A 45-year-old female patient received oral methimazole and propylthiouracil for hyperthyroidism. The drug was discontinued 2 weeks later due to methimazole-induced agranulocytosis. About 1 month later, the patient was re-given methimazole 10 mg thrice daily according to the doctor′s instructions and advice. She developed high fever and chills about 2 hours after the first administration and half on after the second administration, respectively, with a maximum body temperature of 39.5 ℃. The laboratory tests showed WBC 5.99×10 9/L, neutrophil 0.91, C-reactive protein 2.3 mg/L, and negative bacterial blood culture. Drug fever caused by methimazole was considered. Methimazole was stopped and symptomatic treatment was given. Four and a half hours later, the patient′s body temperature dropped to 36.5 ℃. At 1 year of follow-up, the patient did not take methimazole again, and neither high fever nor chills recurred.

A 45-year-old female patient received oral methimazole and propylthiouracil for hyperthyroidism. The drug was discontinued 2 weeks later due to methimazole-induced agranulocytosis. About 1 month later, the patient was re-given methimazole 10 mg thrice daily according to the doctor′s instructions and advice. She developed high fever and chills about 2 hours after the first administration and half on after the second administration, respectively, with a maximum body temperature of 39.5 ℃. The laboratory tests showed WBC 5.99×10 9/L, neutrophil 0.91, C-reactive protein 2.3 mg/L, and negative bacterial blood culture. Drug fever caused by methimazole was considered. Methimazole was stopped and symptomatic treatment was given. Four and a half hours later, the patient′s body temperature dropped to 36.5 ℃. At 1 year of follow-up, the patient did not take methimazole again, and neither high fever nor chills recurred.

OBJECTIVETo investigate the expression level of COX-2, p16(INK4A) and p53 in patients with classic Hodgkin's lymphoma (cHL), and to evaluate their correlation with prognosis.

METHODSThe clinical data and samples of 52 cHL cases were collected. Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state. Correlation between the protein expression and prognosis of patients was analyzed.

RESULTSOf 52 cases, the male and female ratio was 1.6∶1, the age was from 22 to 68 years old. All lesions located primarily in lymph nodes. All samples from 52 cases were stained with COX-2, p16(INK4A) and p53, and the positive expression of COX-2 was found in 28 cases (53.8%）, that of p16(INK4A) in 25 cases (48.1%)and p53 in 42 cases (80.8%）. All patients were divided into two groups according to differences in age (<40 years/ ≥ 40 years), gender (male/female), EBV infection (yes/no), B symptoms (yes/no), and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ), the correlation with COX-2, p16(INK4A) and p53 expression were analyzed, and only p53 expression was correlated with Ann Arbor staging (P=0.027). The statistical analysis of correlations between COX- 2, p16(INK4A) and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008), and p16 (INK4A) was not related to either COX-2 or p53 (P=0.246 and 0.958). Kaplan- Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients'event free survival (EFS) (P=0.003). Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091, 95% CI 0.017-0.505, P=0.006).

CONCLUSIONThe expression rate of COX-2, p16 (INK4A) and p53 in the cHL were relatively high; and they were not statistically correlated with tumor EBV infection status; the COX-2 positive group had poor prognosis, but only event free survival time becomes statistically significant shorter. COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.

Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease-Free Survival ; Epstein-Barr Virus Infections ; Female ; Hodgkin Disease ; diagnosis ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult