bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational carrier — A reproductive haven for offspring of mothers with phenylketonuria (PKU): An alternative therapy for maternal PKU
Authors: Fisch R. O. , Tagatz G. , Stassart J. P. 
Published: November 2004

SummaryMaternal phenylketonuria, PKU, has a detrimental effect on embryogenesis. Infant pathology is independent of fetal genotype, but is directly correlated with excessive phenylalaninaemia throughout pregnancy. Although normal children have been delivered by affected mothers who either had benign hyperphenylalaninaemia or in whom strict diet has apparently maintained maternal phenylalaninaemia in the low normal range from before conception, more abnormal than normal births have been reported. In addition, attempts at dietary management are often unsuccessful; most reported cases documented various severe pathological consequences of maternal PKU. Currently available methods provide viable alternative treatment.In vitro fertilization using the parental gametes, followed by implantation of the pre‐embryo in a surrogate mother, would avoid a metabolic environment impairing normal development, and therefore should be recommended as alternative therapy for potential mothers with PKU.
Scottish frequency of the common G985 mutation in the medium‐chain acyl‐CoA dehydrogenase (MCAD) gene and the role of MCAD deficiency in sudden infant death syndrome (SIDS)
Authors: Dundar M. , Lanyon W. G. , Connor J. M. 
Published: November 2004

SummaryMedium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency, is an autosomal recessive inborn error of metabolism associated with various clinical presentations, including sudden unexplained death in young children. We have determined the Scottish frequency of the common G985 mutation found in Caucasians and in samples from Scottish patients with sudden infant death syndrome (SIDS). The heterozygote frequency of the mutation was found to be 1 in 276 (95% confidence interval: 1/76–1/2279) in 552 healthy controls and 1 in 74 (95% confidence interval: 1/27–1/377) in 233 SIDS patients: a difference that was not statistically significant (Fisher's exact test; two‐sided;p=0.316). None of the SIDS samples was found to be homozygous for the G985 mutation.
Identification of GM2‐gangliosidosis B1 variant carriers
Authors: Ribeiro M. G. , Pinto R. , Oliveira P. , Sá Miranda M. C. 
Published: November 2004

SummaryGM2‐gangliosidosis B1 variant, considered a rare disorder with a wide geographical and ethnic distribution, appears to be exceptionally frequent in Portugal. In order to establish a carrier detection method for this disease we have determined the ratio of enzymatic activities against 4MUGS and 4MUG in urine from B1 variant obligate carriers and controls, using the total extract and the Hex A immunobound to a monoclonal antibody. The Hex A immunoassay was applied to the identification of carriers in B1 variant families and the results obtained were compared with those from DNA analysis. The reliability and feasibility of the Hex A immunoassay make it a suitable method for B1 variant carrier screening, which is particularly important for the prevention of this severe neurological disease in the population at risk.
Impaired degradation of phytanic acid in cells from patients with mitochondriopathies: Evidence for the involvement of ETF and the respiratory chain in phytanic acid α‐oxidation
Authors: Fingerhut R. , Schmitz W. , Garavaglia B. , Reichmann H. , Conzelmann E. 
Published: November 2004

SummaryPhytanic acid α‐oxidation was studied in cultures of skin fibroblasts and myoblasts from patients with various defects of the respiratory chain in order to obtain information on the subcellular site and the mechanism of this pathway. In fibroblasts from patients with complex IV (cytochromec oxidase) deficiency or glutaricaciduria type II, phytanic acid α‐oxidation was reduced to 14% of normal, whereas in myoblasts from patients with complex I (NADH‐Q reductase) deficiency, it was normal. Apparently, at least one step of phytanic acid α‐oxidation occurs in mitochondria and in this process electrons are transferred to the respiratory chain via the electron‐transfer flavoprotein (ETF).
Plasmacis‐dec‐4‐enoic acid measured by isotope dilution mass spectrometry; an improved assay to diagnose medium‐chain acyl‐CoA dehydrogenase deficiency
Authors: Johnson D. W. , Harrison J. R. , Norton W. A. , Poulos A. , Robertson E. F. 
Published: November 2004

