232 research outputs found

    Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose

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    Background: Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. / Methods: After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. / Results: Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. / Conclusions: When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment

    Clinical features of 27 Turkish Propionic acidemia patients with 12 novel mutations

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    Propionic acidemia (PA) is an inherited metabolic disease caused by the deficiency of one of the four biotin-dependent enzymes propionyl-CoA carboxylase (PCC), and is characterized by coma and death in unrecognized patients, additionally late diagnosis leads to severe developmental delay and neurological sequels. Manifestations of PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure. Mutations in PCCA-PCCB genes cause the clinically heterogeneous disease of PA. In this study, we investigate the mutation spectrum of PCCAPCCB genes and phenotypic features of 27 Turkish patients with PA from the South and Southeast parts of Turkey. We report 12 novel PA mutations, five affecting the PCCA gene and 7 affecting the PCCB gene

    The outcome of 41 Late-Diagnosed Turkish GA-1 Patients: A Candidate for the Turkish NBS

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    Background: Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. / Method: This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. / Results: The mean age at diagnosis was 14.8 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. / Conclusion: All GA-1 patients in our study were severely affected since they were latediagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS

    Mucopolysaccharidosis Type-II with Pathognomonic Skin Appearance: A Case with Pebbling Sign

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    Mucopolysaccharidosis type-II (MPS-II) is an X-linked lysosomal storage disorder. Here, we report an 8-year-old boy with pebbling sign in the scapular region, coarse facies, claw hand, diastolic murmur, and hepatomegaly. With decreased iduronate-2-sulfatase activity and hemizygous mutation in the IDS gene, the diagnosis was MPS-II. Pebbling sign is a rare but pathognomonic sign of MPS-II

    Dynamics of Three Agent Games

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    We study the dynamics and resulting score distribution of three-agent games where after each competition a single agent wins and scores a point. A single competition is described by a triplet of numbers pp, tt and qq denoting the probabilities that the team with the highest, middle or lowest accumulated score wins. We study the full family of solutions in the regime, where the number of agents and competitions is large, which can be regarded as a hydrodynamic limit. Depending on the parameter values (p,q,t)(p,q,t), we find six qualitatively different asymptotic score distributions and we also provide a qualitative understanding of these results. We checked our analytical results against numerical simulations of the microscopic model and find these to be in excellent agreement. The three agent game can be regarded as a social model where a player can be favored or disfavored for advancement, based on his/her accumulated score. It is also possible to decide the outcome of a three agent game through a mini tournament of two-a gent competitions among the participating players and it turns out that the resulting possible score distributions are a subset of those obtained for the general three agent-games. We discuss how one can add a steady and democratic decline rate to the model and present a simple geometric construction that allows one to write down the corresponding score evolution equations for nn-agent games

    String Matching and 1d Lattice Gases

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    We calculate the probability distributions for the number of occurrences nn of a given ll letter word in a random string of kk letters. Analytical expressions for the distribution are known for the asymptotic regimes (i) k≫rl≫1k \gg r^l \gg 1 (Gaussian) and k,l→∞k,l \to \infty such that k/rlk/r^l is finite (Compound Poisson). However, it is known that these distributions do now work well in the intermediate regime k≳rl≳1k \gtrsim r^l \gtrsim 1. We show that the problem of calculating the string matching probability can be cast into a determining the configurational partition function of a 1d lattice gas with interacting particles so that the matching probability becomes the grand-partition sum of the lattice gas, with the number of particles corresponding to the number of matches. We perform a virial expansion of the effective equation of state and obtain the probability distribution. Our result reproduces the behavior of the distribution in all regimes. We are also able to show analytically how the limiting distributions arise. Our analysis builds on the fact that the effective interactions between the particles consist of a relatively strong core of size ll, the word length, followed by a weak, exponentially decaying tail. We find that the asymptotic regimes correspond to the case where the tail of the interactions can be neglected, while in the intermediate regime they need to be kept in the analysis. Our results are readily generalized to the case where the random strings are generated by more complicated stochastic processes such as a non-uniform letter probability distribution or Markov chains. We show that in these cases the tails of the effective interactions can be made even more dominant rendering thus the asymptotic approximations less accurate in such a regime.Comment: 44 pages and 8 figures. Major revision of previous version. The lattice gas analogy has been worked out in full, including virial expansion and equation of state. This constitutes the main part of the paper now. Connections with existing work is made and references should be up to date now. To be submitted for publicatio

    Using surface integrals for checking the Archimedes' law of buoyancy

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    A mathematical derivation of the force exerted by an \emph{inhomogeneous} (i.e., compressible) fluid on the surface of an \emph{arbitrarily-shaped} body immersed in it is not found in literature, which may be attributed to our trust on Archimedes' law of buoyancy. However, this law, also known as Archimedes' principle (AP), does not yield the force observed when the body is in contact to the container walls, as is more evident in the case of a block immersed in a liquid and in contact to the bottom, in which a \emph{downward} force that \emph{increases with depth} is observed. In this work, by taking into account the surface integral of the pressure force exerted by a fluid over the surface of a body, the general validity of AP is checked. For a body fully surrounded by a fluid, homogeneous or not, a gradient version of the divergence theorem applies, yielding a volume integral that simplifies to an upward force which agrees to the force predicted by AP, as long as the fluid density is a \emph{continuous function of depth}. For the bottom case, this approach yields a downward force that increases with depth, which contrasts to AP but is in agreement to experiments. It also yields a formula for this force which shows that it increases with the area of contact.Comment: 15 pages, 3 figures, accepted for publication in "Eur. J. Phys." (10/20/2011
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