence, CMV-associated hemophagocytic syndrome in the context of recent corticotherapy for Crohn's disease was established. There is enough evidence that supports the gravity of the CMV infection in the case of inflammatory bowel disease (IBD) patients, especially the ones on immunomodulator treatment. The hemophagocytic syndrome reactively occurs in patients with infections in cases of immunodeficiency, displaying a hematological aspect of multiple organ dysfunction syndrome.

Diabetes mellitus in a patient with glycogen storage disease type Ia: a case report.

PubMed

Cohn, Aviva; Ohri, Anupam

2017-11-12

Glycogen storage disease type Ia is a genetic disorder that is associated with persistent fasting hypoglycemia and the inability to produce endogenous glucose. The development of diabetes with glycogen storage disease is exceedingly rare. The underlying pathogenesis for developing diabetes in these patients is unclear, and there are no guidelines for treatment. We describe a case of a 34-year-old woman of South Asian descent with glycogen storage disease type Ia, who developed uncontrolled diabetes mellitus as a young adult. Hyperglycemia was noted after childbirth, and worsened years later. Treatment for diabetes was difficult due to risks of hypoglycemia from her underlying glycogen storage disease. With minimal hypoglycemic events, the patient's blood glucose improved with exercise in combination with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor. We report a rare case of diabetes in the setting of glycogen storage disease-Ia. Based on the literature, there appears to be a relationship between glycogen storage disease and metabolic syndrome, which likely plays a role in the pathogenesis. The management of glycemic control remains a clinical challenge, requiring management of both fasting hypoglycemia from glycogen storage disease, as well as post-prandial hyperglycemia from diabetes mellitus.

Point of truth calibration for disease prioritisation-A case study of prioritisation of exotic diseases for the pig industry in Australia.

PubMed

Brookes, V J; Barry, S C; Hernández-Jover, M; Ward, M P

2017-04-01

The objective of this study was to trial point of truth calibration (POTCal) as a novel method for disease prioritisation. To illustrate the application of this method, we used a previously described case-study of prioritisation of exotic diseases for the pig industry in Australia. Disease scenarios were constructed from criteria which described potential impact and pig-producers were asked to score the importance of each scenario. POTCal was used to model participants' estimates of disease importance as a function of the criteria, to derive a predictive model to prioritise a range of exotic diseases. The best validation of producers' estimates was achieved using a model derived from all responses. The highest weighted criteria were attack rate, case fatality rate and market loss, and the highest priority diseases were the vesicular diseases followed by swine fevers and zoonotic encephalitides. Comparison of results with a previous study in which probabilistic inversion was used to prioritise diseases for the same group of producers highlighted differences between disease prioritisation methods. Overall, this study demonstrated that POTCal can be used for disease prioritisation. An advantage of POTCal is that valid models can be developed that reflect decision-makers' heuristics. Specifically, this evaluation of the use of POTCal in animal health illustrates how the judgements of participants can be incorporated into a decision-making process. Further research is needed to investigate the influence of scenarios presented to participants during POTCal evaluations, and the robustness of this approach applied to different disease issues (e.g. exotic versus endemic) and production types (e.g. intensive versus extensive). To our knowledge, this is the first report of the use of POTCal for disease prioritisation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Hallervorden-Spatz disease: historical case presentation in the spotlight of nosological evolution.

PubMed

Van Craenenbroeck, Amaryllis; Gebruers, Marilien; Martin, Jean-Jacques; Cras, Patrick

2010-11-15

Baron Dr. Ludo van Bogaert (1897-1989) authored more than 700 publications, gave countless lectures at Belgian and foreign universities and at international congresses, and trained more than 300 specialists from all over the world in the Bunge Institute. He filmed many of his patients suffering from movement disorders. Hallervorden-Spatz disease (HSD) was first described in 1922. The recognition of this well-defined syndrome was followed by several case reports published and in 1936, a new case was reported by Ludo van Bogaert and Clovis Vincent. To the best of our knowledge, this case report can be considered as the first filmed case of HSD. © 2010 Movement Disorder Society.