SummaryAn isotope dilution mass spectrometric assay for plasmacis‐dec‐4‐enoic acid is described. It is quicker, more reliable and more accurate than previous methods. It confirmed previous findings thatcis‐dec‐4‐enoic acid is a reliable indicator for medium‐chain acyl‐CoA dehydrogenase deficiency (MCAD). The plasmacis‐dec‐4‐enoic acid levels of both asymptomatic and symptomatic MCAD patients (3.5–71 µmol/L) are demonstrably higher than those of normal children (0.2–1.7 µmol/L), MCAD heterozygotes (0.1–1.5 µmol/L), those with other fatty acid oxidation defects (0.2–2.2 µmol/L) or those receiving high doses of valproic acid (0.2–0.4 µmol/L).
Effect of betaine onS‐adenosylmethionine levels in the cerebrospinal fluid in a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy
Authors: Kishi T. , Kawamura I. , Harada Y. , Eguchi T. , Sakura N. , Ueda K. , Narisawa K. , Rosenblatt D. S. 
Published: November 2004

SummaryA 16‐year‐old Japanese girl with 5,10‐methylenetetrahydrofolate reductase deficiency showed peripheral neuropathy. There were no significant responses to vitamin B6, vitamin B12 or folate, given alone or in combination. With the addition of betaine monohydrate, she has been free from gait disturbance and muscle weakness. The concentration ofS‐adenosylmethionine in cerebrospinal fluid, which was undetectable before receiving betaine monohydrate, increased to about the normal level 24 months after treatment with betaine monohydrate.
Molecular genetic characterization and urinary excretion pattern of metabolites in two families with MCAD deficiency due to compound heterozygosity with a 13 base pair insertion in one allele
Authors: Gregersen N. , Winter V. , Lyonnet S. , Saudubray J. M. , Wendel U. , Jensen T. G. , Andresen B. S. , Kølvraa S. , Lehnert W. , Bolund L. , Christensen E. , Bross P. 
Published: November 2004

SummaryTwo families with medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency due to compound heterozygosity are described. All patients have a 13 bp insertion in exon 11 of one allele at the MCAD gene locus. In the other allele patients in one of the families harbour the prevalent G985 mutation, and the other family possess an unidentified mutation causing reduced levels of MCAD mRNA. We demonstrate that the disease in these families is inherited as an autosomal recessive trait. Individuals heterozygous for the mutations show heterozygous/control levels of β‐oxidation activities in cultured fibroblasts (9.1–16.3 pmol/min per mg protein; control 10–17 pmol/min per mg protein), and in the excretion of the ‘β‐oxidation metabolites’, hexanoylglycine (<2 µmol/mmol creatinine), suberylglycine (<2 µmol/mmol creatinine) and phenylpropionylglycine (<2 µmol/mmol creatinine). This shows that there is no ‘negative dominance’ from the mutant monomeric protein onto the normal ones, in accordance with the finding of low levels of MCAD mRNA from the allele harbouring the 13 bp insertion as well as the allele with the unidentified mutation, and the low steady‐state level of enzyme protein expressed from the G985‐bearing allele. In the family possessing the G985 and the 13 bp insertion mutations, two asymptomatic compound heterozygous individuals were detected. They exhibited elevated excretion of hexanoylglycine (5–15 µmol/mmol creatinine) and suberylglycine (4–13 µmol/mmol creatinine), together with β‐oxidation activity in fibroblasts in the homozygous range (2.9 pmol/min per mg protein), showing a lack of correlation between the genotype, some biochemical parameters and the clinical phenotype.
Vitamin‐responsive complex I deficiency in a myopathic patient with increased activity of the terminal respiratory chain and lactic acidosis
Authors: Bakker H. D. , Scholte H. R. , Jeneson J. A. L. , Busch H. F. M. , Abeling N. G. G. M. , van Gennip A. H. 
Published: November 2004

