Mechanism of Triamterene-Induced Megaloblastosis

Corcino, José J.; Waxman, Samuel; Herbert, Victor

doi:10.7326/0003-4819-73-3-419

Cited by 48 publications

(13 citation statements)

References 15 publications

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“…Previous workers have reported abnormal dU suppression in patients treated with 5-fluorouracil a) and with the dihydrofolate reductase inhibitors methotrexate (Metz et al, 1968), pyrimethamine (Waxman and Herbert, 1969 a), triamterene (Corcino et al, 1970), and trimethoprim (Herbert et al, 1973;Koutts et al, 1973). Apart from these few situations an abnormal dU suppression test result appears to be specific for vitamin B12 or folate deficiency.…”

Section: Discussionmentioning

confidence: 95%

“…The biochemical basis of this phenomenon was discussed by Metz et al (1968). Though dU suppression tests have been performed on small groups of patients with a few selected abnormalities (Waxman and Herbert 1969 a, b;Corcino et al, 1970;Van der Weyden et al, 1972;Koutts et al, 1973) there has been no study of the specificity and usefulness of this test in the diagnosis of vitamin B12 or folate deficiency when performed as a routine procedure.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Deoxyuridine Suppression Test in Diagnosis of Vitamin B12 or Folate Deficiency

Wickramasinghe¹,

Longland²

1974

BMJ

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Assessment of Deoxyuridine Suppression Test in Diagnosis of Vitamin B12 or Folate Deficiency

Wickramasinghe¹,

Longland²

1974

BMJ

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“…Abnormally high dU-suppressed values have been previously reported in vitamin B12-or folate-deficient patients [2, 5, 9, 13] and in patients re ceiving the dihydrofolate reductase inhibitors methotrexate [7], pyrime thamine [7], triamterene [1] and trimethoprim [2,3]. In the present study, most of the marrow aspirates which gave high dU-suppressed values came from patients who were deficient in either vitamin B 12 or folate.…”

Section: Discussionmentioning

confidence: 53%

Results of Three Years’ Experience with the Deoxyuridine Suppression Test

Wickramasinghe

Saunders²

1977

Acta Haematol

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The results of deoxyuridine (dU) suppression tests performed on 400 marrow samples aspirated over a 3-year period are summarised. High dU-suppressed values were found in all patients with vitamin B₁₂ or folate deficiency, in some patients receiving inhibitors of dihydrofolate reductase, in 4 of 19 epileptics receiving anticonvulsants and in 2 of 21 patients with iron deficiency anaemia. High dU-suppressed values were found even in those vitamin B₁₂- or folate-deficient patients who had serum vitamin B₁₂ and red cell folate levels within the normal range. Conversely, some patients with subnormal serum vitamin B₁₂ levels (including 1 on high doses of penicillin, 1 on anticonvulsant therapy and 2 vegans) and some patients with subnormal red cell folate levels gave normal dU-suppressed values, and were considered not to suffer from the metabolic consequences of vitamin B₁₂ or folate deficiency. All of the patients with megaloblastic erythropoiesis induced by the anti-purine drugs or cyclophosphamide, 4 patients with megaloblastic erythropoiesis associated with primary acquired sideroblastic anaemia, a chronic myeloproliferative disorder or subacute erythraemic myelosis and a proportion of the patients with megaloblastic erythropoiesis associated with anticonvulsant therapy, chronic alcoholism, acute myeloid leukaemia or myelomatosis also gave normal dU-suppressed values. The addition of 1 μg cyanocobalamin per millilitre of marrow culture together with the deoxyuridine caused a significant reduction in the dU-suppressed value in 86% of vitamin B₁₂-deficient patients and the addition of 10 μg pteroylglutamic acid per millilitre of marrow culture caused a significant reduction in 91% of folate-deficient and 57% of vitamin B₁₂-deficient patients.

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“…Those from the RNHRD have been confirmed, by a rheumatologist, as having AS according to the New York criteria. 2 The diagnosis of AS in the overall patient population has been validated in three separate cohorts in which 100% of 146 patients had AS (personal communications M Brown, Oxford), 92.7% of 330 patients had AS (personal communications K Gomez, Bath), and 96% of 50 patients had AS. 3 Data were available for 39 pairs in which both mother and oVspring had AS (21 mother:daughter pairs, 18 mother:son pairs).…”

mentioning

confidence: 99%

Methotrexate and triamterene---a potentially fatal combination?

Richmond

Ogden

et al. 1997

Annals of the Rheumatic Diseases

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Maternal age and the risk of developing ankylosing spondylitisWe read with interest the article by Weinreich and colleagues.1 They showed that transgenic mice born to mothers aged 8 months or older had a significantly lower frequency of murine ankylosing enthesopathy than mice born to younger mothers. They speculated that an age related increase in maternal antibody levels resulted in increasing protection of oVspring against a ubiquitous, potentially arthritogenic, micro-organism. In humans, as in the mouse model, environmental factors must influence the development of ankylosing spondylitis (AS). We sought evidence that the age of conception in women with AS influenced the risk of their oVspring developing disease.We collected data from 3473 patients with AS, regarding the age, and AS status, of relatives. Nine hundred and sixty two were female, male: female ratio 2.6:1. Six hundred and sixty five were recruited from the Royal National Hospital for Rheumatic Diseases (RNHRD), 2779 from the National Ankylosing Spondylitis Society (NASS), and 29 were relatives of RNHRD patients or NASS members, but were not RNHRD patients or NASS members themselves. Those from the RNHRD have been confirmed, by a rheumatologist, as having AS according to the New York criteria.2 The diagnosis of AS in the overall patient population has been validated in three separate cohorts in which 100% of 146 patients had AS (personal communications M Brown, Oxford), 92.7% of 330 patients had AS (personal communications K Gomez, Bath), and 96% of 50 patients had AS.3 Data were available for 39 pairs in which both mother and oVspring had AS (21 mother:daughter pairs, 18 mother:son pairs). There were no families with data available for more than one mother:child pair. The higher than expected ratio of mother:daughter to mother:son pairs is the subject of an ongoing investigation. From our data base we chose 39 control pairs, where the mother had AS and the oVspring did not, by matching the oVspring for sex and age to the nearest year. We were able to match the oVspring for birth rank in 37 cases (20 mother:daughter pairs, 17 mother:son pairs). The oVspring were not matched for sibship size. The maternal ages at birth of oVspring are shown (see table 1). Using paired t tests, we compared maternal ages at childbirth in the groups where the oVspring had AS, and where the oVspring did not have AS. The diVerence in the maternal age at childbirth was significant only when comparing mothers of sons with AS and mothers of sons without AS (p = 0.04; diVerence in mean maternal age at childbirth = 2.78 years). Mothers with AS, whose sons had AS, had given birth at a older age than those whose sons did not have AS.Unlike the situation in the murine model, we find no evidence that increasing maternal age in humans is protective against the development of AS. However, the number of pairs available for our analysis was small. The influence of age at conception, on the development of AS in the oVspring, remains an interesting area that deserves further attentio...

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Mechanism of Triamterene-Induced Megaloblastosis

Cited by 48 publications

References 15 publications

Assessment of Deoxyuridine Suppression Test in Diagnosis of Vitamin B12 or Folate Deficiency

Assessment of Deoxyuridine Suppression Test in Diagnosis of Vitamin B12 or Folate Deficiency

Results of Three Years’ Experience with the Deoxyuridine Suppression Test

Methotrexate and triamterene---a potentially fatal combination?

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