An Ontology to Improve Transparency in Case Definition and Increase Case Finding of Infectious Intestinal Disease: Database Study in English General Practice

PubMed Central

2017-01-01

Background Infectious intestinal disease (IID) has considerable health impact; there are 2 billion cases worldwide resulting in 1 million deaths and 78.7 million disability-adjusted life years lost. Reported IID incidence rates vary and this is partly because terms such as “diarrheal disease” and “acute infectious gastroenteritis” are used interchangeably. Ontologies provide a method of transparently comparing case definitions and disease incidence rates. Objective This study sought to show how differences in case definition in part account for variation in incidence estimates for IID and how an ontological approach provides greater transparency to IID case finding. Methods We compared three IID case definitions: (1) Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) definition based on mapping to the Ninth International Classification of Disease (ICD-9), (2) newer ICD-10 definition, and (3) ontological case definition. We calculated incidence rates and examined the contribution of four supporting concepts related to IID: symptoms, investigations, process of care (eg, notification to public health authorities), and therapies. We created a formal ontology using ontology Web language. Results The ontological approach identified 5712 more cases of IID than the ICD-10 definition and 4482 more than the RCGP RSC definition from an initial cohort of 1,120,490. Weekly incidence using the ontological definition was 17.93/100,000 (95% CI 15.63-20.41), whereas for the ICD-10 definition the rate was 8.13/100,000 (95% CI 6.70-9.87), and for the RSC definition the rate was 10.24/100,000 (95% CI 8.55-12.12). Codes from the four supporting concepts were generally consistent across our three IID case definitions: 37.38% (3905/10,448) (95% CI 36.16-38.5) for the ontological definition, 38.33% (2287/5966) (95% CI 36.79-39.93) for the RSC definition, and 40.82% (1933/4736) (95% CI 39.03-42.66) for the ICD-10 definition. The proportion of

Case report: a case of intractable Meniere's disease treated with autogenic training

PubMed Central

Goto, Fumiyuki; Nakai, Kimiko; Kunihiro, Takanobu; Ogawa, Kaoru

2008-01-01

Background Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now

[Risk factors for ischemic heart disease in Mexico: a case control study].

PubMed

Camacho-Hernández, R; Corona-Muñiz, I; Vázquez-Martínez, J L; Martínez-Rodríguez, F; Escobedo-de la Peña, J

1995-01-01

A case control study was developed in order to assess the strength of the association of modifiable risk factors and the occurrence of coronary heart disease in Mexicans. A total of 284 incident cases of acute myocardial infarction and 284 age and sex matched hospitalized controls were included in the study. Information was obtained in all subjects regarding socio-demographic variables, history of diabetes, hypertension, smoking, obesity and serum cholesterol. A conditional logistic regression model, showed that diabetes mellitus, hypertension, smoking, hypercholesterolemia and obesity, explained the occurrence of coronary heart disease in the studied population. The risk of an acute myocardial infarction heavily increases in the extreme levels of exposure; and this risk is six fold higher in those who daily smoke more than 20 cigarettes, and it is eight fold higher in those subjects with a serum cholesterol greater than 240 mg/dl. Due to the increase in the occurrence of coronary heart disease in Mexico, and the strength of the association observed with these modifiable risk factors, a public health program to decrease its prevalence, is justified.

[Fanconi disease: study of 43 cases in southern Tunisia].

PubMed

Frikha, M; Mseddi, S; Elloumi, M; Bouaziz, M; Khanfir, A; Mnif, J; Saad, A; Souissi, T

1998-11-01

To report the epidemiologic, clinical, biological features and course of Fanconi's anemia in southern Tunisia. During a period of 12 years we observed 43 cases. For each patient, careful clinical, biological (hemogram, myelogram, bone marrow biopsy, hemoglobin electrophoresis, karyotype) and radiological (skeleton X-rays, abdominal echography and intravenous urography) examinations were performed. All the patients who were at a pancytopenia stage were given androgens. None had a bone marrow allograft. There were 24 girls and 19 boys. The mean age at diagnosis was 10 years and 9 months. The familial character was present in 53% of the cases. The most frequent initial complaint was anemic syndrome (69%). In ten cases (24%), the diagnosis has been established during a familial investigation. Malformations were present in all cases (abnormal pigmentation: 86%; skeletal maturation retardation: 83%; facial dysmorphy: 76%; statural hypotrophy: 65%; bone abnormalities: 53%; renal malformations: 44%). Anemia was present in 88% of the cases, thrombocytopenia and neutropenia in all cases. Bone marrow was hypoplastic or aplastic in all cases on biopsies. Spontaneous chromosomal breaks were found in 79% of the studied cases. Fetal hemoglobin was increased in 80% of the studied cases with a mean level of 20.5%. Actuarial survival rate at 5 years was 48%, but long survival durations were rare (eight out of 43 patients). This disease, rare in the world, seems to be frequent in southern Tunisia. A normal karyotype (with classical techniques), found in five patients, could not discard the diagnosis; for this reason, the use of sensitizing agents should improve the sensitivity of the test. Besides, an increased level of fetal hemoglobin enabled us to suggest the diagnosis in some cases. Androgenotherapy increased the survival duration to more than 5 years in eight patients. However, bone marrow allograft remains the only possibility of cure.