SummaryAn 11‐year‐old gril with exercise intolerance, fatiguability from early childhood, had high blood lactate levels. Histochemistry showed increased activity of succinate dehydrogenase at the periphery of the muscle fibres, whereas aggregates of mitochondria were seen by electron microscopy. Biochemical investigation of isolated mitochondria and homogenate from muscle showed evidence of a severe complex I deficiency. In contrast, succinate dehydrogenase, complex II + III and complex IV were increased in activity. Therapy with biotin, riboflavin, nicotinamide, carnitine and amino acids resulted in an improvement of her endurance.31P NMR spectroscopy of her forearm muscle showed a decreased ratio of phosphocreatine (PCr) over ATP. After exercise the PCr recovery rate was 26% of the average rate in 20 healthy untrained controls. When the therapy was suspended the PCr/ATP ratio at rest decreased from 2.60 to 2.34, and the PCr recovery rate after exercise decreased to 21% of the average control rate. The therapy was reinstituted but only riboflavin and carnitine were given. The PCr/ATP ratio increased to 2.60 and the PCr recovery rate increased to 32% of the control rate. Improvement of the energy metabolism in patients with defects in the oxidative phosphorylation may add to the quality of life;31P NMR spectroscopy can measure these improvements.
Possible high frequency of tetrahydrobiopterin deficiency in South Brazil
Authors: Jardim L. B. , Giugliani R. , Coelho J. C. , Dutra‐Filho C. S. , Blau N. 
Published: November 2004

SummaryWe report our experience with the deficiency of 6‐pyruvoyltetrahydropterin synthase, the most common form of tetrahydrobiopterin deficiency. We investigated 5200 patients suspected of having some inborn error of metabolism in a 10‐year period, and detected 30 cases (from 28 sibships) of hyperphenylalaninaemias, HPA. From these, 4 sibships (5 patients) were affected by deficiency of 6‐pyruvoyltetrahydropterin synthase. All of them were ethnically mixed, with some European ancestry detected in all. The age of diagnosis ranged from 2 to 9 years, and all were initially referred for investigation by having mental retardation and seizures. All of them showed low urinary biopterin levels and a marked elevation of neopterin. Although we detected only a few cases of HPA (30), 5 cases of 6‐pyruvoyltetrahydropterin account for almost 20% of this total. The literature, however, reports a proportion of around 0.5%. As the frequency of classical phenylketonuria in our region is similar to that found in Caucasians (1/12 500), we believe that the frequency of this disease in South Brazil may be higher than expected (of the order of 1/400 000). We speculate that this finding could be related to a genetic drift (or founder effect).
l‐2‐Hydroxyglutaric acidaemia: Clinical and biochemical findings in 12 patients and preliminary report onl‐2‐hydroxyacid dehydrogenase
Authors: Barth P. G. , Hoffmann G. F. , Jaeken J. , Wanders R. J. A. , Duran M. , Jansen G. A. , Jakobs C. , Lehnert W. , Hanefeld F. , Valk J. , Schutgens R. B. H. , Trefz F. K. , Hartung H. ‐P. , Chamoles N. A. , Sfaello Z. , Caruso U. 
Published: November 2004

Summaryl‐2‐Hydroxyglutaric acidaemia represents a newly defined inborn error of metabolism, with increased levels ofl‐2‐hydroxyglutaric acid in urine, plasma and cerebrospinal fluid. The concentration in cerebrospinal fluid is higher than in plasma. The other consistent biochemical finding is an increase of lysine in blood and cerebrospinal fluid, but lysine loading does not increasel‐2‐hydroxyglutaric acid concentration in plasma. This autosomal recessively inherited disease is expressed as progressive ataxia, mental deficiency with subcortical leukoencephalopathy and cerebellar atrophy on magnetic resonance imaging. Since these features were described in 8 patients by Barth and co‐workers in 1992, 4 more patients with similar findings have been diagnosed and added to the present series.l‐2‐Hydroxyglutaric acid is found in only trace amounts on routine gas chromatographic screening in normal persons, and its origin, its fate and even its relevance to normal metabolism are unknown. Therefore its catabolism was studied in normal liver. Incubation of rat liver withl‐2‐hydroxyglutaric acid did not produce H2O2, which excluded (peroxisomal)l‐2‐hydroxyacid oxidase as the main route of catabolism. However,l‐2‐hydroxyglutaric acid is rapidly dehydrogenated if NAD+ is added as a co‐factor to the standard reaction medium. This could also be demonstrated in human liver. The preliminary evidence for this enzyme activity in rats and humans,l‐2‐hydroxyglutaric acid dehydrogenase, is given. Further investigations are required to clarify the possible relevance to the metabolic defect inl‐2‐hydroxyglutaric acidaemia.
A Model for Northern Hemisphere Continental Ice Sheet Variation
Authors: Johnson R.G. , McClure B.T. 
Published: December 2004

