Reversible encephalopathy following 5-fluorouracil-based chemotherapy in patients with dihydropyrimidine dehyrogenase deficiency

5-fluorouracil (5-FU) is one of the most frequently used chemotherapy agents for the treatment of a number of solid cancers. We report two patients with advanced gastric cancer who developed acute encephalopathy after receiving chemotherapy composed of 5-FU and oxaliplatin. One patient presented with altered consciousness and the other with generalized tonic clonic seizure. 5-FU-induced encephalopathy was suspected by clinical, radiological and electroencephalographic findings, and both patients had reduced expression of dihyropyrimidine dehydrogenase, the rate-limiting enzyme responsible for the catabolism of 5-FU. The neurological symptoms improved spontaneously, and did not recur in the following cycle of chemotherapy with the administration of a reduced dose of 5-FU. We suggest that the early recognition of this adverse event can reverse 5-FU-induced neurological symptoms and a dose reduction of the offending drug can prevent the recurrence of 5-FU induced encephalopathy.     

Doxorubicin-induced platelet cytotoxicity: a new contributory factor for doxorubicin-mediated thrombocytopenia

Summary.  Background: Doxorubicin (DOX) is a widely used anticancer drug for solid tumors and hematologic malignancy, but its active use is hampered by serious adverse effects, including thrombocytopenia. Although bone marrow toxicity of DOX has been suggested to be the sole mechanism underlying the reduced platelet counts, the direct effects of DOX on platelets have never been examined. Objective: Here, we investigated the DOX-induced platelet cytotoxicity and its underlying mechanism in an effort to elucidate the contribution of platelet cytotoxicity to DOX-induced thrombocytopenia. Results: In freshly isolated human platelets, DOX induced platelet cytotoxicity in a time-dependent and concentration-dependent manner. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent protein thiol depletion were shown to underlie the DOX-induced platelet cytotoxicity. Conspicuously, DOX-treated platelets displayed apoptotic features such as caspase-3 activation, reduced mitochondrial transmembrane potential, and phosphatidylserine exposure. Decreased glutathiolation of procaspase-3 was shown to be a link between protein thiol depletion and caspase-3 activation. It is of note that DOX-mediated platelet cytotoxicity was significantly enhanced by shear stress, a common complicating factor in cancer patients. These in vitro results were further confirmed by an in vivo animal model, where administration of DOX induced a platelet count decrease, ROS generation, caspase-3 activation, protein thiol depletion, and damaged platelet integrity. Conclusion: We demonstrated that DOX can directly induce platelet cytotoxicity through ROS generation, decreased glutathione levels, and protein thiol depletion. We believe that this study provides important evidence for the role of DOX-induced platelet cytotoxicity in the development of thrombocytopenia in DOX-treated patients.     

Case of regional lymphomatoid papulosis confined to the periorbital areas

A localized form of lymphomatoid papulosis (LyP) has been described very rarely. A 38-year-old Korean man presented with a single bean-sized, non-tender, erythematous nodule confined to periorbital areas with three recurrences over a 2-year duration. With findings of biopsy, immunohistochemical staining and T-cell receptor gene rearrangement, LyP was diagnosed. We report a case of CD30 (Ki-1)-positive LyP which developed recurrently and was confined to the periorbital areas.     

Prevalence of hypouricaemia and SLC22A12 mutations in healthy Korean subjects

Aim: Mutations in the SLC22A12 gene, which encodes a uric acid transporter, URAT1, are associated with renal hypouricaemia. This study was designed to measure serum uric acid (Sua) levels and allele frequencies of two common mutations in SLC22A12, W258X and R90H, in healthy Korean subjects. Methods: A total of 909 unrelated Korean adults (male : female, 1:1.23; mean age, 48.4 ± 11.0 years) were recruited among those who had taken a routine health check-up in a health centre in 2003. None of them had hypertension, diabetes mellitus, kidney diseases or liver diseases. Genotyping for W258X and R90H was performed using the TaqMan method. Results: The prevalences of hyperuricaemia (Sua levels, >416 µmol/L) and hypouricaemia (Sua levels, <178 µmol/L) were 4.6% and 3.3%, respectively. A marked male preponderance in the hyperuricaemic group was noted, and the men revealed higher Sua than the women. The Sua showed a positive correlation with serum creatinine level and blood pressure. In the hypouricaemic group, the allele frequencies of W258X and R90H were 11.7% and 6.7%, respectively, and the proportion of subjects with one or both of the mutant alleles was 33.3%. Hyperuricaemic subjects never had either mutation. Conclusion: The W258X and/or R90H mutations in the SLC22A12 gene are one of the major factors responsible for hypouricaemia, and one-third of the hypouricaemic subjects had one or both of the mutant alleles.     

The Evaluation of Relevant Factors Influencing Skin Graft Changes in Color Over Time

BACKGROUND Objective studies evaluating the relevant factors that affect skin graft changes in color over time have yet to be published.
OBJECTIVE Therefore, the patterns of the grafted skin's color changes and the presence of relevant factors were analyzed statistically.
MATERIALS AND METHODS The study included 107 skin grafts in 107 subjects. Using a chromameter, the colors of skin graft, the area adjacent to the recipient site, and the donor site were measured. The grafted skin's color changes and the color difference were analyzed with respect to several factors.
RESULTS Over time, the grafted skin became lighter, redness decreased, yellowness increased, and the color difference decreased. As the donor site was lighter, the grafted skin was lighter and less red. The grafted skin was lighter in females than in males. The skin graft type was not related to the lightness and the redness. The grafted skin was lightest in the upper arm and darkest in the lower leg. The grafted skin was lighter in Fitzpatrick Skin Type III, followed by Type IV and then Type V.
CONCLUSION The factors that affected the skin graft's lightness were time, the lightness of the donor, sex, the hand, the foot, and Fitzpatrick skin type.