Aspects and Intensity of Pediatric Palliative Case Management Provided by a Hospital-Based Case Management Team: A Comparative Study Between Children With Malignant and Nonmalignant Disease

PubMed Central

Colenbrander, Derk A.; Bosman, Diederik K.; Grootenhuis, Martha A.; Kars, Marijke C.; Schouten-van Meeteren, Antoinette YN

2017-01-01

Objectives: Anticipating case management is considered crucial in pediatric palliative care. In 2012, our children’s university hospital initiated a specialized pediatric palliative care team (PPCT) to deliver inbound and outbound case management for children with life-shortening disease. The aim of this report is to gain insight in the first 9 months of this PPCT. Methods: Aspects of care during the first 9 months of the PPCT are presented, and comparison is made between patients with malignant disease (MD) and nonmalignant disease (NMD) in a retrospective study design. Insight in the aspects of care of all patients with a life-shortening disease was retrieved from web-based files and the hour registrations from the PPCT. Results: Forty-three children were supported by the PPCT during the first 9 months: 22 with MD with a median of 50 (1-267) days and 29 minutes (4-615) of case management per patient per day and 21 patients with NMD with a median of 79.5 (5-211) days and 16 minutes of case management per day (6-64). Our data show significantly more interprofessional contacts for patients with MD and more in-hospital contacts for patients with NMD. The median number of admission days per patient was 11 (0-22) for MD (44% for anticancer therapy) and 44 (0-303) for NMD (36% for infectious diseases). Significance of Results: This overview of aspects of pediatric palliative case management shows shorter but more intensive case management for MD in comparison with NMD. This insight in palliative case management guides the design of a PPCT. PMID:28273758

Behcet disease combined with Sjogren syndrome: A unique case report and literature review.

PubMed

Ju, Fang-He; Xu, Ting-Zhen; Hong, Hui-Hua; Mao, He; Wang, Meng; Wang, Zhen

2018-03-01

Behcet disease(BD) and Sjogren syndrome(SS) are separate conditions that rarely concomitantly affect an individual. In theory,mild symptoms of patients with BD or SS are easy to igore and,thus,remain undiagnosed. There,it is reasonable to believe there may be some clinical cases of combined diseases that go undiscovered and which needs to be taken seriously. In addition,it has been suggested that herpes simplex virus(HSV) types 1 and 2 are associated with BD,but have not been shown to be correlated to the direct pathogenesis of BD. The role of HSV in BD needs more research and attention. Here,we report a young woman who had both BD and SS. The first symptom of the disease was fever. However,the HSV type 1 IgG and HSV type 2 IgM antibody results were positive in our case and,which rendered this case unique. BD and SS concomitantly affect the individual,and BD was the acute type. IV methylprednisolone was used for 9 days and then oral glucocorticoids was used to instead,and the treatment works very well. BD and SS can concomitantly affect an individual,and we believe that HSV-2 may be directly related to the pathogenesis of BD. The nature of BD as an auto-inflammatory disorder, autoimmune disorder, or both, is controversial. If we can find more patients who combined affected these two disease, it might helpful for us to understand the nature of BD. For patients with clinical diagnosis of BD or SS,we need to be alert that it may combinded the other disease. Long term follow up and detailed inspection are important means to avoid undiscovered.

Intrathecal antibody production in two cases of yellow fever vaccine associated neurotropic disease in Argentina.

PubMed

Pires-Marczeski, Fanny Clara; Martinez, Valeria Paula; Nemirovsky, Corina; Padula, Paula Julieta

2011-12-01

During the period 2007-2008 several epizootics of Yellow fever with dead of monkeys occurred in southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuated Yellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropic disease are reported rarely. The aim of this study was to confirm two serious adverse events associated to Yellow fever vaccine in Argentina, and to describe the analysis performed to assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinal fluid (CSF). Both cases coincided with the Yellow fever vaccine-associated neurotropic disease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease was identified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AI(IgM) ) was calculated. High AI(IgM) values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination. Copyright © 2011 Wiley Periodicals, Inc.

