MGMT -535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy.

PURPOSE: The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer. PATIENTS AND METHODS: A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay. RESULTS: During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) -535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423-6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P < 0.001 and 0.001, respectively). CONCLUSION: The MGMT -535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.

Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case-control study.

BACKGROUND: Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C-->T and -31T-->C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C-->T, -1464G-->C, -511C-->T, and -31T-->C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD. METHODS: The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls. RESULTS: Individuals with at least one variant allele of the -511C-->T and -31T-->C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P=0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P=0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P=0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P=0.01, respectively), however, there was no significant association between the -511C-->T and -31T-->C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN*2 allele were at a significantly lower risk for COPD compared to subjects carrying no IL1RN*2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P=0.04). In haplotype/diplotype analyses, individuals with one or two copies of the IL1B CCTC haplotype that carried the risk allele at all of the -3737C-->T, -1464G-->C, -511C-->T, and -31T-->C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P=0.01). CONCLUSION: These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population.

Hemophagocytic syndrome associated with bilateral adrenal gland tuberculosis.

We report a case of a patient who presented with hemophagocytic syndrome (HPS) and adrenal crisis associated with bilateral adrenal gland tuberculosis, and resulted in a poor outcome. A 50-year-old man was transferred to our hospital from a local clinic due to fever, weight loss, and bilateral adrenal masses. Laboratory findings showed leukopenia, mild anemia, and elevated lactate dehydrogenase. Computed tomography (CT) of the abdomen revealed bilateral adrenal masses and hepatosplenomegaly. CT-guided adrenal gland biopsy showed numerous epithelioid cells and infiltration with caseous necrosis consistent with tuberculosis. Bone marrow aspiration and biopsy showed significant hemophagocytosis without evidence of malignancy, hence HPS associated with bilateral adrenal tuberculosis was diagnosed. During anti-tuberculosis treatment the patient showed recurrent hypoglycemia and hypotension. Rapid ACTH stimulation test revealed adrenal insufficiency, and we added corticosteroid treatment. But pancytopenia, especially thrombocytopenia, persisted and repeated bone marrow aspiration showed continued hemophagocytosis. On treatment day 41 multiple organ failure occurred in the patient during anti-tuberculous treatment and steroid replacement.

Degranulation and cytokine expression in human cord blood-derived mast cells cultured in serum-free medium with recombinant human stem cell factor.

Human cord blood-derived mast cells (HCMC) grown in medium with serum and recombinant human stem cell factor (rhSCF) with or without interleukin (IL)-6 are less mature than human skin mast cells (HSMC). We found that c-kit-positive HCMC cultured for 8-10 weeks with rhSCF in serum-free medium became sensitive to basic secretatogues and expressed the serine protease, chymase, which is preferentially expressed in HSMC. The HCMC release beta-hexosaminidase (beta-HEX) within 1 min of stimulation with compound 48/80 or substance P, and release was suppressed by pertussis toxin. Approximately 34% of the HCMC in the serum-free culture stained positively with chymase antibody. Chymase and c-kit levels, and responsiveness to basic secretagogues, increased substantially after an additional 2 weeks in a serum-free environment with rhIL-6 and rhSCF. Moreover, Fc(epsilon)RI-dependent activation of the HCMC resulted in induction of cytokines and cyclooxygenase-2. These results show that HCMC can differentiate into a phenotype morphologically and functionally similar to HSMC if exposed to SCF in serum-free medium.

Emphysematous prostatic abscess due to Klebsiella pneumoniae: report of a case and review of the literature.

Emphysematous prostatic abscess is a very rare form of prostatitis. Emphysematous prostatic abscess due to Klebsiella pneumoniae may have a poor prognosis according to a few previous reports. We report a rare case of successfully treated emphysematous prostatic abscess with cystitis due to Klebsiella pneumoniae in a 50-yr-old man with 15-yr history of diabetes mellitus. The patient was referred to the emergency room of our hospital. The KUB film revealed gas shadows in the lower pelvic area suggestive of emphysematous cystitis or emphysematous prostatic abscess. The gas was mainly occupying the prostate and was also seen in the bladder on pelvic CT. The patient was successfully treated with long-term antibiotic use and additional percutaneous drainage of the abscess. Emphysematous prostatic abscess may be misdiagnosed as emphysematous cystitis due to the similar location of gas shadows on radiography. Computerized tomography and transrectal ultrasonography are helpful in making the diagnosis of emphysematous prostatic abscess. Appropriate use of effective antibiotics with drainage of pus is the best treatment. This case emphasizes the importance of timely and accurate diagnosis followed by appropriate treatment in emphysematous prostatic abscess in diabetic patients.

Serum IgE levels in Korean patients with human immunodeficiency virus infection.

BACKGROUND: Human immunodeficiency virus (HIV) infection results in a selective CD4+ T cell depletion and an impairment of T cell regulation. Despite the immune depletion, the progression of HIV infection is accompanied by the stimulation of antibody synthesis. Thus, the prevalence and amplitude of the increase of total serum IgE level and the relationship between the IgE levels and the degree of immunodeficiency were evaluated in patients with HIV infection. METHOD: Twenty-six Korean adults infected with HIV, in different stages, were evaluated for serum IgE level and CD4+ T cell count. Serum IgG, IgM and IgA levels were also determined. All subjects enrolled in this study denied an individual and familial history of atopic diseases. The possibility of parasitic infestation was also excluded by history and stool examination. RESULTS: The mean serum IgE level was 473.5 IU/L with a standard deviation of 671.4 IU/L (range: 15.9-2000 IU/L) and increased serum IgE levels (> 200 IU/L) were found in 38.5% of the study population. The mean serum IgG, IgA and IgM levels were 1,939.5 +/- 588.6 mg/dL (normal: 751-1,560 mg/dL), 388.9 +/- 216.7 mg/dL (normal: 82-453 mg/dL) and 153.6 +/- 75.3 mg/dL (normal: 46-304 mg/dL), respectively. The CD4+ T cell count was inversely correlated to the serum IgE level (r = -0.429, p < 0.05), but not to the other isotypes of immunoglobulin. CONCLUSION: Serum IgE levels are increased in adults with HIV infection and could be useful as a marker of disease progression. Further study is needed to elucidate the causes and clinical significance of these findings.

Two episodes of Stenotrophomonas maltophilia endocarditis of prosthetic mitral valve: report of a case and review of the literature.

Stenotrophomonas maltophilia (previously named Xanthomonas maltophilia) is an aerobic, non-fermentive, Gram-negative bacillus that is wide spread in the environment. It was considered to be an organism with limited pathogenic potential, which was rarely capable of causing diseases in human other than those who were in debilitated or immunocompromised state. More recent studies have established that Stenotrophomonas maltophilia can behave as a true pathogen. Endocarditis due to this organism is rare, and only 24 cases of Stenotrophomonas maltophilia endocarditis have been reported in the medical literature. Most cases were associated with risk factors, including intravenous drug abuse, dental treatment, infected intravenous devices, and previous cardiac surgery. We present a case with two episodes of Stenotrophomonas maltophilia endocarditis after mitral valve prosthesis implantation, which was treated with antibiotics initially, and a combination of antibiotics and surgery later. To our knowledge, this is the first case of repetitive endocarditis due to Stenotrophomonas maltophilia.