The marine record shows that over the last 350 ka Northern Hemisphere ice sheet volumes have fluctuated widely and only on rare short occasions have they been reduced to the present interglacial state. The fluctuations are well synchronized with hemispheric average summer insolation variations of 20 ka periodicity caused by changing orbital parameters. The development of a model which explains the varied amplitudes of the fluctuations and is consistent with the geological record embodies the following arguments: The transition from an interglacial state like today's to a glacial state is initiated when a summer insolation deficit causes a southerly extension of the North Atlantic-Arctic pack ice to 60°N latitude. The extension alters the subpolar low pressure patterns and thus causes a southward diversion of the European Gulf Stream flow. It also produces an enhanced warm West Greenland current. This current causes open seas as far north as Baffin Bay which provides moisture for rapid northern Laurentide ice sheet growth. After several glacial fluctuations driven by insolation variations, the southern Laurentide ice front may reach an extreme extension. This diverts the westerlies and the Gulf Stream thus weakening a dominant subpolar North Atlantic gyre and consequently producing a prolonged cutoff of the West Greenland current and a reduction of high latitude glacial precipitation. The subsequent high insolation can then melt back the eastern pack ice and restore the northern European Gulf Stream. This warms the high latitudes for a time sufficient to melt the continental ice, thus causing the transition back to the interglacial state.An analysis of the record in the context of model suggests that the threshold deficit in average summer insolation that is required to initiate major glacial growth is influenced by the cooling effect of the Greenland ice cap on the seas to the east. The threshold level under conditions like today's is found to lie between −7 and −17 ly/day relative to the present. This threshold will not be crossed for at least 54 millenia due to an interval of smaller orbital eccentricity. Probable melting of the Greenland ice cap about 30 ka AP would ensure the extension of the present interglacial beyond 120 ka AP.
Proneofiber, a New Genus of Vole (Cricetidae: Rodentia) from the Pleistocene Seymour Formation of Texas, and its Evolutionary and Stratigraphic Significance
Authors: Hibbard Claude W. , Dalquest Walter W. 
Published: December 2004

AbstractA new genus and species of a microtine rodent, Proneofiber guildayi, is named on the basis of rooted teeth with cement from the warm Gilliland local fauna, Seymour Formation of Pleistocene age, Knox County, Texas. Proneofiber guildayi is considered to be ancestral to Neofiber, the round-tailed water rat, now living in the extreme southeastern United States. The presence of Pleistocene faunas prior to the first continental glaciation and the existence of three Pearlette-like volcanic ashes in the Plains Region suggest a revision of the age assignment of Pleistocene deposits from the nonglaciated region.
Correlation of the Quaternary Terrace Sequence in the Lower Rhine Valley and Northern Alpine Foothills of Central Europe
Authors: Brunnacker Karl , Löscher Manfred , Tillmanns Wolfgang , Urban Brigitte 
Published: December 2004

AbstractThirteen glacial terraces are known from the western part of the northern Alpine foothills between the Lech and Iller Rivers. In the Lower Rhine region of West Germany, a similar number of terraces are capped by interglacial floodloams and soils. Whereas the environment during individual interglaciations did not differ substantially, the glaciations were progressively more severe. The Main Terrace system of the Rhine may be an exception. The duration of the Quaternary, starting at the base of Praetiglian, is estimated at approximately 2 million yr by paleomagnetic dating. The major cold-warm climatic cycles of the earliest Pleistocene lasted approximately 100,000 yr, the same as those of the Brunhes Chron. The intervening Main Terrace system has not yet been climatically subdivided. Correlation with the Netherlands is possible because of an abundance of paleobotanic and paleomagnetic evidence. In the Alpine foothills, stratigraphically useful indicators of warm climates are missing, but analogies in terrace development permit comparison with the Lower Rhine and Danube. The terrace sequence in the Alpine foothills is incomplete, as are those along most of the other rivers in Europe. Some of the older terraces may have been eroded.
Sea-Level Estimates during the Last Deglaciation Based on δ18O and Accelerator Mass Spectrometry 14C Ages Measured in Globigerina bulloides
Authors: Bard Edouard , Fairbanks Richard , Arnold Maurice , Maurice Pierre , Duprat Josette , Moyes Jean , Duplessy Jean-Claude 
Published: December 2004