Rare esophageal ulcers related to Behçet disease: A case report.

PubMed

Jia, Ning; Tang, Yanping; Liu, Huayi; Li, Yang; Liu, Simiao; Liu, Lei

2017-11-01

The fundamental pathogenesis of Behçet disease (BD) is still unclear and controversial. Many cases of oral aphthous ulcers and genital ulcers related to BD are reported; nevertheless, idiopathic giant esophageal ulcers related to BD are rare. A rare case for esophageal ulcers related to BD is presented. In China, BD is represented with esophageal involvement which is called esophageal BD (EBD). A 56-year-old man diagnosed to the Gastroenterology Department of Integrated Traditional Chinese and Western Medicine Hospital, for multiple discrete, elliptical esophageal ulcers related to BD. The esophageal ulcers were treated with corticosteroid treatment for 12 weeks. The esophageal ulcers were cured. Our report might give further strength to avoiding the erroneous diagnosis or missed diagnosis for EBD, which is different from esophageal carcinoma, esophageal tuberculosis and esophageal Crohns disease.

Tuberculosis masked by immunodeficiency: a review of two cases diagnosed with chronic granulomatous disease.

PubMed

Nacaroğlu, Hikmet Tekin; Bahçeci Erdem, Semiha; Gülez, Nesrin; Ünsal Karkıner, Canan Şule; Devrim, İlker; Genel, Ferah; Köker, Mustafa Yavuz; Can, Demet

2017-03-01

Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency that is characterized by recurrent and life-threatening infections resulting from defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and granuloma formation due to increased inflammatory response. The most commonly involved organs are the lungs, skin, lymph nodes, and liver due to infection. It may present with recurrent pneumonia, hilar lymphadenopathy, empyema, abscess, reticulonodular patterns, and granulomas due to lung involvement. In recent years, mycobacterial disease susceptibility has been reported in CGD cases. This article presents two male cases, one of whom is aged 18 months and the other is aged 5 years, who were diagnosed with CGD and tuberculosis during examination due to extended pneumonia. This report is presented because CGD should be considered not only in the presence of skin abscesses and Aspergillus infections, but also in the differential diagnosis for cases with BCG-itis and/or tuberculosis. It should be kept in mind that mycobacterial infections can occur during the course of the disease.

Rare ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease: A case report.

PubMed

Gao, Yunxia; Zhang, Yifan; Lu, Fang; Wang, Xiaoyue; Zhang, Ming

2018-06-01

Kawasaki disease is a necrotizing vasculitis featuring fever, erythema, conjunctivitis, and lymphadenopathy. Ocular manifestations in Kawasaki disease are commonly limited to anterior segment, posterior segment lesions are rarely reported. We report a unique case of ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease. An 11-year-old Asian girl presented with severe enophthalmos, retinitis, retinal detachment, and choroidal detachment secondary to an unexplained fever for 10 days. To the best of our knowledge, this is the first documented case of incomplete Kawasaki disease with severe posterior segment lesions. The local use of dexamethasone in the eye was effective in our patient. Surgical intervention might not be necessary even though the initial symptoms could be devastating. The eye should be monitoring the eye routinely in patients with Kawasaki disease.

A Classification System to Guide Physical Therapy Management in Huntington Disease: A Case Series.

