Inverse association between habitual alcohol drinking and d-dimer in patients with type 2 diabetes mellitus.

Alcohol is known to inhibit blood coagulation. Patients with diabetes mellitus are prone to show hypercoagulability. However, it remains to be clarified whether and how habitual alcohol drinking affects coagulability in patients with diabetes. The purpose of this study was to determine the relationship between alcohol intake and d-dimer, a sensitive marker of blood coagulation, in patients with diabetes. We investigated the relationship between alcohol intake and d-dimer in plasma of 269 patients with type 2 diabetes by using analysis of covariance and logistic regression analysis after adjustment for age, gender, body mass index, hemoglobin A1c, and histories of smoking and anti-coagulation therapy. Log-transformed d-dimer and HDL cholesterol were significantly lower and higher, respectively, in regular drinkers than in nondrinkers, while there were no significant differences in log-transformed d-dimer and HDL cholesterol in occasional drinkers and nondrinkers. Odds ratios of regular drinkers vs. nondrinkers for high d-dimer (0.46 [0.21-0.98]) and low HDL cholesterol (0.20 [0.08-0.50]) were significantly lower than the reference level, while the odds ratios of occasional drinkers for high d-dimer (1.24 [0.41-3.73]) and low HDL cholesterol (0.43 [0.15-1.25]) were not significantly different from the reference level. HDL cholesterol showed a significant inverse correlation with log-transformed d-dimer both in overall subjects and in nondrinkers. Regular drinking, but not occasional drinking, was associated with lower d-dimer levels, suggesting that habitual alcohol drinking suppresses hypercoagulability in patients with diabetes. There is an alcohol intake-independent inverse association between HDL cholesterol and d-dimer.

Relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with type 2 diabetes mellitus.

Although oxidization of LDL is known to be a crucial step for atherosclerotic progression, the significance of oxidized HDL remains to be clarified. The purpose of this study was to determine the relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with diabetes. The subjects were outpatients with type 2 diabetes (n = 163; median hemoglobin A1c, 6.9%). Activities of blood coagulation and fibrinolysis were evaluated by levels of thrombin-anti-thrombin complex (TAT) and plasmin-α2 plasmin inhibitor complex (PIC), respectively. Relationships of oxidized HDL with TAT and PIC were investigated by using linear regression analysis and logistic regression analysis. Oxidized HDL showed a significant inverse correlation with TAT and a marginally significant correlation with PIC (Spearman's rank correlation coefficient: TAT, - 0.205 [p < 0.01]; PIC, - 0.135 [p = 0.087]). Prevalence of high TAT was significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (20.4 vs. 5.6%, p < 0.05), and prevalence of high PIC was marginally significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (40.7 vs. 24.1%, p = 0.099). In multivariate logistic regression analysis using age, gender, smoking, alcohol drinking, BMI, hemoglobin A1c, therapy for dyslipidemia, therapy for diabetes and anti-coagulation therapy as explanatory variables, odds ratios for high TAT and high PIC in the 3rd tertile group for oxidized HDL versus its 1st tertile group were significantly lower than the reference level of 1.00 (high TAT: 0.19 [0.04-0.99], p < 0.05; high PIC: 0.33 [0.12-0.95], p < 0.05). The frequency of high TAT or high PIC was lower in the higher tertile group for oxidized HDL than in its lower tertile group. Thus, oxidized HDL is thought to be inversely associated with both blood coagulation and fibrinolysis in patients with type 2 diabetes.

Hairy cell leukemia accompanied by Evans syndrome.

We report a case of Western type hairy cell leukemia (HCL), a very rare leukemia in Japan. In this malignancy, leukemic cells in a peripheral blood film may be missed due in part to accompanying pancytopenia and in part to loss of typical cytoplasmic projections if prepared in a conventional Japanese way using forced air-drying. Our present patient also had a variety of autoantibodies and the clinical picture was primarily that of Evans syndrome (ES), suggesting disturbed immune responses associated with the HCL. Although HCL accompanied by either AIHA or ITP has been reported, the occurrence of ES in HCL is extremely rare.

Interleukin-6-producing dermoid cyst associated with multicentric Castleman's disease.

Dysregulated overproduction of interleukin-6 (IL-6) from activated B cells in affected lymph nodes has been implicated in the pathogenesis of multicentric Castleman's disease (MCD), a rare lymphoproliferative disorder accompanied by systemic manifestations. We here report the case of a 32-year-old female presenting with MCD associated with a dermoid cyst in the pelvic cavity. The co-occurrence of MCD and dermoid cyst has not been reported before. Immunohistochemical analysis of the tissue sections showed IL-6 production in CD68-positive macrophage cells, which had infiltrated the dermoid cyst. Removal of the cyst resulted in partial improvement in systemic symptoms accompanied by a decrease in serum IL-6, while complete improvement was obtained by treatment with an anti-IL-6 receptor antibody following resection of the dermoid cyst. To the best of our knowledge, this is the first study to provide evidence of IL-6 production by CD68(+) cells in a dermoid cyst involved in MCD.

The relationship between gastric emptying determined by the breath test and H. pylori.