AbstractCoupled measurements of δ18O and accelerator mass spectrometry (AMS) 14C in a particular species of planktonic foraminifera may be used to calculate sea-level estimates for the last deglaciation. Of critical importance for this type of study is a knowledge of the seasonality of foraminiferal growth, which can be provided by δ18O measurements of modern shells (core tops, plankton tows). Isotopic (δ18O, AMS-14C dating) and faunal records (transfer function sea surface temperature) were obtained from two cores in the North Atlantic at about 37°N. The locations were chosen to obtain high sedimentation rate records removed from the major ice-melt discharge areas of the last deglaciation. Based upon Globigerina bulloides data, four δ18O-based sea-level estimates were calculated: −67 ± 7 m at 12,200 yr B.P. and −24 ± 8 m at about 8200 yr B.P. for core SU 81-18; −83 ± 10 m at 12,200 yr B.P. and −13 ± 11 m at about 8500 yr B.P. for core SU 81-14. Using a second working hypothesis concerning the seasonability of G. bulloides growth, it is suggested that the sea-level rose by about 40 m during the millennium which followed 14,500 yr B.P.
Paleoecology of Late-Glacial Peats from the Bering Land Bridge, Chukchi Sea Shelf Region, Northwestern Alaska
Authors: Elias Scott A. , Short Susan K. , Phillips R. Lawrence 
Published: December 2004

AbstractInsect fossils and pollen from late Pleistocene nonmarine peat layers were recovered from cores from the shelf region of the Chukchi Sea at depths of about 50 m below sea level. The peats date to 11,300−11,000 yr B.P. and provide a limiting age for the regional Pleistocene-Holocene marine transgression. The insect fossils are indicative of arctic coastal habitats like those of the Mackenzie Delta region (mean July temperatures = 10.6–14°C) suggesting that 11,000 yr ago the exposed Chukchi Sea shelf had a climate substantially warmer than modern coastal regions of the Alaskan north slope. The pollen spectra are consistent with the age assignment to the Birch Interval (14,000–9000 yr B.P.). The data suggest a meadow-like graminoid tundra with birch shrubs and some willow shrubs growing in sheltered areas.
General practitioners' detection and management of patients with a dual diagnosis: Implications for education and training
Authors: MARSHALL KELLIE L. , DEANE FRANK P. 
Published: November 2004

AbstractGeneral practitioners (GPs) are in a unique position to detect and manage patients with co‐morbid mental health and substance use disorders (dual diagnosis). It has been estimated that over 30% of patients presenting to general practice have a diagnosable mental disorder and 12% have dual diagnosis. Unfortunately, between 30 and 50% of these problems go undetected in general practice. Limited GP education and training in mental health may account for this deficit, with a little over 8% of GPs receiving any formal postgraduate training in mental health. Prior to developing an educational resource for GPs, the present study aimed to establish baseline estimates of GP treatment practices with patients who have dual diagnosis. Two GP division‐wide surveys of screening, assessment and treatment for dual diagnosis were conducted one year apart. In addition, five GPs conducted a clinical audit of 508 patient consultations. Results indicate that without ongoing targeted interventions, patient management activities such as GP counselling, use of screening devices, referral to specialist services, coordination and use of EPC items are not likely to improve and are at risk of declining.
Implementing integrated treatment for co‐existing substance use and severe mental health problems in assertive outreach teams: training issues
Authors: GRAHAM HERMINE L. 
Published: November 2004

AbstractThis study sought to evaluate systematically training and implementation of a specific integrated treatment approach for co‐occurring problem substance use and mental health within existing assertive outreach (AO) teams. The AO team was treated as a whole unit rather than as individual clinicians. They were provided with training and supervision to deliver a cognitive‐behavioural integrated treatment approach. In a quasi‐experimental time‐lag design three teams were trained immediately and two others after an 18‐month delay. There was evidence that teams acquired confidence and skills relevant to working with combined problems and that these gains were maintained over time. These results were replicated in the two teams trained after the delay. This study suggests that training mental health staff to use an integrated treatment approach is well Recieved and produces lasting changes in confidence and skills. However, there are a number of issues related to staff training, shifting attitudes and implementation of integrated approaches into routine mental health practice. These issues are considered and suggestions made for staff training.