Neurodegeneration with features of NIFID and ALS--extended clinical and neuropathological spectrum.

Heterogeneous clinical and neuropathological features have been observed in the recently described neuronal intermediate filament inclusion disease (NIFID). The immunohistological findings common to all cases are alpha-internexin and neurofilament-positive neuronal cytoplasmic inclusions, which have not been found in comparable density in other neurodegenerative disorders. Notwithstanding these common features, the cases reported so far have shown differences concerning age at onset, constellation and dominance of symptoms as well as type and distribution of additional neuropathological findings. Here we present the first NIFID case that exhibits severe involvement of lower motor neurons. Also, this patient may have had a clinical onset of disease in early childhood, as she was diagnosed as having dysarthria, which could not be attributed to any other cause at the age of 3 years. This case is a further contribution to the spectrum of this novel neurodegenerative disease.

Expression of the high-affinity fluoropyrimidine-preferring nucleoside transporter hCNT1 correlates with decreased disease-free survival in breast cancer.

PURPOSE: Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response. METHODS: We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples. RESULTS: Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis. CONCLUSIONS: These results indicate that the expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy.

[Skin ulceration after leflunomide treatment in two patients with rheumatoid arthritis]. / Hautulzerationen nach Leflunomid Therapie bei zwei Patienten mit rheumatoider Arthritis.

Leflunomide is a disease-modifying antirheumatic drug for the treatment of active rheumatoid arthritis and psoriatic arthritis. Skin ulcerations are not listed as a side effect for this drug, and there has been only one case report on leflunomide associated skin ulcerations. We report on two females, 59 and 63 years old respectively, who were treated with leflunomide for rheumatoid arthritis and subsequently developed severe skin ulcerations. After discontinuation of the drug the skin ulcerations healed complete even if very slowly.