BACKGROUND/AIMS: Helicobacter pylori infection has been implicated in atrophic gastritis and gastric ulcer disease. However, the relationship between gastric emptying and Helicobacter pylori infection is still unclear. METHODOLOGY: One hundred and two consecutive patients with functional dyspepsia were enrolled in this study (53 Helicobacter pylori positive and 49 negative). Gastric emptying was determined using both the 13C-octanoic acid breath test and the paracetamol absorption test. For grading gastric atrophy, the biopsy samples and serum pepsinogen I/II ratio were used. The relationship between gastric emptying, Helicobacter pylori infection and atrophy grade was investigated. RESULTS: There was no significant difference in all gastric emptying parameters between Helicobacter pylori positive and negative patients. However, in Helicobacter pylori positive subjects, pepsinogen I/II ratio correlated with atrophy grade, and it also correlated with all parameters of gastric emptying. Especially in the half-emptying time, an important parameter, there was significant correlation with the pepsinogen I/II ratio (R = -0.39, p < 0.01). This finding implies that gastric emptying is delayed according to the degree of gastric atrophy. CONCLUSIONS: Gastric emptying was not delayed simply according to advanced age, but according to the advance in gastric atrophy.

Effects of Helicobacter pylori eradication therapy on gastric emptying measured using the 13C-octanoic acid breath test and the acetaminophen method.

BACKGROUND: The relationship between Helicobacter pylori eradication and gastric emptying has been reported; however, the effect of eradication therapy on gastric emptying is still unclear. This study evaluated the relationship between three gastric emptying techniques, the scintigraphic technique, the 13C-octanoic acid breath test, and the acetaminophen method, measured simultaneously, and the effect of H. pylori eradication therapy on gastric emptying and abdominal symptoms in patients with functional dyspepsia who were H. pylori positive. METHODS: Fifty-three consecutive patients with positive H. pylori infection were enrolled in this study. In the first 14 patients, gastric emptying was measured using the three gastric emptying techniques. In 42 patients cured of H. pylori infection, the 13C-octanoic acid breath test and the acetaminophen method were performed before and 3 months after eradication. RESULTS: Significant correlations were found between the scintigraphic technique, the 13C-octanoic acid breath test, and the acetaminophen method. Gastric emptying determined by the 13C-octanoic acid breath test and the acetaminophen method was not changed after eradication, on average. In 14 (33.3%) patients a decrease in symptom score after eradication was observed. In four (9.5%) patients, accelerated gastric emptying after eradication may have led to a reduction in the abdominal symptoms. CONCLUSIONS: The 13C-octanoic acid breath test and the acetaminophen method are appropriate for investigating gastric emptying. A causal relationship between improvement of symptoms and accelerated gastric emptying was not found, and the efficacy of H. pylori eradication therapy in patients with functional dyspepsia was minimally exhibited.

Influence of gastritis on cyclooxygenase-2 expression before and after eradication of Helicobacter pylori infection.

OBJECTIVES: Helicobacter pylori infection causes chronic gastritis and induces cyclooxygenase (COX)-2 expression. The relationship between gastritis and COX-2 expression is not well understood, especially long after the organism has been eradicated. We designed a study to elucidate this relationship. METHODS: Four endoscopic gastric biopsies from each of 118 H. pylori-infected subjects were assessed for COX-2 expression immunohistochemically, gastritis, by an updated Sydney System. In the 107 successfully eradicated subjects, the assessment was repeated once yearly, for 3 years. RESULTS: After successful eradication, COX-2 expression was reduced significantly regardless of site. Atrophy improved significantly and intestinal metaplasia improved but not in the antrum greater curvature. After 1 year COX-2 expression was not significantly different in the epithelia with and without intestinal metaplasia. Correlation between COX-2 expression and neutrophil score in the antrum (r = 0.214, P = 0.042) and inflammation in the corpus (r = 0.234, P = 0.025) disappeared after eradication. COX-2 expression correlated well with atrophy and metaplasia before and after eradication. No significant reduction in COX-2 or improvement in gastritis was found in subjects with eradication failure. CONCLUSION: H. pylori infection is associated with the enhancement of COX-2 expression in the gastric mucosa. Eradication therapy reduces COX-2 expression and hence may reduce the risk of cancer development.

Effect of Helicobacter pylori-induced cyclooxygenase-2 on gastric epithelial cell kinetics: implication for gastric carcinogenesis.

BACKGROUND: Cyclooxygenase (COX)-2 induced by Helicobacter pylori is thought to enhance gastric carcinogenesis by affecting the maintenance of epithelial homeostasis. MATERIALS AND METHODS: Gastric biopsies from 160 subjects, 97 with nonulcer dyspepsia (47 H. pylori negative, 50 H. pylori positive) and 63 with gastric cancer were examined immunohistochemically for COX-2 expression, cell proliferation and apoptotic indices. RESULTS: COX-2 expression in corpus was significantly higher in H. pylori positive than in negative non-ulcer dyspepsia (NUD) (p <.05). Regardless of site, gastric cancer subjects had higher COX-2 expression in both antrum and corpus compared with H. pylori negative and positive NUD (p <.005). Proliferation was higher in cancer and H. pylori positive than in negative NUD (p <.0001). Moreover, cancer had enhanced proliferation than H. pylori positive NUD in corpus greater (p =.0454) and antrum lesser (p =.0215) curvatures. Apoptosis was higher in H. pylori positive than in negative NUD (p <.05). However, both had a higher index than the cancer subjects (p <.0001). Apoptosis : proliferation ratio was higher in corpus of H. pylori negative than in positive NUD in greater (p =.0122) and lesser (p =.0009) curvatures. However, both had a higher A:P ratio than cancer cases (p =.0001). A negative correlation between COX-2 expression and A:P ratio was found in corpus greater (r = -.176, p =.0437) and lesser (r = -.188, p =.0312) curvatures. CONCLUSION: The expression of COX-2 is associated with disruption in gastric epithelial kinetics and hence may play a role in gastric carcinogenesis.