PubMed

Fritz, Nora E; Busse, Monica; Jones, Karen; Khalil, Hanan; Quinn, Lori

2017-07-01

Individuals with Huntington disease (HD), a rare neurological disease, experience impairments in mobility and cognition throughout their disease course. The Medical Research Council framework provides a schema that can be applied to the development and evaluation of complex interventions, such as those provided by physical therapists. Treatment-based classifications, based on expert consensus and available literature, are helpful in guiding physical therapy management across the stages of HD. Such classifications also contribute to the development and further evaluation of well-defined complex interventions in this highly variable and complex neurodegenerative disease. The purpose of this case series was to illustrate the use of these classifications in the management of 2 individuals with late-stage HD. Two females, 40 and 55 years of age, with late-stage HD participated in this case series. Both experienced progressive declines in ambulatory function and balance as well as falls or fear of falling. Both individuals received daily care in the home for activities of daily living. Physical therapy Treatment-Based Classifications for HD guided the interventions and outcomes. Eight weeks of in-home balance training, strength training, task-specific practice of functional activities including transfers and walking tasks, and family/carer education were provided. Both individuals demonstrated improvements that met or exceeded the established minimal detectible change values for gait speed and Timed Up and Go performance. Both also demonstrated improvements on Berg Balance Scale and Physical Performance Test performance, with 1 of the 2 individuals exceeding the established minimal detectible changes for both tests. Reductions in fall risk were evident in both cases. These cases provide proof-of-principle to support use of treatment-based classifications for physical therapy management in individuals with HD. Traditional classification of early-, mid-, and late

MR imaging of pseudosarcoma in Paget's disease of bone: a report of two cases.

PubMed

Tins, B J; Davies, A M; Mangham, D C

2001-03-01

Pseudosarcoma is a rare manifestation of Paget's disease of bone. We report the MR imaging of two cases highlighting the difficulties in diagnosis. One of the cases is the first time this condition has been described outside the long bones of the lower limb.

Validation of diagnosis of aplastic anaemia in La Rioja (Spain) by International Classification of Diseases codes for case ascertainment for the Spanish National Rare Diseases Registry.

PubMed

Ruiz, Elena; Ramalle-Gómara, Enrique; Quiñones, Carmen; Rabasa, Pilar; Pisón, Carlos

2015-05-01

To analyse the validity of diagnosis of aplastic anaemia (AA) by International Classification of Diseases codes in hospital discharge data (MBDS) and the mortality registry (MR) of La Rioja to detect cases to be included in the Spanish National Rare Diseases Registry. International Classification of Diseases (ICD) codes were used to detect AA cases during the period 2007-2012 from two administrative databases: the MBDS and the MR of La Rioja (Spain). Medical records of population selected by merging both databases were used to confirm true AA cases. The annual mean incidence rate of AA was calculated using confirmed incident cases. By merging both databases, 62 hypothetical AA incident patients were detected during the period 2007-2012. The medical records of the 89% of them could be revised, and they confirmed that only the 15% of the patients actually suffered AA. The annual mean AA incidence in La Rioja was 4.17 per million inhabitants (6.23 per million, males; 2.10 per million, females). The MBDS and the MR are not in themselves sufficient to ascertain AA cases in La Rioja and medical records should be reviewed to confirm true AA cases to be included in the Spanish National Rare Diseases Registry. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Disseminated cat-scratch disease: case report and review of the literature.

PubMed

Chang, Chih-Chen; Lee, Chia-Jie; Ou, Liang-Shiou; Wang, Chao-Jan; Huang, Yhu-Chering

2016-08-01

Cat scratch disease (CSD) can present as a systemic disease in 5-10% of cases and lead to various disease entities. A previously healthy 16-month-old boy presented with fever for 7 days without other obvious symptoms. Abdominal computed tomography scan demonstrated enlarged right inguinal lymph nodes and multiple small round hypodensities in the spleen. Despite antibiotic treatment for 1 week, the fever persisted and the intrasplenic lesions progressed. Inguinal lymph node biopsy confirmed CSD by immunohistochemistry staining. The diagnosis of CSD was also supported by a history of contact, imaging and serological findings. The patient recovered after treatment with azithromycin for a total of 5 weeks and, in serial follow-up, the hepatosplenic micro-abscesses resolved after 4th months.

Disseminated cat-scratch disease: case report and review of the literature.

PubMed

Chang, Chih-Chen; Lee, Chia-Jie; Ou, Liang-Shiou; Wang, Chao-Jan; Huang, Yhu-Chering

2016-01-12

Cat scratch disease (CSD) can present as a systemic disease in 5-10% of cases and lead to various disease entities. A previously healthy 16-month-old boy presented with fever for 7 days without other obvious symptoms. Abdominal computed tomography scan demonstrated enlarged right inguinal lymph nodes and multiple small round hypodensities in the spleen. Despite antibiotic treatment for 1 week, the fever persisted and the intrasplenic lesions progressed. Inguinal lymph node biopsy confirmed CSD by immunohistochemistry staining. The diagnosis of CSD was also supported by a history of contact, imaging and serological findings. The patient recovered after treatment with azithromycin for a total of 5 weeks and, in serial follow-up, the hepatosplenic micro-abscesses resolved after 4th months.

