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  • 1
    Electronic Resource
    Electronic Resource
    Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency (1999)
    Springer
    European journal of pediatrics 158 (1999), S. 734-739 
    Details
    ISSN: 1432-1076
    Keywords: Key words Haemolytic uraemic syndrome ; Pulmonary hypertension ; Cobalamin ; Methylcobalamin ; Methionine synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. Conclusion A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051190
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  • 2
    Electronic Resource
    Electronic Resource
    Remethylation defects: guidelines for clinical diagnosis and treatment (1998)
    Springer
    European journal of pediatrics 157 (1998), S. S77 
    Details
    ISSN: 1432-1076
    Keywords: Key words Homocysteine metabolism ; Folate metabolism ; Vitamin B12 metabolism ; Methylmalonic aciduria ; Betaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The main remethylation defects include disorders which all have defective methionine synthesis in common. Methylenetetrahydrofolate reductase deficiency impairs methyltetrahydrofolate synthesis, defects in cytosolic reduction of hydroxocobalamin (CblC/D) impair the synthesis of both methyl- and adenosyl cobalamin and deficiencies of methionine synthase (CblE/G) are associated with defective methyl cobalamin synthesis. The clinical presentation is characterized by acute neurological distress in early infancy. In childhood, patients present with progressive encephalopathy with an end-stage which has many signs in common with the adult onset form. In fact, both have more or less severe signs of subacute degeneration of the cord. Cobalamin defective patients must be treated with parenteral supplementation of hydroxocobalamin (1–2 mg per dose). Some methylenetetrahydrofolate patients could be folate responsive and must have a high-dosage folate trial. In addition, oral betaine supplementation (2–9 g per day depending on age) appears an effective means to prevent further neurological deterioration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014307
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetic comparison of leucovorin and levoleucovorin (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 569-573 
    Details
    ISSN: 1432-1041
    Keywords: Leucovorin ; l-leucovorin folates pharmacokinetics isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic values of d,l-leucovorin and l-leucovorin were compared in eight healthy volunteers following oral administration of 25 mg d,l-leucovorin and 12.5 mg l-leucovorin. Serum levels of l-5-for-myltetrahydrofolate, l-5-methyltetrahydrofolate, and total reduced folates were measured by an established microbiological method. Pharmacokinetic data for both preparations were consistent with those previously reported for d,l-leucovorin, with essentially complete first pass metabolism to l-5-methyltetrahydrofolate, the active metabolite. No differences were found between the two preparations in serum concentrations of active folate fractions, AUC, or Cmax, or in clearance and volume of distribution estimates. These data suggest that after administration of 25 mg of d,l-leucovorin, the d-diastereoisomer has no significant effect on the standard pharmacokinetic measurements of the active l-folates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02440861
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  • 4
    Electronic Resource
    Electronic Resource
    Study of folate in psoriasis: blood levels, intestinal absorption and cutaneous loss (1973)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 89 (1973), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serum, red cell and squame folate content have been measured in fifty cases of psoriasis with extensive lesions. Reduced serum and red cell folate have been found in 44% of the patients. Folic acid absorption, studied in twenty-six patients, was impaired in four and significantly increased in all the others.Squame folate content has been found too low to explain the folate deficiency. Malabsorption is a possible hypothesis but it occurs too rarely (four cases). The most likely explanation of folate deficiency seems to be an increased utilization of folate by the skin epidermal cells as a result of the rapid turnover rate.The increased absorption found in most cases investigated could be a compensatory mechanism to equilibrate folate balance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1973.tb02987.x
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  • 5
    Electronic Resource
    Electronic Resource
    A study of the mechanisms of cytotoxicity of Ara-C on three human leukemic cell lines (1989)
