Refractory Intestinal Behçet-Like Disease Associated with Trisomy 8 Myelodysplastic Syndrome Resolved by Parenteral Nutrition.

Intestinal Behçet disease (BD), associated with myelodysplastic syndrome (MDS), is often refractory to treatment. An 80-year-old man with trisomy 8 MDS (refractory anemia) developed intermittent fever. Despite investigations to exclude infectious disease, autoimmune disease, and malignancy as the cause of the fever, the etiology could not be determined. A colonoscopy revealed several shallow round ulcers in the ileocecal region and ascending colon, and the biopsy specimens showed nonspecific inflammation. Thereafter, the patient experienced abdominal pain and diarrhea. Other than an oral aphthous ulcer, the patient did not show symptoms to meet the diagnostic criteria for BD. The patient was diagnosed with intestinal ulcers (intestinal BD-like disease) with MDS and trisomy 8. After treatment failure with 5-aminosalicylic acid, steroid, colchicine, and azacitidine, cerebral infarction occurred. Eating was difficult because of the patient's impaired consciousness; hence, total parenteral nutrition (TPN) was commenced. The fever and abdominal symptoms improved with bowel rest over approximately 1 month. Small amounts of food were orally administered to the patient following recovery from the after-effects of the cerebral infarction, but diarrhea and fever repeatedly flared up. Therefore, TPN was continued at home. The patient has not experienced any further intestinal BD symptoms for approximately 1 year with bowel rest. Nutritional therapy, including bowel rest, may be an effective treatment option for intestinal BD with MDS, and might be used as an induction therapy of remission or a supportive therapy for other treatments.

Immunological Correlates of Prevention of the Onset of Seasonal H3N2 Influenza.

On influenza virus infection or vaccination, immune responses occur, including the production of antibodies with various functions that contribute to protection from seasonal influenza virus infection. In the current study, we attempted to identify the antibody functions that play a central role in preventing the onset of seasonal influenza by comparing the levels of several antibody titers for different antibody functions between 5 subclinically infected individuals and 16 patients infected with seasonal H3N2 virus. For antibody titers before influenza virus exposure, we found that the nAb titers and enzyme-linked immunosorbent assay titers against hemagglutinin and neuraminidase (NA) proteins in the subclinically infected individuals were significantly higher than those in the patients, whereas the NA inhibition titers and antibody-dependent cellular cytotoxicity activities did not significantly differ between subclinically infected individuals and infected patients. These results suggest that nAb and enzyme-linked immunosorbent assay titers against hemagglutinin and NA serve as correlates of symptomatic influenza infection.

CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study.

Tacrolimus is metabolized by CYP3A and has highly variable pharmacokinetics. To study the factors contributing to this high variability in pharmacokinetics and to investigate the possibility of genotype-specific clinical applications, the effect of differing CYP3A5 genotypes on the intrasubject coefficients of variation for tacrolimus was investigated. Genotyping for CYP3A5*3 was performed in healthy volunteers who had previously participated in the pharmacokinetic study of 2 tacrolimus formulations with a 2 x 2 cross-over design. Intrasubject coefficients of variation calculated from analysis of variation in CYP3A5*1/*1+*1/*3 (n = 16) and CYP3A5*3/*3 (n = 13) groups were compared. The intrasubject CVs of AUClast and Cmax in the CYP3A5*3/*3 group were about 41.1% and 52.4% greater than those in the CYP3A5*1*1+*1/*3 group. The estimated total sample size for the bioequivalence study of tacrolimus with a 2 x 2 cross-over design was increased by 93.3% for AUClast (n = 30 versus 58) and 121.4% for Cmax (n = 28 versus 62) in the CYP3A5*3/*3 group compared with the CYP3A5*1/*1+*1/*3 group. The intraindividual variability of tacrolimus PK parameters may be associated with the CYP3A5 genotype. We propose that genotyping for CYP3A5 will provide a more efficient approach for bioequivalence designs and therapeutic drug monitoring.