Pasquale Madonna

Homozygous C677T Mutation of the 5,10 Methylenetetrahydrofolate Reductase Gene and Hyperhomocysteinemia in Italian Patients With a History of Early-Onset Ischemic Stroke

To the Editor: Case-control1 2 and prospective3 4 studies have suggested an association between moderate hyperhomocysteinemia and risk of ischemic stroke. Homozygosity for the C-to-T substitution at nucleotide 677 of the gene of 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with a 50% reduction of the activity of this enzyme5 and is the most common inherited cause of moderate hyperhomocysteinemia. In 1996 Klujitmans et al6 reported a threefold increase in the risk of early-onset cardiovascular disease in homozygotes for the C677T MTHFR mutation. However, the association of this genetic marker with arterial vascular events has been disputed by a nested case-control study.7 Markus et al8 recently failed to show an association between cerebrovascular disease and the MTHFR genotype, a comparable prevalence of homozygosity for the C677T MTHFR mutation being detectable in a population of 345 patients with ischemic stroke or transient ischemic attacks (TIA) and in 161 control subjects (10.7% versus 13.7%, respectively). Nor were nonfasting log homocysteine plasma levels able to identify subjects with a stroke history in that setting, as judged by the analysis of a subgroup of patients (n=160) and control subjects (n=75) in whom this amino acid was measured. However, as expected, the authors found a significant relationship between MTHFR genotype and homocysteine levels, the latter being also independently related to log serum folate. In the frame of a larger study on juvenile thrombotic events, we have evaluated a population of 60 consecutive patients with a history of early-onset ischemic stroke (29 females and 31 males, aged 5 to 64 years [mean age, 38; mean age at time of diagnosis, 34; range 4 to 49 years]) documented within 72 to 96 hours from the event by CT and/or MRI scans. Subjects who had suffered from TIA or who exhibited abnormalities of carotid …

Severe pancytopenia and intrahepatic cholestasis in a patient with a history of Hodgkin’s disease.: Responsiveness to high-dose pulse steroid therapy and diagnosis of a late relapse

A 47-year-old male, treated 7 years earlier for Hodgkins disease (HD), was admitted with persistent fever, liver enlargement, and increased cholestasis parameters. He developed acute bone marrow failure and progressive worsening of his clinical condition and cholestasis markers without showing evidence of HD recurrence or second malignancy. High-dose intravenous pulse methylprednisolone therapy was given, after which resolution of pyrexia and progressive improvement in performance status and in hematological counts and cholestasis parameters were observed. During this phase, a bone biopsy showed HD marrow infiltration. This clinical course may reflect tumor cytokine-induced phenomena, significantly affected by high-dose steroids.