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 251-255 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The main biochemical determinants involved in cytosine arabinoside (Ara-C) metabolism were studied in one lymphoblastic (Reh) and two myeloid (HL60 and K562) human leukemic cell lines exhibiting various sensitivities to Ara-C, Reh being the most and HL60 the least sensitive. The level of intracellular Ara-C accumulation and Ara-CTP formation was far more important in Reh cells than in myeloid cell lines but was not closely related to deoxycytidine kinase activity or to deoxycytidine triphosphate pool size. The level of Ara-C incorporated into DNA was similar in the three cell lines. Ara-CTP formation correlated better with the cytotoxicity to clonogenic cells than did Ara-C incorporation into DNA. DNA polymerase α was moderately inhibited to various degrees, depending on the cell line; this moderate inhibition does not seem sufficient to explain the inhibition of DNA synthesis. The activity of DNA ligase, the enzyme joining the Okazaki fragments, which was not detected in Reh cells, was strongly inhibited by Ara-C in HL60 and to a lesser degree, in K562 cells. The inhibition of DNA ligase probably also contributes to the inhibition of DNA synthesis and, thus, to the cytotoxic effect of Ara-C and may explain the smaller size of DNA fragments observed following Ara-C treatment. The variations in each critical determinant observed in these three cell lines increase the complexity and plurality of the mechanisms of Ara-C action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257628
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  • 6
    Electronic Resource
    Electronic Resource
    Prophylaxis of folate deficiency in acutely ill patients: results of a randomized clinical trial (1988)
    Springer
    Intensive care medicine 14 (1988), S. 640-645 
    Details
    ISSN: 1432-1238
    Keywords: Serum folate ; Erythrocyte folate ; Folinic acid ; Acute ill patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A trial was carried out of prophylaxis of folate deficiency in 105 acutely ill patients immediately following admission to an ICU with evaluation of folate status. These patients were fed either orally or by enteral or parenteral nutrition. Three groups were established regardless of the type of nutrition: Group 1 received 5 mg/day parenteral folinic acid; Group 2 received 50 mg/week parenteral folinic acid;-Group 3 received no parenteral folinic acid. Before treatment, 19% of the patients presented very low serum folate levels (less than 2.7 ng/ml). Two of them developed acute folate deficiency with severe hematological disturbances quite reversed with folinic acid. Folate levels were inversely correlated with the severity of the clinical status and were lower in septic and feverish patients. The effect of folinic acid administration was assessed after seven days of treatment: daily administration of 5 mg folinic acid appeared to be the best regiment with normalization of serum folate levels in all cases; results appeared to be better than with 50 mg once weekly. Oral and enteral administration of folate supplies considered to be physiological (300 μg/day folic acid) did not appear to be sufficient to normalize in all cases blood folate levels in these acutely ill patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00256769
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  • 7
    Electronic Resource
    Electronic Resource
    “Folate-losing gastropathy” and intestinal folate absorption in patients with Ménétrier's disease (giant hypertrophic gastritis) (1978)
    Springer
    Digestive diseases and sciences 23 (1978), S. 143-147 
    Details
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The gastric loss of serum nonprotein components, such as vitamins has not been, to our knowledge, demonstrated in Ménétrier's disease (MD). The intestinal absorption and the gastric leakage of folic acid were investigated in 4 patients with documented MD; in each case there was an increased gastric clearance of plasma proteins as demonstrated by51Cr-labeled albumin tests. All the patients had a low serum level of folate and a flat curve of serum folate concentrations after an oral load of folic acid. The gastric loss of folate was determined in the patients and in 5 control subjects from the folate concentrations (before and after an intravenous injection of folinic acid) in basal and histamine-stimulated gastric secretion. A significant increase in concentrations and outputs of folate in gastric juice was observed in MD patients compared to controls, before as well as after gastric stimulation. None of the patients had abnormalities in jejunal morphology or in xylose absorption. The present study shows that folic acid should be added to the list of serum components which may be lost in excess into the gastric lumen in MD patients. The responsibility of this “folate-losing gastropathy” in the folate deficiency which may be observed in MD patients has to be discussed in relation to associated abnormalities in small-intestinal transport of folate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01073190
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