A report of three cases of untreated Graves' disease associated with pancytopenia in Malaysia.

PubMed

Rafhati, Abdullah Noor; See, Chee Keong; Hoo, Fan Kee; Badrulnizam, Long Bidin Mohamed

2014-01-01

Generally, clinical presentations of Graves' disease range from asymptomatic disease to overt symptomatic hyperthyroidism with heat intolerance, tremor, palpitation, weight loss, and increased appetite. However, atypical presentation of Graves' disease with hematological system involvement, notably pancytopenia, is distinctly uncommon. Hereby, we present and discuss a series of three untreated cases of Graves' disease clinically presented with pancytopenia and the hematological abnormalities that responded well to anti-thyroid treatment. With resolution of the thyrotoxic state, the hematological parameters improved simultaneously. Thus, it is crucial that anti-thyroid treatment be considered in patients with Graves' disease and pancytopenia after a thorough hematological evaluation.

Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verlander, P.C.; Kaporis, A.G.; Qian, L.

1994-09-01

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutationsmore » are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.« less

Puffy skin disease (PSD) in rainbow trout, Oncorhynchus mykiss (Walbaum): a case definition.

PubMed

Maddocks, C E; Nolan, E T; Feist, S W; Crumlish, M; Richards, R H; Williams, C F

2015-07-01

Puffy skin disease (PSD) is a disease that causes skin pathology in rainbow trout, Oncorhynchus mykiss (Walbaum). Incidence of PSD in UK fish farms and fisheries has increased sharply in the last decade, with growing concern from both industry sectors. This paper provides the first comprehensive case definition of PSD, combining clinical and pathological observations of diseased rainbow trout from both fish farms and fisheries. The defining features of PSD, as summarized in the case definition, were focal lateral flank skin lesions that appeared as cutaneous swelling with pigment loss and petechiae. These were associated with lethargy, poor body condition, inappetance and low level mortality. Epidermal hyperplasia and spongiosis, oedema of the dermis stratum spongiosum and a mild diffuse inflammatory cellularity were typical in histopathology of skin. A specific pathogen or aetiology was not identified. Prevalence and severity of skin lesions was greatest during late summer and autumn, with the highest prevalence being 95%. Atypical lesions seen in winter and spring were suggestive of clinical resolution. PSD holds important implications for both trout aquaculture and still water trout fisheries. This case definition will aid future diagnosis, help avoid confusion with other skin conditions and promote prompt and consistent reporting. © 2014 John Wiley & Sons Ltd.

Classification algorithm of lung lobe for lung disease cases based on multislice CT images

NASA Astrophysics Data System (ADS)

Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Mishima, M.; Ohmatsu, H.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2011-03-01

With the development of multi-slice CT technology, to obtain an accurate 3D image of lung field in a short time is possible. To support that, a lot of image processing methods need to be developed. In clinical setting for diagnosis of lung cancer, it is important to study and analyse lung structure. Therefore, classification of lung lobe provides useful information for lung cancer analysis. In this report, we describe algorithm which classify lungs into lung lobes for lung disease cases from multi-slice CT images. The classification algorithm of lung lobes is efficiently carried out using information of lung blood vessel, bronchus, and interlobar fissure. Applying the classification algorithms to multi-slice CT images of 20 normal cases and 5 lung disease cases, we demonstrate the usefulness of the proposed algorithms.

Flexor Tendon Rupture Due to Previously Undiagnosed Kienböck Disease: A Case Report.

PubMed

Turner, Kenrick; Sheppard, Nicholas N; Norton, Samuel E

2017-05-01

Spontaneous flexor tendon rupture is rare and most common in the little finger. The pathogenesis of spontaneous tendon ruptures is unclear but may occur through attrition or mechanical abrasion over a bony prominence. Kienböck disease is avascular necrosis of the lunate, with an unknown etiology. We present a case of spontaneous rupture of flexor digitorum profundus due to Kienböck disease, which we believe is the first recorded case of flexor tendon rupture attributable to osteonecrosis of the lunate. The patient underwent single-stage reconstruction of FDP and regained a good range of motion at the affected DIPJ. This case illustrates the the importance of plain radiographs in the assessment of a patient presenting with spontaneous flexor tendon rupture in the hand to exclude bony pathology as a cause.

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